Allyl 3-cyclohexylpropionate

Endpoint summary

Description of key information

The substance is acutely toxic via the oral and dermal route and needs to be classified according to CLP.

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Pre-GLP, pre-guideline study, which is to a great extent according to principles similar to those described in OECD TG 401

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Groups of 10 young adult rats evenly divided by sex were fasted for approximately 18 h prior to treatment. Animals had access to water ad libitum, and the food was replaced in cages as soon as animals received their respective doses. All doses were given by intubation. The usual observation period was 2 weeks. LD50 were computed by the method of Litchfield & Wilcoxon (1949).

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Osborne-Mendel

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Fasting period before study: 18 h
- Diet: ad libitum
- Water: ad libitum

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: no data

Doses:

no data

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: close observation until animals appeared normal and showed weight gain.
- Other examinations performed: clinical signs

Statistics:

LD50 was computed by the method of Litchfield & Wilcoxon (1949).

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

585 mg/kg bw

Based on:

test mat.

95% CL:

480 - 714

Mortality:

the death was recorded starting at 4 h and on day 6 post-dose

Clinical signs:

other: other: Depression, rough fur

Gross pathology:

no data

Other findings:

no data

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The substance was acutely toxic to rats in an acute oral toxicity test with a LD50 value of 585 mg/kg bw. The substance is classified into Acute Toxicity Category IV according to CLP.

Executive summary:

The acute oral (gavage) toxicity of the allyl 3-cyclohexylpropionate was studied in a non-GLP test in male and female Osborne-Mendel rats according to principles generally similar to those of OECD TG 401. 5 animals per sex per dose were exposed to single oral (gavage) doses (dose levels were not reported). Animals were observed during a period of 14 days. Time of death was recorded between 4 h and 6 days post-dose. The LD50 value was 585 mg/kg/day with a 95% confidence interval of 480 and 714 mg/kg/bw. Depression and rough fur were observed as toxic signs.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

380 mg/kg bw

Quality of whole database:

The two available studies follow principles that are generally similar to those of OECD TG 401 and are reliable with restrictions.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Remarks:

Non-GLP study, slightly deviating from current testing guidelines

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

necropsy of surivors and gross pathological examination not reported

Principles of method if other than guideline:

Groups of four animals were exposed topically to one dermal dose of test substance. Animals were observed during a period of 14 days.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

Not reported

Type of coverage:

not specified

Vehicle:

not specified

Details on dermal exposure:

Not reported

Duration of exposure:

Not reported

Doses:

0.313, 1.25 and 5.0 g/kg body weight

No. of animals per sex per dose:

4

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: not reported

Statistics:

Not reported

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

1 600 mg/kg bw

Based on:

test mat.

95% CL:

430 - 2 770

Mortality:

In the low-dose group, no animal died during the observation period of 14 days. In the mid-dose group, one animal died on day one following dermal exposure. In the high-dose group, all animals died within the 14-day observation period; three animals were found dead on day 1 following dermal exposure, one animal died on observation day 4.

Clinical signs:

other: other: Ataxia was observed in one animal of the mid-dose group.

Gross pathology:

Not reported

Other findings:

The skin irritation potential of the substance was observed and moderate redness and oedema were observed in animals of all dose groups.

Interpretation of results:

Toxicity Category IV

Conclusions:

The substance was acutely toxic to rabbits in an acute dermal toxicity test with an LD50 value of 1600 mg/kg body weight. The substance is classified into Acute Toxicity Category IV according to CLP.

Executive summary:

The acute dermal toxicity of the test substance allyl cyclohexyl propionate was studied in a non-GLP test according to principles slightly deviating from those of current guidelines. Groups of four animals were exposed to single dermal doses of 0.313, 1.25 and 5.0 g/kg body weight. Animals were observed during a period of 14 days. No mortality was observed in the low-dose group, whereas one animal in the mid-dose group and 4 animals in the high-dose group died within the observation period. The LD50 value was 1.6 g/kg bw with a 95% confidence interval of 0.43 to 2.77 g/kg bw. Ataxia was observed in one animal dosed with 1.25 g/kg bw. Slight to moderate skin irritation was observed in animals of all dose groups.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 600 mg/kg bw

Quality of whole database:

One study is available, which is reliable with restrictions

Additional information

The substance allyl 3-cyclohexylpropionate is acutely toxic when applied via the oral or dermal route. The LD50 values are lower for the oral route with values ranging from 380 mg/kg (guinea pigs) to 585 mg/kg (rats) and are higher for the dermal route with a value of 1600 mg/kg in the rat.

Justification for selection of acute toxicity – oral endpoint
Two valid studies on the acute oral toxicity are available, which are used in a weight-of-evidence approach.

 

The acute oral (gavage) toxicity of the allyl 3-cyclohexylpropionate was studied in a non-GLP test in male and female Osborne-Mendel rats according to principles generally similar to those of OECD TG 401. 5 animals per sex per dose were exposed to single oral (gavage) doses (dose levels were not reported). Animals were observed during a period of 14 days. Time of death was recorded between 4 h and 6 days post-dose. The LD50 value was 585 mg/kg/day with a 95% confidence interval of 480 and 714 mg/kg/bw. Depression and rough fur were observed as toxic signs.

 

The acute oral (gavage) toxicity of the allyl 3-cyclohexylpropionate was studied in a non-GLP test in guinea pigs according to principals generally similar to those of OECD TG 401. Groups of guinea pigs consisting of both males and females were exposed to single oral (gavage) doses (dose levels were not reported). Animals were observed during a period of 14 days. Time of death was recorded between 1 h and 6 days post-dose. The LD50 value was 380 mg/kg bw with a 95 % confidence interval of 172 and 834 mg/kg bw. Depression, salivation, haemorrhage in small intestine were reported as toxic signs.

 

Justification for selection of acute toxicity – dermal endpoint
One valid study on the acute dermal toxicity is available.

 

The acute dermal toxicity of the test substance allyl cyclohexyl propionate was studied in a non-GLP test according to principles slightly deviating from those of current guidelines. Groups of four animals were exposed to single dermal doses of 0.313, 1.25 and 5.0 g/kg body weight. Animals were observed during a period of 14 days. No mortality was observed in the low-dose group, whereas one animal in the mid-dose group and 4 animals in the high-dose group died within the observation period. The LD50 value was 1.6 g/kg bw with a 95% confidence interval of 0.43 to 2.77 g/kg bw. Ataxia was observed in one animal dosed with 1.25 g/kg bw. Slight to moderate skin irritation was observed in animals of all dose groups.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available studies are considered reliable for this assessment.

 

Oral toxicity:

Based on the above stated assessment of the acute oral toxicity of Allyl 3-cyclohexylpropionate, the oral LD50 values of 380 mg/kg bw (guinea pig) and 585 mg/kg bw (rat) lead to the classification of Category 4, "Warning - H302: Harmful if swallowed" according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council, as amended for the 17th time in Regulation (EU) 2021/849) as implementation of UN-GHS in the EU.

 

Dermal toxicity:

Based on the above stated assessment of the acute dermal toxicity of Allyl 3-cyclohexylpropionate, the dermal LD50 value of 1600 mg/kg bw leads to the classification of Category 4, "Warning - H312: Harmful in contact with skin" according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council, as amended for the 17th time in Regulation (EU) 2021/849) as implementation of UN-GHS in the EU.