Cinnamyl butyrate

Endpoint summary

Description of key information

Acute Oral Toxicity: 

Acute oral toxicity dose was predicted based on OECD QSAR toolbox for target substance Cinnamyl butyrate (103-61-7) estimated to be 3331.84 mg/kg bw on rats,and the QSAR prediction done using the Danish (Q)SAR Databasefor target substance Cinnamyl butyrate (103-61-7) was estimated to be 3900 mg/kg bw on rats and for differentstudies available on target substance Cinnamyl butyrate (103-61-7) was considered to be >5000 mg/kg bw on rats and for the structurally similar read across substance Ethyl Butyrate (CAS No. 105-54-4) was considered to be 5000 mg/kg bw on rats and for Cinnamyl acetate (103-54-8) was considered to be 3300 mg/kg bw on rats. All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation Cinnamyl butyrate (103-61-7) can be classified as category V of acute oral toxicity.

Acute Dermal Toxicity:

Acute dermal toxicity dose was predicted based on OECD QSAR toolbox for target substance Cinnamyl butyrate (103-61-7) estimated to be 5092.86 mg/kg bw on rabbits andfor differentstudies available on target substance Cinnamyl butyrate (103-61-7) was considered to be >5000 mg/kg bw on rabbits and for the structurally similar read across substance Ethyl Butyrate (CAS No. 105-54-4) was considered to be >2000 mg/kg bw on rabbits and and for Cinnamyl acetate (103-54-8) was considered to be > 5000 mg/kg bw. All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Cinnamyl butyrate (103-61-7) can be classified as category V of acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

Data is from Danish QSAR

Qualifier:

equivalent or similar to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction is done by using Danish QSAR database

GLP compliance:

not specified

Test type:

other: no data available

Limit test:

no

Specific details on test material used for the study:

- Name of the test material: Cinnamyl butyrate
- IUPAC name: (2E)-3-phenylprop-2-en-1-yl butanoate
- Molecular formula: C13H16O2
- Molecular weight: 204.267 g/mol
- Substance type: Organic
- Smiles: c1(\C=C\COC(CCC)=O)ccccc1

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: unspecified

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No data available

Doses:

3900 mg/kg bw

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

not specified

Dose descriptor:

LD50

Effect level:

3 900 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

No data available

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Based on the QSAR prediction done using the Danish (Q)SAR Database, the LD50 was estimated to be 3900 mg/kg bw on rats for test substance (2E)-3-phenylprop-2-en-1-yl butanoate (103-61-7) orally.

Executive summary:

Based on the QSAR prediction done using the Danish (Q)SAR Database, the LD50 was estimated to be 3900 mg/kg bw on rats for (2E)-3-phenylprop-2-en-1-yl butanoate (103-61-7) having Reliability Index: 0.86(moderate prediction quality)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 331.84 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 092.86 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3

Additional information

Acute Oral Toxicity: 

In different studies, Cinnamyl butyrate (103-61-7) has been investigated for acute oral toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for Cinnamyl butyrate (103-61-7) along with the study available on it’s structurally similar read across substance Ethyl Butyrate (CAS No. 105-54-4) and Cinnamyl acetate (103-54-8). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for Cinnamyl butyrate (103-61-7).The LD50 was estimated to be 3331.84 mg/kg bw,when male and female Osborne-Mendel rats were orally exposed with Cinnamyl butyrate (103-61-7) via gavage.

The above study was further supported bythe QSAR prediction done using the Danish (Q)SAR Databasefor target substance Cinnamyl butyrate (103-61-7). Based on the QSAR prediction done using the Danish (Q)SAR Database, the LD50 was estimated to be 3900 mg/kg bw on rats for (2E)-3-phenylprop-2-en-1-yl butanoate (103-61-7) having Reliability Index: 0.86(moderate prediction quality)

The above study was further supported by D. Belsito et. al. (Food and Chemical Toxicology, 45, (2007) S1–S23); D. L. J. Opdyke (Food and Cosmetics Toxicology,Volume 16, Supplement 1, 1978, Page 691); Timothy B. Adams et. al. (Food and Chemical Toxicology 42 (2004) 157-185) and S.P. Bhatia et. al. (Food and Chemical Toxicology, 45, (2007), S62–S65) for the target substance Cinnamyl butyrate (103-61-7). Acute oral toxicity study was done in 10 rats using test material (2E)-3-phenylprop-2-en-1-yl butanoate (103-61-5) following14 days of observation period.No Mortality was observed at dose 5000 mg/kg bw. Hence,LD50 value was considered to be >5000 mg/kg bw,when rats were treated with (2E)-3-phenylprop-2-en-1-yl butanoate (103-61-5)orally.

This is further supported by Sustainability Support Services (Europe) AB (study number:19122,2017) for the structurally similar read across substance Ethyl Butyrate (CAS No. 105-54-4). The study now reported was designed and conducted to determine the acute oral toxicity profile of Ethyl Butyrate (CAS No. 105-54-4) in Sprague Dawley rats. Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item(Step - I). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. As no mortality were observed at 24 hours after the dosing, additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups. The acute oral LD50 (Cut-off value) of Ethyl Butyrate (CAS No. 105-54-4) was 5000 mg/kg body weight.  Thus, it was concluded that the acute toxicity study of Ethyl Butyrate (CAS No. 105-54-4), when administered via oral route in Sprague Dawley rats falls into the “Category Unclassified” criteria of CLP.

