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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Comparable to guideline study reliable with restrictions Only short study report: no details of test item (purity, stability, description), some details of test system missing (no. of animals, sex, age, weight, housing and environmental conditions, acclimatization period), no details of administration (administration volume, data of preliminary test for choice of dose levels), information missing if individual animal approach or pooled treatment group approach was used, details of response data by dose level for every test animal, no details on method of determination of cell proliferation.

Data source

Reference
Reference Type:
publication
Title:
Structure activity relationships in skin sensitization using the murine local lymph node assay
Author:
Ashby, J. et al.
Year:
1995
Bibliographic source:
Toxicology 103: 177 - 194.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
, adopted 2002-04-24
Deviations:
yes
Remarks:
, see "rationale for reliability"
Principles of method if other than guideline:
In the publication, it was stated that the method followed during the investigation was according to Kimber, I. & Basketter, D.A. (1992). The murine local lymph node assay: a commentary on collaborative studies and new directions. Fd. Chem. Toxicol. 30: 165 - 169.
GLP compliance:
not specified
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Dimethyl sulphate (DMS)
No further information on the test material was stated.

In vivo test system

Test animals

Species:
mouse
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No further information on the test animals was stated.

Study design: in vivo (LLNA)

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
0.25 %, 0.5 %, and 1.0 %
No. of animals per dose:
No data
Details on study design:
Groups of mice are exposed daily, for 3 consecutive days, to various concentrations of the test chemical or to the relevant vehicle alone, on the dorsum of both ears. Subsequently (conventionally 5 days following the initiation of exposure), mice are injected intravenously with [3H]thymidine and activity measured as a function of isotope incorporation in draining auricular lymph node (Kimber and Basketter, 1992). The policy is to classify as potential sensitizers those chemicals which provoke, at least one concentration, a 3-fold or greater increase in isotope incorporation compared with vehicle-treated controls. Materials which fail to stimulate such responses are regarded as not possessing significant sensitizing potential (Kimber and Basketter, 1992).
No further information on the study design was stated.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
mercaptobenzothiazole (CAS No 149-30-4)
Statistics:
The criteria to identify the test item as skin sensitizer was a 3-fold or greater increase in isotope incorporation compared with vehicle-treated controls.

Results and discussion

Positive control results:
Mercaptobenzothiazole and hexyl cinnamic aldehyde gave a positive response, i.e. both were found to be skins sensitisers. Both substnace provoked a 3-fold or greater increase in isotope incorporation compared with vehicle-treated controls.
Stimulation index (Mercaptobenzothiazole):
10 % concentration: 4.5
25 % concentration: 4.6
50 % concentration: 5.5

Stimulation index (Hexyl cinnamic aldehyde):
10 % concentration: 3.2
25 % concentration: 6.0
50 % concentration: 10.0

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: Dimethyl sulfate provoked a 3-fold or greater increase in isotope incorporation compared with vehicle-treated controls. Stimulation index: 0.25 % concentration: 3.8 0.5 % concentration: 6.0 1.0 % concentration: 5.7
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: No data

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
Dimethyl sulfate is a skin sensitiser.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is classified as skin sensitiser.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is classified as Category 1.
Executive summary:

Note: The LLNA test has certain limitations, e.g. false positive findings with certain skin irritants. It is noted in the European Union Risk Assessment Report, "that the postive response with DMS may be due to the corrosive properties".

(Reference: EU RAR "Dimethyl sulphate (CAS # 77-78-1, EC # 201-058-1). EUR 19838 EN. Institute for Health and Consumer Protection. ECB - Existing Substances. Final Report, 2002).