o-TOLUIDINE CAS N°: 95-53-4 - UNEP Chemicals

OECD SIDS o-TOLUIDINE
males or females, respectively (not adjusted for the stability of the test substance in the diet: 7-day
stability samples were 58.6 % (500 ppm), 68 % (3000 ppm) and 66.8 % (6000 ppm) (for general
toxicity see chapter 3.1.5 repeated dose toxicity). When compared to the controls a statistical
significant increase in nuclear grains and in the percentage of cells responding was seen in male and
female rats at 6000 ppm but not at 3000 ppm. Therefore slides from rats dosed with 500 ppm were
not scored (DuPont, 1994).
Conclusion
Genotoxicity test results are as typical for the class of aromatic amines. o-Toluidine showed
positive as well as negative results in point mutation assays in bacteria and yeast. Results from tests
with mammalian cell systems (HPRT, TK, UDS) were inconsistent, too, and appear to be protocol
dependent. However positive and negative results were independent of the presence or absence of a
metabolic activation system. In in-vitro tests for chromosomal aberrations o-toluidine yielded
positive results in several cell systems and did induce micronuclei in human lymphocytes in-vitro.
In in-vivo tests for chromosomal aberrations o-toluidine yielded negative results in bone marrow of
mice. o-Toluidine did not induce micronuclei in the in-vivo mouse micronucleus tests following
intraperitoneal or oral application. However, SCE assay in mice and UDS-test in rats gave positive
results in vivo. o-Toluidine did not induce point mutations in the in-vivo SLRL-test with
Drosophila melanogaster. Overall, o-toluidine showed potential for mutagenic activity in vitro and
clastogenic activity in vitro and in vivo.
3.1.7 Carcinogenicity
In vivo Studies
Oral
There are several carcinogenicity studies available in rats and mice that are not performed according
to the criteria of today. Limitations include study documentation in general, as well as number of
animals used, level and number of dosages, treatment time and the lack of investigations during the
course of the studies. Nevertheless, the studies are considered of sufficient good quality to allow an
evaluation of this endpoint.
Studies with rats
In a carcinogenicity bioassay 50 rats/sex and dose group were fed 0, 3000 or 6000 ppm
(approximately 0, 225 and 450 mg/kg bw/day) o-toluidine hydrochloride for a period of 104 weeks
(females and all control animals) and 101 weeks (males), respectively. Additional 20 rats/sex served
as control animals. No clinical pathology, no hematology and no interim kill were performed (NCI,
1979). In each sex, a significant positive dose-related trend in mortality rates was reported but
individual animal data were not given. According to the authors no clinical signs could clearly be
related to the administration of o-toluidine hydrochloride. Mean body weights of both, dosed males
and females were lower than those of the corresponding matched controls and were reported to be
dose-related throughout the bioassay, but individual animal data were not given. Histopathology
revealed in males and in females tumors in different organs (low, high doses versus controls)
including multiple organs, localization not otherwise specified (sarcomas, NOS: m: 3/50, 11/49
versus 0/20; f: 1/50, 2/49 versus 0/20; fibrosarcomas, m: 8/50, 20/50 versus 0/20, osteosarcomas, m:
3/50, 5/50 versus 0/20, f: 0/50, 18/50 versus 0/20, malignant mesothelioma, m 4/50, 2/49 versus
0/20, f: 0/50, 0/49 versus 0/20), subcutaneous tissue (fibromas, m: 28/50, 27/49 versus 0/20, f: 4/50,
2/49 versus 0/20; fibrosarcomas, m: 1/50, 2/49 versus 0/20), spleen (sarcomas, NOS, m: 1/49, 3/42
versus 0/20, f: 1/49, 3/49 versus 0/20; angiosarcomas, m: 7/49, 0/42 versus 0/20, f: 7/49, 9/49
versus 0/20; fibromas, m: 10/49, 2/49 versus 0/20, f: 4/49, 6/49 versus 0/20), urinary bladder
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