N,N'-bis{N-[N-(4-chlorophenyl)carbamimidoyl]carbamimidoyl}hexane-1,6-bis(aminium) diundec-10-enoate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation

Remarks:

in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other:

Remarks:

This is a scientific study in accordance with generally accepted scientific principles. The salt chlorhexidine digluconate was used instead of chlorhexidine base. Due to the high level of structural similarity it is considered that the derived data also apply to the chlorhexidine base taking into account the differences in the stated concentrations. The study was specifically conducted to compare the sensitivity of the two standard skin sensitisation tests which are recommended by the OECD guideline 406. Only 5 animals/group were used, but 5 groups were used which received different concentrations of the test substance increasing the total number of animals and the sensitivity of the assay. There was no positive control in a strict way, but all other tested substances (including known skin sensitizers) in the study (chloraniline, eugenol, formaldehyde, mercaptobenzothiazole and neomycin sulphate) gave positive results demonstrating the validity of the assay. These alterations and the fact that the digluconate salt was used are not considered to be of bigger concern and the study is regarded relevant to assess also the sensitisation potential of chlorhexidine base.

Data source

Reference

Reference Type:

publication

Title:

Comparison of the sensitivities of the Buehler test and the guinea pig maximization test for predictive testing of contact allergy

Author:

Frankild S, Volund V, Wahlberg JE & Andersen KE

Year:

2000

Bibliographic source:

Acta Derm Venereol 80, 256-262

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

Pilot study: Yes
The procedure was performed according to Magnusson and Kligman. The GPMT procedure was modified with a multiple-dose design: 30 animals were assigned to one control group of 5 animals and 5 test groups containing 5 animals each, using different induction concentrations of the allergen for each group. Simultaneous increases in both intradermal and topical doses induction doses were used. In the multiple-dose GPMT procedure pretreatment with SDS was omitted.

Deviations:

no

Type of study:

guinea pig maximisation test

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

Source: Salblins, Malmö, Sweden
Weight at study initiation: 300-350 g

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Executive summary:

Chlorhexidine tested using chlorhexidine digluconate was not sensitising in a GPMT using a multiple dose design. This test is considered the most relevant because it used several doses of the test substances, increasing the sensitivity of the assay, and was performed in accordance with current guideline. The weakly positive responses in a Buehler test in the same study and of a GMPT and a SIAT in another study may have been due to an irritant effect rather than a sensitisation and therefore do not provide reliable evidence for a sensitisation. The same holds true for the PLNA in mice. Regarding related substances, chlorhexidine diacetate was not sensitising in a modified Buehler test.

In humans, allergic reactions to chlorhexidine have been described. Allergic contact dermatitis to chlorhexidine is known but is rare (1 % or lower). In view of the widespread and worldwide use of chlorhexidine digluconate (and other chlorhexidine salts) over several decades, allergic reactions to chlorhexidine are considered an uncommon event.

In summary, it is concluded that chlorhexidine digluconate is not a skin sensitizer in standard animal tests. Allergic reactions in humans are rare.