Registration Dossier

Administrative data

Description of key information

Acute Oral Toxicity: LD50 > 2000 mg/kg (male/female Wistar rats)

Acute Inhalation Toxicity: >5.1 mg/L ( Alpk:APfSD rats)

Acute Dermal Toxicity: LD50 > 2000 mg/kg (male/female Wistar rats)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 June 2003 to 10 July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD, EU & US EPA test guidelines in compliance with GLP
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
not specified
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Species: Rat, Wistar strain Crl:(WI) BR (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC). Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals: 6 Animals. Each dose group consisted of 3 animals of one sex (females were nulliparous and non-pregnant).
Age and body weight: Young adult animals (approx. 8 weeks old) were selected. Bodyweight variation did not exceed +1- 20% of the sex mean.
Identification: Earmark.

ANIMAL HUSBANDRY
Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0°C (actual range: 17.2-23.2°C), a relative humidity of 30-70% (actual range: 48 - 83%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
Accommodation: Group housing of 3 animals per sex per cage in labelled Macrolon cages (type IV; height 18 cm.) containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany).
Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany).
Water: Free access to tap-water.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The toxicity of the test substance was assessed by stepwise treatment of groups of 3 animals.
The first group was treated at a dose level of 2000 mg/kg body weight. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.
Doses:
2000 mg/kg (2.062 ml/kg) body weight.
Dose volume calculated as dose level: specific gravity.
No. of animals per sex per dose:
3 males and 3 females all receiving 2000 mg/kg
Control animals:
no
Details on study design:
TREATMENT
A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health.
Method: Oral gavage, using a stainless steel stomach tube.
Fasting: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the test substance.
Frequency: Single dosage, on day 1.
Dose level (volume): 2000 mg/kg (2.062 ml/kg) body weight. Dose volume calculated as dose level: specific gravity.

OBSERVATIONS
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Necropsy: At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortaliy occurred.
Clinical signs:
Hunched posiure and piloerection were observed among all females on day 1. Males were without clinical signs.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
No further findings detailed in the study report.

TABLE 1: CLINICAL SIGNS

TEST DAY

 

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

HOURS AFTER TREATMENT

MAX

0

2

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

GRADE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

FEMALES 2000 MG/KG

ANIMAL 1

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hunched posture

(1)

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Piloerection

(1)

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 2

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hunched posture

(1)

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Piloerection

(1)

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 3

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hunched posture

(1)

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Piloerection

(1)

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

MALES 2000 MG/KG

ANIMAL 4

NO CLINICAL SIGNS NOTED

 

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 5

NO CLINICAL SIGNS NOTED

 

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 6

NO CLINICAL SIGNS NOTED

 

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

- = SIGN NOT OBSERVED; . = OBSERVATION NOT PERFORMED; + = ANIMAL DEAD

 

TABLE 2: BODYWEIGHTS (GRAM)

SEX/DOSE LEVEL

ANIMAL

DAY 1

DAY 8

DAY 15

FEMALES 2000 MG/KG

 

1

167

215

232

 

2

173

216

247

 

3

171

217

237

 

MEAN

170

216

239

 

ST.DEV.

3

1

8

 

N

3

3

3

MALES 2000 MG/KG

 

4

254

321

346

 

5

254

338

381

 

6

263

340

375

 

MEAN

257

333

367

 

ST.DEV.

5

10

19

 

N

3

3

3

 

TABLE 3: MACROSCOPIC FINDINGS

ANIMAL ORGAN

FINDING

DAY OF DEATH

FEMALES 2000 MG/KG

1

No findings noted

Scheduled necropsy Day 15 after treatment

2

No findings noted

Scheduled necropsy Day 15 after treatment

3

No findings noted

Scheduled necropsy Day 15 after treatment

MALES 2000 MG/KG

4

No findings noted

Scheduled necropsy Day 15 after treatment

5

No findings noted

Scheduled necropsy Day 15 after treatment

6

No findings noted

Scheduled necropsy Day 15 after treatment

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value of HATCOL 3331 in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

Assessment of acute oral toxicity with HATCOL 3331 in the rat (Acute Toxic Class Method).

The study was carried out based on the guidelines described in: Environmental Protection Agency (EPA): Health Effects Test Guidelines OPPTS 870.1100. "Acute Oral Toxicity"; EC Commission Directive 96/54/EC, Part B.1 tris "Acute Toxicity-Oral, Acute Toxic Class Method", OECD No.423, "Acute Oral Toxicity - Acute Toxic Class Method" and JMAFF Japanese test guidelines.

 

HATCOL 3331 was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg bodyweight. Animals were subjected to daily observations and weekly determination of bodyweight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred.

Hunched posture and piloerection were observed among all females on day 1. Males were without clinical signs.

The body weight gain shown by the animals over the study period was considered to be normal.

No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of HA TCOL 3331 in Wistar rats was established to exceed 2000 mg/kg bodyweight.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 3331 does not have to be classified and has no obligatory labelling requirement for oral toxicity.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 June 2003 to 10 July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD, EU & US EPA test guidelines in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
not specified
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Species: Rat, Wistar strain Crl:(WI) BR (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC). Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals: 6 Animals. Each dose group consisted of 3 animals of one sex (females were nullparous and non-pregnant).
Age and body weight: Young adult animals (approx. 8 weeks old) were selected. Bodyweight variation did not exceed +/- 20% of the sex mean.
Identification: Earmark.

Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0°C (actual range: 17.2-23.2°C), a relative humidity of 30-70% (actual range: 48 - 83%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
Accommodation: Group housing of 3 animals per sex per cage in labelled Macrolon cages (type IV; height 18 cm.) containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany).
Water: Free access to tap-water.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test substance was dosed undiluted as delivered by the sponsor.
STUDY DESIGN: The toxicity of the test substance was assessed by stepwise treatment of groups of 3 animals. The first group was treated at a dose level of 2000 mg/kg body weight. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.
TREATMENT: A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health.
Method: Oral gavage, using a stainless steel stomach tube.
Fasting: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3- hours after administration of the test substance.
Frequency: Single dosage, on day 1.
Dose level (volume): 2000 mg/kg (2.02 ml/kg) body weight. Dose volume calculated as dose level: specific gravity.
Doses:
Single dosage, on day 1.
No. of animals per sex per dose:
3 males & 3 females - all in the dose group
Control animals:
no
Details on study design:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Necropsy: At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
No statistical analysis was perfonned (The method used is not intended to allow the calculation of a precise LD50 value).
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture and piloerection were shown by all males on day 1 and by all females between days 1 and 3. In additon, all males showed lethargy on day 1.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
No abnormalites were found at macroscopic post mortem examination of the animals.
Other findings:
No further findings noted in the study report.

TABLE 1: CLINICAL SIGNS

TEST DAY

 

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

HOURS AFTER TREATMENT

MAX

0

2

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

GRADE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

FEMALES 2000 MG/KG

ANIMAL 1

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hunched Posture

(1)

1

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Piloerection

(1)

1

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 2

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hunched Posture

(1)

1

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Piloerection

(1)

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 3

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hunched Posture

(1)

1

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

SKIN/FUR/PLUMGAE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Piloerection

(1)

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

MALES 2000 MG/KG

ANIMAL 4

BEHAVIOUR

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Lethargy

(3)

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hunched Posture

(1)

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Piloerection

(1)

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 5

BEHAVIOUR

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Lethargy

(3)

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hunched Posture

(1)

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Piloerection

(1)

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 6

BEHAVIOUR

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Lethargy

(3)

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hunched Posture

(1)

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Piloerection

(1)

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-=SIGN NOT OBSERVED/ .=OBSERVTAION NOT PERFORMED/ +=ANIMAL DEAD

 

TABLE 2: BODY WEIGHTS (GRAMS)

SEX/DOSE LEVEL

ANIMAL

DAY 1

DAY 8

DAY 15

FEMALES 2000 MG/KG

 

1

162

213

225

 

2

163

210

227

 

3

162

210

222

 

MEAN

162

211

225

 

ST.DEV.

1

2

3

 

N

3

3

3

MALES 2000 MG/KG

 

4

246

306

344

 

5

258

320

350

 

6

259

329

380

 

MEAN

254

318

358

 

ST.DEV.

7

12

19

 

N

3

3

3

 

TABLE 3:MACROSCOPIC FINDINGS

ANIMAL ORGAN

FINDING

DAY OF DEATH

FEMALES 2000 MG/KG

1

No findings noted

Scheduled necropsy Day 15 after treatment

2

No findings noted

Scheduled necropsy Day 15 after treatment

3

No findings noted

Scheduled necropsy Day 15 after treatment

MALES 2000 MG/KG

4

No findings noted

Scheduled necropsy Day 15 after treatment

5

No findings noted

Scheduled necropsy Day 15 after treatment

6

No findings noted

Scheduled necropsy Day 15 after treatment

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value of HATCOL 3344 in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

Assessment of acute oral toxicity with HATCOL 3344 in the rat (Acute Toxic Class Method).

The study was carried out based on the guidelines described in: Environmental Protection Agency (EPA): Health Effects Test Guidelines OPPTS 870.1100. -Acute Oral Toxicity; EC Commission Directive 96/54/EC, Part B.1 tris "Acute Toxicity-oral, Acute Toxic Class Method", DECO No.423, "Acute Oral Toxicity - Acute Toxic Class Method" and JMAFF Japanese test guidelines.

HATCOL 3344 was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kgbody weight. Animals were subjected to daily observations and weekly determination of bodyweight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred.

Hunched posture and piloerection were shown by all males on day 1 and by all females between days 1 and 3. In addition, all males showed lethargy on day 1.

The body weight gain shown by the animals over the study period was considered to be normal.

No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of HATCOl 3344 in Wistar rats was established to exceed 2000 mg/kgbody weight.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 671548JEEC), HATCOL 334 does not have to be classified and has no obligatory labelling requirement for oral toxicity.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 November 2002 to 12 December 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD, EU & US EPA test guidelines in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
not specified
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Species: Rat, Wistar strain Cri:(Wl) BR (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC). Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals: 6 Animals. Each dose group consisted of 3 animals of one sex (females were nullparous and non-pregnant).
Age and body weight: Young adult animals (approx. 9 weeks old) were selected. Body weight variation did not exceed +1- 20% of the sex mean.
Identification: Earmark.

