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Administrative data

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:
other: 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 diivided 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 (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): 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).
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:
Depression, rough fur
Body weight:
no data
Gross pathology:
no data
Other findings:
no data
Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
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 inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: pre-GLP and pre-guideline study. Missing particle size and animal mortality statistics.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Single Vapor Exposure: Six male rats were exposed for one, four or eight hours to concentrations ranging from 40 to 23000 ppm. The nominal concentrations were calculated by the standard gas concentration formula of Jacobs and were also checked by chemical analysis. Glass bottles of 1 liter capacity containing distilled water were connected with the sampling port of the chamber, and the vapour drawn through the water by suction. To this aqueous sample was added 0.01 N bromine in acetic acid, in the presence of mercuric acetate catalyst. The excess bromine was reduced by iodide and the iodine titrated with 0.01 N thiosulfate according to the method of Reid and Beddard.
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Long-Evans
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 100 - 200 g
- Fasting period before study: no data
- Housing: in groups of five or six
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: no data
- Exposure chamber volume: 19.5 liters in capacity
- Method of holding animals in test chamber:
- Source and rate of air: air flow from 8.6 to 12.9 L/min, depending on the concentration of allyl alcohol desired
- Method of conditioning air: no data
- System of generating particulates/aerosols: a modified version of the motor-driven syringe assembly described by Carpenter and his associates delivered allyl alcohol from 10 mL Luer-Lok syringe into the chamber through an evaporation through which air was forced at a uniform rate.
- Method of particle size determination: no data
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: no data

TEST ATMOSPHERE
- Brief description of analytical method used: no data
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: no data
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): no data
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
1 - 8 h
Concentrations:
from 40 to 2300 ppm
No. of animals per sex per dose:
6 rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: at least 10 days after the exposure
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no data
- Other examinations performed: clinical signs, histopathology
Statistics:
no data
Sex:
male
Dose descriptor:
LC50
Effect level:
795 ppm
Based on:
test mat.
95% CL:
218 - 978
Exp. duration:
1 h
Remarks on result:
other: included 25 % loss of the test item
Sex:
male
Dose descriptor:
LC50
Effect level:
124 ppm
Based on:
test mat.
95% CL:
95 - 169
Exp. duration:
4 h
Remarks on result:
other: included 25 % loss of the test item
Sex:
male
Dose descriptor:
LC50
Effect level:
57 ppm
Based on:
test mat.
95% CL:
50 - 65
Exp. duration:
8 h
Remarks on result:
other: included 25 % loss of the test item
Mortality:
no data
Clinical signs:
other: Apearance of anxiety, lacrimation, tremors. Coma occasionally preceded the death and diarrhea before death.
Body weight:
no data
Gross pathology:
edema and congestion of the lungs (confirmed microscopically), visceral congestion, discolored livers, some with necrotic areas, swollen and discolored kidneys.
Interpretation of results:
Toxicity Category I
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LC50 of Allyl alcohol to rats was 124 ppm or 0.297 mg/L.
Executive summary:

In the acute inhalation experiments, six male rats were exposed for one four or eight hours to concentrations ranging from 40 to 2300 ppm. The exposure to the test item was accompanied by an appearance of anxiety, lacrimation and tremors. Diarrhea occured before death and coma occasionally preceded the death. The common gross findings in rats that died were edema and congestion of the lungs (confirmed microscopically), visceral congestion and discolored livers, some with necrotic areas. The kidneys were swollen and discolored. The LC50 of 1, 4 and 8 hours were 795, 124 and 57 ppm respectively (included 25 % loss of allyl alcohol, as stated in the chemical analysis).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
297 mg/m³
Quality of whole database:
One study on allyl alcohol is available which can be seen as worst case for allyl 3-cyclohexylpropionate.

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:
other: Non-GLP study, slightly deviating from current testing guidelines
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
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
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:
Ataxia was observed in one animal of the mid-dose group.
Body weight:
Not reported
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
Remarks:
Migrated information Criteria used for interpretation of results: EU
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. Information on the acute toxicity via inhalation is not available for allyl 3-cyclohexylpropionate. However, the acute inhalation study Dunlop et al. (1958) with allyl alcohol is used as worst case approach. For more details please see read-across document under Chapter 13 Assessment Reports.


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.

Justification for selection of acute toxicity – inhalation endpoint
The supporting acute toxicity study Dunlap et al., (1958) with allyl alcohol is used as worst case approach assuming that allyl alcohol is more toxic via the inhalation route than allyl 3-cyclohexylpropionate.

For more information please see read-across document under Chapter 13 Assessment Reports.

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

Justification for classification or non-classification

- 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 "R22 Harmful if swallowed" according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and 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 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 "R21 Harmful in contact with skin" according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and 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 implementation of UN-GHS in the EU.

- inhalation toxicity:

Based on the rationale given in the read-across document attached in IUCLID Ch. 13, while there is no acute inhalation study with the substance, in analogy to the oral and dermal routes, for which the metabolite of Allyl 3 -cyclohexylpropionate, allyl alcohol, was classified in Category 3 while experimental data for Allyl 3-cyclohexylpropionate required a Category 4 classification, also for the inhalation route allyl alcohol is classified in Category 3 and thus a Category 4 classification is proposed for Allyl 3 -cyclohexylpropionate.

Thus, for Allyl 3 -cyclohexylpropionate the classification as "R20 Harmful by inhalation" according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and as Category 4, "Warning - H332: Harmful if inhaled" according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU applies.