Registration Dossier

Administrative data

Description of key information

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

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

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 August 2015 to 01 September 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD, EU, US EPA & Japanese test guidelines in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
See Any other information
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
see Any other information
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
see Any other information
Qualifier:
according to
Guideline:
other: JMAFF Guidelines (2000), including the most recent revisions.
Deviations:
yes
Remarks:
see Any other information
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Species: Rat, Wistar strain Crl:WI (Han) (outbred, SPF-Quality). Recognized by international guidelines as the recommended test system (e.g. OECD, EC).
Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals: 6 Females (nulliparous and non-pregnant). Each dose group consisted of 3 animals.
Age and body weight: Young adult animals (approx. 10-11 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean.
Identification: Earmark and tail mark
Health inspection: At least prior to dosing. It was ensured that the animals were healthy and without any abnormality that might affect the study integrity.

Animal husbandry
Conditions
Environmental controls for the animal room are set to maintain 18 to 24°C, a relative humidity of 40 to 70%, at least 10 air changes/hour, and a 12-hour light/12-hour dark cycle: the photoperiod is between 07:00 and 19:00 hrs daily. The light/dark cycle may be interrupted for study related activities. Any variations to these conditions will be evaluated and maintained in the raw data.

Accommodation
Group housing of 3 animals per cage in labeled Makrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
Acclimatization period was at least 5 days before start of treatment under laboratory conditions.

Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
Water: Free access to tap water.

Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed according to facility standard procedures. There were no findings that could interfere with the study.
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
Vehicle: Corn oil (Fagron Capelle a/d IJssel, The Netherlands) (specific gravity 0.92)
Rationale: The vehicle was selected based on trial preparations performed at WIL Research Europe and on test substance data supplied by the Sponsor.
There was no information available regarding the solubility or stability in vehicle.
Preparation: The preparations (w/w) were dosed within 4 hours after adding the vehicle to the test substance. Homogeneity was assessed by visual inspection of the solutions and the formulations were stirred during dosing, which ensures homogeneity sufficient for these kinds of studies.
Adjustment was made for specific gravity of the vehicle. No correction was made for purity of the test substance.

The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. 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 (10 mL/kg) body weight.
No. of animals per sex per dose:
3 animals
Control animals:
no
Details on study design:
Treatment
Method: Oral gavage, using plastic feeding tubes. The test item preparations were stirred on a magnetic stirrer during dosing.
Fasting: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available ad libitum.
Frequency: Single dosage on Day 1.
Dose level (volume): 2000 mg/kg (10 mL/kg) body weight.

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 signs 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 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).
Preliminary study:
Preiminary study not undertaken.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture (grade 1) and/or piloerection (grade 1) were noted for four females on Day 1 and/or 2.
Alopecia (grade 1), noted for one animal, from Day 6 onwards, is commonly seen in group housed rats and therefore no toxicological significance was attached to this finding.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected for 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 specified in the study report.

MORTALITY DATA

TEST DAY

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

HOURS AFTER TREATMENT

0

2

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

FEMALES 2000 MG/KG

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

FEMALES 2000 MG/KG

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

 

CLINICAL SIGNS

TEST DAY

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

HOURS AFTER TREATMENT

0

2

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

MAX GRADE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

FEMALES 2000 MG/KG

ANIMAL 1

No clinical signs noted

 

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

ANIMAL 2

Posture

-Hunched posture

Skin / fur

-Alopecia

 

 

(1)

 

(3)

 

 

1

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

1

 

 

-

 

1

 

 

-

 

1

 

 

-

 

1

 

 

-

 

1

 

 

-

 

1

 

 

-

 

1

 

 

-

 

1

 

 

-

 

1

 

 

-

 

1

ANIMAL 3

No clinical signs noted

 

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

 

-

FEMALES 2000 MG/KG

ANIMAL 4

Posture

-Hunched posture

Skin / fur

-Piloerection

 

 

(1)

 

(1)

 

 

1

 

-

 

 

1

 

1

 

 

1

 

1

 

 

1

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

ANIMAL 5

Posture

-Hunched Posture

Skin / fur

-Piloerection

 

 

(1)

 

(1)

 

 

1

 

-

 

 

1

 

1

 

 

1

 

1

 

 

1

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

ANIMAL 6

Posture

-Hunched Posture

Skin / fur

-Piloerection

 

 

(1)

 

(1)

 

 

1

 

-

 

 

1

 

1

 

 

1

 

1

 

 

1

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

 

 

-

 

-

- = Sign not observed

 

BODY WEIGHTS (GRAM)

SEX/DOSE LEVEL

ANIMAL

DAY 1

DAY 8

DAY 15

FEMALES 2000 MG/KG

 

1

2

3

 

MEAN

ST. DEV.

