Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation
Remarks:
no data
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: The cited statement is taken from the European Union Risk Assessment Report for hydrogen peroxide.
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Type of study:
not specified
Species:
human
Sex:
male/female
Details on test animals and environmental conditions:
Members of the general Finnish population
Route:
epicutaneous, open
Vehicle:
other: hair dresser's chemicals
Concentration / amount:
3%
Route:
epicutaneous, open
Vehicle:
other: hair dresser's chemicals
Concentration / amount:
3%
No. of animals per dose:
Not applicable
Details on study design:
Not applicable
Challenge controls:
Not applicable
Positive control substance(s):
no
Positive control results:
Not applicable
Reading:
other: not applicable
Group:
other: not applicable
Dose level:
3%
No. with + reactions:
2
Total no. in group:
158
Clinical observations:
Test persons were also allergic to other substances in the tested mixtures
Remarks on result:
other: Reading: other: not applicable. Group: other: not applicable. Dose level: 3%. No with. + reactions: 2.0. Total no. in groups: 158.0. Clinical observations: Test persons were also allergic to other substances in the tested mixtures.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Hydrogen peroxide is not a skin sensitiser.
Executive summary:

The following text is copied from the EU Risk Assessment Report (2003), pg. 114-115:

"The skin sensitising property of nine different 3% hydrogen peroxide preparations was studied with guinea pigs using a modification of the Magnusson-Kligman procedure (Du Pont, 1953). For sensitisation five animals were given six intradermal injections of 0.1 ml 0.1% hydrogen peroxide over a 2-week period; another group of five animals received six times one drop of 3% hydrogen peroxide to the abraded skin. After a 2-week rest period the animals were challenged with a single treatment of the previous type. The skin reactions were observed at 1, 24 and 48 hours. Primary irritancy of substance on intact skin was also studied in the ten animals before the sensitisation treatment and prior to the challenge. The study does not meet modern requirements due to few animals used and inadequate reporting. However, based on summary results, all the nine hydrogen peroxide substances appeared not to sensitise (ten animals used per substance).

There is one clinical report of two cases on positive patch tests to hydrogen peroxide (Aguirre et al., 1994). The first case was a 20-year-old woman, with no previous history of atopy and allergies, who had been working as a hairdresser for 4 years, the other case was a 27-year-old housewife, with no atopy or previous allergies, who had dyed her hair herself at home every 1 to 2 months for the last 6 years. In both cases the skin reactions to 3% hydrogen peroxide were strong; the former patient was positive also for nickel sulfate and 4-aminophenol, the latter for nickel sulfate, PPD, formaldehyde, 4-aminophenol, glyceryl monothioglycolate and cocamidopropylbetaine. The authors reported that 156 other hairdressers patch tested with the hairdresser’s series of chemicals were all negative to hydrogen peroxide 3%. The Dermatological Department at the Finnish Institute of Occupational Health has since 1985 tested dermatitis patients having had exposure to hairdressing chemicals (mainly hairdressers) with a series of test substances containing 3% hydrogen peroxide in water. Computerised records were available concerning test results since 1991: 130 patients have been tested with no allergic reactions, one patient exhibited an irritant reaction. The Finnish Register of Occupational Diseases which was searched from 1975 through 1997 did not contain any cases of allergic dermatosis caused by hydrogen peroxide. The Dermatology Department of the University Central Hospital in Turku, Finland, patch tested 59 patients with 3% hydrogen peroxide during 1995-96, no positive reactions were found (Kanerva et al., 1998).

In spite of two reported cases of positive patch tests to hydrogen peroxide and the uncertainty surrounding an outdated animal study (with a negative result), and on recognition of the widespread occupational and consumer use over many decades, it may be confidently stated that the potential of hydrogen peroxide to cause skin sensitisation is extremely low and therefore do not meet the criteria for classification."

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitisation is a systemic effect. In order to be systemically available, a chemical needs to be absorbed, either via the oral, inhalation or dermal route. Dissolution of solids is generally assumed to be a prerequisite for absorption. As the reaction mass of magnesium carbonate and magnesium hydroxide and magnesium oxide and magnesium peroxide is a solid inorganic multi-constituent substance, this means that Mg2+, OH- and hydrogen peroxide are the species to be taken into account when assessing its toxicity.

 

For hydrogen peroxide a EU Risk Assessment Report is available, in which the skin sensitisation potential of the substance is assessed based on the available human and non-human information. In this report it is concluded that the substance should not be classified as a skin sensitiser.

 

In the REACH registration dossier for magnesium hydroxide a weight of evidence approach is developed that takes into account the results from a local lymph node assay (LLNA), an expert opinion from the Informationsverbund Dermatologischer Kliniken (IVDK; Schnuch, A. 2010) based on 20 years of observations in > 190.000 patients, and read-across to test data for magnesium chloride and other metal hydroxides. Although the results of the local lymph node assay (LLNA) test on magnesium hydroxide were apparently positive it is proposed that the positive result should be interpreted as a false positive and that magnesium hydroxide thus should not be classified as a skin sensitizer.

Given the combination of the epidemiological data, the negative magnesium chloride guinea pig maximisation test and the history of false positives using the LLNA test, the weight of evidence thus suggests that the positive results obtained in the LLNA test are inaccurate and, as a consequence, a skin sensitizing effect of magnesium hydroxide is unlikely. Therefore, it was concluded that magnesium hydroxide was not to be classified as a skin sensitizer.

 

Based on the above information and recognizing that the reaction mass of magnesium carbonate and magnesium hydroxide and magnesium oxide and magnesium peroxide has been manufactured and used in industry for many years without any evidence for this substance to exert skin sensitization effects, it may be confidently stated that the potential of the reaction mass to cause skin sensitisation is negligible, and that additional animal testing will not be of added value to the risk assessment.

Justification for classification or non-classification

In accordance to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification is not necessary for skin sensitisation based on the available information for read-across substances hydrogen peroxide and magnesium hydroxide.