Allyl heptanoate

Endpoint summary

Description of key information

Oral: LD50 = 238 mg/kg bw allyl heptanoate (value derived from read across compound allyl hexanoate LD50 = 218 mg/kg bw)
Dermal: LD50 = 810 mg/kg bw allyl heptanoate

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

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

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

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.

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 for allyl hexanoate was 218 mg/kg bw with a 95% confidence level ranging from 186 to 255 mg/kg bw.

The available data on acute oral toxicity meet the criteria for Acute Tox. Cat. 3 (H301) according to Regulation (EC) 1272/2008.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

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:

238 mg/kg bw

Based on:

other: allyl heptanoate

Remarks on result:

other: value derived from read-across substance allyl hexanoate (LD50 = 218 mg/kg bw)

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 for allyl hexanoate was 218 mg/kg bw with a 95% confidence level ranging from 186 to 255 mg/kg bw. Based on the molecular weight the derived LD50 value for allyl heptanoate was 238 mg/kg bw.

The available data on acute oral toxicity meet the criteria for Acute Tox. Cat. 3 (H301) according to Regulation (EC) 1272/2008.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

238 mg/kg bw

Quality of whole database:

Two reliable studies with read across compound allyl hexanoate. In the key study pure compound was administered and in the supporting study the compound with vehicle polyethylene glycol was administered. In the supporting study with allyl heptanoate, the test item was administered in rats by the ratio 1:1 with corn oil vehicle.

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

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

Remarks:

Groups of three animals (rabbits), except the high dose group of two animals, were exposed topically to one dermal dose of test substance.

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

Type of coverage:

not specified

Vehicle:

not specified

Duration of exposure:

14 days

Doses:

313 mg/kg, 625 mg/kg, 1250 mg/kg and the max dose : 5000 mg/kg

No. of animals per sex per dose:

2 for the max dose and 3 for each dose

Control animals:

not specified

Preliminary study:

none

Sex:

not specified

Dose descriptor:

LD50

Effect level:

810 mg/kg bw

Mortality:

1250 mg/kg lethal (3/3 deaths)
5000 mg/kg lethal (2/2 deaths)

Clinical signs:

other: at 5000 mg/kg : severe diarrhea in 2/2 at 1250 mg/kg : diarrhea in 1/3 and ataxia in 2/3

Other findings:

0.313 g/kg no effects
0.625 g/kg nonspecific effects (0 deaths)

Route	Dose mg/Kg	Death/ nb. of Animals	Obseravation Day
			1	2	3	4	5	6	7	8	9	10	11	12	13	14
Dermal	313	0/3	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	625	0/3	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1250	3/3	0	0	1	0	1	0	0	0	1	0	0	0	0	0
	5000	2/2	2	0	0	0	0	0	0	0	0	0	0	0	0	0

Interpretation of results:

other: Toxicity Category III

Executive summary:

The acute dermal toxicity of allyl heptanoate was assessed in an acute dermal toxicity study performed equivalent or similar to OECD Guideline 402. Groups consisting of 3 rabbits each, except the high dose group of 2 animals, were treated topically with a single dose of 313, 625, 1250 and 5000 mg/kg bw of the target substance. Animals were observed during a period of 14 days. No mortality occurred at 313 and 625 mg /kg bw. All animals died at 1250 and 5000 mg/kg bw. The calculated LD50 value was 810 mg/kg bw.

The available data on acute dermal toxicity meet the criteria for Acute Tox. Cat. 3 (H311) according to Regulation (EC) 1272/2008.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

810 mg/kg bw

Quality of whole database:

Pre-GLP and pre-guideline study.

Additional information

- oral toxicity:

The read across substance allyl hexanoate is acutely toxic to rats with oral LD50 = 218 mg/kg bw. This value corresponds to an allyl heptanoate dose of 234 mg/kg bw (Jenner 1964). In supporting studies, LD50 oral (rat) = 500 mg/kg allyl heptanoate; 5 male and 5 female rats per dose (vehicle 50 % corn oil) and LD50 oral (guinea pig) = 444 mg/kg bw allyl heptanoate (vehicle 50 % corn oil) (Jenner 1964). Another supporting study (Meisel 1982) shows an oral LD50 = 276 mg/kg for allyl hexanoate in female rats. The value derived to allyl heptanoate is 301 mg/kg bw.

- dermal toxicity

In a short study (Opdyke 1974) in rabbit the LD50 = 810 mg/kg bw allyl heptanoate.

Justification for selection of acute toxicity – oral endpoint
The acute oral toxicity study in rat with read across compound allyl hexanoate has the lowest LD50 = 218 mg/kg. Derived LD50 for allyl heptanoate is 238 mg/kg.

Justification for selection of acute toxicity – dermal endpoint
Only one reliable acute dermal toxicity study is available.

Justification for classification or non-classification

- oral toxicity:

Based on the above stated assessment of the acute oral toxicity of allyl heptanoate, the oral LD50 values of 238 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 on the acute dermal toxicity of allyl heptanoate, the dermal LD50 value of 810 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:

No data available.