4,4'-thiodiethylene hydrogen -2-octadecenylsuccinate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23rd February 1981 - 25th May 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

4 animals per group

GLP compliance:

not specified

Remarks:

Unlikely due to the age of the study

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

1

Reference substance name:

4,4'-thiodiethylene hydrogen -2-octadecenylsuccinate

EC Number:

299-434-3

EC Name:

4,4'-thiodiethylene hydrogen -2-octadecenylsuccinate

Cas Number:

93882-40-7

Molecular formula:

C48H86O8S

IUPAC Name:

2-octadecenylsuccinic anhydride, thiodiethanol esterification products

Test material form:

solid

Remarks:

Waxy Solid

Specific details on test material used for the study:

Description: Off white, very thick liquid
Density: 0.9987 g/ml at 60-65 degree C
Date of Receipt: February 26, 1981
Storage: Room temperature
Preparation of Dosing Material Mixtures: The test material was warmed in a water bath to 60°C to facilate handling. P40 mixture was required

The material was applied directly on to the exposed skin of the anirial, and spread evenly over the entire area.

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Preparation of Animals:
On the day before dosing (approximately 20 hours prior to dosing), the hair of each rabbit was closely clipped from the trunk (dorsal and ventral surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 20% of the body surface
area. No abrasions were made, I.e., the skin of all the animals remained intact.

Husbandry:
Housing: Individually housed
Cage: Suspended, stainless steel
Environmental Conditions: Temperature: monitored twice daily
Temperature range during study: 62 to 76F
Humidity: monitored daily
light cycle: 12 hours light, 12 hours dark
Food:Purina Rabbit Chow
Water Automatic watering system, ad libitum, Municipal water supply
Identification: Each animal was identified with a monel ear tag bearing a unique number prior to testing
Selection: Animal considered unsuitable for study because of poor health or outlying body weights were exlcuded for slection. Animal for study were selected from those remaining.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The material was applied directly on to the exposed skin of the anirial, and spread evenly over the entire area. A layer of 8-ply gauze was then wrapped around the animal to cover the application site. The animal was then wrapped in an impervious plastic sleeve,
designed to contain the test material without leakage or undue pressure. The sleeve was secured with masking tape and Elizabethan collars were placed on all animals.

Duration of exposure:

Following approximately 24 hours of exposure, the wrappings were removed and the amount of residual test material was estimated visually. After 30 minutes, dermal observations were made.

Doses:

Doses groups were 50, 200, 794, 3160 mg/kg

No. of animals per sex per dose:

16 animals (2 animals per sex per dose)

Control animals:

not required

Details on study design:

Preparation of Animals
On the day before dosing (approximately 20 hours prior to dosing), the hair of each rabbit was closely clipped from the trunk (dorsal and ventral surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 20% of the body surface
area. No abrasions were made, i.e. the skin of all the animals remined intact.

Administration of Test Material:
The material was applied directly on to the exposed skin of the anirial, and spread evenly over the entire area. A layer of 8-ply gauze was then wrapped around the animal to cover the application site. The animal was then wrapped in an impervious plastic sleeve,
designed to contain the test material without leakage or undue pressure. The sleeve was secured with masking tape and Elizabethan collars were placed on all animals.

Following approximately 24 hours of exposure, the wrappings were removed and the amount of residual test material was estimated visually. After 30 minutes, dermal observations were made.

Experimental Evaluation (In-Life):
Viability Check: Twice Daily
Observations of Pharmacologic and-Toxicologic Signs: Approximately 1, 2, and 4 hours after dosing and daily thereafter for fourteen days.
Body Weights: Pre-cjose, at the time of clipping (weights used for calculation of doses)
Day of Dosing flay 7 and 14
Evaluation of Skin Irritation: Observations or erythema and edema or other evidence of irritation or injury were made approximately 30 minutes after removal of the occlusive wrapping and aqain at Days 3, 7, 10 and 14.

Post Mortem:
All animals surviving at termination of the observation period (Day 14) were killed by an intravenous or intracardiac overdose of sodium pento’arbital and examined grossly. All abnormalities were recorded but no tissues were saved.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 160 mg/kg bw

Based on:

test mat.

Mortality:

All of the animals survived at all dose levels

Clinical signs:

other: Animals at the 50 mg/kg dose level exhibited slight (well-defined) erythema with occasional edema. 3 of the 4 animals were free of signs of dermal irritation by Day 7 and the fourth animal exhibited only barely perceptible erythena on Day 7 and 10. At the

Gross pathology:

One animal (no. 7214, female) in the 50 mg/kg group exhibited a numher of abnormalities in the gastrointestinal tract (red gastric serosa, hardening and thickening of the intestine). The presence of these findings in a single animal in the lowest dose group is not considered to represent an effect of the test material.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

No mortality was observed in any acute study performed. No systemic toxicity was observed in any study that would be linked to mortality. No systemic toxicity to cause lethality by dermal application is expected for doses up to 5000 mg/kg as evident by the high concentration tested in the acute oral. Therefore no classification is required.

Conclusions:

All of the animals survived at all dose levels; therefore the LD50 is greater than 3160 mg/kg.

Executive summary:

This study was conducted in order to evaluate the acute dermal toxicity of the Substance. On the day before dosing (approximately 20 hours prior to dosing), the hair of each rabbit was closely clipped from the trunk (dorsal and ventral surface and sides from scapular to pelvic area) with an electric clipper. The material was applied directly on to the exposed skin of the anirial, and spread evenly over the entire area. A layer of 8-ply gauze was then wrapped around the animal to cover the application site. Doses of 50, 200, 794 and 3160 mg/kg of body weiqht were administered to sixteen rabbits (two per sex per dose level) for 24 hours. Animals were monitored for observation of pharmacologic and toxicologic signs at approximately 1, 2, and 4 hours after dosing and daily thereafter for fourteen days. No mortality, bodyweight effects, pharmacologic and toxicologic signs and treatment related macrospic effects were noted in any animals. Erythema and/or edema were observed in all animals and incidences of necrosis were observed in animals treated at > or equal to 794 mg/kg.

All of the animals survived at all dose levels; therefore the LD50 is considered to be greater than 3160 mg/kg.