Registration Dossier

Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
other: Evaluation of collected data.
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
2g. Collection of data by the Scientific Committee on Occupational Exposure Limits, a committee of the European Commission established in 1995 to advise on occupational exposure limits for chemicals in the workplace within the framework of Directive 98/24/EC, the chemical agents directive; and Directive 90/394/EEC, the carcinogens at work directive.

Data source

Reference
Reference Type:
review article or handbook
Title:
Handbook of Intermediary Metabolism of Aromatic CompoundsRecommendation from the Scientific Committee on Occupational Exposure Limits for N-methylaniline
Author:
Scientific Committee on Occupational Exposure Limits
Year:
2010
Bibliographic source:
Scientific Committee on Occupational Exposure Limits (SCOEL), SCOEL/SUM/178, September 2010.

Materials and methods

Principles of method if other than guideline:
Tests were performed before the existence of international guidelines, references:
1. Treon, J.F. et al., 1949. The toxic properties of xylidine and monomethylaniline I. J. of industrial hygiene & toxicology, 31, 1949, pages: 1-20.
2. Treon, J.F. et al., 1950. The toxic properties of xylidine and monomethylaniline II. Arch. of industrial hygiene & occupational medicine Vol. 1, pages: 506-524.
3. Lin JK, Hsu SM, Wu YH. Methemoglobin induced by carcinogenic aminoazo dyes in rats. Biochem Pharmacol. 1972 Aug 1;21(15):2147-50.
4. Holzer N. & Kiese M., 1960. Bildung von Nitrosobenzol, anilin und Haemiglobin in Katzen und Hunden nach intravenoeser Injektion von N-Alkylanilinenj. Naunyn-Schmiedebergs Archiv fuer experimejntelle Pathologie und Pharmakologie, 238:546-556.

GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
other: Rabbits, rats, guinea pigs, cats, dogs and monkeys.
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
intravenous
Vehicle:
not specified
Doses:
Doses specified: 18 to 54 mg/kg, but broader ranges were probably tested.
No. of animals per sex per dose:
Not specified.
Control animals:
not specified

Results and discussion

Effect levelsopen allclose all
Sex:
not specified
Dose descriptor:
other: minimum lethal dose
Effect level:
24 mg/kg bw
Based on:
test mat.
Remarks on result:
other: in cats and rabbits
Sex:
not specified
Dose descriptor:
other: LOEL
Effect level:
18 mg/kg bw
Based on:
test mat.
Remarks:
Dosed i.v. in cats
Remarks on result:
other: Based on aenemia.

Any other information on results incl. tables

After a single i.v. injection of 18 -24 mg N-methylaniline per kg in cats caused a rapid increase of MetHb up to levels > 60 -70%.

In rabbits and cats, Heinz-bodies were observed in erythrocytes (inclusions composed of denatured hemoglobin) after i.v. injection of 36 mg/kg bw or higher.

Aenemia was observed after i.v. injection of N-methylaniline at 18 mg/kg in cats (LOEL).

Applicant's summary and conclusion

Conclusions:
In comparison to aniline, N-methylaniline is about twice as potent in causing MetHb formation. The LOEL (i.v.) for aenemia in cats was 18 mg/kg bw.