Cinnamaldehyde

Endpoint summary

Description of key information

Acute oral toxicity: 

The acute oral toxicity dose (LD50) was considered based on different studies conducted on rats, mice and guinea pigs for the test chemical. The LD50 value is >2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral toxicity.

 

Acute Inhalation Toxicity:

The acute inhalation toxicity study need not be conducted because exposure to humans via inhalation route is not likely taking into account due to the low vapour pressure of the test chemical, which is reported to be 0.0289 mm Hg. Thus, exposure to inhalable dust, mist and vapour of the chemical is highly unlikely. Therefore this study is considered for waiver. 

 

Acute Dermal toxicity:

Based on all the available data, it was concluded that the test chemical was not toxic when applied dermally to the test animals. Thus, from all the observations and results, the LD₅₀ of the test chemical was observed to be >2000 mg/kg bw, and is not classified as per the CLP criteria of classification and labelling.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from publication

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Acute oral toxicity of test chemical in rats

GLP compliance:

not specified

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:

Fasting period before study: 18 hours

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

not specified

Doses:

2220 mg/kg bw

No. of animals per sex per dose:

10 (5/sex)

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Other examinations performed: clinical signs

Statistics:

not specified

Preliminary study:

not specified

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 220 mg/kg bw

Based on:

test mat.

95% CL:

> 1 910 - < 2 600

Remarks on result:

other:

Remarks:

No data

Mortality:

Death observed within 2-3 hours.

Clinical signs:

Clinical signs observed were depression, diarrhea and scrawny appearance

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

Interpretation of results:

other: Not classified

Conclusions:

The acute oral LD50 value was considered to be 2220 mg/kg bw rats were treated with test chemical via oral route.

Executive summary:

Acute oral toxicity study of test chemical was conducted on 5 male and 5 female rats at the dose concentration of 2220 mg/kg bw. The test chemical was administered via oral intubation route. All animals were maintained under close observation for recording toxic signs and time of death for 14 days. Clinical signs of depression, diarrhea and scrawny appearance followed by death within 2 -3 hrs. Therefore, LD50 value was considered to be 2220 mg/kg bw with 95% confidence level of 1910 -2600 mg/kg bw, when rats were treated with test chemical via oral route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 400 mg/kg bw

Quality of whole database:

Data is from a Klimisch 2 source and provides a robust study summary.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Waiver

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:

comparable to guideline study with acceptable restrictions

Justification for type of information:

Data is from study report

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

According to OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

not specified

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

Albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

Age : 8 to 10 weeks
Sex : Male and female
Body weight range : 200±20g
Identification : By cage tag and corresponding colour body marking
Acclimatization : The healthy wistar albino rats selected for study acclimatized to standard laboratory condition for period of one week under close Veterinary supervision.
Randomization : After acclimation and Veterinary examination all the animals randomly divided into two groups and each group having five male and five female rats.
Nutritional conditions : Animals were fasted overnight prior to test and food was offered three hours after dosing.

Husbandry: Fasting
Environmental conditions: Air conditioned rooms with 10-15 air changes per hour, temperature between 22-250C, relative humidity 40-60% and illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.
Accommodation: Groups of three animals of same sex in polypropylene cages with stainless steel grill top, facilities for food and water bottle, and bedding of clean paddy husk.
Diet: Pelleted feed supplied
Water: Fresh and clean water filtered through ‘Aqua Guard on line water filter’, was kept in glass bottles Ad libitum

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

Ten healthy wistar albino rats of both sex (ranging b.wt 200±20 gm) selected for study after acclimatization. Approximate 10 percent back skin of total body surface area was prepared 24 hrs prior to application of test compound. The test drug Cinnamaldehyde was applied dermally at the dose level of 2000 mg/kg b.wt for each animal. The treated animals were observed for clinical signs of intoxication and mortality at different time interval for a period of 14 days. The body weight of each rat was observed on day 0 (pre treatment), 7th and 14th (post treatment). The necropsy was performed on all animals at termination of the study.

