Registration Dossier

Administrative data

Description of key information

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scientifically valid protocol but not according to guidelines.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Guinea pigs were exposed epicutaneously with a paste of 25% PACM in USP Hydrophilic ointment, followed by 3 weeks of either thrice weekly applications of the same paste or intradermal injections of PACM in methanol/ethylene glycol. After a 2 week rest period, they were challenged with dermal application PACM to both intact and abraded skin, and assessed 24 hours later for sensitisation.
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study was conducted well before an OECD guideline for a LLNA was available.
Species:
guinea pig
Strain:
Hartley
Sex:
male
Route:
epicutaneous, open
Vehicle:
other: U.S.P. Hydrophilic ointment
Route:
intradermal
Vehicle:
other: U.S.P. Hydrophilic ointment
Details on study design:
- Ten male albino guinea pigs were used to test for sensitization
- Each guinea pig received a single application of a paste containing 25% PACM in U.S.P. Hydrophilic Ointment.
- No injection of an adjuvant was noted in the protocol.
- The induction was followed in five of the guinea pigs by nine dermal doses, three per week, of 25% PACM paste
- In the other five guinea pigs, four intradermal injections of 0.1 mL of a 5% solution of PACM in methanol/ethylene glycol (15:85)
- Following these treatments, the animals were given a 2 week rest period, which was followed by a challenge dermal application of either 2% or 10% PACM (in ointment) to both intact and an abraded skin site
- Irritation was evaluated 24 hours after the treatment
Positive control substance(s):
no
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
2%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
intact skin for initial dermal exposure.
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 2%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: intact skin for initial dermal exposure..
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
4
Total no. in group:
5
Clinical observations:
Intact skin for initial dermal exposure. All positive responses were mild.
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 4.0. Total no. in groups: 5.0. Clinical observations: Intact skin for initial dermal exposure. All positive responses were mild..
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
2%
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
Abraded skin for initial dermal exposure. 4 of 5 showed mild responses
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 2%. No with. + reactions: 5.0. Total no. in groups: 5.0. Clinical observations: Abraded skin for initial dermal exposure. 4 of 5 showed mild responses.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
Abraded skin for initial dermal exposure. 4 of 5 animals showed mild-moderate responses.
Remarks on result:
other: see Remark
Remarks:
Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 5.0. Total no. in groups: 5.0. Clinical observations: Abraded skin for initial dermal exposure. 4 of 5 animals showed mild-moderate responses..

The results provided in the table above refer to challenge by intradermal injection.

Interpretation of results:
sensitising
Remarks:
Migrated information weak sensitizer
Conclusions:
4-4’-Methylenedicyclohexanamine was tested in a guinea pig sensitisation assay and found to be a weak sensitizer.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

skin sensitization

The test material was capable of producing a sensitization reaction in the guinea pig when the induction phase of the test exposed the animals either topically or intradermally. Two of the 10 PACM-induced animals were sensitized, which indicates the material to be weak to mild with regard to its sensitization properites. [Kennedy, 1991]

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.

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

Based on the available data, 4,4'-Methylenedicyclohexanamine is subject to C&L according to Regulation 1272/2008/EC: Regulation 1272/2008/EC: Category 1B, H317 “May cause an allergic skin reaction.