2-hexylcyclopentan-1-one

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980-09-04 to 1980-10-14

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This method is similar to OECD guideline 402, and the study was conducted to GLP. Slight deviations did not effect the study validity: animals were housed 2/cage, abrasions were made in some animals, and limited details on test substance.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Animals were housed 2/cage (guideline requires individual housing). Abrasions were made in 3 females and 2 males (abrading the skin is not recommended in OECD TG 402)

GLP compliance:

yes

Remarks:

Report states that "this study was conducted in compliance with the FDA's Good Laboratory Practices effective 6/20/79" [i.e. 20 June 1979]. No certificate of GLP compliance was included

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-hexylcyclopentan-1-one

EC Number:

235-970-6

EC Name:

2-hexylcyclopentan-1-one

Cas Number:

13074-65-2

Molecular formula:

C11H20O

IUPAC Name:

2-hexylcyclopentan-1-one

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): 80-75, hexyl cyclopentanone
- Physical state: clear liquid
- Analytical purity: no data in study report
- Impurities (identity and concentrations): no data in study report
- Composition of test material, percentage of components: no data in study report
- Isomers composition: not applicable
- Purity test date: no data in study report
- Lot/batch No.: no data in study report
- Expiration date of the lot/batch: no data in study report
- Stability under test conditions: no data in study report
- Storage condition of test material: no data in study report
- Other: specific gravity 0.86 [g/mL]

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: 2.1 to 2.6 kg
- Fasting period before study: not applicable
- Housing: 2/cage in suspended wire mesh cages
- Diet (e.g. ad libitum): fresh Purina rabbit chow, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data, although study report states that the room was "temperature controlled"
- Humidity (%): no data in study report
- Air changes (per hr): no data in study report
- Photoperiod (hrs dark / hrs light): no data in study report

IN-LIFE DATES: no data in study report

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: abdomen, 200 sq. cm
- % coverage: 10%
- Type of wrap if used: gauze patches, secured with adhesive tape. The trunks were wrapped with "impervious material".

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the exposure site was wiped, but not washed, to remove excess material
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 12.2-15.1 mL
- Concentration (if solution): not applicable
- Constant volume or concentration used: no. Volume was adjusted to account for specific gravity and weight of test animal

VEHICLE: not applicable

Duration of exposure:

24 hours

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: rabbits were observed daily for 14 days for signs of toxicity, pharmacological effects and mortality.
- Necropsy of survivors performed: yes
- Other examinations performed: dermal reactions were scored by the Draize method at 1, 7, and 14 days post-exposure. Body weights were recorded pre-test and at 14 days (survivors only)

Statistics:

no data

Results and discussion

Preliminary study:

None

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Only dose tested. 95% confidence interval not calculated

Mortality:

One male rabbit died on day 5. All other animals survived to the end of the observation period

Clinical signs:

other: Clinical signs of toxicity (including lethargy, diarrhoea and ptosis) were noted in isolated instances throughout the observation period

Gross pathology:

The internal organs of survivors appeared normal. Skin ulceration was noted in 1/9 surviving animals, while the remaining survivors had scaly skin. In the animal that died, the heart was moderately dilated, the lungs were collapsed, and the pleural cavity contained dark fluid

Other findings:

Skin oedema, generally slight on day 1, was minimal on day 7. Erythema was slight on day 1 in all animals; on day 7, 4/9 animals continued to display slight erythema while 2/9 had moderate eschar. 3/9 animals were non-erythemous at the application site on day 7. On day 14, 8/9 animals were non-erythemous and non-oedematous at the exposure sites. Severe eschar and slight oedema were observed in one animal at day 14 only.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal toxicity of hexyl cyclopentanone was determined to be greater than 5000 mg/kg bw in rabbits (limit test).

Executive summary:

In an acute dermal toxicity study, conducted according to GLP and similar to OECD TG402 (not available at time of study), a group of 5 male and 5 female New Zealand white rabbits received a single application of neat hexyl cyclopentanone to the clipped skin of the abdomen. Half of the test sites were abraded. This treated area was subsequently covered for 24 hours, and the application site was wiped on patch removal to remove excess material.

Animals were observed for clinical signs of toxicity for 14 days, and body weights were recorded at the start and end of the study. All animals were examined for gross pathological changes. Dermal reactions were scored by the Draize system 1, 7 and 14 days after application.

One male rabbit died on day 5 post-exposure, showing dilation of the heart, lung collapse and dark fluid in the pleural cavity at necropsy. No other deaths occurred during the observation period. There were no treatment-related gross pathological observations in the survivors. Oedema and erythema was seen in all surviving animals on day 1, but 8/9 animals had returned to normal by the end of the observation period.

From the results of this study, the acute dermal LD50 of hexyl cyclopentanone in rabbits was determined to be greater than 5000 mg/kg bw.