Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was performed similar to OECD406 guideline. Limited details on methods and the results.

Data source

Reference
Reference Type:
publication
Title:
Structure activity relationships in skin sensitization using the murine local lymph node assay
Author:
Ashby, J., Basketter, D.A., Paton, D., Kimber, I.
Year:
1995
Bibliographic source:
Toxicology, Vol. 103, pp 177-194

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
GLP compliance:
not specified
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
2-chloroethanol, no further details.

In vivo test system

Test animals

Species:
mouse
Strain:
not specified
Sex:
not specified

Study design: in vivo (LLNA)

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
2.5, 5, 10%
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 nodes.
Statistics:
3-fold or greater increase in proliferative activity is regarded as a positive response.

Results and discussion

In vivo (LLNA)

Results
Parameter:
SI
Remarks on result:
other: In this article called T/C ratio (ratio of isotope incorporation test groups/control groups): 1.2, 1.0, 1.6

Any other information on results incl. tables

2 -chloroethanol is reported to be inactive in the local lymph node assay (LLNA).

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Not sensitizing.
Executive summary:

Murine local lymph assay node data for 106 chemicals are listed. Among these, 73 are active in the assay indicating their potential as skin sensitizing agents. Broad structure activity relationships (SAR) are suggested based on the electrophilic theory of skin sensitization suggested by Landsteiner and Jacobs in 1936, and elaborated by Dupuis and Benezra in 1982. Eight classes of agent are discerned; electrophiles, potential electrophiles after metabolism, Michael-reactive agents, benzoylating agents, ionic chemicals and miscellaneous agents. The electrophilic theory cannot at present fully explain the activity of agents in the last two classes. That fact will hopefully focus research into their mode of action. Some chemicals fit equally into more than one class, and such agents are entered into the several classes in order not to bias the analysis. Attention is given to why not all chemicals of a class are active in the assay. It is concluded that a combination of inappropriate lipophilicity, molecular size and metabolic detoxification are responsible for these inactivities. Given a sufficient number of analogues tested within each class it should be possible eventually to predict with accuracy the skin sensitizing potential of new members of the class. However, the present analysis is qualitative, not quantitative. Finally, the parallelism between sensitizing potential and mutagenic potential for chemicals is explored further.