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Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Data is from experimental study report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
The objective of the study was to assess the dermal toxicity of the given test chemical after single dose application by dermal route in rats.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Castor oil, ethoxylated
EC Number:
500-151-7
EC Name:
Castor oil, ethoxylated
Cas Number:
61791-12-6
Molecular formula:
C57H104O9(CH2CH2O)n
IUPAC Name:
Castor oil, ethoxylated
Details on test material:
- Name of test material (as cited in study report):Castor Oil, ethoxylated
- Substance type:Organic
- Physical state:Pale Yellow liquid
- AI Content:99.12%
- Lot/batch No.:Lot 1/12
- Storage condition of test material:Keep Container tightly closed at room temperature.
- Other:
Handling and Disposal
Safety precautions : Aprons, masks, caps, gloves and goggles were used to ensure the health and safety of the personnel.
Disposal : The remaining unused test item was disposed as per internal SOPs of sa-FORD.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source:In-House Bred at Sa-Ford, Animal Facility.
- Age at study initiation:Healthy young adult animals were used for the study.
- Females were nulliparous and non pregnant.
- Weight (Prior to Treatment):Male:Minimum: 223 g and Maximum: 259 g , Female:Minimum: 234 g and Maximum: 248 g
- Housing:The animals were housed individually in polycarbonate cages.
- Bedding : All cages were provided with corn cobs.
- Room Sanitation : The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
- Cages and water bottle : All the cages and water bottles were changed at least twice every week.
- Diet (e.g. ad libitum):All animals were provided conventional laboratory rodent diet (Nutrivet Life Sciences, Pune) ad libitum.
- Water (e.g. ad libitum):Aqua guard filtered tap water was provided ad libitum via drinking bottles.
- Acclimation period:All animals were acclimatized to the test conditions for 5 days prior to administration of the test item.
- Randomization : Animals were selected manually. No computer generated randomization program was used.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):Minimum: 20.00 °C and Maximum: 23.10 °C
- Humidity (%):Minimum: 38.40% and Maximum: 56.00%
- Air changes (per hr):More than 12 changes per hour
- Photoperiod (hrs dark / hrs light):12:12

IN-LIFE DATES: From: February 12, 2014 To: March 03, 2014

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure:The test item was applied uniformly over clipped dorsal area of rat skin.
- % coverage:Approximately 10% body surface area of rat.
- Type of wrap if used:The porous gauze dressing and non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done):The residual test item was removed by using distilled water.
- Time after start of exposure:24-hour.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):A limit dose of 2000 mg/ kg body weight of test item was applied.
Duration of exposure:
24 hrs
Doses:
2000 mg/kg body weight.
No. of animals per sex per dose:
10 (Five per sex)
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:Daily
- Necropsy of survivors performed: yes, at the end of 14 day observation period, all the surviving rats were euthanised by overdose of CO2 and subjected to gross pathology examination, for external and internal observations.
- Other examinations performed: Clinical signs : After test item administration, individual animals were frequently observed at 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all animals were observed once a day during the 14 day observation period.
Body weight: All rats were weighed on days 0 (prior to dosing), 7 and 14.
other: Local Signs/Skin Reactions - All animals were observed once daily during days 1-14 (in common with clinical signs).
- Mortality - Animals were observed twice daily for any mortality during the experimental period.
Statistics:
No statistical analysis was performed since the study was terminated with limit test.

Results and discussion

Preliminary study:
not specified
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Non toxic to animals
Mortality:
No mortality was observed at limit dose of 2000 mg/kg body weight of test item during the 14 day observation period.
Clinical signs:
other: In males, animal nos. 1 to 4 were normal throughout the experimental period, while animal no. 5 was observed normal at 1, 2, 3, 4 hours and from day 1 to 5 and with mild alopecia on day 6 to 8 followed by normal clinical sign till day 14. In females, an
Gross pathology:
The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality.
Other findings:
not specified

Any other information on results incl. tables

Table 1: Individual Animal Body Weight (g) andBody Weight Changes(%)

 

Dose:2000 mg/ kg bodyweight                                                                              Density:0.9793

Animal No.

Sex

Dose (ml) Applied*

Body Weight (gram)

Body Weight Change (%)

Day 0

Day 7

Day 14

Day 0-7

Day 0-14

1

Male

0.47

232

233

264

0.43

13.79

2

0.46

223

215

272

-3.59

21.97

3

0.50

245

254

276

3.67

12.65

4

0.47

232

213

231

-8.19

-0.43

5

0.53

259

257

270

-0.77

4.25

6

Female

0.49

239

248

254

3.77

6.28

7

0.48

234

228

234

-2.56

0.00

8

0.51

248

246

252

-0.81

1.61

9

0.48

236

242

256

2.54

8.47

10

0.50

246

246

248

0.00

0.81

Key:* = Based on density of test item and day 0 body weight taken prior to dose application.

