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

OECD SIDS o-TOLUIDINE
Inhalation
There are no studies available
Studies in Humans
No data available.
Conclusion
Repeated dose studies show that o-toluidine is markedly toxic to erythrocytes and a methemoglobin
forming chemical. This was demonstrated in elevated methemoglobin levels up to 19.0 % in the
subacute feeding study as well as in the marked splenic toxicity in the subacute gavage and
subchronic feeding studies, leading to hypercellularity in the bone marrow. Further target organs
were liver and kidney (hemosiderin deposition) and urinary bladder (hyperplasia). Based on the
hematological findings no NOAEL could be derived, the LOAEL (rat, 14-day feeding study) was
500 ppm (approx. 23.7 and 25.5 mg/kg bw/day for males and females, respectively).
3.1.6 Mutagenicity
Studies in Animals
In vitro Studies
In tests according to the current standard, o-toluidine was not mutagenic in Salmonella typhimurium
strains TA97, TA98, TA100, TA102, TA104, TA1535, TA1537, TA1538 and Escherichia coli
WP2urA, WP2urA/pKM101 without S9-mix and with S9-mix derived from rat or hamster liver
using a dose-range from 0.10 µg/plate up to 6666 µg/plate (Microbiol Associates Inc., 1996; Zeiger
and Haworth, 1985; JETOC, 1997; Matsushima, Maramatsu and Haresku, 1985; Rexroat and
Probst, 1985; Zeiger et al., 1992). Ames tests with Salmonella typhimurium TA 100 gave no
indication of gene mutation without S9-mix and in the presence of rat liver S9-mix but yielded
positive results in the presence of 30 % hamster liver S9-mix (Zeiger and Haworth, 1985; Zeiger et
al., 1992).
Gene mutations in mammalian cell system (Chinese Hamster V79 cells; HPRT test) were not
observed in the presence and in the absence of S9-mix. The positive controls were tested with the
same dosages (0.25 - 2.00 mg/ml) and were functional (Fox and Delow, 1985). However, Kuroda,
Yokoiyama and Kada (1985) found a dose-dependent increase in mutagenic activity without
metabolic activation in V79 cells. Addition of S9-mix diminished the frequencies of mutations
induced by o-toluidine.
Results from Mouse Lymphoma assay (thymidin kinase locus test) with o-toluidine were
inconsistent. Amacher and Turner (1985) reported negative results in the presence and in the
absence of S9-mix whereas Myhr, Bowers and Caspari (1985) in the absence of S9-mix, published
positive results without information whether small or large colonies were evaluated. Testing in the
presence of S9-mix was not done by them. In both publications tests were carried out up to
cytotoxic concentrations.
Chromosome aberrations were seen in in-vitro tests, which were performed with Chinese Hamster
Lung (CHL) cells and Chinese Hamster Ovary (CHO) cells in the presence and in the absence of
metabolic activation systems and concentrations ranging from 16 to 5000 µg/ml (Gulati, Sabharwal
and Shelby, 1985; Ishidate and Sofuni, 1985; Ishidate, Harnois and Sofuni, 1988). In all studies
positive results were obtained at non-cytotoxic concentrations.
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