Conditions: A controlled environment was maintained in the room with optimal conditions considered as being approximately 15 air changes per hour, a temperature of 21± 3°C, a relative humidity of 30-70% and 12 hours artificial fluorescent light and 12 hours dark per day. Deviations from the maximum level for relative humidity (with a maximum of 20%) occurred which might have been caused by cleaning procedures in the room. Based on laboratory historical data these deviations were considered not to have affected the study integrity.
Accommodation: Group housing of 3 animals per sex per cage in labelled Macrolon cages (type IV; height 18 cm.) containing purified sawdust as bedding material. Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Free access to standard pelleted laboratory animal diet.
Water: Free access to tap water.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test substance was dosed undiluted as delivered by the sponsor.
A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health.
Method: Oral gavage, using a stainless steel stomach tube.
Fasting: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until approximately 3-4 hours after administration of the test substance.
Frequency: Single dosage, on day 1.
Dose level (volume): 2000 mg/g (2.0 ml/g) body weight. Dose volume calculated as dose level: specific gravity.
Doses:
Single does
No. of animals per sex per dose:
Each dose group consisted of 3 animals of one sex (females were nullparous and non-pregnant).
Control animals:
no
Details on study design:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration). 8 and 15
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Necropsy: At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture was noted in all animals on day 1.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strin.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
No further findings detailed in the study report.

CLINICAL SIGNS

TEST DAY

 

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

HOURS AFTER TREATMENT

MAX GRADE

0

2

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

FEMALES 2000 MG/KG

ANIMAL 1

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hunched posture

(1)

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 2

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hunched posture

(1)

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 3

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hunched posture

(1)

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

MALES 2000 MG/KG

ANIMAL 4

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hunched posture

(1)

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 5

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hunched posture

(1)

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 6

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hunched posture

(1)

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-=Sign not observed; .=Observation not performed; +=Animal dead

BODY WEIGHTS (GRAM)

SEX/DOSE LEVEL

ANIMAL

DAY 1

DAY 8

DAY 15

FEMALES 2000 MG/KG

 

1

193

234

251

 

2

183

228

247

 

3

198

244

260

 

MEAN

191

235

253

 

ST.DEV.

8

8

7

 

N

3

3

3

MALES 2000 MG/KG

 

4

319

413

464

 

5

313

383

420

 

6

309

379

423

 

MEAN

314

392

436

 

ST.DEV.

5

19

25

 

N

3

3

3

 

MACROSCOPIC FINDINGS

ANIMAL ORGAN

FINDING

DAY OF DEATH

FEMALES 2000 MG/KG

1

No findings noted

Scheduled necropsy Day 15 after treatment

2

No findings noted

Scheduled necropsy Day 15 after treatment

3

No findings noted

Scheduled necropsy Day 15 after treatment

MALES 2000 MG/KG

4

No findings noted

Scheduled necropsy Day 15 after treatment

5

No findings noted

Scheduled necropsy Day 15 after treatment

6

No findings noted

Scheduled necropsy Day 15 after treatment

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value of HATCOL 5236 in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

Assessment of acute oral toxicity with HATCOL 5236 in the rat (Acute Toxic Class Method).

The study was carried out based on the guidelines described in: Environmental Protection Agency (EPA): Health Effects Test Guidelines OPPTS 870.1100. "Acute Oral Toxicity", June 1996; EC Commission Directive 96/54/EC, Part B.1 tris "Acute Toxicity-Oral, Acute Toxic Class Method" and OECD No.423, "Acute Oral Toxicity - Acute Toxic Class Method".

HATCOL 5236 was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred.

Hunched posture was noted in all animals on day 1.

The body weight gain shown by the animals over the study period was considered to be normal.

No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of HATCOL 5236 in Wistar rats was established to exceed 2000 mg/kgbody weight.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 5236 does not have to be classified and has no obligatory labelling requirement for oral toxicity.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions.Limited documentation but relevant data given.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Adopted 24 February 1987
Deviations:
yes
Remarks:
limited documentation, limited information on test substance given, no necropsy performed
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Weight at study initiation: mean: 185 g (males), 150 g (females)- Fasting period before study: 18 h before until 3 h after dosing
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
2 % solution in water
Details on oral exposure:
VEHICLE- Concentration in vehicle: 20 %- Amount of vehicle (if gavage): 10 mL/kg bw- Justification for choice of vehicle: no dataMAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
2000 mg / kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days- Frequency of observations and weighing: observation after 1, 6, 24 and 48 h, weighing after 24 h, 1 and 2 weeks- Necropsy of survivors performed: no- Other examinations performed: clinical signs, body weight
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No clinical signs of toxicity were observed up to the end of the 14-day observation period.
Body weight:
No effect on body weight was noted.
Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
CLP: not classifiedDSD: not classified
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
04 Nov - 02 Dec 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study. For read-across, maximum reliability score is 2.
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
yes
Remarks:
limited information on test substance
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Charles River Wiga GmbH, Sulzfeld, Germany- Age at study initiation: 8 weeks- Weight at study initiation: males: 255 ± 8.8 g, females: 172 ± 12.0 g- Fasting period before study: overnight before substance application until 3 h after dosing- Housing: animals were housed individually in polycarbonate cages- Diet: RMH-B, Hope Farms, Woerden, The Netherlands, ad libitum- Water: tap-water, ad libitum- Acclimation period: at least 5 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 20 - 21- Humidity (%): 55 - 70- Air changes: air conditioned room- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 5.5 mL/kg bw
Doses:
Pilot study: 1800, 3200 and 5000 mg/kg bwMain study: 5000 mg/kg bw
No. of animals per sex per dose:
Pilot study: 1 Main study: 5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days- Frequency of observations and weighing: animals were observed daily for clinical signs of toxicity, and individual body weights were determined weekly- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period, neither in the pilot nor in the main study.
Clinical signs:
No clinical signs of toxicity were observed up to the end of the 14-day observation period.
Body weight:
No effect on body weight was noted.
Gross pathology:
Necropsy revealed no substance-related findings.
Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
CLP: not classifiedDSD: not classified
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
14 Apr - 12 Jun 1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (limited information on test material).
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted in 1987
Deviations:
yes
Remarks:
limited data on test material
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD (SD)BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: male rats: Charles River Laboratories, Inc., Hollister, CA, USA; female rats: Charles River Laboratories, Inc., Portage, MI, USA- Age at study initiation: 6 - 13 weeks- Weight at study initiation: 274 - 292 g (males) and 221 - 256 g (females)- Fasting period before study: food, but not water, was withheld 17 to 20 h prior to administration - Housing: 5 animals of the same sex were housed in suspended screen-bottom stainless steel cages- Diet: Laboratory Rodent Diet #5001, PMI Feeds, Inc., ad libitum- Water: ad libitum- Acclimation period: at least 7 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 19 - 25 (days 0 through 3), 18 - 26 (days 4 through 14)- Humidity (%): 50 ± 20- Photoperiod (hrs dark / hrs light): 12/12IN-LIFE DATES: From: 21 Apr 1997: To: 5 May 1997
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.11 mL/kg bw (average bulk density of 0.95 g/mL)DOSAGE PREPARATION: calculation was done for each animal based on its fasted body weight
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days- Frequency of observations and weighing: clinical observations were conducted at 1, 2.5, and 4 h after test material administration and daily thereafter for 14 days. Mortality checks were conducted twice a day (morning and afternoon) for 13 days after test material administration and again in the morning of Day 14. Body weights were determined before test material administration (Day 0), at Day 7 and at Day 14.- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occured during the study period.
Clinical signs:
No clinical signs of toxicity were observed up to the end of the 14-day observation period. According to the author one male animal exhibited soft stool 1 h post-dose and returned to normal appearance 2.5 h post-dose.
Body weight:
No effect on body weight was noted.
Gross pathology:
Necropsy revealed no substance-related findings.
Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
CLP: not classifiedDSD: not classified
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
06 Nov - 20 Nov 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline studyLimited details on test compound. For read-across, maximum reliability score is 2.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
: Limited details on test compound
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: ICO: OFA-SD (IOPS Caw)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Iffa Crédo, France- Age at study initiation: 6 weeks- Weight at study initiation: males: 173 ± 3 g, females: 144 ± 7 g- Housing: 5 animals per polycarbonate cage (48x27x20 cm)- Fasting period before study: 18 h before until 4 h after dosing- Diet: ad libitum (Rats - Mice substance ref. A04 C)- Water: ad libitum- Acclimation period: 5 dENVIRONMENTAL CONDITIONS- Temperature (°C): 19 - 25- Humidity (%): 30 - 70- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.13 mL taking into account the specific gravity of 0.94
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days- Frequency of observations and weighing: daily, weighing on Days 1, 5, 8 and 15 - Necropsy of survivors performed: yes- Other examinations performed: gross pathology
Statistics:
Not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality
Clinical signs:
Hypokinesia was observed 2 and 4 h after treatment. From Day 2 to the end of the study, no clinical signs were observed.
Body weight:
Normal body weight gain
Gross pathology:
No apparent abnormalities
Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
CLP: not classifiedDSD: not classified
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
28 Mar - 4 Nov 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (no analytical purity; method shortly described)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
no analytical purity; method shortly described
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Taconic Farms
- Fasting period before study: overnight
- Housing: individually in single wire bottom stainless steel suspended cages
- Diet: Purina Dawley Chow # 5002
- Water: Automatic watering; ad libitum

