Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Oral LD50 > 2000 mg/kg

Dermal LD50> 2000 mg/kg

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:
2014-07-14 to 2014-08-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline Study
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK.
- Age at study initiation: 12 weeks
- Weight at study initiation: 147 - 177 g
- Fasting period during the study: Animals were fasted for overnight period before test item administration and for approximately 3-4 h after dosing.
- Housing: Animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet: Food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: 15 air changes/hour
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From: 2014-07-14 to 2014-08-12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
SPECIFIC GRAVITY OF TEST ITEM: 0.893

MAXIMUM DOSE VOLUME APPLIED: 2.24 mL/kg bw
Doses:
2000 mg/kg
No. of animals per sex per dose:
- Sighting test: 1 female/dose
- Main test: 4 females/dose
Control animals:
no
Details on study design:
Duration of observation period following administration: 14 days
- Frequency of observations: Clinical observations were made 0.5, 1, 2, and 4 h after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily.
- Frequency of weighing: Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: Yes; at the end of the observation period the animals were killed by cervical dislocation and were subjected to a macroscopic examination.
Statistics:
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test item was made.
Preliminary study:
- No mortality or signs of systemic toxicity were noted during the observation period.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality observed
Mortality:
No mortality was observed.
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Body weight:
All animals showed expected gains in body weight over the observation period.
Gross pathology:
No abnormalities were observed at necropsy.
Other findings:
None

Individual body weights and body weight changes:

Dose level mg/kg

Animal number and sex

Body weight (g) at Day

Body weight gain (g) during week

0

7

14

1

2

2000

1-0

177

198

203

21

5

2-1

148

172

186

24

14

2-2

149

166

180

17

14

2-3

150

176

189

26

13

2-4

147

167

177

20

10
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the oral LD50 is higher than 2000 mg/kg bw in rats, therefore the substance is not classified according to CLP Regulation (EC) No. 1272 /2008.
Executive summary:

Test Guidance

OECD Guideline 420 and EC Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Method and materials

Following a sighting study at the dose level of 2000 mg/kg bw, an addition 4 fasted female Wistar rats (RccHan™:WIST) were given a single oral (gavage) dose of the test material at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

Results

No mortality was observed. No signs of systemic toxicity were noted during the observation period. All animals showed expected gains in body weight over the observation period. No abnormalities were observed at necropsy. In this study, the oral LD50 of the test item was considered to be higher than 2000 mg/kg bw in female rats.

Conclusion

Under the test conditions, the oral meadian LD50 is higher than 2000 mg/kg bw in female rats, therefore the substance is not classified according to CLP Regulation (EC) No. 1272 /2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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:
2014-07-17 to 2014-07-31
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline Study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK.
- Age at study initiation: 8-12 Weeks
- Weight at study initiation: Female: 225 - 247g, Males: 280 - 297g
- Fasting period before study: None
- Housing: Animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24 h exposure period and in groups of five, by sex, for the remainder of the study.
- Diet: Food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 °C
- Humidity (%): 30-70 %
- Air changes: 15 air changes/hour
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From: 2014-07-17 to 2014-07-31
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Back and flanks
- % coverage: ca. 10% of the total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Cotton wool moistened with distilled water to remove any residual test item.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Specific gravity of test item: 0.893
- Dose volume: 2.24 mL/kg bw
- Constant volume or concentration used: Yes
Duration of exposure:
24 h
Doses:
Single dose level of 2000 mg/kg bw
No. of animals per sex per dose:
5 male/5 female
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 h after dosing and subsequently once daily for 14 days.
- Frequency of weighing: Individual body weights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: Yes, at the end of the study the animals were killed by cervical dislocation and subjected for macroscopic examination.
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
There were no signs of dermal irritation.
Body weight:
All animals showed expected gains in body weight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy

Individual body weights and body weight changes:

Dose level mg/kg

Animal number and sex

Body weight (g) at Day

Body weight gain (g) during week

0

7

14

1

2

2000

1-0 Male

280

291

308

11

17

1-1 Male

296

304

343

8

39

1-2 Male

286

301

330

15

29

1-3 Male

288

297

310

9

13

1-4 Male

297

306

332

9

26

2-0 Female

225

227

230

2

3

2-1 Female

237

241

246

4

5

2-2 Female

247

250

259

3

9

2-3 Female

245

248

260

3

12

2-4 Female

241

246

257

5

11
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the acute dermal LD50 is higher than 2000 mg/kg bw in rats therefore the substance is not classified according to CLP Regulation (EC) No. 1272/2008.
Executive summary:

Test Guidance

OECD Guideline 402 and EC Method B.3 (Acute Toxicity Dermal)

Method and materials

A group of ten Wistar (RccHanTM:WIST) rats (5 males and 5 females) were given a single dermal application of test item at 2000 mg/kg bw. The test item was placed directly on back and flanks of the skin representing approximately 10 % of the total body surface of the animals. The test site was then covered by a semi-occlusive dressing for 24 h. Animals were then observed for mortality, clinical signs and bodyweights for 14 days.

Results

No mortality and no clinical signs were observed during the study. There were no signs of dermal irritation. All animals showed expected gains in body weight over the observation period. No macroscopic abnormalities were observed at necropsy. The combined dermal LD50 was considered to be higher than 2000 mg/kg bw in rats.

Conclusion

Under the test conditions, the acute median dermal LD50 is higher than 2000 mg/kg bw in rats therefore it is not classified according to CLP Regulation (EC) No. 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Oral

In a key study performed in accordance with OECD Guideline 420 and EC Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure), following a sighting study at the dose level of 2000 mg/kg bw, an addition 4 fasted female Wistar rats (RccHan™:WIST) were given a single oral (gavage) dose of the test material at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

No mortality was observed. No signs of systemic toxicity were noted during the observation period. All animals showed expected gains in body weight over the observation period. No abnormalities were observed at necropsy. In this study, the oral LD50 of the test item was considered to be higher than 2000 mg/kg bw in female rats.

Under the test conditions, the oral median LD50 is higher than 2000 mg/kg bw in female rats, therefore the substance is not classified according to CLP Regulation (EC) No. 1272 /2008.

Dermal

In an OECD Guideline 402 and EC Method B.3 (Acute Toxicity Dermal) study a group of ten Wistar (RccHanTM:WIST) rats (5 males and 5 females) were given a single dermal application of test item at 2000 mg/kg bw. The test item was placed directly on back and flanks of the skin representing approximately 10 % of the total body surface of the animals. The test site was then covered by a semi-occlusive dressing for 24 h. Animals were then observed for mortality, clinical signs and bodyweights for 14 days.

No mortality and no clinical signs were observed during the study. There were no signs of dermal irritation. All animals showed expected gains in body weight over the observation period. No macroscopic abnormalities were observed at necropsy. The combined dermal LD50 was considered to be higher than 2000 mg/kg bw in rats.

Under the test conditions, the acute median dermal LD50 is higher than 2000 mg/kg bw in rats therefore it is not classified according to CLP Regulation (EC) No. 1272/2008.

Justification for classification or non-classification

No toxicity is oberved in both the acute oral and dermal toxicity studies in the rat. The acute median LD50 for both the oral and dermal routes is higher than 2000 mg/kg bw in rats therefore it is not classified for acute toxicity according to CLP Regulation (EC) No. 1272/2008.