Allyl hexanoate

Endpoint summary

Description of key information

Oral: LD50 = 218 mg/kg body weight leading to classification into CLP Acute Toxicity Hazard Category 3
Dermal: LD50 = 820 mg/kg body weight leading to classification into CLP Acute Toxicity Category 3
Inhalation: no information 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:

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)

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
- Young, adult rats
- 180 to 350 g
- Animals were fasted 18 hours prior to oral exposure

ENVIRONMENTAL CONDITIONS
- No details on environmental conditions provided

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No details reported

Doses:

Not reported

No. of animals per sex per dose:

Five males, five females per dose group

Control animals:

not specified

Details on study design:

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

Statistics:

LD50 values were computed by the method of Litchfield and Wilcoxon (1949)

Sex:

male/female

Dose descriptor:

LD50

Effect level:

218 mg/kg bw

Based on:

test mat.

95% CL:

186 - 255

Mortality:

Animals were found dead between 4 and 18 hours after single oral exposure

Clinical signs:

other: Depression, scrawny appearance

Gross pathology:

No data

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance was acutely toxic to rats after a single oral exposure. Due to the observed LD50 of 218 mg/kg bw the substance is to be classified into Acute Toxicity Hazard Category 3 according to the CLP regulation (second amendment of March 2011).

Executive summary:

The acute oral toxicity of the test substance allyl caproate (allyl hexanoate) was studied in a pre-GLP, pre-guideline study which to a great extent followed the standard acute method described in OECD TG 401. Groups of 10 rats of the Osborne-Mendel strain evenly distributed between the sexes received single oral doses of the test substance by oral gavage. The animals were then observed for signs of toxicity during a period of 14 days. Non-mortal clinical effects including depression and scrawny appearance were observed. In this study, mortality of exposed animals was observed between 4 and 18 hours after a single oral exposure. The LD50 value calculated by the method of Litchfield and Wilcoxon (1949) was 218 mg/kg bw with a 95% confidence level ranging from 186 to 255 mg/kg bw. This LD50 value triggers classification according to CLP (second amendment of March 2011) into Acute Toxicity Hazard Category 3.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

218 mg/kg bw

Quality of whole database:

All studies are pre-GLP and pre-OECD, but they follow principals similar to those of testing guidelines

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:

792 mg/m³ air

Quality of whole database:

The 4-hour LC50 value for allyl alcohol of 124 ppm is used to estimate an inhalation LC50 value for allyl hexanoate by taking into account the molecular weight of the substances. This conversion gives an estimated 4-hour LC50 value for allyl hexanoate of 792 mg/m3.

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, slightly deviating from guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Principles of method if other than guideline:

Groups of three animals, except the high dose group of two 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

Duration of exposure:

Not reported

Doses:

0.313, 0.625, 1.25 and 5.0 g/kg bw

No. of animals per sex per dose:

3, except high dose: 2

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:

820 mg/kg bw

Based on:

test mat.

95% CL:

700 - 940

Mortality:

In the low dose groups 313 and 625 mg/kg bw, no animal died during the observation period of 14 days. In the dose group of 1250 mg/kg bw, one animal died on day one and two animals died on day two following dermal exposure. In the high dose group of 5000 mg/kg bw, all animals died on day one following dermal exposure.

Clinical signs:

other: Diarrhea was obserwed in one animal at 625 and 1250 mg/kg bw dose groups, whereas at 5000 mg/kg bw dose group symptom was obserwed in two animals.

Gross pathology:

Not reported

Other findings:

In the dose group of 313 mg/kg bw, a moderate redness was obserwed in one animal, whereas moderate edema was obserwed in all three animals. In the dose group of 625 mg/kg bw, the both moderate redness and moderate edema were obserwed in all three animals. In the dose group of 1250 mg/kg bw, the both slight rednes and moderate redness were obserwed in one out of trhee animals, whereas slight edema was obserwed in two out of three animals.

Interpretation of results:

Toxicity Category III

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 820 mg/kg bw. The substance is classified into Acute Toxicity Category III according to CLP.

Executive summary:

The acute dermal toxicity of the test substance allyl hexanoate was studied in a non-GLP test according to principles slightly deviating from those of current guidelines. Groups of three animals were exposed to single dermal doses of 0.313, 0.625 and 1.25 g/kg bw, whereas a group of 2 animals was exposed to single dermal dose of 5.0 g/kg bw. Animals were observed during a period of 14 days. No mortality was observed in 0.313 and 0.625 g/kg bw dose groups. In 1.25 and 5.0 g/kg bw dose groups, respectively three out of three and two out of two animals were died within the first days of the observation period. The LD50 value was 0.82 g/kg bw with a 95 % confidence interval of 0.70 to 0.94 g/kg bw. Diarrhea was observed in one animal dosed with 0.625 and 1.25 g/kg bw and in two out of two animals dosed with 5.0 g/kg bw. Slight to moderate skin irritation was observed in animals of 0.313 to 1.25 g/kg bw dose groups.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

820 mg/kg bw

Quality of whole database:

One reliable with restrictions study and two unreliable studies are available.

Additional information

- oral toxicity:

The substance Allyl hexanoate is acutely toxic to rats with oral LD50 = 218 mg/kg bw and in guinea pig with oral LD50 = 280 mg/kg bw, as reported in weight of evidence studies (Jenner et al, 1964).

- dermal toxicity:

The substance Allyl hexanoate is acutely toxic in a reliable with restrictions key study in rabbit with dermal LD50 = 820 mg/kg bw (Opdyke, 1974). In addition, unreliable supporting studies in rabbit show dermal LD100 = 5000 mg/kg bw and dermal LD50 = 266 mg/kg bw (Shelanski & Moldovan, 1971).

Justification for selection of acute toxicity – oral endpoint
All available studies are reliable with restrictions and the study yielding the lowest LD50 value was chosen.

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 hexanoate.

Justification for selection of acute toxicity – dermal endpoint
The most reliable study was chosen as key study

Justification for classification or non-classification

- oral toxicity:

Based on the above stated assessment of the acute oral toxicity of Allyl hexanoate, the oral LD50 values of 218 mg/kg bw 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 3, "Danger - H301: Toxic 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 hexanoate, the dermal LD50 value of 820 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 3, "Danger - H311: Toxic 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 above stated assessment of the acute inhalation toxicity of Allyl alcohol as worst case approach for Allyl hexanoate the classification of "R23 Toxic by inhalation" according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and of Category 3, "Danger - H331: Toxic 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.