Route of administration:
oral: gavage
Doses:
15000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 15 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No clinical signs of toxicity related to the administration of the test substance were observed up to the end of the 14-day observation period. However, all animals exhibited clear, oily perineal staining on the 1st, 2nd, and 3rd day following treatment; this condition normally regarded as an adverse effect, was considered to be a consequence of the high dose level administered and not considered a toxic sign.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
7 Dec - 23 Dec 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (no analytical purity reported)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
adopted in 1992
Deviations:
yes
Remarks:
no analytical purity reported
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
other: Albino Rats (Outbred). Stock: Sprague-Dawley-derived (CD) [Crl: CD (SD) IGS BR]
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Kingston, New York, USA
- Age at study initiation: 9-12 weeks
- Weight at study initiation: 279-318 g (males), 204-219 g (females)
- Fasting period before study: animals were fasted overnight prior administration
- Housing: 2 to 6 animals of the same sex per cage (during acclimation) und individual (during study) per cages. Cages were suspended, stainless cages with wire mesh bottoms.
- Diet: certified Rodent Diet, No. 5002 (PMI Nutrition International, Inc., St. Louis, MO), ad libitum
- Water: automatic watering system, Municipal water supply (Elizabethtown Water Company), ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 26
- Humidity (%): 30 -70
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2 mL/kg



Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were checked for viability daily. Each animal was examined (general condition, skin and fur, eyes nose, oral cavity, abdomen and external genitalia as well as evaluations of respiration and palpation for tissue masses) approximately 1, 2, and 4 hours after dosing and daily thereafter for 14 days. Individual body weights were determined on day 0 (at the time of fasting), day 1 (just prior to dosing; weights were used for calculation of doses), day 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, food consumption, macroscopic post-mortem examination.
Key result
Sex:
male/female
Dose descriptor:
LD100
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No clinical signs of toxicity related to the administration of the test substance were observed up to the end of the 14-day observation period. However alopecia extremities on snout was seen in a single animal on day 9 through day 15 after the dose administration. This finding was not considered to be related to the administration of the test substance.
Body weight:
No effect on body weight was noted.
Gross pathology:
Necropsy revealed no substance-related findings.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (Only 2 male and 2 female rats were used, details on test substance not documented).
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
: Only two male and two female animals used
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Alderley Park SPF albino
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: males: 215 g - 237 g; females: 145 g - 163 g
- Fasting period before study: 24 h
Route of administration:
oral: unspecified
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
2000 mg/kg
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Duration of observation period following administration: not stated
- Other examinations performed: body weight, macroscopic abnormalities (post mortem)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No significant signs of toxicity in females but males showed slight toxicity following a 2000 mg/kg bw dose.
Body weight:
Initial loss of weight (due to predose fasting) with normal weight gain after dosing.
Gross pathology:
Necropsy and histopathological examination revealed no substance-related findings.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
August 30th, 1983 - September 13th, 1983
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Insufficient for assessment due to reduced animal number. Only 2 male and 2 female animals were used, details on test substance not documented.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
: Only two male and two female animals used, details on test substance not documented
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: >6 weeks
- Weight at study initiation: males: 282.5 g; females: 166.0 g
- Fasting period before study: 15 h
- Housing: Makrolon Type III cages
- Diet (e.g. ad libitum): Altromin-Haltungsdiät 1324 ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: > 6 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 50
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg
VEHICLE
- Concentration in vehicle: 20%
- Amount of vehicle (if gavage): 1.62 ml - 2.95 ml depending on body weight

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg
Doses:
2000 mg/kg
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
- Frequency of observations and weighing: evaluation of mortality: twice daily; weighting on days 0, 2, 7 and 14
- Necropsy of survivors performed: yes
- Duration of observation period following administration: 14 d
- Other examinations performed: body weight, macroscopic abnormalities (post mortem)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
None
Clinical signs:
No significant signs of toxicity except for transient rough fur and reduced activity direct after dosing
Body weight:
Normal weight gain after dosing.
Gross pathology:
No macroscopic findings

The limit dose of 2000 mg/kg showed no mortality in male and female rats. Although only 2 animals per sex were tested, the observations do not indicate a toxic effect.

Interpretation of results:
not classified
Remarks:
Migrated information The acute oral lethal dose was greater than 2000 mg/kg in male and female rats. Criteria used for interpretation of results: EU
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions. Limited documentation but relevant data given.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Adopted 24 February 1987
Deviations:
yes
Remarks:
limited documentation, limited information on test substance given, no necropsy performed
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: mean: 185 g (males), 150 g (females)
- Fasting period before study: 18 h before until 3 h after dosing
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
2 % solution in water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 %
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: no data

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
2000 mg / kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation after 1, 6, 24 and 48 h, weighing after 24 h, 1 and 2 weeks
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No clinical signs of toxicity were observed up to the end of the 14-day observation period.
Body weight:
No effect on body weight was noted.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
K1

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 Mar - 05 Apr 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (only few data on test item and animal husbandry were given)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
(No details on test material and limited data on animal husbandry)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Alpk:APfSD
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Alderly Park, Cheshire, UK
- Age at study initiation: approx. 7 weeks
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Source and rate of air: dried and filtered air
- System of generating aerosols: glass concentric jet atomiser
- Method of particle size determination: Marple Cascade Impactor
- Temperature, humidity, pressure in air chamber: 20 L/min

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetrically
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.51 µm/2.51
Analytical verification of test atmosphere concentrations:
yes
Remarks:
particulate concentrations of the test atmospheres close to the animals breathing zone were measured gravimetrically
Duration of exposure:
4 h
Concentrations:
5.0 mg/L (nominal)
5.10 mg/L (analytical)
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for gross clinical abnormalities during exposure and were checked daily thereafter. A detailed examination was conducted after exposure on day 1 and on consecutive days, up to and including day 15. Individual body weights were recorded on Day 1 and Days 2, 3, 8 and day 15.
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.1 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred during the study period.
Clinical signs:
other: Some clinical signs were noticed, which consisted of hunched position, chromodacryorrhea, piloerection, staining around nose and wet fur. These signs however occurred during or just after exposure and were clearly consistent with the use of restraint for
Body weight:
No effect on body weight was noted.
Gross pathology:
Necropsy and histopathological examination revealed no substance-related findings.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5.1 mg/m³
Quality of whole database:
K2

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 to 23 July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OCED, EU & US EPA test guidelines in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
not specified
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Species: Rat, Wistar strain Crl:(WI) BR (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC). Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals: 5 males and 5 females (females were nullparous and nonpregnant).
Age and body weight: Young adult animals (approx. 8 weeks old) were selected. Bodyweight variation did not exceed +/- 20% of the sex mean.
Identification: Earmark

Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0°C (actual range: 18.1-23.7°C), a relative humidity of 30-70% (actual range: 44-78%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures In the room might have caused the fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
Accommodation: Individually housed In labelled Macrolon cages (type III height 15 cm.) containing purified sawdust as bedding material (SAWI, Jetu Werk. Rosenberg, Germany).
Acclimatisation: period was at least 5 days before start of treatment under laboratory conditions.
Diet: Free access to standard pelleted laboratory animal diet (from A1tromin (code VRF i), Lage, Germany).
Water: Free access to tap-water.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
A health Inspection was performed prior to commencement of treatment to ensure that the animals were In a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.
Method: Dermal application.
Clipping: One day before exposure (day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
Application: The test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm2 for males and 18 cm2 for females. The test substance was held in contact with the skin with a dressing consisting of a surgical gauze patch (Surgy 1 D) successively covered with aluminium foil and Coban flexible bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.
Frequency: Single dosage. on day 1.
Dose level (volume): 2000 mg/kg (2.02 ml/kg) body weight. Dose volume calculated as follows: dose level: specific gravity.
Application period: 24 hours, after which dressings were removed and the skin cleaned of residual test substance using water.
Duration of exposure:
24 hours
Doses:
Single dosage, on day 1.
No. of animals per sex per dose:
5 males & 5 females - all dosed
Control animals:
not required
Details on study design:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Necropsy: At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
No statistical analysis was performed.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
All females and some males showed scales, scabs and/or general/maculate erythema on the treated skin site during the observation period from day 3 onwards. In addition chromodacryorrhoea was noted among some animals on days 1 and/or 2, with diarrhoea in one male between days 2 and 4.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
No further findings noted in the study report.

TABLE 1: CLINICAL SIGNS

TEST DAY

 

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

HOURS AFTER TREATMENT

MAX

0

2

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

GRADE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

MALES 2000 MG/KG

ANIMAL 1

NO CLINICAL SIGNS NOTED

 

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 2

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Scales (Treated Skin)

(3)

-

-

-

-

-

-

-

-

1

1

1

1

1

1

1

1

1

Scabs (Treated Skin)

(3)

-

-

-

-

-

-

-

-

1

1

1

1

1

2

2

1

1

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chromadacryorrhoea (Nose)

(3)

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 3

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Diarrhoea

(1)

-

-

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

Chromodacryorrhoea (Snout)

(3)

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 4

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chromodacryorrhoea (Nose)

(3)

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 5

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

General Erythema (Treated Skin)

(4)

-

-

-

-

1

1

1

-

-

-

-

-

-

-

-

-

-

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chromodacryorrhoea (Snout)

(3)

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

FEMALES 2000 MG/KG

ANIMAL 6

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Erythema Maculate (Treated Skin)

(4)

-

-

-

-

2

2

1

1

1

1

1

1

1

1

-

-

-

Scales (Treated Skin)

(3)

-

-

-

-

-

-

-

-

1

1

1

1

1

1

1

1

1

Scabs (Treated Skin)

(3)

-

-

-

-

-

-

-

1

1

1

1

1

1

1

1

1

1

ANIMAL 7

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Erythema Maculate (Treated Skin)

(4)

-

-

-

-

1

1

1

1

1

-

-

-

-

-

-

-

-

Scales (Treated Skin)

(3)

-

-

-

-

-

-

-

-

1

-

-

-

-

-

-

-

-

Scabs (Treated Skin)

(3)

-

-

-

-

-

-

-

1

1

1

1

1

1

1

1

1

1

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chromodacryorrhoea (Snout)

(3)

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 8

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Scales (Treated Skin)

(3)

-

-

-

-

-

-

-

-

1

1

-

-

-

-

-

-

-

ANIMAL 9

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Scales (Treated Skin)

(3)

-

-

-

-

-

-

-

-

1

1

-

-

-

-

-

-

-

ANIMAL 10

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Scales (Treated Skin)

(3)

-

-

-

-

1

1

1

1

1

1

1

1

1

-

-

-

-

Scabs (Treated Skin)

(3)

-

-

-

-

-

-

-

-

-

-

-

-

-

1

1

1

1

-=SIGN NOT OBSERVED/ .=OBSERVATION NOT PERFORMED/ +=ANIMAL DEAD

 

TABLE 2: BODYWEIGHTS (GRAMS)

SEX/DOSE LEVEL

ANIMAL

DAY 1

DAY 8

DAY 15

MALES 2000 MG/KG

 

1

285

334

390

 

2

266

303

352

 

3

273

303

336

 

4

283

322

372

 

5

247

280

311

 

MEAN

271

308

352

 

ST.DEV.

