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Toxicological information

Direct observations: clinical cases, poisoning incidents and other

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Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-guideline study, GLP status not known, published in peer reviewed literature, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
publication
Title:
The identification of contact allergens by human assay III. The maximisation test: A procedure for screening and rating contact sensitizers
Author:
Kligman AM
Year:
1966
Bibliographic source:
J. Invest. Derm. Vol 47, 393-409

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
skin sensitisation
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
25 healthy adult males were used. Two main procedures were involved; (a) the potential induction of an immune response; (b) a challenge of that response.
Induction: 1.0 mL of undiluted xylene was applied on "Webril" patches (1.5" x 1.5") under an occlusive dressing to the forearm or calf of the subject. There was a total of five 48 hour exposures to exactly the same skin site. For 24 hours before each application 1.0 mL of 5% aqueous sodium lauryl sulphate (irritant) was administered.
Challenge: 0.4 mL of 5% aqueous sodium lauryl sulphate was applied on "Webril" patches (1" x 1") under an occlusive dressing to the back for 1 hour followed by undiluted xylene for 48 hours. The challenge reaction is assessed immediately after removal of the dressing and again 2 days later and the degree of sensitisation classified on a 1-5 scale.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
No further details

Method

Type of population:
other: volunteer
Subjects:
25 males (90% were black) aged 18 - 50 years.

Ethical approval:
not specified
Route of exposure:
dermal
Reason of exposure:
intentional
Exposure assessment:
measured
Details on exposure:
A total of five applications of undiluted test material to inflamed skin on the forearm or calf (same site on each occasion, pre-treated with SLS) followed by challenge (100%, 25% mixed xylenes) on the back. An occlusive dressing was applied.

Results and discussion

Clinical signs:
None
Results of examinations:
The sensitisation rate was 0/24 indicating that mixed xylenes was not a skin sensitiser under the conditions of the study.

Any other information on results incl. tables

Mixed xylenes was not a sensitiser under the conditions of the study.

Applicant's summary and conclusion

Conclusions:
The human maximization test devised by Albert Kligman is a highly sensitive detector of skin sensitizing potential. In this assay, xylene was tested at 100% and subjects challenged at 25%. No skin sensitization resulted.
Executive summary:

The skin sensitisation potential of mixed xylenes was investigated in an early human maximisation test employing a total of five applications to inflamed skin on the forearm or calf (same site on each occasion, pre-treated with SLS) followed by challenge (100%, 25% mixed xylenes) on the back. The sensitisation rate was 0/24 indicating that mixed xylenes was not a skin sensitiser under the conditions of the study. The results for more than 80 chemicals are presented in this paper which demonstrates the very considerable predictive sensitivity of ths assay.