1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-nortall-oil alkyl derivs.

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 August 1990 to 13 September 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

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 the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-nortall-oil alkyl derivs.

EC Number:

263-171-2

EC Name:

1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-nortall-oil alkyl derivs.

Cas Number:

61791-39-7

Molecular formula:

Not applicable (a generic molecular formula cannot be provided for this specific UVCB substance).

IUPAC Name:

2-{2-[(8Z)-heptadec-8-en-1-yl]-4,5-dihydro-1H-imidazol-1-yl}ethan-1-ol; 2-{2-[(8Z)-heptadec-8-en-1-yl]-4,5-dihydro-1H-imidazol-1-yl}ethyl (9Z)-octadec-9-enoate

Details on test material:

- Name of test material (as cited in study report): EH & S 588
- Lot/batch No.: V0G188
- Other: Lab ID number: 90-0156

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazelton Research Products, Inc., Denver PA
- Age at study initiation: Young adult
- Weight at study initiation: 2-3 kg
- Fasting period before study:
- Housing: Each animal was housed in a wire mesh cage.
- Diet: ad libitum; Agway ® ProLab Rabbit Formula (Agway, Inc., Syracuse, NY)
- Water: ad libitum; fresh tap water
- Acclimation period: five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not stated
- Humidity (%): Not stated
- Air changes (per hr): Not stated
- Photoperiod (hrs dark / hrs light): 12 hour light-dark cycle

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

EXPOSURE CALCULATION
The approximate area dosed on each rabbit was 130cm2. Based on an average body weight of 2.13 kg times the dose level of 2000 mg/kg, the average dose was determined to be 4260 mg. Therefore, the approximate amount of test material applied per unit of exposed skin was calculated to be 32.8 mg/cm2.

TEST SITE
The fur on the back of each rabbit was clipped with electric clippers on the day prior to dose administration. The test article was applied topically to the clipped area at a dose level of 2000 mg/kg body weight. Each test site was covered with gauze and then occluded with a layer of plastic wrap and a stockinette sleeve held in place with tape.

REMOVAL OF TEST SUBSTANCE
The binders were removed 24 hours after dose administration and the exposure sites gently wiped with a clean water-moistened gauze to remove as much non-absorbed test article as possible.

Duration of exposure:

24 hours

Doses:

2000 mg /kg body weight

No. of animals per sex per dose:

five male and five female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for pharmacotoxic signs and mortality three times on the day of dose administration and twice daily thereafter. Individual bodyweights were recorded prior to dose administration on study day 1 and on days 4, 8 and 15 (study termination).
- Necropsy of survivors performed: yes; All animals were euthanized with an injection of sodium pentobarbitol on study day 15 and subjected to gross necropsy examination. The external body surface and orifices, major visceral organs, body cavities and the carcass were examined and the results recorded. No tissues were saved.

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 95% confidence limits not reported.

Mortality:

All animals survived to study termination.

Clinical signs:

other: A gel-like substance in the waste tray and soft stools.

Gross pathology:

No internal abnormalities were noted during gross necropsy examination of the animals. Gross necropsy confirmed eschar sloughing.

Other findings:

All animals appeared normal from study days 8-15. Test article application caused severe dermal irritation characterised by edema and eschar formation.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute dermal LD50 of the test material is considered to be greater than 2000 mg/kg body weight.

Executive summary:

The test material was applied topically to five male and five female New Zealand White Rabbits at a dose level of 2000 mg/kg body weight for a period of 24 hours. The animals were observed for pharmacotoxic signs and mortality during a 15 day observation period.

All animals survived to study termination (day 15). Under the conditions of this study, the acute dermal LD₅₀ of the test material is considered to be greater than 2000 mg/kg body weight.