2-hexylcyclopentan-1-one

Endpoint summary

Description of key information

In reliable limit tests, the acute oral and dermal toxicity of hexyl cyclopentanone was determined to be greater than 5000 mg/kg bw in rats and rabbits, respectively (Moreno, 1980). No acute inhalation studies are available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980-09-03 to 1980-09-17

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This method is similar to OECD guideline 401, and the study was conducted to GLP. Only male rats used and limited details on test substance.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Limit test using only male rats (group of 10) and details on test substance (e.g. purity) not included in report.

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

Species:

rat

Strain:

Wistar

Sex:

male

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: 200 to 232 g
- Fasting period before study: 16 to 20 hours
- Housing: 5/cage in suspended wire mesh cages
- Diet (e.g. ad libitum): fresh Purina rat 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

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE: not applicable

MAXIMUM DOSE VOLUME APPLIED: no data in study report

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

10 males

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the rats were observed 3 to 4 hours after dosing, and once daily for 14 days
- Necropsy of survivors performed: yes. At 14 days the survivors were sacrificed. All animals were examined for gross pathology
- Other examinations performed: no data in study report

Statistics:

Not applicable

Preliminary study:

None

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Only dose tested (limit test). 95% confidence levels not relevant as no deaths occurred

Mortality:

All animals survived to the end of the 14-day observation period

Clinical signs:

other: 9/10 animals had diarrhoea on day 1. On days 2-5, there were isolated instances of prostration, tachypnea, piloerection, lethargy, flaccid muscle tone, ptosis, emaciation and brown staining of the anogenital area. All animals were normal from day 5 until

Gross pathology:

9/10 animals were normal. One animal had white nodules (3-6 mm) on all lobes of the left lung

Other findings:

No data in study report

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

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

Executive summary:

In an acute oral toxicity study, conducted according to GLP, and similar to OECD TG401 (not available at time of study), a group of 10 male Wistar rats was administered a single dose of neat hexyl cyclopentanone by gavage. Animals were observed for clinical signs of toxicity for 14 days. All survivors were examined for gross pathological changes.

No deaths occurred during the observation period. On day 1, 9/10 animals had diarrhoea. There were isolated instances of clinical signs in the early part of the observation period, but the animals were generally healthy on days 5 through 14. One animal was found at necropsy to have white nodules (3-6 mm) on all lobes of the left lung.

From the results of this study, the acute oral LD50 of hexyl cyclopentanone in rats was determined to be greater than 5000 mg/kg bw (limit test).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Acceptable

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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.

Reason / purpose for cross-reference:

reference to same study

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

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

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

Preliminary study:

None

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Acceptable

Additional information

Justification for selection of acute toxicity – oral endpoint
Good-quality study, to GLP

Justification for selection of acute toxicity – dermal endpoint
Good-quality study, to GLP

Justification for classification or non-classification

Based on the results of reliable limit tests in laboratory animals, classification under the EU DSD or CLP regulations as acutely toxic by the oral or dermal routes is not required.