Registration Dossier

Toxicological information

Exposure related observations in humans: other data

Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2003-01-24
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature

Data source

Reference
Reference Type:
publication
Title:
Proposal for a risk assessment methodology for skin sensitisation based on sensitization potency data
Author:
Griem P. et al.
Year:
2003
Bibliographic source:
Regulatory Toxicology and Pharmacology 38, 269 - 290

Materials and methods

Endpoint addressed:
skin sensitisation
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: To propose a quantitative risk assessment methodology for skin sensitization aiming at the derivation of safe exposure levels for sensitizing chemicals, used e.g., as ingredients in consumer products.
- Short description of test conditions:
Data was obtained on known human sensitizing chemicals, for which both, an EC3 value from LLNA and a NOEL and/or LOEL from HRIPT or HMT were available. When no LOEL (and no NOEL) was identified, i.e., when the sensitization rate was below 50%, a factor of 3 for sensitization rates between 10 and 25% and a factor of 10 for sensitization rates between 25 and 50% were used to extrapolate to a LOEL value. The reported concentrations were converted into specific and molar area dose values. Since according to the standard protocol, 25 µL test solution are distributed over this surface, multiplication of the concentration of the chemical in the test solution (in percent) with a factor of 250 results in the specific area dose value (in µg/cm2).
For human tests, the reported area dose was used if given in the literature. Otherwise it was calculated by dividing the amount of test substance by the area of the application site. If no quantitative information on amount of test material applied and/or the size of the application area was available, it was assumed that 400 mg of test solution was used on a 2 X 2-cm Webril patch (4 cm2), resulting in estimation of the specific area dose value (in µg/cm2) by multiplication of the concentration of the chemical in the test solution (in percent) with a factor of 1000. A comparison of the LLNA and human area doses was then performed
- Parameters analysed / observed: NOEL, LOEL, EC3
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
Not specified

Method

Ethical approval:
not specified

Results and discussion

Results:
- A comparison of the area doses of LLNA and human test results revealed that sensitization thresholds are very similar in mice and humans, despite of the fact that the area doses for different chemicals ranged over several orders of magnitude.
- The correlation of human NOEL and human LOEL values with murine EC3 values revealed no significant differences, i.e., the EC3 values were not significantly closer to the human LOEL values than to the human NOEL values
-Thus, EC3 value can be used as a surrogate value for the human NOEL that can be used as a starting point in quantitative sensitization risk assessment.

Any other information on results incl. tables

- It was found that, with respect to quantitative sensitization risk assessment, the local lymph node test (LLNA) performed in mice is most relevant because by means of its EC3 value it provides a quantitative measure of sensitizing potency. A comparison of LLNA EC3 values with HRIPT and HMT LOEL and NOEL values was carried out in this study and revealed that the EC3, expressed as area dose, can be used as a starting point (as a surrogate NOEL) in risk assessment.

Applicant's summary and conclusion

Executive summary:

In this study, a risk assessment procedure for measuring the skin sensitizing potential of a chemical is proposed. Data was obtained on known human sensitizing chemicals, for which both, an EC3 value from LLNA and a NOEL and/or LOEL from HRIPT or HMT were available. The NOEL for the test substance, tert-butyl glycidyl ether was 800 µg / cm2. The test substance, tert-butyl glycidyl ether was categorised as a 'skin - sensitizer' under UN GHS "Category 1B."