Chromium trioxide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

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:

Studies on Contact Sensitivity to Chromium in the Guinea Pig. The Role of Valence in the Formation of the Antigenic Determinant

Author:

Siegenthaler et al.

Year:

1983

Bibliographic source:

THE JOURNAL OF I NVESTIGATIVE DERMATOLOGY, 80:44-47,1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Principles of method if other than guideline:

The sensitization was done in the following manner: 5 injections of 0.2 ml each of emulsion containing either 1 mg/ ml of potassium dichromate (Merck, Darmstadt, FRG) in Freund's complete adjuvant (FCA) (DIFCO Laboratories, Detroit, Michigan) or 2 mg/ml of chromium chloride (Merck, Darmstadt, FRG) in FCA were given into the footpad and nape of the neck. Animals were restimulated once a week by an intradermal injection of 25 µg either of potassium dichromate or chromium chloride in 0.1 ml 0.15 M NaCl solution into the skin of the right flank. Simultaneously 0.02 ml of either 0.5% potassium dichromate or chromium chloride solution in 1 % Triton X-100 were applied epicutaneously on the skin of the left flank. The boosting was continued weekly until a positive reaction to the hapten was observed. The animals were then challenged epicutaneously with both haptens and the skin inflammation evaluated 24 hr later according to an arbitrary scale: red, swollen = 2, red, contluent = 1, red spots = 0.5.

GLP compliance:

not specified

Remarks:

published study

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

available data, published before LLNA declared as gold standard

Test material

Test material information

Constituent 1

Reference substance name:

Potassium dichromate

EC Number:

231-906-6

EC Name:

Potassium dichromate

Cas Number:

7778-50-9

Molecular formula:

Cr2H2O7.2K

IUPAC Name:

sodium dichromate

Details on test material:

Cr (K2Cr2O7)

Specific details on test material used for the study:

potassium dichromate (Merck, Darmstadt, FRG)

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Rockefeller

Sex:

male/female

Details on test animals and environmental conditions:

Inbred strain 2 and partially inbred strain Rockefeller guinea pigs of either sex were used. They weighed about 350- 400 g when sensitization was begun. The animals were bred at the Institute for Biochemical Research, Füllinsdorf, Switzerland. They were fed on pellet diet supplemented ad libitum with water containing vitamin C.

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

other: Freund's adjuvant (FCA)

Concentration / amount:

5 injections of 0.2 ml each of emulsion containing either 1 mg/ ml of potassium dichromate in Freund's complete adjuvant (FCA)

Day(s)/duration:

not specified

Adequacy of induction:

not specified

Induction 2

Route:

intradermal and epicutaneous

Vehicle:

other: intradermal: 0.1 ml 0.15 M NaCl solution; epicutaneously: 1% Tritox X-100

Concentration / amount:

intradermal: 25 µg potassium dichromate in NaCl solution; epicutaneously: 0.02 ml of 0.5% potassium dichromate in Triton X-100

Day(s)/duration:

once a week for 4-6 weeks until positive reaction occured

Adequacy of induction:

not specified

Challenge

No.:

#1

Route:

other: epicutaneously

Vehicle:

not specified

Concentration / amount:

not specified

Day(s)/duration:

24h

Adequacy of challenge:

not specified

No. of animals per dose:

11 animals

Details on study design:

see above

Challenge controls:

not specified

Positive control substance(s):

no

Results and discussion

Positive control results:

none

In vivo (non-LLNA)

Results

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

not specified

No. with + reactions:

11

Total no. in group:

11

Remarks on result:

positive indication of skin sensitisation

Any other information on results incl. tables

All guinea pigs sensitized with potassium dichromate in FCA and boosted several times epicutaneously and intradermaliy with the same hapten responded after 4-6 weeks to an epicutaneous challenge with this hexavalent chromium salt.

Applicant's summary and conclusion

Conclusions:

Guinea pigs sensitized with either the trivalent chromium chloride or the hexavalent potassium dichromate are capable of reacting in vivo and in vitro to challenges with both chromium salts. This double reactivity is retained also after repeated restimulations with only 1 of these chromium compounds.

Executive summary:

The results of this study show that Cr (VI) tested as potassium dichromate is able to induce skin sensitisation in guinea pigs. Also, there is evidence of cross-reactivity between Cr(VI) and Cr(III) compounds. The experiments in guinea pigs showed that animals which were sensitised to Cr(VI) compounds produced a positive skin response when challenged with Cr(III) compounds, and that animals sensitised to Cr(III) give a positive skin response when challenged with Cr(VI).