Hexyl acrylate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Remarks:

Freud's Complete Adjuvant Test

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

Data source

Reference

Reference Type:

publication

Title:

Sensitizing potential of 14 mono (meth) acrylates in the guinea pig

Author:

H. B. Van Der Walle, G. Klecak, H. Geleick, T. Bensink

Year:

1982

Bibliographic source:

Contact Dermatitis Vol. 8:223-235

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Principles of method if other than guideline:

Albino female guinea pigs (350-450 g) of the Dunkin Hartley outbred strain (Olac Ltd. Bicester England). Guinea pigs were housed in pairs and fed a pellet diet supplemented with water containing vitamin C ad libitum.

Skin irritation was assessed by a single open application of 0.025 mL to a 2 cm2 area of the clipped flank of 8 animals. A mixture of 2 parts Methyl Ethyl Ketone and one part peanut oil by volume was used as a solvent. Skin reactions were read after 24 and 48 hours and reported as maximum non-irritating concentration (m.n.i.c).

Induction- On days 0, 2, 4, 7, and 9 intradermal injections with 0.1 mL of test substance emulsified in FCA were given in the shoulder area.

Challenge- Animals were challenged epicutaneously onto the shaven right flank at day 21 and shaven left flank on day 35. N-hexyl acrylate was solubilized inFCA and 0.025 mL was applied to a 2 cm2 area.

Concentrations: Induction- 0.5 M of n-hexyl acrylate in FCA; Challenge- maximum non-irritating concentration, 1M

GLP compliance:

not specified

Type of study:

Freund's complete adjuvant test

Justification for non-LLNA method:

Study conducted prior to development of LLNA method.

Test material

Test material information

Constituent 1

Reference substance name:

Hexyl acrylate

EC Number:

219-698-5

EC Name:

Hexyl acrylate

Cas Number:

2499-95-8

Molecular formula:

C9H16O2

IUPAC Name:

hexyl prop-2-enoate

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Polysciene Inc.
- Expiration date of the lot/batch: not specified

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Institute for Biomedical Research Fullinsdorf Switzerland
- Females (if applicable) nulliparous and non-pregnant: not specified
- Microbiological status of animals, when known: not specified
- Age at study initiation: not specified
- Weight at study initiation: 350 - 450 g
- Housing: pair housed
- Diet (e.g. ad libitum): Pellet diet
- Water (e.g. ad libitum): water supplmented with vitamin C
- Acclimation period: not specified

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal

Vehicle:

arachis oil

Concentration / amount:

Concentration: 0.5 M (8.6%); Amount: 0.1 mL n-hexyl acrylate in peanut oil

Day(s)/duration:

Day 0, 2, 4, 7 and 9

Adequacy of induction:

not specified

Challenge

Challenge 1

No.:

#1

Route:

epicutaneous, open

Vehicle:

arachis oil

Concentration / amount:

Concentration 1.0 M/ Amount applied 0.025 mL

Day(s)/duration:

Day 21/ 24 hours duration

Adequacy of challenge:

highest non-irritant concentration

Challenge 2

No.:

#2

Route:

epicutaneous, open

Vehicle:

arachis oil

Concentration / amount:

Concentration 1.0 M/ Amount applied 0.025 mL

Day(s)/duration:

Day 35/ 24 hours duration

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

Experimental: 8; Control: 4 - 6

Details on study design:

RANGE FINDING TESTS:
Skin irritation was assessed by a single open application of 0.025 mL to a 2 cm2 area of the clipped flank of 8 animals. A mixture of 2 parts Methyl Ethyl Ketone and one part peanut oil by volume was used as a solvent. Skin reactions were read after 24 and 48 hours and reported as maximum non-irritating concentration (m.n.i.c).

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 5
- Exposure period: Day 0, 2, 4, 7 and 9
- Test groups: 0.1 mL intradermal injections of 0.5M of n-hexyl acrylate in FCA and equal volume of distilled water
- Control group: Same treatment as test group with acrylate omitted
- Site: 4X6 cm clipped area of shoulder
- Frequency of applications: single
- Duration: not applicable for injection
- Concentrations: 0.5 M

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: Day 21 and Day 35
- Test groups: Day 21: 0.025 mL of solubilized n-hexyl acrylate in FCA onto an uncovered area of 2 cm2; Day 35: 0.025 mL of solubilized n-hexyl acrylate in FCA onto an uncovered area of 2 cm2
- Control group: Same treatment as test group with acrylate omitted
- Site: Day 21: shaved right flank; Day 35: shaved left flank
- Concentrations: 1.0 M
- Evaluation (hr after challenge): 24 and 48 hours

Positive control substance(s):

no

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1.0 M

No. with + reactions:

8

Total no. in group:

8

Remarks on result:

positive indication of skin sensitisation

Results 2

Key result

Reading:

rechallenge

Hours after challenge:

48

Group:

test chemical

Dose level:

1.0 M

No. with + reactions:

8

Total no. in group:

8

Remarks on result:

positive indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

The Freud's complete adjuvant test to assess the skin sensitization potential of n-hexyl acrylate (>99% purity) was positive. This finding warrants the classification of n-hexyl acrylate as a skin sensitizer Ctaegory 1B under the Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).

Executive summary:

N-hexyl Acrylate (>99% purity) was examined for its potential to be a skin sensitizer using the Freud's complete adjuvant test described by Klecak and Geleick. Following a preliminary irritation test, 8 guinea pigs were treated by intradermal injection (0.5M; 8.6% (w/v) vehicle/ n-hexyl acrylate) to induce sensitization. Guinea Pigs were challenged by topical application (1.0 M; 17.2% w/v n-hexyl acrylate in peanut oil). Indications of sensitization were noted in all eight animals. This finding warrants the classification of n-hexyl acrylate as a skin sensitizer Category 1B under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).