Aniline

Respiratory sensitisation

Administrative data

Endpoint:

respiratory sensitisation

Remarks:

other: electrophilic reaction anaylsis

Type of information:

other: electrophilic reaction chemistry analysis

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

publication

Title:

Electrophilic reaction chemistry of low molecular weight respiratory sensitizers

Author:

Enoch

Year:

2009

Bibliographic source:

Chem. Res. Toxicol. 22, 1447-1453

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Aniline

EC Number:

200-539-3

EC Name:

Aniline

Cas Number:

62-53-3

Molecular formula:

C6H7N

IUPAC Name:

aniline

Results and discussion

Results:

The difference in respiratory sensitization between aniline (negative: often cited as as being examples of nonrespiratory-sensitizin monofunctional chemicals) and 4-phenylenediamine (positive) can be explained by their ability to give rise to compounds that undergo the Michael reaction. The ability of a chemical to undergo the Michael reaction with proteins has been suggested to be responsible for a range of toxicities including skin sensitization and acute aquatic toxicity. Previous analysis of the same two chemicals in the LLNA revealed that aniline was a very weak skin sensitizer, while 4-phenylenediamine was a strong skin sensitizer. Subsequent analysis suggested that the aniline result was more than likely a false positive result due to the ability of aniline to act as an irritant (irritants often act as false positives in the LLNA). The differing activities for both skin and respiratory sensitization can be explained in terms of the ability of 4-phenylenediamine to be oxidized to 4-benzoquinone diimine reactive species. An analogous oxidation is not possible for aniline.

Applicant's summary and conclusion

Executive summary:

The difference in respiratory sensitization between aniline (negative: often cited as as being examples of nonrespiratory-sensitizin monofunctional chemicals) and 4-phenylenediamine (positive) can be explained by their ability to give rise to compounds that undergo the Michael reaction. The ability of a chemical to undergo the Michael reaction with proteins has been suggested to be responsible for a range of toxicities including skin sensitization and acute aquatic toxicity. Previous analysis of the same two chemicals in the LLNA revealed that aniline was a very weak skin sensitizer, while 4-phenylenediamine was a strong skin sensitizer. Subsequent analysis suggested that the aniline result was more than likely a false positive result due to the ability of aniline to act as an irritant (irritants often act as false positives in the LLNA). The differing activities for both skin and respiratory sensitization can be explained in terms of the ability of 4-phenylenediamine to be oxidized to 4-benzoquinone diimine reactive species. An analogous oxidation is not possible for aniline.