15

21

31

 

N

5

5

5

FEMALES 2000 MG/KG

 

6

191

214

233

 

7

192

212

236

 

8

204

227

245

 

9

186

224

268

 

10

198

218

235

 

MEAN

194

219

243

 

ST.DEV.

7

6

15

 

N

5

5

5

 

TABLE 3: MACROSCOPIC FINDINGS

ANIMAL ORGAN

FINDINGS

DAY OF DEATH

MALES 2000 MG/KG

1

No findings noted

Schedule necropsy Day 15 after treatment

2

No findings noted

Schedule necropsy Day 15 after treatment

3

No findings noted

Schedule necropsy Day 15 after treatment

4

No findings noted

Schedule necropsy Day 15 after treatment

5

No findings noted

Schedule necropsy Day 15 after treatment

FEMALES 2000 MG/KG

6

No findings noted

Schedule necropsy Day 15 after treatment

7

No findings noted

Schedule necropsy Day 15 after treatment

8

No findings noted

Schedule necropsy Day 15 after treatment

9

No findings noted

Schedule necropsy Day 15 after treatment

10

No findings noted

Schedule necropsy Day 15 after treatment

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 value of HATCOL 3344 in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

Assessment of acute dermal toxicity with HATCOL 3344 in the rat.

The study was carried out based on the guidelines described in: Environmental Protection Agency (EPA): Health Effects Test Guidelines OPPTS 870.1200. "Acute Dermal Toxicity, ECCommission Directive 92169/EEC, Part B.3, "Acute Toxicity-Dermal", OECD No102, "AcuteDermal Toxicity" and JMAFF: Japanese Test Guidelines.

HATCOL 3344 was administered to five Wistar rats of each sex by dermal application at 2000mg/kg body weight for 24 hours. Animals were subjected to daily observations and weeklydetermination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred.

All females and some males showed scales, scabs and/or general/maculate erythema on the treated skin site during the observation period from day 3 onwards. In addition chromodacryorrhoea was noted among some animals on days 1 and/or 2, with diarrhoea in one male between days 2 and 4.

The body weight gain during the observation period was within the range expected for rats used in this type of study.

No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of HATCOL 3344 in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 3344 does not have to be classified and has no obligatory labelling requirement for dermal toxicity.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02 July to 16 July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD, EU & US EPA test guidelines in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
not specified
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
not specified
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Species: Rat, Wistar strain Crl:(WI) BR (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC) Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals: 5 males and 5 females (females were nulliparous and nonpregnant).
Age and body weight: Young adult animals (approx. 9-10 weeks old) were selected. Bodyweight variation did not exceed +/- 20% of the sex mean.
Identification: Earmark

Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0°C (actual range: 17.2 - 23.7°C), a relative humidity of 30-70% (actual range: 44 - 83%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
Accommodation: Individually housed in labelled Macrolon cages (type III, height 15 cm.) containing purified sawdust as bedding' material (SAWI, Jelu Werk, Rosenberg, Germany).
Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany).
Water: Free access to tap-water.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 hours
Doses:
Single dose 2000 mg/kg
No. of animals per sex per dose:
5 males & 5 females each received a single dose of the substance at 2000 mg/kg
Control animals:
no
Details on study design:
TREATMENT: A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.
Method: Dermal application.
Clipping: One day before exposure (day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
Application: The test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm2 for males and 18 cm2 for females. The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminium foil and Coban flexible bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.
Frequency: Single dosage, on day 1.
Dose level (volume): 2000 mg/kg (2.061 ml/kg) body weight. Dose volume calculated as follows: dose level : specific gravity.
Application: period 24 hours, after which dressings were removed and the skin cleaned of residual test substance using water.

OBSERVATIONS
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Necropsy: At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
No statistical analysis was performed.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture and/or chromodacryorrhoea were noted among all animals on day 2. In addition, maculate erythema or scales were seen on the treated skin site of one male and female between days 3 and 7.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mor!em examination of the animals.
Other findings:
No further findings detailed in the study report.

BDOYWEIGHTS (GRAM)

SEX/DOSE LEVEL

ANIMAL

DAY 1

DAY 8

DAY 15

MALES 2000 MG/KG

 

1

330

352

400

2

334

359

413

3

321

344

383

4

357

380

433

5

334

350

389

MEAN

335

357

404

ST.DEV.

13

14

20

N

5

5

5

FEMALES 2000 MG/KG

 

6

229

231

242

7

241

241

260

8

242

246

259

9

245

252

243

10

253

281

296

MEAN

242

250

260

ST.DEV.

9

19

22

N

5

5

5

 

MACROSCOPIC FINDINGS

ANIMAL ORGAN

FINDING

DAY OF DEATH

MALES 2000 MG/KG

1

No findings noted

Scheduled necropsy Day 15 after treatment

2

No findings noted

Scheduled necropsy Day 15 after treatment

3

No findings noted

Scheduled necropsy Day 15 after treatment

4

No findings noted

Scheduled necropsy Day 15 after treatment

5

No findings noted

Scheduled necropsy Day 15 after treatment

FEMALES 2000 MG/KG

6

No findings noted

Scheduled necropsy Day 15 after treatment

7

No findings noted

Scheduled necropsy Day 15 after treatment

8

No findings noted

Scheduled necropsy Day 15 after treatment

9

No findings noted

Scheduled necropsy Day 15 after treatment

10

No findings noted

Scheduled necropsy Day 15 after treatment

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 value of HATCOL 3331 in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

Assessment of acute dermal toxicity with HATCOL 3331 in the rat.

The study was carried out based on the guidelines described in: Environmental Protection Agency (EPA): Health Effects Test Guidelines OPPTS 870.1200. "Acute Dermal Toxicity", EC Commission Directive 92/69/EEC, Part B.3, "Acute Toxicity-Dermal", OECD No.402, "Acute Dermal Toxicity" and JMAFF: Japanese Test Guidelines.

HATCOL 3331 was administered to five Wistar rats of each sex by dermal application at 2000, mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred.

Hunched posture and/or chromodacryorrhoea were noted among all animals on day 2. In addition, maculate erythema or scales were seen on the treated skin site of one male andfemale between days 3 and 7.

The body weight gain during the observation period was within the range expected for rats used in this type of study.

No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of HATCOL 3331 in Wistar rats was established to exceed 2000 mg/kgbody weight.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 3331 does not have to be classified and has no obligatory labelling requirement for dermal toxicity.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 September 2003 to 15 October 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD, EU & US EPA test guidelines in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
not specified
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Species: Rat, Wistar strain Crl:(WI) BR (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC). Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals: 5 males and 5 females (females were nullparous and nonpregnant).
Age and body weight: Young adult animals (approx. 9 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean.
Identification: Earmark

Conditions: Animals were housed in a controlled environment. in which optimal conditions were considered to be approximately 15 air changes per hour. a temperature of 21.0 ± 3.0°C (actual range: 17.2 - 22.3°C), a relative humidity of 30-70% (actual range: 39 -78%) and 12 hours artificial fluorescent light and 12 hours darkness per day.
Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
Accommodation: Individually housed in labelled Macrolon cages (type II, height 15 cm) containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany).
Water: Free access to tap-water.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The test substance was dosed undiluted as delivered by the sponsor.
A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.
Method: Dermal application.
Clipping: One day before exposure (day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
Application: The test substance was applied in an area of approx. 10% of the total body surface, Le. approx. 25 cm2 for males and 18 cm2 for females. The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch, successively covered with aluminium foil and Coban flexible bandage". A piece of Micropore tape was additionally used for fixation of the bandages in females only.
Frequency: Single dosage, on day 1.
Dose level (volume): 2000 mg/kg (2.0 ml/kg) body weight. Dose volume calculated as follows: dose level: specific gravity.
Application period: 24 hours, after which dressings were removed and the skin cleaned of residual test substance using Water.
Duration of exposure:
24 hours
Doses:
Single dosage. Dose level (volume): 2000 mg/kg (2.0 ml/kg) body weight.
No. of animals per sex per dose:
5 males and 5 females
Control animals:
yes, concurrent no treatment
Details on study design:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Necropsy: At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
Not specified in the study report.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Chromodacryorrhoea (nose), hunched posture and lethargy were noted among the animals.
The animals had recovered from the symptoms by day 3.
Erythema was seen in the treated skin-area of one animal on day 3.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormaliies were found at macroscopic post mortem examination of the animals.
Other findings:
No further findings specified in the study report.

CLINICAL SIGNS

TEST DAY

 

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

HOURS AFTER TREATMENT

MAX GRADE

0

2

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

MALES 2000 MG/KG

ANIMAL 1

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chromodacryorrhoea (Nose)

(3)

-

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 2

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chromodacryorrhoea (Nose)

(3)

-

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 3

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chromodacryorrhoea (Nose)

(3)

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 4

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hunched posture

(1)

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chromodacryorrhoea (Nose)

(3)

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 5

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chromodacryorrhoea (Nose)

(3)

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

FEMALES 2000 MG/KG

ANIMAL 1

BEHAVIOUR

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Lethargy

(3)

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chromodacryorrhoea (Nose)

(3)

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 7

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chromodacryorrhoea (Nose)

(3)

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 8

NO CLINICAL SIGNS NOTED

 

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 9

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Erythema maculate (treated skin)

(4)

-

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chromodacryorrhoea (Nose)

(3)

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 10

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chromodacryorrhoea (Nose)

(3)

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-= Sign not observed; .=Observation not performed; +=Animal dead

 

BODY WEIGHTS (GRAMS)

SEX/DOSE LEVEL

ANIMAL

DAY 1

DAY 8

DAY 15

MALES 2000 MG/KG

 

1

373

377

423

 

2

329

346

371

 

3

315

334

356

 

4

334

354

385

 

5

347

369

386

 

MEAN

340

356

384

 

ST.DEV.

