Sodium dithionite

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

other: human data

Adequacy of study:

supporting study

Reliability:

other: not rated acc. to Klimisch

Rationale for reliability incl. deficiencies:

other: Any kind of reliability rating is not considered to be applicable, since human studies/reports are not conducted/reported according to standardised guidelines.

Data source

Reference

Reference Type:

review article or handbook

Title:

Final report on the safety assessment of sodium sulfite, potassium sulfite, ammonium sulfite, sodium bisulfite, ammonium bisulfite, sodium metabisulfite and potassium metabisulfite

Author:

Nair, B. & Elmore, A.R.

Year:

2003

Bibliographic source:

International Journal of Toxicology 22(2): 63 - 88.

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Sodium sulphite

EC Number:

231-821-4

EC Name:

Sodium sulphite

Cas Number:

7757-83-7

Molecular formula:

NA2SO3

IUPAC Name:

disodium sulfite

Constituent 2

Reference substance name:

Disodium disulphite

EC Number:

231-673-0

EC Name:

Disodium disulphite

Cas Number:

7681-57-4

Molecular formula:

Na2S2O5

IUPAC Name:

disodium disulphite

Constituent 3

Reference substance name:

Dipotassium disulphite

EC Number:

240-795-3

EC Name:

Dipotassium disulphite

Cas Number:

16731-55-8

Molecular formula:

K2S2O5

IUPAC Name:

dipotassium disulfite

Constituent 4

Reference substance name:

Sodium hydrogensulfite

EC Number:

231-548-0

EC Name:

Sodium hydrogensulfite

Cas Number:

7631-90-5

Molecular formula:

NaHSO3

IUPAC Name:

sodium hydrogensulfite

Details on test material:

- Name of test material (as cited in study report):
1) sodium sulfite
2) sodium metabisulfite
3) potassium metabisulfite
4) sodium bisulfite
5) metabisulfite

Method

Type of population:

general

Details on study design:

Petersen and Menné (1992):
The investigators patch tested 1762 dermatologic patients with sodium sulfite 1% petrolatum (pet.). Following 2 days of occlusive exposure, reactions were recorded. The European standard series was also tested.

Combe Incorporated (1996):
In the study of Combe incorporated from 1996 a hair-colouring agent with 0.64% sodium sulfite was used in a repeat insult open patch test involving 100 participants. The panelists received 0.2 mL or 0.2 g of the test material directly onto a designated area of the back. The procedure was repeated until nine consecutive applications had been made for every Monday, Wednesday, and Friday for 3 consecutive weeks. Reactions were scored just before the next application. The panelists were then allowed a 10- to 14-day nontreatment period, after which a challenge or retest application was applied once to a previously unexposed site. Retest doses were equivalent to any of the original nine exposures and were scored 24 and 48 hours after application. Comparisons were made between the sensitizing doses and the retest doses.

Combe Incorporated (1998):
Samples of 0.5% sodium sulfite in a topical feminine cream were patch tested by Combe Incorporated in 1998 using 100 panelists. The semiocclusive patch, containing 0.2 mL or 0.2 g of the test material, was affixed directly onto the back and removed after 24 hours. The procedure was repeated until nine consecutive applications had been made for every Monday, Wednesday, and Friday for 3 consecutive weeks. Reactions were scored just before the next application. The panelists were then allowed a 10- to 14-day nontreatment period, after which a challenge or retest application was applied once to a previously unexposed site. Retest doses were equivalent to any of the original nine exposures and were scored 24 and 48 hours after application.

Vena et al. (1994):
Vena, Foti, and Angelini (1994) reported the results of patch testing 2894 eczematous patients over a 2-year period. The test substances tested were as follows: sodium metabisulfite (1% pet.), potassium metabisulfite (1 % pet.), sodium bisulfite (1% and 5% pet.), and sodium sulfite (1 % pet.). In addition prick and intradermal tests with 20 patients with a sodium metabisulfite solution (10 mg/mL) were conducted. Furthermore, an oral challenge of five patients with 30 and 50 mg sodium metabisulfite was carried out.

References:
- Petersen, C.S., and T. Menné 1992 Consecutive patch testing with sodium sulfite in eczema patients. Contact Dermatitis 27: 344 - 345.
- Combe Incorporated. 1996 100 human subject insult open patch test skin irritation/sensitisation evaluation. Unpublished data submitted by CTFA. (9 pages.)
- Combe Incorporated. 1998. 100 human subject insult semi-occlusive patch test skin irritation/sensitization evaluation. Unpublished data submitted by CTFA. (10 pages.)
- Vena, G.A., C Foti, and G. Angelini. 1994 Sulfite contact allergy. Contact Dermatitis 31: 172 - 175.

Results and discussion

Results of examinations:

Petersen and Menné (1992):
Patch testing results of the test material sodium sulfite 1% petrolatum (pet.): following 2 days of occlusive exposure, positive reactions were observed in 25 patients of 1762 patients (1.4% incidence). Seven of the 25 tested positive only to sodium sulfite (the European standard series was also tested). Only 3 of the 25 patients had previous contact with ketoconazole cream (contains sodium sulfite). The investigators did not consider it worthwhile to routinely patch test with sodium sulfite because the "clinical relevance of the positive reactions to sodium sulfite remains to be established."

Combe Incorporated (1996):
Repeat insult open patch testing of a hair-colouring agent with 0.64% sodium sulfite showed no adverse reactions and according to the investigators, the test material cannot be considered a primary irritant or primary sensitizer.

Combe Incorporated (1998):
Patch testing of samples of 0.5% sodium sulfite in a topical feminine cream showed no adverse reactions and according to the investigators, the test material cannot be considered a primary irritant and primary sensitizer.

Vena et al. (1994):
The results of patch testing 2894 eczematous patients over a 2-year period showed the following findings: positive reactions to sodium metabisulfite 1% pet. (following a 2-day occlusive exposure) were noted in 50 patients (1.7% incidence). All 50 patients also reacted to potassium metabisulfite 1 % pet., and to sodium bisulfite 1% and 5% pet. Only two reacted to sodium sulfite 1 % pet. Prick and intradermal tests of 20 patients with a sodium metabisulfite solution (10 mg/mL) were negative and oral challenge of five patients with 30 and 50 mg sodium metabisulfite did not provoke a flare-up of dermatitis or patch test. The dermatitis was considered occupational in seven cases. Five of the remaining 43 cases were considered allergic contact dermatitis resulting from the use of topical preparations.

Applicant's summary and conclusion

Conclusions:

Based on the summarised information by the authors appr. 2-5% of asthmatics are sensitive towards sulfite substances
According to the authors of the review, sodium and potassium sulfite salts produced positive reactions in dermatologic patients sensitive to sulfites under patch test.
In conclusion the CIR panel rated sodium sulfite, potassium sulfite, ammonium sulfite, sodium hydrogensulfite, ammonium hydrogensulfite, sodium metabisulfite and potassium metabisulfate as safe for use in cosmetic formulations.