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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation, other
Remarks:
in vivo study (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Modified Draize test. In this test, sensitization was induced by 4 (instead of 10) intradermal injections followed by intradermal and topical challange procedures. The test modification as compared to the original Draize method was validated by the performing Laboratory. Therefore the results of the investigation are considered valid. No individal scores were presented in this publication.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
Maximisation test
Deviations:
yes
Remarks:
modified Draize test
Principles of method if other than guideline:
Modified Draize test. In the Draize test, sensitization is induced by 10 intradermal injections. In this study, the equivalent total dose was administered on one occasion as 4 intradermal injections.
GLP compliance:
no
Remarks:
at the time the study was performed, GLP was not compulsory
Type of study:
Draize test
Justification for non-LLNA method:
Study was performed in 1978
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Own colony inbred
- Weight at study initiation: 350 g
Route:
intradermal
Vehicle:
no data
Concentration / amount:
20% as AAC (Application Challenge Concentration)
0.25% as IIC (Injection Challenge Concentration)
Route:
intradermal and epicutaneous
Vehicle:
no data
Concentration / amount:
20% as AAC (Application Challenge Concentration)
0.25% as IIC (Injection Challenge Concentration)
No. of animals per dose:
A total of 10 test animal was used and 4 challenge control animals
Details on study design:
RANGE FINDING TESTS
Intradermal injection: Four animals of the same sex were each injected intradermally on the shaved flanks with 0.1 mL aliquots of a range of concentrations of test item in a suitable solvent. The reactions were examined for size, erythema and oedema 24 hours later and the concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration (IIC).
Topical application: Aliquots (0.1 mL) of a range of concentrations of the test item in a suitable solvent were applied in small circular areas to the shaved flanks of 4 guinea pigs of the same sex. The reactions were examined 24 hours later for erythema and the highest concentration which caused no irritation was selected as the application challenge concentration (AAC).

MAIN STUDY
A. INDUCTION EXPOSURE
At Day 0, in 10 animals, 0.1 mL aliquots of the test item at 2.5 times the IIC were injected intradermally at 4 sites which overlie the 2 axillary and inguinal lymph nodes.
B. CHALLENGE EXPOSURE
14 days after induction, each animal was challenged intradermally in one flank and topically in the other with 0.1 mL aliquots of the test item at the respective ICC and ACC: the topical challenge was made by spreading 0.1 mL of the test substance onto the shaved flank in a small circular area, which was not covered. Twenty-four hours later the reactions were scored and apparent sensitization reactions confirmed 7 days later by a second challenge with controls included.
In the absence of sensitization reactions at first challenge, the induction and challenge procedures were repeated, but this time a confirmatory challenge with controls was included irrespective of any apparent sensitization reactions at the previous challenge.
Challenge controls:
At each challenge with controls, 4 previously untreated animals of the same sex and similar weight to the test animals were treated intradermally and topically on opposite flanks with 0.1 mL aliquots of test substance at the ICC and ACC respectively.
Positive control substance(s):
no
Key result
Reading:
other: not further specified
Dose level:
0.25-20%
No. with + reactions:
0
Total no. in group:
10

Scoring: Each injection reaction was given a total score based on size (2 largest diameters), erythema and oedema. Individual reactions were considered positive when their total score was significantly greater than the average for total score for control reactions. Application reactions were scored on a 0 to +++ scale and individual reactions were considered positiveif they were a) + or greater and b) there were no erythema reactions in controls.

Interpretation of results:
GHS criteria not met
Conclusions:
In this modified Magnusson Kligman maximisation test, benzophenone did not show a sensitizing effect in guinea pigs.
Executive summary:

Benzophenone was applied to 10 guinea pigs in a modified Draize test. After induction (Day 0) with 4 intradermal injections to each animal with a 1% benzophenone concentration, combined intradermal (0.25% benzophenone) and topical challenge (20% benzophenone) procedures followed on day 14 and were repeated on days 35 and 42.

Benzophenone did not show a sensitising response in this test system and is thus considered to be a non-sensitising substance.

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

Benzophenone was applied to 10 guinea pigs in a modified Draize test. After induction (day 0) with 4 intradermal injections to each animal with a 1% benzophenone concentration, combined intradermal (0.25% benzophenone) and topical challenge (20% benzophenone) procedures followed on day 14 and were repeated on days 35 and 42. Benzophenone did not show a sensitising response in this test system (Sharp, 1978).

The sensitizing potential of benzophenone was determined in guinea pigs according the Magnusson & Kligman method (1970). Sensitization was produced by intradermal injections and topical application at a 1 and 10% concentration and a challenge concentration of 1 and 5%. None of the 20 test animals showed a positive response (Calas et al., 1977).

Benzophenone also was tested in 25 human volunteers by the maximization test as published by Kligman (1966). The material was tested at a 6% concentration in petrolatum and produced no positive reactions (Opdyke, 1979).


Migrated from Short description of key information:
Skin sensitisation, guinea pig: negative in a Maximisation test equivalent or similar to OECD Guideline 406 (Sharp, 1978; Calas et al., 1977)
Skin sensitisation, human volunteers: negative in a Maximisation test (Opdyke, 1979)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Based on the widespread exposure and the long term experience with benzophenone in humans, it can be concluded that the substance is not a significant respiratory sensitiser.


Migrated from Short description of key information:
No data available.

Justification for classification or non-classification

Skin sensitisation

The experimental data are not indicating a possible skin sensitisation potential. Therefore, there is no need for a classification according to the criteria of EC Directive 1272/2008 and of the GHS.

Respiratory sensitisation

There are no experimental studies available. Based on the widespread exposure and the long term experience with benzophenone in humans, it can be concluded that the substance is not a significant respiratory sensitiser. Therefore, there is no need for a classification according to the criteria of EC Directive 1272/2008 and of the GHS.