Registration Dossier

Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study not conducted in compliance with GLP and test standard not referenced within the report, however data included for OECD SIDS dossier. Approach considered valid as an in vitro skin irritation test did not demonstrate the potential for the substance to be a skin irritant.

Data source

Reference
Reference Type:
other: Not specified
Title:
Unnamed
Year:
1976
Report Date:
2003

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The guideline followed is not specified within the SIDS dossier; only the end result.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
CAS No: 68442-68-2
EINECS No: 270-485-3
EINECS Name: Benzenamine, N-phenyl-, styrenated
CAS Name: Benzenamine, N-phenyl-, styrenated
Substance type: organic
Physical status: liquid
Purity: > 98 % w/w
Result: Molecular weight: 320

Test animals

Species:
rabbit
Strain:
not specified
Details on test animals and environmental conditions:
Not specified

Test system

Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
Not specified
Duration of treatment / exposure:
Not specified
Observation period:
Not specified
Number of animals:
Unknown
Details on study design:
Not specified

Results and discussion

In vivo

Results
Irritation parameter:
other: Not specified
Basis:
other: Not specified
Time point:
other: unknown
Score:
0.46
Irritant / corrosive response data:
Primary Skin Irritation. Was originally classified as non-irritating; however, according to current classifications, it would be a mild irritant. The result
was 0.46.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The study was originally classified as non-irritating; however, according to current classifications, it would be a mild irritant. The result was 0.46. However, this does not result in classification under the current EU CLP scheme. Read across to supporting substance, CAS No. 68442 -68 -2, by structural analogue. This approach considered valid as an in vitro skin irritation test did not demonstrate the potential for the substance to be a skin irritant.
Executive summary:

Study not conducted in compliance with GLP and test standard not referenced within the report, however data included for OECD SIDS dossier. Was originally classified as non-irritating; however, according to current classifications, it would be a mild irritant. The result was 0.46. Does not result in classification under the current EU CLP scheme. Read across to supporting substance, CAS No. 68442 -68 -2, by structural analogue.

This substance has been supported under Environmental Protection Agency’s (EPA’s) High Production Volume (HPV) Challenge Program. The American Chemical Councils RAPA Panel, has derived a “Substituted Diphenylamines” category of chemicals for this substance, please refer to EPA reference 201-14700A located at

 

http://www.epa.gov/hpv/pubs/summaries/subdipha/c13378rt.pdf

 

Relying on several factors specified in EPA’s guidance document on “Development of Chemical Categories in the HPV Challenge Program,” in which use of chemical categories is encouraged, the following closely related chemicals constitute a chemical category:

 

Structural Similarity. A key factor supporting the classification of these chemicals as a category is their structural similarity (see Figure 1). All share a common starting material; Diphenylamine (Benzenamine, N-phenyl-, CAS# 122-39-4), a common synthetic pathway, and all compounds in this category are diamines with various substitutions.

 

Similarity of Physicochemical Properties. The similarity of the physicochemical properties of these materials parallels their structural similarity. All are off-white to light brown solids or viscous liquids intended for use as antioxidants in finished rubber articles or as antidegradant additives that extend the useful life of heavy-duty industrial functional fluids used in high-speed, high-temperature and/or high-load applications. As a class, these amine-based antidegradant compounds are less migratory (more polymer-bound) and less staining than the Substituted p-Phenylenediamine antidegradants. The use of these materials requires that they be stable under high temperatures. Their low volatility is due to their low vapor pressure, highly viscous or solid form. The existing information for these materials indicates that they have low water solubility and high flash points.

 

Toxicological Similarity. Review of existing published and unpublished test data for Substituted Diphenylamines shows the aquatic and mammalian toxicity among the materials within this category are similar.

 

Mammalian Toxicology - Acute. Data on acute mammalian toxicity were reviewed, and the findings indicate a low concern for acute toxicity for all materials. Data are available for most members of the category indicating that the category has been well tested for acute mammalian effects. Therefore, for the purposes of the HPV Program, no additional acute mammalian toxicity testing is proposed.

 

Mammalian Toxicology - Mutagenicity. Data from bacterial reverse mutation assays, in vitro and in vivo chromosome aberration studies, as well as additional supporting in vitro and in vivo genetic toxicity studies were reviewed, and the findings indicate a low concern for mutagenicity either for aryl or alkyl substituted materials. Similarly, the data for a mixed aryl/alkyl substituted molecule also indicates a lack of mutagenicity. Data are available for several members of the category or close structural analogs, and these data can be bridged to the other members of the category. Therefore, for the purposes of the HPV Program, the category has been adequately tested for mutagenicity, and no additional mutagenicity testing is proposed.

 

Mammalian Toxicology – Repeated Dose Toxicity. Data from repeated-dose toxicity studies were reviewed. Sufficient data are not available to adequately represent the Substituted Diphenylamines for the purposes of the HPV Program, and additional testing is proposed on the smallest aryl- and akyl-substituted materials.

 

Mammalian Toxicology - Reproductive and Developmental Toxicity. Data from reproductive and developmental toxicity studies were reviewed. Sufficient data are not available to adequately represent the Substituted Diphenylamines for the purposes of the HPV Program, and additional testing is proposed, and additional testing is proposed. It is proposed to test the smallest aryl- and akyl-substituted materials.

 

Conclusion. Based upon the data reviewed in “Substituted Diphenylamines” category of chemicals, the physicochemical and toxicological properties of the Substituted Diphenylamine category members are similar and follow a regular pattern as a result of that structural similarity. Therefore, the definition of a chemical category has been met, and read across is considered appropriate for the category of chemical.