Duration of exposure:

14 days

Doses:

Total: 20
Limit test: 2000 mg/Kg bw: 5/sex/dose
Confirmatory test: 2000 mg/Kg bw: 5/sex/dose

No. of animals per sex per dose:

10 (5male & 5 female)

Control animals:

not required

Details on study design:

APPLICATION OF TEST COMPOUND:
The test substance was applied uniformly over an exposed area of skin. The test compound was held in contact with the skin with an impervious dressing secured in place with an adhesive tape. The animals were then housed individually in cages with a collar around the neck in order to avoid the ingestion of the test compound. After 24 hours, the dressing was removed and the site of application was cleaned with lukewarm water wiping the test compound.

Statistics:

No Data Available

Preliminary study:

The test compound applied at the dose level of 2000 mg/kg b.wt in Wistar albino rats did not show any mortality throughout the observation period. Clinical signs observed at this dose levels were decrease in cage side activity, abdominal respiration, and lacrimation. Moderate to severe degree of erythema and edema was also observed at the site of application at high level. This condition was observed upto 6 days from the day of application of test compound. Necropsy finding did not reveal any significant gross pathological changes in any of the Wistar albino rat.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

dissolved

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No incidence of mortality was observed in Wistar albino rats after application of test compound.The period of application of test compound was 24 hours

Clinical signs:

The Wistar albino rats treated with the test compound showed moderate to severe clinical signs of intoxication viz; decrease in cage side activity, lacrimation and abdominal respiration. The local signs of dermal toxicity viz; erythema and edema were observed. This condition was observed upto 6 days from the day of application of test compound.

Body weight:

The body weight of all the animals was recorded on day 0 (pre treatment) and then 7th and 14th (post treatment) showed slightly decrease on day 7th while normal increase on day 14th when compared to day 0.

Gross pathology:

Pathology
Necropsy
Necropsy was carried out on all the animals that died during the study or surviving animals were sacrificed at the end of the study to observe any gross pathological changes.

The toxicity of the test compound following dermal administration was assessed. Five female and five male rats were used per step for each dose level. The rats were observed for incidence of mortality and signs of intoxication for 14 days after the administration of test article.

Group	Dose (mg/kg)	WISTAR ALBINO RATS
		Nos. per group	Animal ID
Group-I	2000 mg/kg b. wt	10 (5 male & 5 female)	20170-1, 2, 3, 4, 5, 6,7,8,9,10
Group-II	2000 mg/kg b. wt	10 (5 male & 5 female)	20170-11, 12, 13 14, 15,16,17, 18,19,20

Interpretation of results:

other: Not Classified

Conclusions:

Based on all the available data, it was concluded that the acute dermal LD50 of test chemical was observed to be more than 2000 mg/kg b.wt. in Wistar albino rats when applied by dermal route.

Executive summary:

An acute dermal toxicity study of test chemical was performed as per OECD TG 402 in Wistar Rats. Five male and five female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Rats free from injury and irritation of skin were selected for the study. 24 hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight of test item moistened with 0.2 ml distilled water was applied by single dermal application and observed for 14 days after treatment. On test day 0, an amount of test item calculated based on body weight and moistened with 0.2 ml distilled water was applied uniformly over an exposed area of skin with an impervious dressing secured in place with an adhesive tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed. The animals were observed daily for mortality and clinical signs, during the acclimatization period. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1-14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs / Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were re­corded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically. No mortality was observed in any animal till the end of the experimental period. Sever to moderate clinical signs of intoxication were observed like decrease in cage side activity, lacrimation and abdominal respiration.Local signs of dermal toxicity like erythema and edema were observed. The body weight gain was observed in male and female animals on day 7 and 14 as compared to day 0, except decline in mean body weight gain was observed in males on day 7. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality. Hence, LD50 value was considered to be >2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that test chemical does not exhibit acute dermal toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Data is from a Klimisch 2 source and provides a robust study summary.