The above study was further supported by S.P. Bhatia et. al. (Food and Chemical Toxicology 45 (2007) S53–S57); D. L. J. Opdyke (Food and Cosmetics Toxicology ,Volume 11, Issue 6, December 1973, Page 1063); U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) and D. Belsito et. al.( (Food and Chemical Toxicology, 45, (2007), S1–S23) for structurally similar read across substance Cinnamyl acetate (103-54-8). In acute-oral toxicity study ,the toxic effects of cinnamyl acetate (103-54-8) were assessed in group of 10 rats by oral route in the concentration of 1460, 2220, 3330 and 5000 mg/kg/bodyweight. Observations were made for 14 days.No deaths occurred at the 1460 mg/kg ,1/10 deaths occurred at 2220 m g/kg; 6/10 deaths at 3330 mg/kg and 10/10 at 5000 mg/kg .All deaths occurred within the first 48 h.Clinical signs observed during the study included slow respiration, lethargy, depression and coarse tremors in high doses.Therefore,LD50 value is considered to be 3300mg/kg body weight(95% C.I. 2900–3700 mg/kg),when rats were exposed to Cinnamyl acetate (103-54-8)by oral route .

Thus, based on the above studies on Cinnamyl butyrate (103-61-7) and it’s structurally related read across substances , it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Cinnamyl butyrate (103-61-7) can be classified as category V of acute oral toxicity.

Acute Dermal Toxicity:

In different studies, Cinnamyl butyrate (103-61-7) has been investigated for acute dermal toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rabbits for Cinnamyl butyrate (103-61-7) along with the study available on structurally similar read across substance Ethyl Butyrate (CAS No. 105-54-4) and Cinnamyl acetate (103-54-8). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for Cinnamyl butyrate (103-61-7).The LD50 was estimated to be 5092.86 mg/kg bw,when male and female New Zealand White rabbits were exposed occlusively with Cinnamyl butyrate (103-61-7) by dermal application for 24 hours.

The above study was further supported by D. L. J. Opdyke (Food and Cosmetics Toxicology,Volume 16, Supplement 1, 1978, Page 691); S.P. Bhatia et. al. (Food and Chemical Toxicology, 45, (2007), S62–S65) and D. Belsito et. al. (Food and Chemical Toxicology, 45, (2007) S1–S23) for the target substance Cinnamyl butyrate (103-61-7). In acute dermal toxicity study,4 rabbits were occlusively treated with (2E)-3-phenylprop-2-en-1-yl butanoate(103-61-7) in the concentration of 5000 mg/kg bw by dermal application.No mortality was observed in treated rabbits at dose 5000 mg/kg bw.Therefore, LD50 value was considered to be >5000 mg/kg bw,when rabbits were treated with (2E)-3-phenylprop-2-en-1-yl butanoate(103-61-7)by dermal application for 24 hours. 

Also these results are further supported by Sustainability Support Services (Europe) AB (study number : 19123,2017)for the structurally similar read across substance Ethyl Butyrate (CAS No. 105-54-4). The study now reported was designed and conducted to determine the acute dermal toxicity profile of Ethyl Butyrate (CAS No. 105-54-4) in Sprague Dawley rats. The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.  It was concluded that the acute dermal median lethal dose (LD50) of Ethyl Butyrate (CAS No. 105-54-4), when administered to male and female Sprague Dawley rats was considered to be greater than 2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that Ethyl Butyrate (CAS No. 105-54-4) does not classify as an acute dermal toxicant. CLP Classification: “Unclassified”.

This is further supported by S.P. Bhatia et. al. (Food and Chemical Toxicology 45 (2007) S53–S57); D. L. J. Opdyke (Food and Cosmetics Toxicology ,Volume 11, Issue 6, December 1973, Page 1063) and D. Belsito et. al.(Food and Chemical Toxicology, 45, (2007), S1–S23) for structurally similar read across substance Cinnamyl acetate (103-54-8). In acute-dermal  toxicity study ,the toxic effects of cinnamyl acetate were assessed in group of 10 rabbits by dermal application.single dermal application of cinnamyl acetate at a dose level of 5000 mg/kg/bodyweight which was applied for 24 h under occlusion. Observations were made over a 14-days period. No effects were observed during the study. Therefore,LD50 value is considered to be >5000mg/kg body weight,when rabbits were exposed to cinnamyl acetate(103-54-8) by dermal application.

Thus, based on the above studies on Cinnamyl butyrate (103-61-7) and it’s structurally similar read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Cinnamyl butyrate (103-61-7) can be classified as category V of acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on Cinnamyl butyrate (103-61-7) and it’s structurally similar read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation Cinnamyl butyrate (103-61-7) can be classified as category V for acute oral and dermal toxicity.