N

 

196

189

191

 

192

4

3

 

215

214

229

 

219

8

3

 

218

218

242

 

226

14

3

FEMALES 2000 MG/KG

 

4

5

6

 

MEAN

ST. DEV.

N

 

177

156

183

 

172

14

3

 

201

173

208

 

194

19

3

 

215

187

218

 

207

17

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

FEMALES 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 2,2-Bis[[3-(dodecylthio)-1-oxopropoxy]methyl]propane-1,3-diyl bis[3-(dodecylthio)propionate] in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

Assessment of acute oral toxicity with 2,2-Bis[[3-(dodecylthio)-1-oxopropoxy]methyl]propane-1,3-diyl bis[3-(dodecylthio)propionate] in the rat (Acute Toxic Class Method).

 

The study was carried out based on the guidelines described in:

OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method"

Commission Regulation (EC) No 440/2008, B1 tris: "Acute Oral Toxicity, Acute Toxic Class Method"

EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity"

JMAFF Guidelines (2000), including the most recent revisions.

 

2,2-Bis[[3-(dodecylthio)-1-oxopropoxy]methyl]propane-1,3-diyl bis[3-(dodecylthio)propionate] was administered by oral gavage to two subsequent groups of three female 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 mortality occurred.

Hunched posture (grade 1) and/or piloerection (grade 1) were noted for four females on Day 1 and/or 2.

The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

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

 

The oral LD50 value of 2,2-Bis[[3-(dodecylthio)-1-oxopropoxy]methyl]propane-1,3-diyl bis[3-(dodecylthio)propionate] in Wistar rats was established to exceed 2000 mg/kg body weight.

 

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

 

Based on these results, 2,2-Bis[[3-(dodecylthio)-1-oxopropoxy]methyl]propane-1,3-diyl bis[3-(dodecylthio)propionate] does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
K1

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 April 2017 to 25 April 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
OECD GUIDELINES FOR TESTING OF CHEMICALS (No.: 402, 24th Feb. 1987)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
Commission Regulation (EC) No 440/2008, B.3 (L 142, 30 May 2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
OPPTS 870.1200 (EPA 712-C-98-192, August 1998)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
No further details specified.
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Species and strain: Crl:WI Wistar rats
Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld, Germany
Hygienic level at arrival: SPF
Hygienic level during the study: Standard housing conditions
Justification of strain: The Wistar rat is one of the standard rodent species used in acute toxicity studies.
Number of animals: 5 animals/sex
Sex: Male and female, female rats were nulliparous and non-pregnant.
Age of animals at dosing: Young adult rats
Body weight range at dosing: Between 218 g and 254 g
Acclimation time: 5 days

Husbandry
Animal health: Only healthy animals were used for the study.
The staff Veterinarian certified the health status.
Room-Box: 242/7
Housing: Individual caging
Cage type: Type II. polypropylene/polycarbonate
Bedding: Lignocel 3/4-S Hygienic Animal Bedding was available to animals during the study. Copy of the Certificate of Analysis is retained in the archive at CiToxLAB Hungary Ltd.
Nesting: Nest building material Arbocel Crinklets natural was available to animals during the study. Copy of the Certificate of Analysis is retained in the archive at CiToxLAB Hungary Ltd.
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 19.4–24.7°C
Relative humidity: 30–58%
Ventilation: 15-20 air exchanges/hour
Enrichment: Rodents were housed with deep wood sawdust bedding to allow digging and other normal rodent activities.
Temperature and relative humidity were recorded twice daily during the study.

Food and Water Supply
Animals received ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance", ad libitum, and tap water from the municipal supply, as for human consumption from a 500 mL bottle, ad libitum. The food is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study and the water was considered fit for human consumption.
The batch of feed employed in the study was as follow:
• 285 17890, expiry date: 31 August 2017
The supplier provided an analytical certificate for the batch used. A copy of the certificate will be archived with the raw data.

Water quality control analysis is performed once every three months and microbiological assessment is performed monthly by Veszprém County Institute of State Public Health and Medical Officer Service. The quality control results are retained in the archives at CiToxLAB Hungary Ltd.

Animal Identification
Animals were individually identified using numbers written on the tail with an indelible pen. The numbers were given on the basis of CiToxLAB Hungary Ltd.'s Master File for each animal allocated to the treatment groups. The cages were identified by cards containing information about study code, sex, dose group, cage number and individual animal number.
Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
Formulation
The test item was powdered and administered as a single dose. Sufficient water was used to dampen the test material to ensure good contact with the skin.