 

Table 2: Individual Animal Clinical Signs and Symptoms

 

Dose:2000 mg/kg body weight

Animal No.

Sex

Hour(s) - Day 0

Day

1

2

3

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1

Male

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

2

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

3

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

4

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

5

1

1

1

1

1

1

1

1

1

12+

12+

12+

1

1

1

1

1

1

6

Female

1

1

1

1

1

65+

65+

65+

65+

65+

147+

65+

147+

146

146

146

1

1

1

1

7

1

1

1

1

1

1

1

1

1

12+

12+

12+

12+

12+

1

1

1

1

8

1

1

1

1

1

65+

65+

65+

65+

65+

65+

146

1

1

1

1

1

1

9

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

10

1

1

1

1

1

65+

65+

65+

65+

147+

65+

147+

65+

147+

146

146

146

1

1

1

1

Key: 1 = Normal, 12 = Alopecia, 65 = Erythema, 146 = Scab, 147 = Scale, + = Mild

 

Table 3: Individual Animal Mortality Record

 

Dose:2000 mg/kg body weight

       Animal No.

Sex

Days of Observation (0 to 14)

Morning Observations

Evening Observations

1

Male

No mortality and morbidity

No mortality and morbidity

2

No mortality and morbidity

No mortality and morbidity

3

No mortality and morbidity

No mortality and morbidity

4

No mortality and morbidity

No mortality and morbidity

5

No mortality and morbidity

No mortality and morbidity

6

Female

No mortality and morbidity

No mortality and morbidity

7

No mortality and morbidity

No mortality and morbidity

8

No mortality and morbidity

No mortality and morbidity

9

No mortality and morbidity

No mortality and morbidity

10

No mortality and morbidity

No mortality and morbidity


Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Conclusions:
Under the conditions of this, the acute dermal median lethal dose LD50 was considered to be >2000 mg/kg body weight, when Wistar rats were treated with given test chemical by dermal aaplication. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical does not exhibit acute dermal toxicity i.e it is acutely non toxic to animals.

Executive summary:

Acute dermal toxicity study of the given test chemical was conducted as per OECD No.402 in Wistar rats. Five male and five female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Rats free from injury and irritation of skin were selected for the study. Twenty four hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/kg body weight of test item was applied by single dermal application and observed for 14 days after treatment. On test day 0, as such test item was applied directly on the intact skin of clipped area of rats; the surgical gauze patch was put on to the intact skin of clipped area. This surgical gauze patch was covered with a non-irritating adhesive tape. The dressing was wrapped around the abdomen and anchored with non-irritating adhesive tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed. The animals were observed daily for mortality and clinical signs, during the acclimatization period. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1‑14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs/Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were re­corded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically. No mortality was observed in any animal till the end of the experimental period. In males, animal nos. 1 to 4 were normal throughout the experimental period, while animal no. 5 was observed normal at 1, 2, 3, 4 hours and from day 1 to 5 and with mild alopecia on day 6 to 8 followed by normal clinical sign till day 14. In females, animal no. 6 was observed normal at 1, 2, 3, 4 hours and on day 1, mild erythema from day 2 to 7, mild scaling on day 6 and 7 and scab from day 8 to 10 followed by normal clinical sign till day 14. Animal no. 7 was observed normal at 1, 2, 3, 4 hours and from day 1 to 5 and mild alopecia from day 6 to 10 followed by normal clinical sign till day 14. Animal no. 8 was observed normal at 1, 2, 3, 4 hours and on day 1, mild erythema from day 2 to 7 and scab on day 8 followed by normal clinical sign till day 14.Animal no. 9 was observed normal throughout the experimentation period. Animal no. 10 was observed normal at 1, 2, 3, 4 hours and on day 1, mild erythema from day 2 to 7, mild scaling from day 5 to 7 and scab from day 8 to 10 followed by normal clinical sign till day 14. The body weight gain was observed in male and female animals on day 7 and 14 as compared to day 0, except decline in mean body weight gain was observed in males on day 7. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality. Under the conditions of this, the acute dermal median lethal dose LD50 was considered to be >2000 mg/kg body weight, when Wistar rats were treated with given test chemical by dermal application. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical does not exhibit acute dermal toxicity i.e it is acutely non toxic to animals.