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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2000
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
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:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
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.
GLP compliance:
no
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no further data

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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
physiological saline
Concentration / amount:
Concentrations used for induction expressed as chlorhexidine digluconate: 0.001-1 % in saline (intradermal); 0.01-10 % in saline (topical); tested up to highest concentration tolerated systemically and not producing skin necrosis
Concentration Freunds Complete Adjuvant (FCA): not reported
Concentrations used for challenge: 0.1 and 0.3 % in saline (up to maximum non-irritant concentration)
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
Concentrations used for induction expressed as chlorhexidine digluconate: 0.001-1 % in saline (intradermal); 0.01-10 % in saline (topical); tested up to highest concentration tolerated systemically and not producing skin necrosis
Concentration Freunds Complete Adjuvant (FCA): not reported
Concentrations used for challenge: 0.1 and 0.3 % in saline (up to maximum non-irritant concentration)
No. of animals per dose:
5/group (5 treatment groups)
Details on study design:
Induction schedule: day 0 (intradermal + FCA) – day 7 (topical, occlusive)
Challenge schedule: day 21 (challenge) – day 35 (rechallenge)
Rechallenge: Yes
Scoring schedule: 48 h and 72 h after challenge
Challenge controls:
5
Positive control substance(s):
yes
Remarks:
chloraniline, eugenol, formaldehyde, mercaptobenzothiazole and neomycin sulphate

Study design: in vivo (LLNA)

Statistics:
Logistic regression analysis, X2 test, Fisher's exact test

Results and discussion

Positive control results:
The other 5 tested substances gave a positive reaction

In vivo (non-LLNA)

Results
Reading:
other: detailed scoring not reported
Remarks on result:
other: Reading: other: detailed scoring not reported.

Any other information on results incl. tables

Results of pilot studies: Highest non-irritating topical concentration for challenge: 0.3 %.

Challenge: No animals in the test groups and no animals in the control showed a positive response to chlorhexidine digluconate in the challenge.

Re-challenge: Not explicitly stated, but chlorhexidine digluconate was reported to give negative result in the complete test.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under the conditions of the assay, chlorhexidine digluconate was not sensitising in a GPMT.
Executive summary:

This is a scientific study in accordance with generally accepted scientific principles. The study was specifically conducted to compare the sensitivity of two standard skin sensitisation tests recommended by the OECD guideline 406.

Under the conditions of the assay, chlorhexidine digluconate was not sensitising in a GPMT.

Therefore it is concluded that also chlorhexidine base is can be considered as not sensitising in a GPMT.