22

17

25

 

N

5

5

5

FEMALES 2000 MG/KG

 

6

194

203

217

 

7

240

250

263

 

8

250

254

282

 

9

248

251

273

 

10

200

215

223

 

MEAN

226

235

252

 

ST. DEV.

27

24

30

 

N

5

5

5

 

MACROSCOPIC FINDINGS

ANIMAL ORGAN

FINDINGS

DAY OF DEATH

MALES 2000 MG/KG

1

No findings noted

Schedule necropsy Day 15 after treatment

2

No findings noted

Schedule necropsy Day 15 after treatment

3

No findings noted

Schedule necropsy Day 15 after treatment

4

No findings noted

Schedule necropsy Day 15 after treatment

5

No findings noted

Schedule necropsy Day 15 after treatment

FEMALES 2000 MG/KG

6

No findings noted

Schedule necropsy Day 15 after treatment

7

No findings noted

Schedule necropsy Day 15 after treatment

8

No findings noted

Schedule necropsy Day 15 after treatment

9

No findings noted

Schedule necropsy Day 15 after treatment

10

No findings noted

Schedule necropsy Day 15 after treatment

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 value of HATCOL 5236 in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

Assessment of acute dermal toxicity with HATCOL 5236 in the rat.

The study was carried out based on the guidelines described in: "Acute Toxicity-Dermal", OECD No.402 (1987); "Acute Dermal Toxicity, EC Commission Directive 92/69/EEC, Part B.3 (1992); Environmental Protection Agency (EPA): Health Effects Test Guidelines OPPTS 870.1200 (1996), "Acute Dermal Toxicity" and JMAFF: Japanese Test Guidelines (2000).

HATCOL 5236 was administered to five Wistar rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred.

Chromodacryorrhoea (nose), hunched posture and lethargy were noted among the animals.

The animals had recovered from the symptoms by day 3.

Erythema was seen in the treated skin-area of one animal on day 3.

The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.

No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of HATCOL 5236 in Wistar rats was established to exceed 2000 mg/kgbody weight.

Based on these results and according to the:

OECD Harmonized Integrated Hazard Classification System for Human Health and Environmental Effects of Chemical Substances (OECD, 1998), HATCOL 5236 does not have to be classified for acute toxicity by the dermal route.

EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 5236 does not have to be classified and has no obligatory labelling requirement for dermal toxicity.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 June 2010 To 08 July 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Wistar strain, Crl:WI (Han)
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany.- Age at study initiation: Young adult animals (approx. 11 weeks old)- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.- Housing: Individually housed in labeled Macrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Woody-Clean type 3/4, Tecnilab-BMI BV, Someren, The Netherlands) and paper as cage-enrichment (Enviro-dri, Tecnilab-BMI BV, Someren, The Netherlands). - Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).- Water (e.g. ad libitum): Free access to tap water.- Acclimation period: The acclimatization period was at least 5 days before the start of treatment under laboratory conditions.- Health inspection: A health inspection was performed prior to treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.Results of analysis for diet (nutrients and contaminants), sawdust, paper and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.ENVIRONMENTAL CONDITIONS- Temperature (°C): 19.9 – 21.5ºC- Humidity (%): 41 - 78%Temporary deviations from the maximum level of relative humidity occurred. Laboratory historical data do not indicate an effect of the deviations.- Air changes (per hr): approximately 15 air changes per hour- Photoperiod (hrs dark / hrs light): 12 hours artificialfluorescent light and 12 hours darkness per day. IN-LIFE DATES: From: 24 June 2010 To 08 July 2010
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.The test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D)*, successively covered with aluminum foil and Coban elastic bandage*. A piece of Micropore tape* was additionally used for fixation of the bandages in females only.*. Manufacturers: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul, Minnesota, U.S.A. (Coban & Micropore).Frequency: Single dosage, on Day 1.Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.
Duration of exposure:
24 hours.
Doses:
2000 mg/kg (2.105 mL/kg) body weight.Dose volume calculated as dose level (g/kg) / specific gravity
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Dose level (volume): 2000 mg/kg (2.105 mL/kg) body weight.Dose volume calculated as dose level (g/kg) / specific gravity.DOSAGE PREPARATION: The test substance was dosed undiluted as delivered by the sponsor.Duration of observation period following administration: 14 days- Frequency of observations and weighing:Mortality/Viability: Twice dailyBody weights: Days 1 (pre-administration), 8 and 15.Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.- Necropsy of survivors performed: yes- Other examinations performed: none.
Statistics:
None.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Chromodacryorrhoea (snout) was noted for two males and two females on Day 1. One of these females also showed lethargy and ptosis on Day 1. No further clinical signs were observed.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The dermal LD50 value of Decanoic acid, mixed esters with heptanoic acid, octanoic acid and trimethylolpropane in Wistar rats was established to exceed 2000 mg/kg body weight.Based on these results, Decanoic acid, mixed esters with heptanoic acid, octanoic acid and trimethylolpropane does not have to be classified and has no obligatory labeling requirement for acute dermal toxicity according to the:- Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007),- Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures.
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study with acceptable restrictions. (Lack of data on test material.)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted in 1987
Deviations:
yes
Remarks:
(no data on test substance purity)
Qualifier:
equivalent or similar to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
adopted in1992
Deviations:
yes
Remarks:
(no data on test substance purity)
Qualifier:
equivalent or similar to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
adopted in 1998
Deviations:
yes
Remarks:
(no data on test substance purity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan
- Age at study initiation: 9 - 10 weeks
- Weight at study initiation: 247 - 253 g (males), 217 - 239 g (females)
- Housing: animals were group housed by sex upon receipt and individually housed upon assignment to study in compliance with the National Research Council " Guide for the Care and Use of Laboratory Animals".
- Diet: Harlan Teklad Rodent Diet, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 22
- Humidity (%): 23 - 59
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 9 Jan 2006
To: 23 Jan 2006
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped skin of the dorsal area of the trunk
- Type of wrap if used: the treated skin site was covered with a gauze patch/dental dam, wrapped with an elastic bandage and secured with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test substance was removed with water
- Time after start of exposure: 24 h
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were recorded immediately after dosing and at approximately 1, 2.5 and 4 h after dosing and daily thereafter through Day 15. Animals were weighed prior to dosing on Day 1 and on Days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: Mortality/morbidity (twice daily)
Statistics:
Body weights were summarized using descriptive statistics (mean and standard deviation).
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No clinical signs of toxicity were observed up to the end of the 14-day observation period.
Body weight:
Body weight gains of all animals were within the normal ranges during the whole study period.
Gross pathology:
Necropsy revealed no substance-related findings.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
EU: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
K1

Additional information

Acute Oral Toxicity

HATCOL 3331

Assessment of acute oral toxicity with HATCOL 3331 in the rat (Acute Toxic Class Method).

HATCOL 3331 was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg bodyweight. Animals were subjected to daily observations and weekly determination of bodyweight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred. Hunched posture and piloerection were observed among all females on day 1. Males were without clinical signs. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of HA TCOL 3331 in Wistar rats was established to exceed 2000 mg/kg bodyweight.

 

HATCOL 3344

Assessment of acute oral toxicity with HATCOL 3344 in the rat (Acute Toxic Class Method).

HATCOL 3344 was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg/body weight. Animals were subjected to daily observations and weekly determination of bodyweight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred. Hunched posture and piloerection were shown by all males on day 1 and by all females between days 1 and 3. In addition, all males showed lethargy on day 1. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of HATCOL 3344 in Wistar rats was established to exceed 2000 mg/kgbody weight.

 

HATCOL 5236

Assessment of acute oral toxicity with HATCOL 5236 in the rat (Acute Toxic Class Method).

HATCOL 5236 was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred. Hunched posture was noted in all animals on day 1. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of HATCOL 5236 in Wistar rats was established to exceed 2000 mg/kg/body weight.

 

HATCOL 1510

In the study conducted with CAS 11138-60-6 in accordance with OECD Guideline 401, the oral LD50 value in ICO: OFA-SD (IOPS Caw) rats was found to be > 2000 mg/kg body weight.

 

CAS 78-16-0

In the first study conducted with CAS 78-16-0 in accordance with OECD Guideline 401, the oral LD50 value in Crl:CD (SD)BR rats was determined to be > 2000 mg/kg body weight.

In the second study with CAS 78-16-0 in accordance with EU Method B.1, the oral LD50 value in Wistar rats was determined to be > 5000 mg/kg body weight

HATCOL 2937

In the study conducted with CAS 91050-89-4 in accordance with OECD Guideline 401, the oral LD50 value in Crl:CD (SD)BR was determined to be > 2000 mg/kg body weight.

CAS 68855-18-5

An acute oral toxicity study with Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol (CAS 68855-18-5) was performed according to OECD Guideline 401 (standard acute method) and GLP (Doyle, 1996). In a preliminary study, the test item was administered by gavage to two Alderley Park albino rats (Alpk: APfSD) per sex at 2000 mg/kg bw (limit test). Five further animals per sex were then treated with the same dose for the main study. The animals were subjected to daily observations and determinations of body weights on test Days -1 (prior to fasting), 1, 3, between Days 4 and 6, and on Day 8 and 15. Macroscopic examination was performed after terminal sacrifice. No mortality occurred and no clinical signs of toxicity were observed during the study period. No effects on body weights were noted and necropsy revealed no treatment-related findings. The oral LD50 value in rats was determined >2000 mg/kg bw.