Procedure
The back of each animal was shaved (approximately 10% area of the total body surface) approximately 24 hours prior to treatment. The test item was applied to the shaved skin as a single dose and remained in contact with the skin for the 24-hour exposure period. Sterile gauze pads were placed on the skin of rats to cover the test item. These gauze pads were kept in contact with the skin using a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap for 24 hours.
At the end of the exposure period, the treated area of skin with the test item was washed with water at body temperature.
Duration of exposure:
A single dermal application was made.
Doses:
The test item was not expected to be lethal at 2000 mg/kg bw. A limit test was therefore performed.
No. of animals per sex per dose:
10 (5 males/5 females)
Control animals:
not required
Details on study design:
OBSERVATIONS
Clinical Observations
Clinical observations were performed on the day of treatment at 1 and 5 hours after application of the test item and once each day for 14 days thereafter.
Observations included the skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Skin Irritation
Adverse skin reactions at the site of application were recorded daily following the removal of the dressing.

Measurement of Body Weight
The body weights were recorded on Day 0 (before test item administration) and on Days 7 and 14 just before necropsy.

NECROPSY
Macroscopic examination was performed on all animals. All animals were anaesthetised with pentobarbital sodium and exsanguinated.
Following confirmation of death, after examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed. All macroscopic changes were recorded.
Statistics:
The method used was not intended to allow the calculation of a precise LD50 value.
Body weight and body weight gain are summarised in tabular form. Clinical signs and necropsy findings are described and summarised in tabular form.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The test item did not cause mortality at the dose level of 2000 mg/kg bw.
Clinical signs:
There were no systemic clinical signs noted in any animal throughout the study.
Body weight:
There were no treatment related effects on body weight or body weight gain during the observation period.
Gross pathology:
There was no evidence of any gross observations at a dose level of 2000 mg/kg bw.
Other findings:
Local Dermal Signs
No adverse local dermal signs were observed after treatment with the test item or during the 14 days observation period.

Clinical Observations

DOSE LEVEL: 2000 mg/kg bw                                                                                          SEX: MALE

Cage No.

Animal No.

Observations

Observations days

Frequency

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1h

5h

1

7960

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

2

7961

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

3

7962

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

4

7963

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

5

7964

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

DOSE LEVEL: 2000 mg/kg bw                                                                                            SEX: FEMALE

Cage No.

Animal No.

Observations

Observations days

Frequency

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1h

5h

6

7975

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

7

7976

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

8

7977

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

9

7978

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

10

7979

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

Remarks:   + = present

h = hour                  Treatment day = Day 0

Frequency of observation = number of occurrence of observation / total number of observations

 

Body Weight Data

DOSE LEVEL: 200 mg/kg bw                                     SEX: MALE

Cage No.

Animal No.

Body weight (g)

Days

Body Weight Gain (g)

0

7

14

0-7

7-14

0-14

1

7960

220

252

290

32

38

70

2

7961

244

300

353

56

53

109

3

7962

251

300

350

49

50

99

4

7963

230

279

325

49

46

95

5

7964

224

263

296

39

33

72

Mean:

233.8

278.8

322.8

45.0

44.0

89.0

Standard deviation:

13.2

21.6

29.4

9.5

8.3

17.2

DOSE LEVEL: 200 mg/kg bw                                   SEX: FEMALE

Cage No.

Animal No.

Body weight (g)

Days

Body Weight Gain (g)

0

7

14

0-7

7-14

0-14

6

7975

233

235

247

2

12

14

7

7976

222

227

234

5

7

12

8

7977

218

235

252

17

17

34

9

7978

232

233

239

1

6

7

10

7979

254

259

302

5

43

48

Mean:

231.8

237.8

254.8

6.0

17.0

23.0

Standard deviation:

14.0

12.3

27.3

6.4

15.2

17.3

 

Macroscopic Findings

DOSE LEVEL: 2000 mg/kg bw                                                                             SEX: MALE

Cage No.

Animal No.

Necropsy Date/ Necropsy Day

External Observations

Internal Observations

Organ / Tissue

1

7960

25 April 2017

Day 14

No external observations

No internal observations

Not applicable

2

7961

25 April 2017

Day 14

No external observations

No internal observations

Not applicable

3

7962

25 April 2017

Day 14

No external observations

No internal observations

Not applicable

4

7963

25 April 2017

Day 14

No external observations

No internal observations

Not applicable

5

7964

25 April 2017

Day 14

No external observations

No internal observations

Not applicable

DOSE LEVEL: 2000 mg/kg bw                                                                                    SEX: FEMALE

Cage No.

Animal No.

