Methyl cinnamate

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: pre-guideline study but performed fulfilling basic scientific principles

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

Modified Challenge with intradermal and occlusive application

GLP compliance:

no

Type of study:

guinea pig maximisation test

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Route:

intradermal

Vehicle:

other: water, Freund's Complete Adjuvant (FCA) and petrolatum

Concentration / amount:

Induction: 2 intradermal injections of 5% aqueous solution and 2 5%solutions in Freunds' Complete Adjuvant (each 0.1 ml) and 25% in petrolatum on day 8 occlusive for 2 days (total dose 20 mg intradermally plus 250 mg epicutaneously)
Challenge: On day 21 with 25% in petrolatum occlusive for 24 hours.

Route:

epicutaneous, occlusive

Vehicle:

other: water, Freund's Complete Adjuvant (FCA) and petrolatum

Concentration / amount:

Induction: 2 intradermal injections of 5% aqueous solution and 2 5%solutions in Freunds' Complete Adjuvant (each 0.1 ml) and 25% in petrolatum on day 8 occlusive for 2 days (total dose 20 mg intradermally plus 250 mg epicutaneously)
Challenge: On day 21 with 25% in petrolatum occlusive for 24 hours.

No. of animals per dose:

5 animals

Details on study design:

On day 0, the animals were injected intradermally with 0.1 ml of a 5% solution of the compound, with 0.1 ml of a 5% emulsion of the compound in FCA and with 0.1 ml of FCA alone, each injection was given twice. In addition, on day 8 the compound, dissolved in petrolatum up to 25%, was applied to a clipped skin area of the neck and kept under occlusive bandage for 2 days (total dose 20 mg intraderzzally plus 250 mg epicutaneously).0n day 21, an occlusive patch test with the compound in petrolatum was applied to the flank for 24 hours and the reactions were read 24 and 48 hours after removing the patch.

Positive control substance(s):

no

Reading:

other: 1st (24h after challenge) and 2nd (48 after challenge) reading

Hours after challenge:

48

Group:

test chemical

Dose level:

25% solution

No. with + reactions:

3

Total no. in group:

5

Remarks on result:

other: Reading: other: 1st (24h after challenge) and 2nd (48 after challenge) reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25% solution. No with. + reactions: 3.0. Total no. in groups: 5.0.

Reading:

rechallenge

Hours after challenge:

144

Group:

test chemical

Dose level:

25%

No. with + reactions:

4

Total no. in group:

5

Remarks on result:

other: Reading: rechallenge. . Hours after challenge: 144.0. Group: test group. Dose level: 25%. No with. + reactions: 4.0. Total no. in groups: 5.0.

Authors conclusion: 60% of the animals show positive test reactions 24 h and 48 h after removing the occlusive challenge patch. Furthermore, epicutaneous tests one week later are positive in 4/5 of the guinea pigs.

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The treatment with methyl cinnamate causes sensitization in about 60% (first and second reading) and 80% (rechallenge) of the guinea pigs in the Maximization test.

Executive summary:

In this Maximization test (intradermal induction and occlusive challenge) 4 out of 5 animals showed positive reaction following rechallenge.

Thus, in this test methyl cinnamate is considered a skin sensitizer.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Methyl cinnamate has been studied for skin sensitisation in multiple tests.

In the key study (Maximization test) the test article was intradermally and epicutaneously induced (deviation from guideline) and occlusively challenged showing positive reactions in 60% resp. 80% of test. Also, in this study rather high doses were applied (total dose 20 mg intradermally plus 250 mg epicutaneously). Nevertheless, the substance is considered sensitising in this test. This finding is supported by three more studies, performed by the same author, testing the substance in a Draize test model, an Open Epicutaneous test and a Freund's Complete Adjuvant test, all showing positive reaction when high doses were applied but also showing, that with 3% challenge concentration no sensitisation was observed.

Thus, in this array of sensitisation tests the Authors concluded that methyl cinnamate is a weak sensitizer.

A guinea pig sensitization test used as supportive study (RIFM, 1971b) was conducted on white male guinea pigs, weighing approximately 311–397 g. Methyl cinnamate was tested as a 0.1% suspension in 5% ethyl alcohol in distilled water. Induction consisted of ten intradermal injections made over a period of three and a half weeks. A 0.05 ml aliquot of methyl cinnamate was used for the first intradermal induction injection and a 0.1 ml aliquot of methyl cinnamate was used for the second - tenth intradermal injections. Following a ten-day rest period, an intradermal challenge injection with a 0.05 ml aliquot of a 0.1% suspension of methyl cinnamate in 5% ethyl alcohol in distilled water was administered. Reactions were read 24 h later. No sensitization reactions were produced.

The results from other reports (Hausen et al., 1995) supported the conclusion for negative sensitisation at low concentrations as above. Two separate modified FCATs were conducted in guinea pigs to evaluate sensitization to 10% methyl cinnamate in acetone. No sensitization effects were observed.

The absence of skin sensitisation potential through methyl cinnamate in low concentrations is also supported by a study where methyl cinnamate was applied to 25 volunteers (see IUCLID section 7.10.4) confirming no sensitisation potential. However, no information on the amount applied in this test is available.

Migrated from Short description of key information:
Skin sensitization was observed with test article based on the available data (60% at 1st and 2nd challenge resp. 80% sensitisation at re-challenge).

Justification for selection of skin sensitisation endpoint:
Available test (Maximization test) according to current OECD 406 guideline.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data, methyl cinnamate does require classification as a skin sensitizer. In the guinea pig maximisation test identified as the key study 60% of the animals showed a positive response after intradermal induction with 5% test substance. Therefore, the substance is classified as a Category 1B according to CLP (Regulation EC No.1272/2008) and as a skin sensitiser, R43, according to DSD (Directive 67/548/EEC). Data on respiratory sensitization are lacking..