2-ethylhexyl 12-(acetoxy)octadecanoate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylhexyl 12-(acetoxy)octadecanoate

EC Number:

263-233-9

EC Name:

2-ethylhexyl 12-(acetoxy)octadecanoate

Cas Number:

61800-40-6

Molecular formula:

C28H54O4

IUPAC Name:

2-ethylhexyl 12-(acetoxy)octadecanoate

Test material form:

liquid

Specific details on test material used for the study:

Batch: 2137-0
Stability: Stable

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals were received from Covance Research Products, Inc., Denver, PA on 27 Feb 2013. Following an acclimation period of at least one week, five healthy male and five healthy, non-pregnant and nulliparous female New Zealand White rabbits were randomly assigned to the treatment group using standard methods of randomization.

The animals were born on 22 Sep 2012 and 25 Sep 2012. The pretest body weight range was 2.3 - 2.8 kg for males and 2.4 - 2.9 kg for females. The weight variation of the animals used did not exceed ± 20% of the mean weight.

The animals were identified by cage notation and a uniquely numbered metal ear tag and housed one per cage in suspended wire cages. Absorbent paper bedding was placed beneath the cages and changed at least three times per week. Fresh PMI Rabbit Chow (Diet #5321) was provided daily. Water was available ad Iibitum. The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled, had a 12-hour light\dark cycle, and was kept clean and vermin free.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
Approximately 24 hours prior to application of the test article, the dorsal area of the trunk of each animal was clipped free of hair. The prepared site was approximately 10% of the body surtace and remained intact.

DOSING:
A single dose of the test article was applied to the prepared site, over a porous gauze dressing measuring 10 x 15 cm at a dose level of 2000 mg/kg. The dose was based on the sample weight as calculated from the specific gravity. The torso was wrapped with a piece of porous dressing (semi-occlusive) and was secured with non-irritating tape. The test article remained in contact with the skin for 24 hours at which time the wrappings were removed. Residual test article was removed by gently washing with distilled water.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test article was removed by gently washing with distilled water.

VEHICLE
No vehicle

Duration of exposure:

The test article remained in contact with the skin for 24 hours at which time the wrappings were removed.

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males and 5 females were dosed at 2000 mg/kg

Control animals:

no

Details on study design:

The test sites were scored for dermal irritation at 24 hours postdose and on Day 14 using the numerical Draize scoring code below:
Erythema & Eschar
No erythema - 0
Very slight erythema (barely perceptible) - 1
Well defined erythema - 2
Moderate to severe erythema - 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) - 4

Edema:
No edema - 0
Very slight edema (barely perceptible) - 1
Slight edema (edges of area well-defined by definite raising) - 2
Moderate edema (raised approximately 1.0 mm) - 3
Severe edema (raised more than 1.0 mm, extending beyond the area of exposure) - 4

The animals were observed 1 and 4 hours postdose and once daily for 14 days for mortality, toxicity and
pharmacological effects.

Body weights were recorded pretest, weekly and at termination.

All animals were humanely sacrificed using CO2 following study termination and examined for gross pathology.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

All ten rabbits survived the single 2000 mg/kg 24-hour dermal exposure.

Clinical signs:

There were no abnormal physical signs observed.

Body weight:

All of the animals gained body weight by study termination.

Gross pathology:

The gross necropsy of all animals revealed no observable abnormalities.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 of CAS# 1365345-64-7 (SE7B Batch 2137-0) is greater than 2000 mg/kg of body weight in rabbits.

Executive summary:

Objective: To determine the potential for toxicity of the test article when applied dermally. This study is designed to comply with the standards set forth in OECD GUIDELINES FOR TESTING CHEMICALS, NUMBER 402, adopted February 24, 1987.

Method Synopsis:

Five healthy male and five healthy female New Zealand White rabbits were dosed dermally with CAS# 1365345-64-7 (SE7B Batch 2137-0) at 2000 mg/kg of body weight. The test article was kept in contact with the skin for 24 hours. Dermal responses were recorded at 24 hours postdose and on Day 14. Animals were observed for mortality, toxicity and pharmacological effects at 1 and 4 hours postdose and once daily for 14 days. Body weights were recorded pretest, weekly and at termination. All animals were examined for gross pathology.

Summary:

All ten rabbits survived the single 2000 mg/kg 24-hour dermal exposure. There were no abnormal physical signs observed. At 24 hours, erythema was very slight to well-defined and edema was absent to slight. By Day 14, erythema and edema were absent. All of the animals gained body weight by study termination. The gross necropsy of all animals revealed no observable abnormalities.

Conclusion: The dermal LD50 of CAS# 1365345-64-7 (SE7B Batch 2137-0) is greater than 2000 mg/kg of body weight in rabbits.