Necropsy Date/ Necropsy Day

External Observations

Internal Observations

Organ / Tissue

6

7975

25 April 2017

Day 14

No external observations

No internal observations

Not applicable

7

7976

25 April 2017

Day 14

No external observations

No internal observations

Not applicable

8

7977

25 April 2017

Day 14

No external observations

No internal observations

Not applicable

9

7978

25 April 2017

Day 14

No external observations

No internal observations

Not applicable

10

7979

25 April 2017

Day 14

No external observations

No internal observations

Not applicable

 

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal median lethal dose (LD50) of the test item 2,2-Bis[[3-(dodecylthio)-1-oxopropoxy]methyl]propane-1,3-diyl bis[3-(dodecylthio)propionate] was found to be greater than 2000 mg/kg body weight in male and female Crl:WI rats.
Executive summary:

An acute dermal toxicity study was performed with the test item 2,2-Bis[[3-(dodecylthio)-1-oxopropoxy]methyl]propane-1,3-diyl bis[3-(dodecylthio)propionate] in Crl:WI Wistar rats, in compliance with OECDGuideline No.: 402.

 

A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). The test item was powdered and applied as a single dermal 24-hour exposure followed by a 14-day observation period.

 

Clinical observations were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14 (before necropsy). Gross macroscopic examination was performed on all animals at the end of the 2-week observation period (Day 14).

 

The results of the study were summarised as follows:

Mortality

Test item did not cause mortality at the dose level of 2000 mg/kg bw.

 

Systemic clinical signs

There were no systemic clinical signs noted in any animal throughout the study.

 

Local dermal signs

No adverse local dermal signs were observed after treatment with the test item or during the 14 days observation period.

 

Body weight and body weight gain

There were no treatment related effects on body weight or body weight gain during the observation period.

 

Necropsy

There was no evidence of any gross observations at a dose level of 2000 mg/kg bw.

 

Conclusions

The acute dermal median lethal dose (LD50) of the test item 2,2-Bis[[3-(dodecylthio)-1-oxopropoxy]methyl]propane-1,3-diyl bis[3-(dodecylthio)propionate] was found to be greater than 2000 mg/kg body weight in male and female Crl:WI rats.

 

According to the GHS criteria, 2,2-Bis[[3-(dodecylthio)-1-oxopropoxy]methyl]propane-1,3-diyl bis[3-(dodecylthio)propionate] can be ranked as "Category 5" or "Unclassified" for acute dermal exposure.

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 

2,2-Bis[[3-(dodecylthio)-1-oxopropoxy]methyl]propane-1,3-diyl bis[3-(dodecylthio)propionate] was administered by oral gavage to two subsequent groups of three female 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 mortality occurred.

Hunched posture (grade 1) and/or piloerection (grade 1) were noted for four females on Day 1 and/or 2.

The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

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

 

The oral LD50 value of 2,2-Bis[[3-(dodecylthio)-1-oxopropoxy]methyl]propane-1,3-diyl bis[3-(dodecylthio)propionate] in Wistar rats was established to exceed 5000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Acute Dermal Toxicity

An acute dermal toxicity study was performed with the test item 2,2-Bis[[3-(dodecylthio)-1-oxopropoxy]methyl]propane-1,3-diyl bis[3-(dodecylthio)propionate] in Crl:WI Wistar rats.

A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). The test item was powdered and applied as a single dermal 24-hour exposure followed by a 14-day observation period.

Clinical observations were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14 (before necropsy). Gross macroscopic examination was performed on all animals at the end of the 2-week observation period (Day 14).

 

The results of the study were summarised as follows:

Test item did not cause mortality at the dose level of 2000 mg/kg bw.

There were no systemic clinical signs noted in any animal throughout the study.

No adverse local dermal signs were observed after treatment with the test item or during the 14 days observation period.

There were no treatment related effects on body weight or body weight gain during the observation period.

There was no evidence of any gross observations at a dose level of 2000 mg/kg bw.

 

The acute dermal median lethal dose (LD50) of the test item 2,2-Bis[[3-(dodecylthio)-1-oxopropoxy]methyl]propane-1,3-diyl bis[3-(dodecylthio)propionate] was found to be greater than 2000 mg/kg body weight in male and female Crl:WI rats.

Justification for selection of acute toxicity – oral endpoint

Endpoint conclusion derived in GLP accredited laboratory study in accordance with OECD Guideline 423, EU Method B.1 tris and US EPA Procedure 870.1100

Justification for selection of acute toxicity – oral endpoint

Endpoint conclusion derived in GLP accredited laboratory study in accordance with OECD Guideline 402, EU Method B.3 and US EPA Procedure 870.1200

Justification for classification or non-classification

Acute Oral Toxicity

2,2-Bis[[3-(dodecylthio)-1-oxopropoxy]methyl]propane-1,3-diyl bis[3-(dodecylthio)propionate] does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).

Acute Dermal Toxicity

According to the GHS criteria, 2,2-Bis[[3-(dodecylthio)-1-oxopropoxy]methyl]propane-1,3-diyl bis[3-(dodecylthio)propionate] can be ranked as "Category 5" or "Unclassified" for acute dermal exposure.