Benzyl cinnamate

Endpoint summary

Description of key information

The substance is not acute toxic. For oral acute toxicity the LD50 was determined to be 3280 mg/kg bw and for dermal acute toxicity the LD50 > 3000 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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

Groups of test animals (10 per dose group) received the test substance dissolved in corn oil (500 mg/mL) via oral gavage.
Doses ranged from 2.0 to 5.0 g per kg bw. Animals were observed for 14 days post treatment.

GLP compliance:

no

Remarks:

test carried out pre-GLP-guideline

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Charles River

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200-300 g
- Fasting period before study: 48 hours
- Housing: wire mesh cages in air conditioned room
- Diet: regular diet of Lab Blox; ad libitum
- Water: ad libitum

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

Concentration: 500 mg/mL (w/v)

Doses:

2.0, 2.25, 3.0 and 5.0 g/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, food consumption

Statistics:

Oral LD50 was calculated according to the method of Litchfield, V.T. and Wilcoxon, F., Journal of Pharmacology and Experimetnal Therapeutics, Vol 96, p 99, 1949.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 280 mg/kg bw

Based on:

test mat.

95% CL:

>= 2 620 - <= 4 100

Mortality:

8 animals dosed with 5 g/kg bw died within 24 hours post-dosing, the remaining 2 showed a normal increase in body weight at the end of the 14 days observation period.

Clinical signs:

Animals dosed with 5 g/kg bw showed CNS effects 18 hours post-dosing.
Animals dosed at the three lower levels did not show any symptoms prior to death and behaved as normal laboratory animals.

Body weight:

Normal body weight increase.
All surviving animals ate well.

Results:

Doses (g/kg bw)	Response (deaths)	% observed	% expected	Observed minus expected	(CHI)^2
2.0	2/10	20	17	3	.006
2.25	2/10	20	23	3	.005
3.0	4/10	40	43	3	.004
5.0	8/10	80	79	1	.015

N¹ = 40

ED84 = 5.48

ED50 = 3.28

ED16 = 1.96

S= [(ED84/ED50) + (ED50/ED16)] / 2 = 1.67

fED50 = S^2.77 / √ N¹= 1.25

ED50 * fED50 = 4.1

ED50 / fED50 = 2.62

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008

Conclusions:

The oral LD50 was calculated to be 3.28 g/kg bw with 19/20 confidence limit of 2.62 to 4.1 g/kg bw.

Executive summary:

In the current study the oral LD50 of the test substance was determined in rats in an oral (gavage) acute toxicity test.

No OECD guideline was followed and the study was not GLP.

The rats were fed 2.0, 2.25, 3.0 or 5.0 g/kg bw of the test material dissolved in corn oil, via a rigid stomach tube. 10 animals per dose were used. Following the administration of each dose level the animals were observed for 14 days for signs of toxicity.

8/10 animals dosed with 5 g/kg bw died within 24 hours post-dosing, the remaining 2 showed a normal increase in body weight at the end of the 14 days observation period. All surviving animals ate well and gained body weight in a normal way.

Animals dosed with 5 g/kg bw showed CNS effects 18 hours post-dosing. Animals dosed at the three lower levels did not show any symptoms prior to death and behaved as normal laboratory animals.

The oral LD50 was calculated to be 3.28 g/kg bw with 19/20 confidence limit of 2.62 to 4.1 g/kg bw.

As the LD50 > 2,000 mg/kg bw, the test item is not to be classified as acute toxic according to the CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3 280 mg/kg bw

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

Additional information

Acute oral toxicity

For this endpoint there is 1 study in rats is available.

In this key study the oral LD50 of the test substance was determined in rats in an oral (gavage) acute toxicity test. The rats received doses of 2.0, 2.25, 3.0 or 5.0 g/kg bw of the test material. 8/10 animals dosed with 5 g/kg bw died within 24 hours post-dosing and showed CNS effects 18 hours post-dosing. Animals dosed at the three lower levels did not show any symptoms prior to death and behaved as normal laboratory animals.

The oral LD50 was calculated to be 3.28 g/kg bw with 19/20 confidence limit of 2.62 to 4.1 g/kg bw.

Acute dermal toxicity

For this endpoint there is 1 study available. In this study the acute dermal toxicity of the test substance was tested in rabbits. No guideline was followed and the study was not according to GLP.

The test material was applied once to the clipped backs of the animals and 1, 2 or 3 g/kg bw of the test item were applied under occlusive conditions. The animals were covered with a rubber sleeve and placed in an animal holder for 24 hours. After exposure for 24 hours skin reactions were recorded, the test material was removed and the animals were observed for the following 14 days.

No animals died during the course of the study. The initial moderate erythema on the treated backs was fully reversible after 48 hours. The animals consumed their daily ration, gained weight, behaved normal and showed no toxicity signs. From this it can be concluded that the dermal LD50 > 3000 mg/kg bw.

Justification for classification or non-classification

Acute oral toxicity

According to the EU Regulation No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures (CLP) the substance is not considered to be classified as acute toxic because the LD50 is 3280 mg/kg bw, which is > 2000 mg/kg bw (Table 3.1.1).

Acute dermal toxicity

According to the EU Regulation No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures (CLP) the substance is not considered to be classified as acute toxic because the LD50 is > 3000 mg/kg bw, which is > 2000 mg/kg bw (Table 3.1.1).