 

CAS 31335-74-7

A short summary of an acute oral toxicity study with 2,2-dimethyl-1,3-propanediyl dioctanoate (CAS 31335-74-7) is available (Robinson, 1993). No information is given on the guideline followed or on GLP compliance. However, it is stated that the study was performed as a limit test. Two rats per sex (strain not specified) were orally administered the test item via gavage at a dose of 2000 mg/kg bw. During the 8-day observation period the animals were subjected to daily observations and weighing on Days 1 and 8. Macroscopic examination was performed after terminal sacrifice. No mortality occurred and no clinical signs of toxicity were observed during the study period. No effects on body weights were noted and necropsy revealed no treatment-related findings. The oral LD50 value in rats was determined >2000 mg/kg bw.

 

CAS 67989-24-6

An acute oral toxicity study 9-octadecenoic acid (Z)-, ester with 2,2-dimethyl-1,3-propanediol (CAS 67989-24-6) was performed similar to OECD Guideline 401 (standard acute method, limit test) and in compliance with GLP (Potokar, 1988). The test item was administered by oral gavage to five Wistar rats per sex at a dose of 2000 mg/kg bw. The animals were subjected to daily observations for clinical signs, and twice daily for morbidity and mortality. Body weights were determined weekly on test Days -1, 2, 7, and 14 and macroscopic examinations were performed after terminal sacrifice. No mortality occurred and no clinical signs of toxicity were observed during the study period. No effects on body weights were noted and necropsy revealed no treatment-related findings. The oral LD50 value in rats was determined >2000 mg/kg bw.

 

CAS 85711-80-4

An acute oral toxicity study with 1,3-Propoanediol, 2,2-dimethyl-, C5-9 carboxylates (CAS 85711-80-4) is available (Bouffechoux, 1995). No information is given on the guideline followed or on GLP compliance. However, it is stated that the study was performed as a limit test. Five female Swiss mice were orally administered the test item via gavage at a dose of 2000 mg/kg bw. During the 14-day observation period the animals were subjected to clinical observations and weighing. No necropsy was performed after terminal sacrifice. No mortality occurred and no clinical signs of toxicity were observed during the study period. No effects on body weights were noted. The oral LD50 value in mice was determined >2000 mg/kg bw.

 

CAS 85186-86-3

An acute oral toxicity study with Fatty acids, C8-18 and C18-unsatd., esters with neopentylglycol (CAS 85186-86-3) was performed according to OECD Guideline 420 (fixed dose procedure, limit test) and GLP (Pooles, 2012). The test item was administered by gavage to five Wistar (RccHanTM:WIST) rats per sex at a dose of 2000 mg/kg bw. The animals were subjected to daily observations for clinical signs, and twice daily for morbidity and mortality. Body weights were determined weekly on test Days 0, 7, and 14. Macroscopic and histopathologic examinations were performed after terminal sacrifice. No mortality occurred and no clinical signs of toxicity were observed during the study period. No effects on body weights were noted and necropsy revealed no treatment-related findings. The oral LD50 value in rats was determined >2000 mg/kg bw.

 

CAS 42222-50-4

There is only one acute oral toxicity study with limited reporting available for 2,2-dimethyl-1,3-propanediyl dioleate (CAS 42222-50-4).

Supporting data are available for 2,2-dimethyl-1,3-propanediyl dioleate (CAS 42222-50-4). An acute oral toxicity study was performed similar to OECD Guideline 401 (standard acute method, limit test) but not in compliance with GLP (Weiß, no year reported). The test item was orally administered (not further specified) to five Wistar Unilever (HsdCpb: WV) per sex at a dose of 2100 mg/kg bw. During the 14-day observation period the animals were examined for clinical signs. No mortality occurred during the study period and no clinical signs of toxicity were observed up to study termination. The oral LD50 value in rats was determined >2100 mg/kg bw.

 

CAS 85005-25-0

An acute oral toxicity study with Neopentyl Glycol Diisostearate (Fatty acids, C14-18 and C18-unsatd., branched and linear, esters with neopentyl glycol) (CAS 85005-25-0) was performed according to OECD Guideline 401 (standard acute method) and GLP (Bien, 1993). The test item was administered by oral gavage to five Bor: WISW (SPF cbp) rats per sex at 2000 mg/kg bw (limit test). The animals were subjected to daily observations and weekly determination of body weights. Macroscopic examination was performed after terminal sacrifice. No mortality occurred and no clinical signs of toxicity were observed during the study period. No effects on body weights were noted and necropsy revealed no treatment-related findings. The oral LD50 value in rats was determined >2000 mg/kg bw.

 

CAS 78-16-0

An acute oral study was performed according to EU Method B.1 (limit test) and GLP, however only limited information about the test substance was given (Reijnders, 1987). The test substance was administered by gavage to male and female Wistar rats. In a pilot study one animal per sex was administered 1800, 3200 and 5000 mg/kg bw. In the main study five males and females received 5000 mg/kg bw. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No treatment related abnormalities and effects on body weight were observed in the pilot and main study. The oral LD50 value in rats was found to exceed 5000 mg/kg bw.

Another acute oral toxicity study was conducted comparable to OECD Guideline 401 (limit test) and GLP, again limited information about the test substance was given (Glaza, 1997). 5 male and female Crl:CD (SD)BR rats were exposed to 2000 mg/kg bw test substance by gavage. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice. No clinical signs or substance related abnormalities on body weights or at necropsy were observed. The LD50 was found to exceed 2000 mg/kg bw.

A second study performed comparable to OECD Guideline 401 is available (Robinson, 1991) but due to inacceptable restrictions this study is not considered for classification. Only 2 Alderley Park SPF albino rats per sex were exposed to the limit dose of 2000 mg/kg bw and observed for 8 days. Slight piloerection as minimal sign of toxicity was observed in male animals until Day 5. No signs of toxicity were observed in the females. The LD50 was found to exceed 2000 mg/kg bw.

 

CAS 97281-24-8

An acute oral toxicity study Fatty acids, C8-10, mixed esters with neopentyl glycol and trimethylolpropane (CAS 97281-24-8) was performed similar to OECD Guideline 401 (standard acute method, limit test) and in compliance with GLP (Potokar, 1988). The test item was administered by gavage to five Wistar rats per sex at a dose of 2000 mg/kg bw. The animals were subjected to daily observations for clinical signs, and twice daily for morbidity and mortality. Body weights were determined weekly on test Days -1, 2, 7, and 14 and macroscopic examinations were performed after terminal sacrifice. No mortality occurred and no clinical signs of toxicity were observed during the study period. No effects on body weights were noted. Necropsy revealed for males; haemangioma of the left renal lymph node in 1/5 animals, and mild hypoplasia of the right testis in 1/5 animals. 1/5 females showed high grade hydrometra and haemangioma of the left renal lymph node. The oral LD50 value in rats was determined >2000 mg/kg bw.

 

CAS 11138-60-6

A reliable acute oral toxicity study was conducted withFatty acids, 8-10 (even numbered), di- and triesters with propylidynetrimethanol according to OECD Guideline 401 (standard acute method, limit test). Upon treatment of male and female rats with 2000 mg/kg bw of the test substance no mortality or enduring adverse effect was observed during the 14 d observation period. The animals had normal weight gain until the end of the observation period (Clouzeau, 1990). The LD50 value was therefore determined to be > 2000 mg/kg bw.

 

CAS 91050-89-4

An acute oral toxicity study was performed with Fatty acids, C8-10, triesters with trimethylolpropane (CAS 91050-89-4) comparable to OECD 401 (limit test) (Kästner, 1983).Only limited documentation was available but all relevant data were given. The test substance was administered by gavage to 5 male and female Wistar rats at 2000 mg/kg bw. Animals were subjected to daily observations and weekly determination of body weight. No treatment related clinical signs of toxicity were observed up to the end of the 14-day observation period. In addition no effect on body weight was noted. Thus, the oral LD50 value in rats was found to exceed 2000 mg/kg bw.

 

CAS 85005-23-8

An acute oral toxicity study was conducted according to OECD Guideline 423 (Acute Toxic Class Method). Upon treatment of male and female Wistar rats with 2000 mg/kg bw of the test substance no mortality or any adverse effect was observed during the 14 d observation period. The animals had normal weight gain until the end of the observation period (Busschers, 1997). The LD50 value was therefore determined to be > 2000 mg/kg bw.

 

Formerly CAS 85186-89-6

An acute oral toxicity study (limit test) with Fatty acids, C8-10(even), C14-18(even) and C16-18(even)-unsatd., triesters with trimethylolpropane (CAS 85186-89-6) was performed according to OECD Guideline 401 and GLP (Kuszewski, 1996). The test substance was administered by gavage at a concentration of 2000 mg/kg bw to groups of five male and female Hsd/Cpb:WU rats. The animals were observed for 14 days following administration. No mortalities occurred during the study period. No clinical signs of toxicity, only slight changes in body weights for some animals and no differences at macroscopic examination were reported. The acute oral LD50 was found to be greater than 2000 mg/kg bw.

 

CAS 403507-18-6

An acute oral toxicity study with Fatty acids, C16-18 and C18-unsatd., branched and linear ester with trimethylolpropane (CAS 403507-18-6) was performed comparable to OECD Guideline 423 (acute toxic class method, limit test) and under GLP conditions (Sanders, 2002). The test substance was administered by gavage to three Sprague-Dawley CD (Crl: CD IGS® BR) male and female rats at 2000 mg/kg bw. Animals were subjected to daily observations and weekly determination of body weight. Gross pathology examination was performed after terminal sacrifice (Day 15). No treatment related abnormalities with regard to clinical signs, body weights and necropsy were observed. The oral LD50 value in rats was found to exceed 2000 mg/kg bw.

 

CAS 91050-90-7

An acute oral toxicity study (limit test) with Fatty acids, C16-18, triesters with trimethylolpropane (CAS 91050-90-7) is available, which was performed according to EU Method B.1 and GLP (Potokar, 1989). The test substance was administered by gavage at a concentration of 2000 mg/kg bw to groups of five male and female Wistar rats. The animals were observed for 14 days following administration, body weights were determined weekly. No mortalities occurred during the study period. No clinical signs of toxicity, no changes in body weight and no differences at macroscopic examination were reported. The acute oral LD50 was found to be greater than 2000 mg/kg bw.

