4,4'-methylenebis(cyclohexylamine)

Endpoint summary

Description of key information

All available animal studies suggest that 4,4'-methylenedicyclohexanamine is a weak dermal sensitiser (DuPont 1985, BASF 1956, Kennedy 1991). In vivo studies are technically complicated due to the corrosive nature of the substance which is classified as skin corrosive substance Cat. 1B. It is commonly known that substances showing a low to moderate frequency of sensitisation effects in humans or low to moderate potency in animals can be presumed to produce sensitisation in humans and are classified in Category 1B.

4,4'-Methylenedicyclohexanamine falls into this category.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Remarks:

Historical study

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: similar to guideline study, non-GLP, but using a high-lipid diluent to maximize percutaneous absorption.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

high-lipid diluent to maximize percutaneous absorption

Principles of method if other than guideline:

similar to a Buehler protocol

GLP compliance:

not specified

Type of study:

Buehler test

Justification for non-LLNA method:

Historical study available

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

no data

Route:

other: dermal application to abraded skin

Vehicle:

other: acetone/dioxane (1:1 v/v) with 13% guinea pig fat.

Concentration / amount:

Induction: no data. Challenge: 2% in acetone/dioxane (1:1 v/v) with 13% guinea pig fat.

Day(s)/duration:

9 times over 3 weeks

Route:

other: dermal application to intact and abraded skin

Vehicle:

other: acetone/dioxane (1:1 v/v) with 13% guinea pig fat.

Concentration / amount:

Induction: no data. Challenge: 2% in acetone/dioxane (1:1 v/v) with 13% guinea pig fat.

Day(s)/duration:

once to intact and abraded skin

No. of animals per dose:

5 guinea pigs challenged with intact skin, 5 guinea pigs challenged with abraded skin

Details on study design:

The test material, as a solution in acetone/dioxane (1:1 v/v) with 13% guinea pig fat, was applied to the abraded skin of 10 guinea pigs 9 times over 3 weeks. After a 2 week rest period, the material was reapplied at a level of 2% in the same diluent to intact and abraded skin, as a challenge dose. Sensitization of the animals was then assessed qualitatively.

Challenge controls:

no data

Positive control substance(s):

no

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

2% on challenge

No. with + reactions:

7

Total no. in group:

10

Clinical observations:

assume reading was 24 h after challenge.

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 2% on challenge. No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: assume reading was 24 h after challenge..

Conclusions:

4,4'-Methylenedicyclohexanamine was a weak sensitiser on abraded skin of guinea pigs in an exaggerated protocol using a diluent of acetone/dioxane with 13% fat content, .

Executive summary:

The test material, as a solution in f.a.d. was applied to the abraded skin of 10 guinea pigs 9 times over a 3-week period. Following a two-week rest period, the material was reapplied as a 2 % solution in f.a.d. twice to intact and abraded skin for the challenge test. Seven of the ten guinea pigs became sensitized when treated in this manner. One of these animals showed a consistently positive reaction, while the other six animals showed transitory positive reactions. On the basis of these results, the test material can be classified as a weak skin sensitizer.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The evidence in the literature regarding the skin sensitisation caused by this substance is not particularly robust. The SIDS initial assessment profile for C1 -C13 primary amines group (which includes 4,4'-methylenebis(cyclohexylamine)) is reporting no evidence of sensitization for the group members. DMDC a close structural analogue to PACM is not a skin sensitizer. PACM appears to be a weak sensitiser in guinea pigs so the precautionary approach is adopted and the material is considered a sensitiser. Personal protective equipment (gloves, eye protection) is recommended for use with this substance due to its corrosive properties and should protect for potential sensitisation.

Migrated from Short description of key information:
4-4’-Methylenedicyclohexanamine is a weak sensitiser in guinea pigs.

Justification for selection of skin sensitisation endpoint:
Weight of evidence suggests that the substance has weak sensitising properties.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

In the absence of relevant data, PACM is not classified as a respiratory sensitiser.

Justification for classification or non-classification

Animal studies suggest that 4,4'-methylenedicyclohexanamine is a weak dermal sensitiser. In vivo studies are technically complicated due to the corrosive nature of the substance. Substances showing a low to moderate frequency of sensitisation effects in humans or low to moderate potency in animals can be presumed to produce sensitisation in humans and are classified in Category 1B according to CLP regulation 1272/2008. 4,4'-Methylenedicyclohexanamine falls into this category.