Additional information

Acute oral toxicity:

In different studies, the given test chemical has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats, mouse and guinea pigs for test chemical. The studies are summarized as below:

 

Study 1:

Acute oral toxicity study of test chemical was conducted on 5 male and 5 female rats at the dose concentration of 2220 mg/kg bw. The test chemical was administered via oral intubation route. All animals were maintained under close observation for recording toxic signs and time of death for 14 days. Clinical signs of depression, diarrhea and scrawny appearance followed by death within 2 -3 hrs. Therefore, LD50 value was considered to be 2220 mg/kg bw with 95% confidence level of 1910 -2600 mg/kg bw, when rats were treated with test chemical via oral route.

 

Study 2:

Acute oral toxicity study of test chemical was conducted on rats at the dose concentration of 3400 mg/kg bw. The test chemical was administered via oral gavage route. All animals were maintained under close observation for recording toxic signs and time of death for 14 days. 50% mortality was observed. Therefore, LD50 value was considered to be 3400 mg/kg bw, when rats were treated with test chemical via oral route.

 

Study 3:

Acute oral toxicity study of test chemical was conducted on mice at the dose concentration of 3400 mg/kg bw. The test chemical was administered via oral gavage route. All animals were maintained under close observation for recording toxic signs and time of death for 14 days. 50% mortality was observed. Therefore, LD50 value was considered to be 3400 mg/kg bw, when mice were treated with test chemical via oral route.

Study 4:

Acute oral toxicity study of test chemical was conducted on mice at the dose concentration of 2225 mg/kg bw. The test chemical was administered via oral: unspecified route. All animals were maintained under close observation for recording toxic signs and time of death for 14 days. Clinical signs observed were motor suppression, blepharoptosis, and convulsions. Ataxia, tachypnea, dilation of ear vessels, loss of righting reflex.50% mortality was observed. Therefore, LD50 value was considered to be 2225 mg/kg bw, when mice were treated with test chemical via oral route.

 

Thus, based on the above summarized studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral toxicity.

 

Acute Inhalation Toxicity:

The acute inhalation toxicity study need not be conducted because exposure to humans via inhalation route is not likely taking into account due to the low vapour pressure of the test chemical, which is reported to be 0.0289 mm Hg. Thus, exposure to inhalable dust, mist and vapour of the chemical is highly unlikely. Therefore this study is considered for waiver.

 

Acute Dermal Toxicity:

Study 1:

An acute dermal toxicity study of test chemical was performed as per OECD TG 402 in Wistar Rats. Five male and five female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Rats free from injury and irritation of skin were selected for the study. 24 hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight of test item moistened with 0.2 ml distilled water was applied by single dermal application and observed for 14 days after treatment. On test day 0, an amount of test item calculated based on body weight and moistened with 0.2 ml distilled water was applied uniformly over an exposed area of skin with an impervious dressing secured in place with an adhesive tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed. The animals were observed daily for mortality and clinical signs, during the acclimatization period. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1-14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs / Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were re­corded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically. No mortality was observed in any animal till the end of the experimental period. Sever to moderate clinical signs of intoxication were observed like decrease in cage side activity, lacrimation and abdominal respiration. Local signs of dermal toxicity like erythema and edema were observed. The body weight gain was observed in male and female animals on day 7 and 14 as compared to day 0, except decline in mean body weight gain was observed in males on day 7. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality. Hence, LD50 value was considered to be >2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that test chemical does not exhibit acute dermal toxicity.

 

Thus, based on all the available data, it was concluded that the test chemical was not toxic when applied dermally to the test animals. Thus, from all the observations and results, the LD₅₀of the test chemical was observed to be >2000 mg/kg bw, and is not classified as per the CLP criteria of classification and labelling.

Justification for classification or non-classification

Based on all the available data of the test chemical, it was concluded that the test chemical is not toxic when administered via oral and dermal route. Also, exposure of the test chemical through inhalation route is not likely to be possible taking into account the low vapour pressure of the test chemical. Thus, based on the criteria of CLP (Classification, Labelling and Packaging), the test chemical is not likely to be classified.