Methyl cinnamate

Endpoint summary

Description of key information

LD50(oral, rat): 2610 mg/kg bw;
LD50 (dermal, rabbit): > 5000 mg/kg bw

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:

N/A

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well documented, available information contributing to assessment.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Sprague-Dawley albino rats of both sexes (weighing 150 to 250 grams) were used in the acute oral toxicity studies.

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

five (fasted overnight) were given exploratory doses of a test compound by intubation.

Doses:

6 g/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

In order to find proper dosage levels for LD50 determinations, five to six rats (fasted overnight) were given exploratory doses of a test compound by intubation. Following dosing, all animals were kept for a two-day observation period. The toxic signs and mortality were recorded at one, four, 24, and 48 hours. Based on the results obtained from the range-finding study, the determination of the LD50 of each test material was initiated by giving graded dosage levels to six groups of five rats of both sexes via the same route. Where the range-finding study results indicated the test substance to be relatively nontoxic, a single group of five rats of both sexes was dosed at 6 grams or 6 ml/kg. Higher dosages were not used in order to conserve material and LD50's would have little meaning. Toxic signs and mortality were recorded at one and four hours and then once daily for a period of 14 days. A necropsy was performed on all animals that died during the study and on those killed by cervical dislocation at termination.

Statistics:

N/A

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 610 mg/kg bw

Based on:

test mat.

95% CL:

> 2 000 - < 3 410

Remarks on result:

other: Clinical signs of toxicity were depression and decrease in respiration at 3160 mg/kg and higher.

Mortality:

no details known, as certain sections of the report were blanked out for confidentiality reasons by the data owner.

Clinical signs:

other: Depression, decrease in respiration at 3.16 g/kg and higher

Gross pathology:

The stomachs of animals that died 24 hours following the administration of test article were filled with fluid. No tissue damage was seen in any animal killed at the termination of the study.

Other findings:

N/A

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results in this acute study, LD50 (oral, rat) is considered to be 2610 mg/kg body weight.

Executive summary:

This study was performed to evaluate the acute toxicity of various test substances, amongst them methyl cinnamate (the other substance identities were blanket out by data owner for confidentiality reasons). Rats were applied at dosage levels up to 6 g/kg body weight. five to six rats (fasted overnight) were given exploratory doses of a test compound by intubation. Following dosing, all animals were kept for a two-day observation period. Depression and decrease in respiration were observed at 3.16 g/kg and higher. The stomachs of animals that.died 24 hours following the administration of test article were filled with fluid. No tissue damage was seen in any animal killed at the termination of the study.

Therefore, it is concluded that methyl cinnamate is considered non-classifiable according to CLP (Regulation EC No 1272/2008) in this acute oral toxicity study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 610 mg/kg bw

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:

N/A

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well documented, available information is sufficient for assessment.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

not specified

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:

New Zealand white rabbits of both sexes (weighing 2.5 to 3.0 kg.) were used.

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The data obtained from acute oral LD50 studies in rats indicated relatively low toxicity of all test materials. Higher dosages were not used since LD50 values would have little meaning. Therefore, only one selected dose level of each compound was applied to a group of four rabbits of both sexes (weighing 2.5 to 3.0 kg). The dose site, approximately 240- cm2 (about 10% of body surface) was closely clipped. The skin of two of the animals was abraded and the skin of the two remaining animals was left intact. The skin was slightly moistened with physiological saline prior to application. Solid test materials were first ground to fine powders and then applied to the rabbit skin and covered with a nonabsorbent binder.

Duration of exposure:

24 hr

Doses:

5 g/kg bw

No. of animals per sex per dose:

2

Control animals:

yes, concurrent no treatment

Details on study design:

Animals were immobilized for 24 hours in stocks. Immediately following the removal of the binders, the local effects of the test compounds were scored according to the method of Draize. Toxic effects, dermal irritation, and mortality were recorded daily for 14 days. A necropsy was performed on each animal that died during the experiment and on those killed (by air embolism) at termination. Abnormal tissues and samples of adrenal, kidney, liver, lung, spleen, gonads, urinary bladder, bone, and skin were preserved in 10% formalin for possible histologic examination.

Statistics:

N/A

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No adverse effects were observed during the test.

Mortality:

There was no mortality observed with methyl cinnamate during the test.

Clinical signs:

other: All animals appeared to be normal throughout the entire 14-day observation period.

Gross pathology:

No gross pathologic findings occurred in the rabbit that were killed at termination.

Other findings:

N/A

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results given in this study, the dermal LD50 value is considered to be greater than 5000 mg/kg body weight.

Executive summary:

This study was conducted to investigate the acute dermal toxicity of test substance. Rabbits were applied at dosage level of 5 g/kg body weight. There was no mortality of methyl cinnamate applied animals during the test. All animals appeared to be normal throughout the entire 14-day observation period. No gross pathologic findings occurred in the rabbit that were killed at termination. There was no skin irritation to either intact or abraded skin following treatment with test substance.

Therefore, test substance failed to cause acute dermal toxicity to rabbits during the test period.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Additional information

According to the toxicokinetic assessment, the potential exposure route of methyl cinnamate is via oral or dermal while the inhalation is an irrelevant route due to the high boiling point and low vapor pressure of methyl cinnamate. The available data are sufficient for assessment. Thus, there is no safety assessment concern for the inhalation route.

There is one available report published by RIFM (report no. 2110) to evaluate the acute toxicity of methyl cinnamate. In this report, rats were applied at dosage levels up to 6 g/kg body weight. Five to six rats (fasted overnight) were given exploratory doses of a test compound by intubation. Following dosing, all animals were kept for a two-day observation period. Depression and decrease in respiration were observed at 3.16 g/kg and higher. The stomachs of animals that died 24 hours following the administration of test article were filled with fluid. No tissue damage was seen in any animal killed at the termination of the study. The LD50 in this study was determined to be2610 mg/kg bw. This finding is supported by acute oral toxicity studies performed with ethyl cinnamate and cinnamaldehyde, both metabolising in vivo through cinnamic acid as methyl cinnamate (for more details see endpoint summary to repeated dose endpoint). The LD50 values determined using rats, mice and guinea pigs were 4000 mg/kg (ethyl cinnamate) and 3400 mg/kg (cinnamaldehyde) respectively.

Moreover, it was reported that rabbits were applied at dosage level of 5 g/kg body weight via dermal route. There was no mortality during the test. All animals appeared to be normal throughout the entire 14-day observation period. No gross pathologic findings occurred in the rabbit that were killed at termination.There was no skin irritation to either intact or abraded skin following treatment with test substance.

Therefore, test article was considered to be of no acute toxicity via dermal and oral route.

Justification for selection of acute toxicity – oral endpoint
Study performed with methyl cinnamate, whereas supporting studies are performed using ethyl cinnamate and cinnamaldehyde.

Justification for selection of acute toxicity – inhalation endpoint
According to the toxicokinetic assessment, the potential exposure route of methyl cinnamate is via oral or dermal while the inhalation is an irrelevant route due to the high boiling point and low vapor pressure of methyl cinnamate. The available data are sufficient for assessment. Thus, there is no safety assessment concern of this route.

Justification for classification or non-classification

Based on the available data, methyl cinnamate is not subject to classification for acute toxicity according to CLP (Regulation EC No.1272/2008) and DSD (Directive 67/548/EEC). Also no specific target organ toxicity upon single exposure classification is required according to CLP based on observations in the available acute studies by oral and dermal route. Data via inhalative exposure for acute toxicity is lacking but not required.