Cinnamaldehyde

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2013

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Cinnamaldehyde

EC Number:

203-213-9

EC Name:

Cinnamaldehyde

Cas Number:

104-55-2

Molecular formula:

C9H8O

IUPAC Name:

3-phenylacrylaldehyde

Test material form:

liquid

Details on test material:

-- Name of test material: 2-Propenal-3-phenyl
- Molecular formula: C9H8O
- Molecular weight: 132.16 g/mol
- Smiles notation: c1(ccccc1)/C=C/C=O
- InChl: 1S/C9H8O/c10-8-4-7-9-5-2-1-3-6-9/h1-8H/b7-4+
- Substance type: organic
- Physical state: Liquid

Test animals

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

Administration / exposure

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

Results and discussion

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.

Effect levels

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.