 

CAS 85116-93-4

An acute oral toxicity study (limit test) was conducted withFatty acids, C16-18 (even numbered), esters with pentaerythritol(CAS 85116-93-4) comparable to OECD Guideline 401 (Potokar, 1983). Reporting of test conditions and results was limited. The test substance was administered by gavage at a concentration of 2000 mg/kg bw to 2 male and female Wistar rats each. The animals were observed for 14 days following administration. No mortalities occurred during the study period. No significant signs of toxicity except for transient rough fur and reduced activity direct after dosing were observed. Normal weight gain was observed after dosing. Finally no macroscopic findings were found at necropsy. The acute oral LD50 was found to be greater than 2000 mg/kg bw.

 

CAS 67762-53-2

The acute toxicity via the oral route of Fatty acids, C5-9 tetraesters with pentaerythritol has been investigated in two studies with rats (CAS No. 67762-53-2).

An acute oral toxicity study (limit test) was performed according to OECD Guideline 420 (fixed dose procedure) (Zolyniene, 1999). Groups of 5 males and females fasted CD Sprague-Dawley rats received single oral gavage doses of 2000 mg/kg bw. The animals were observed for 14 days following administration. No mortalities occurred. One animal showed alopecia extremities on snout which was not considered treatment related. No further clinical signs of toxicity were reported. No effect on body weight was noted. Finally necropsy revealed no substance-related findings. Thus, the acute oral LD50 was found to be greater than 2000 mg/kg bw.

Another acute oral toxicity study (limit test) was performed comparable to OECD Guideline 401 (D’Aleo, 1984). The test substance was administered by gavage at a concentration of 15000 mg/kg bw to groups of 5 male and female Sprague-Dawley rats. The animals were observed for 14 days following administration. No mortalities occurred. All animals exhibited clear, oily perineal staining on the 1st, 2nd, and 3rd day following treatment. This condition normally regarded as an adverse effect, was considered to be a consequence of the high dose level administered and not considered a toxic sign. No further clinical signs of toxicity were reported. The acute oral LD50 was found to be greater than 15000 mg/kg bw.

In summary, the oral LD50 of Fatty acids, C5-9 tetraesters with pentaerythritol is greater than 2000 mg/kg bw.

 

CAS 68424-31-7

The study conducted with Fatty acids, C5-10, esters with pentraerythritol (CAS No.68424-31-7) (Robinson, 1991) with limitations (reduced animal number), revealed but revealed no mortality and no other toxic effects, but an initial weight loss after treatment of rats with 2000 mg/kg bw. However this effect was completely reversible and the animals showed subsequently normal body weight gain.

 

CAS 71010-76-9

An acute oral toxicity study with Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS 71010-76-9) was performed according to OECD Guideline 425 (up and down procedure, limit test) and GLP (Mallory, 2006). Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid was administered by gavage to one female Sprague-Dawley rat at the starting dose of 2000 mg/kg bw. Since no mortality and no other toxic effects could be detected during the 14 day study period, 4 further female animals were equally dosed with 2000 mg/kg bw. No clinical signs of toxicity were observed up to the end of the 14-day observation period. No effect on body weight was noted. Finally, necropsy revealed non substance-related findings. The oral LD50 value in female rats was found to exceed 2000 mg/kg bw.

 

CAS 85586-24-9

An acute oral toxicity study (limit test) was conducted with Fatty acids, C8-10, tetraesters with pentaerythritol (CAS 85586-24-9) (Kästner, 1981). The test did not follow a specific guideline and was not GLP-compliant. Thus, only limited details were reported. The test substance was administered by gavage at a concentration of 5 mL/kg (4800 mg/kg bw) to 10 male Wistar rats. The animals were observed for 14 days following administration. No mortalities occurred during the study period. Ruffled fur and slight sedation was observed during the first 24 h after dosing. The acute oral LD50 was found to be greater than 4800 mg/kg bw.

 

CAS 19321-40-5

An acute oral toxicity study with Pentaerythritol tetraoleate (CAS 19321-40-5) was performed according to OECD Guideline 423 (acute toxic class method, limit test) and GLP (Pels Rijcken, 1997). Pentaerythritol tetraoleate was administered by oral gavage to three Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No treatment related abnormalities were observed. The oral LD50 value in rats was found to exceed 2000 mg/kg bw.

 

CAS 62125-22-8

The acute toxicity via the oral route of 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) has been investigated in rats in three studies (CAS No. 62125-22-8).

Two acute oral toxicity studies (limit tests) were performed according to OECD Guideline 401 ((1) Debets, 1984, GLP-compliant; (2) Bouffechoux, 1997). The test substance was administered by gavage at a concentration of (1) 5000 mg/kg bw and (2) 5 mL/kg (corresponding to 4600 mg/kg bw, based on density of 0.92 g/mL) to groups of five male and female Wistar rats. The animals were observed for 14 days following administration. No mortalities occurred. No clinical signs of toxicity, no changes in body weights and no differences at macroscopic examination were reported. The acute oral LD50 was found to be greater than (1) 5000 mg/kg bw and (2) 4600 mg/kg bw.

Another acute oral toxicity study (limit test) was performed comparable to OECD Guideline 401 (Sugar, 1981). The test substance was administered by gavage at a concentration of 10000 mg/kg bw (1.5 mL/100 g bw) to groups of five male and female CD rats. The animals were observed for 14 days following administration. No mortalities occurred. All the rats were hypoactive at the 4 h observation time point. No further signs of toxicity were noted during the study period. The acute oral LD50 was found to be greater than 10000 mg/kg bw.

In summary, the oral LD50 of 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) is greater than 5000 mg/kg bw.

HATCOL 2937

An acute oral toxicity study was performed with Fatty acids, C8-10, triesters with trimethylolpropane (CAS 91050-89-4) comparable to OECD 401 (limit test) (Kästner, 1983).Only limited documentation was available but all relevant data were given. The test substance was administered by gavage to 5 male and female Wistar rats at 2000 mg/kg bw. Animals were subjected to daily observations and weekly determination of body weight. No treatment related clinical signs of toxicity were observed up to the end of the 14-day observation period. In addition no effect on body weight was noted. Thus, the oral LD50 value in rats was found to exceed 2000 mg/kg bw.

Acute Inhalation Toxicity

CAS 68855-18-5

For acute inhalation toxicity, one study is available within the NPG esters and was considered for assessment of all NPG esters and of two TMP esters and read-across was conducted based on a category and/or weight of evidence approach.

An acute inhalation toxicity study was performed with Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol (CAS 68855-18-5) according to OECD Guideline 436 (acute toxic class method) under GLP conditions. Three RccHanTM:WIST rats per sex were exposed for 4 hours to 5.22 mg/L (mean achieved concentration) test substance aerosol by nose only inhalation (Griffiths, 2012). The test concentration was chosen based on the outcome of a preliminary test with two rats at a dose of 2.14 mg/L. In the main study, the animals were subjected to daily observations for clinical signs, and twice daily for morbidity and mortality. Body weights were determined prior to treatment and afterwards on test Days 1, 3, 7, and 14. After terminal sacrifice the animals were submitted to full external and internal observation. Detailed macroscopic examination of the respiratory tract was performed to determine signs of irritancy or local toxicity. No mortality occurred throughout the study period. Signs of hunched posture and pilo-erection were commonly seen in animals for short period on removal from the chamber following 4-h inhalation studies. Wet fur was commonly recorded both during and for a short period after exposure. These observations were considered to be associated with the restraint procedure and, in isolation, were not indicative of toxicity. In addition, an increased respiratory rate was noted in all animals. On removal from the chamber and 1 h post-exposure, all animals exhibited increased respiratory rate and ataxia. One day after exposure, all animals still showed increased respiratory rate and also hunched posture as well as occasional instances of pilo-erection. All animals recovered to appear normal from Days 5 to 8 post-exposure. All animals showed the expected body weight gain during the study, except for one female which not gained weight during the final week of the 14-day observation period. In addition, one male exhibited a slight loss in body weight on the first day of exposure. Necropsy revealed no treatment-related findings. The inhalation LC50 value in rats was determined >5.22 mg/L.

For acute inhalation toxicity, one study is available within the TMP esters. Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol (CAS 68855-18-5) and Fatty acids, C5-10, esters with pentraerythritol (CAS 68424-31-7) were used for assessment of the TMP esters and read-across was conducted based on a category approach.

 

CAS 78-16-0

An acute inhalation toxicity study was performed with 2-ethyl-2-[[(1-oxoheptyl)oxy]methyl] propane-1,3-diyl bisheptanoate (CAS 78-16-0). 5 male and female rats (strain not specified) were exposed for 1 hour to 20 mg/L test substance vapour (Anonimous, 1978). The test substance caused no clinical signs, body weight changes or abnormalities in necropsy during the 15 day study period. Only one animal died on day 14. The LC50 was therefore found to be greater than 20 mg/L air, however since the original report is not available and because of only one hour of exposure this study is found insufficient for hazard assessment.

For acute inhalation toxicity, three studies are available from the PE esters within the polyol esters category. Fatty acids, C5-10, esters with pentraerythritol (CAS 68424-31-7), Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS 85536-35-2) and Fatty acids, C5-9 tetraesters with pentaerythritol has been investigated in rats in two studies (CAS No. 67762-53-2) were used for assessment of the PE esters and read-across was conducted based on a category and/or weight of evidence approach.

 

CAS 67762-53-2

The acute toxicity via the inhalation route of Fatty acids, C5-9 tetraesters with pentaerythritol has been investigated in rats in two studies (CAS 67762-53-2).

The first study was conducted comparable to OECD Guideline 403 and according to GLP. 10 male and female Sprague-Dawley rats were exposed for 4 hours to 0.48 or 4.06 mg/L test substance aerosol by whole body inhalation exposure (Mekitarin, 1990). No mortality, clinical signs, body weight changes or abnormalities in necropsy were observed during the 15 day study period in any group. The LC50 was therefore found to be greater than 4.06 mg/L.

In the second study 10 male and 5 female CD Sprague-Dawley rats were exposed for 4 hours to 5.5 mg/L test substance aerosol by nose/head only inhalation (Hoffman, 1999). No mortalities occurred during the study period. Nasal discharge was noted as the only sign of clinical toxicity. The test group females lost weight during the first week after the test material exposure, but gained weight during the second week after exposure. In all other animals no effect on body weight was noted. Necropsy examination revealed no substance-related findings. The LC50 was therefore found to be greater than 5.50 mg/L.

In summary, the LC50 of Fatty acids, C5-9 tetraesters with pentaerythritol is greater than 5.5 mg/L.

 

CAS 68424-31-7

An acute inhalation toxicity study was performed with Fatty acids, C5-10, esters with pentraerythritol (CAS 68424-31-7) comparable to OECD Guideline 403. 5 male and female Alpk:APfSD rats were exposed for 4 hours to 5.0 mg/L test substance aerosol by nose only inhalation (Parr-Dobrzanski, 1994). The test substance caused no mortality, body weight changes or abnormalities in necropsy during the 15 day study period. Some clinical signs were noticed, which consisted of hunched position, chromodacryorrhea, piloerection, staining around nose and wet fur. These signs however occurred during or just after exposure and were clearly consistent with the use of restraint for exposure. The LC50 was therefore found to be greater than 5.1 mg/L.

 

CAS 85536-35-2

An acute inhalation toxicity study was performed with Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS 85536-35-2) comparable to OECD Guideline 403. 5 male and female Alpk:APfSD rats were exposed for 4 hours to 5.0 mg/L test substance aerosol by nose only inhalation (Parr-Dobrzanski, 1994). The test substance caused no mortality, body weight changes or abnormalities in necropsy during the 15 day study period. Clinical signs during and immediately after exposure included hunched posture, chromodacryorrhea, piloerection, stains around the nose and wet fur. In general, animals showed a rapid recovery from these effects by Day 2, although, hunched posture and piloerection persisted in few animals to Days 4 and 8, respectively. No effect on body weight was noted. Necropsy and histopathological examination revealed non substance-findings. The LC50 was therefore found to be greater than 5.0 mg/L.

Acute Dermal Toxicity

For acute dermal toxicity, one study is available for the NPG esters and was considered for assessment of 2,2-dimethyl-1,3-propanediyl dioleate (CAS 42222-50-4). No reliable studies on the acute dermal toxicity are available for NPG esters within the polyol esters category. In regard to the estimated low dermal absorption calculated with DERMWIN (v 2.0, 2011, see toxicokinetic chapter), dermal uptake of the sub-category members is considered as low. Therefore, dermal exposure for the NPG esters within the polyol esters category is not expected to be associated with any adverse effects on human health as dermal absorption can be considered as nearly negligible.

 

Acute Dermal Toxicity 

Assessment of acute dermal toxicity with HATCOL 3331 in the rat.

HATCOL 3331 was administered to five Wistar rats of each sex by dermal application at 2000, mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred. Hunched posture and/or chromodacryorrhoea were noted among all animals on day 2. In addition, maculate erythema or scales were seen on the treated skin site of one male and female between days 3 and 7. The body weight gain during the observation period was within the range expected for rats used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of HATCOL 3331 in Wistar rats was established to exceed 2000 mg/kg/body weight.

 

Assessment of acute dermal toxicity with HATCOL 3344 in the rat.

HATCOL 3344 was administered to five Wistar rats of each sex by dermal application at 2000mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred. All females and some males showed scales, scabs and/or general/maculate erythema on the treated skin site during the observation period from day 3 onwards. In addition chromodacryorrhoea was noted among some animals on days 1 and/or 2, with diarrhoea in one male between days 2 and 4. The body weight gain during the observation period was within the range expected for rats used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of HATCOL 3344 in Wistar rats was established to exceed 2000 mg/kg body weight.

 

Assessment of acute dermal toxicity with HATCOL 5236 in the rat.

HATCOL 5236 was administered to five Wistar rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred. Chromodacryorrhoea (nose), hunched posture and lethargy were noted among the animals. The animals had recovered from the symptoms by day 3. Erythema was seen in the treated skin-area of one animal on day 3. The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity. No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of HATCOL 5236 in Wistar rats was established to exceed 2000 mg/kg/body weight.

CAS 42222-50-4

An acute dermal toxicity study was performed with 2,2-dimethyl-1,3-propanediyl dioleate (CAS 42222-50-4) according to OECD Guideline 402 (standard acute method, limit test) and GLP (Haferkorn, 2012). Five WiCD/Crl:CD(SD) rats per sex were dosed 2000 mg/kg bodyweight for 24 hours on the back skin under occlusive conditions. The animals were subjected to daily observations and body weights were determined prior to test material administration and weekly thereafter. Skin reactions (erythema and oedema) were observed and scored 24, 48, 72 and 96 h after test substance application (Days 2-5), as well as on Days 8-12 during the 14-day observation period. Macroscopic examinations were performed after terminal sacrifice. No mortality occurred and no clinical signs of systemic toxicity were observed during the study period. No skin erythema and edema (scores 0) were observed 24, 48 and 72 h after substance application and up to the end of the 14-day observation period. No effects on body weights were noted and necropsy revealed no treatment-related findings. The dermal LD50 value in rats was determined >2000 mg/kg bw.

For acute dermal toxicity, four studies are available from TMP esters group and were considered for assessment of TMP esters within the polyol esters category and read-across was conducted based on a category approach.

 

CAS 78-16-0

Two acute dermal toxicity studies are available for 2-ethyl-2-[[(1-oxoheptyl)oxy]methyl]propane -1,3-diyl bisheptanoate (CAS 78-16-0). Both were conducted comparable to “16 CFR 1500.40” guideline as a limit test.

In the first study, 10 New Zealand White rabbits (5 with intact, 5 with abraded skin) were exposed to 5000 mg test substance/kg bw for 24 hours on the back skin under occlusive conditions (Moreno, 1978). The observation period was 14 days. No mortality occurred during the study period.

Slight to moderate diarrhea was observed in 5/10 animals on Days 8 to 14. Slight yellow discharge around the nose of one animal was observed on Days 6, 9 and 10 and worsened on Days 11 through 14.

On Day 1, all 5 animals with intact skin and 4/5 animals with abraded skin showed moderate erythema according to the Draize scoring system. One animal with abraded skin showed slight erythema formation. No edema was observed in any animal (shaved or abraded) after 24 h. No necropsy was performed. Thus, the acute dermal LD50 in rabbits was found to exceed 5000 mg/kg bw.

In the second study, 10 albino rabbits (5 with intact and 5 with abraded skin) were exposed to 2000 mg/kg bw test substance for 24 hours (Morgareidge, 1974). No mortalities or clinical signs were observed. Therefore, the LD50 was found to exceed 2000 mg/kg bw. In summary, the LD50 was found to exceed 2000 mg/kg bw.

 

CAS 11138-60-6

An acute dermal toxicity (limit test) was performed on Fatty acids, 8-10 (even numbered), di- and triesters with propylidynetrimethanol (CAS 11138-60-6) according to OECD Guideline 402 and GLP (Blanset, 1997). 5 male and female New Zealand White rabbits were exposed to 2000 mg test substance /kg bw for 24 hours on the back skin under semiocclusive conditions. The observation period was 14 days. No mortality or clinical signs of systemic toxicity were noted in any animal during the study period. 4 male animals lost 0.1 kg body weight whereas the remaining animals had a constant body weight over the study period. Necropsy at study termination revealed no abnormalities. Thus, the acute dermal LD50 in rabbits for Fatty acids, 8-10 (even numbered), di- and triesters with propylidynetrimethanol was found to exceed 2000 mg/kg bw.

 

CAS 403507-18-6

An acute dermal toxicity (limit test) was performed on Fatty acids, C16-18 and C18-unsatd., branched and linear ester with trimethylolpropane (CAS 403507-18-6) according to OECD Guideline 402 and GLP (Sanders, 2004). 5 male and female Sprague-Dawley CD (Crl: CD IGS® BR) rats each were exposed to 2000 mg test substance /kg bw for 24 hours on the back skin under semiocclusive conditions. The observation period was 14 days. No mortality, clinical signs of systemic toxicity and changes in body weight were noted in any animal during the study period. Necropsy at study termination revealed no abnormalities. Thus, the acute dermal LD50 in rats for Fatty acids, C16-18 and C18-unsatd., branched and linear ester with trimethylolpropane was found to exceed 2000 mg/kg bw.

For acute dermal toxicity, two studies are available for the PE esters and were considered for assessment of members of PE esters within the polyol esters category and read-across was conducted based on a category and/or approach.

 

CAS 71010-76-9

An acute dermal toxicity study (limit test) was performed on Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS 71010-76-9) comparable to OECD Guideline 402 and GLP (Mallory, 2006). 5 male and female Sprague-Dawley rats were exposed to 2000 mg test substance /kg bodyweight for 24 hours on the back skin under semiocclusive conditions. The observation period was 14 days. No clinical signs of systemic toxicity were noted in any animal during the study period. Body weight gain and necropsy at study termination revealed no abnormalities. Thus, the acute dermal LD50 in rats for Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid was found to exceed 2000 mg/kg bw.

 

CAS 62125-22-8

An acute dermal toxicity test (limit test) was performed on 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8) according to OECD Guideline 402 and GLP (Debets, 1984). 5 male and female Wistar rats each were exposed to 2000 mg test substance /kg bw for 24 hours on the back skin under occlusive conditions. The observation period was 14 days. No mortality and clinical signs of systemic toxicity were noted in any animal during the study period. Body weight gain and necropsy at study termination revealed no abnormalities. Thus, the acute dermal LD50 in rats 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) was found to exceed 2000 mg/kg bw.

Conclusion for acute toxicity

Several studies are available investigating the acute oral toxicity of polyol esters category members resulting in oral LD50 values greater than 2000 mg/kg bw. Five reliable studies investigating the acute inhalation toxicity within the polyol esters category are available resulting in LC50 values > 5.0 mg/L. Seven reliable acute dermal toxicity studies consistently showed no effects at the limit dose of 2000 mg/kg bw.

Justification for classification or non-classification