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

OECD SIDS o-TOLUIDINE
3.1.4 Sensitisation
Studies in Animals
No animal studies on sensitization are available.
Studies in Humans
No valid data available.
40 dermatitis patients, known to be hypersensitive to p-phenylene-diamine, were patch tested with
2 % o-toluidine in yellow paraffin. 25 % of the patients showed positive reactions (Kleniewska,
1975). The study is not assignable because only patients with dermatitis and already sensitized to
p-phenylene diamine are examined.
Conclusion
There are no valid data available to evaluate the sensitization potential of o-toluidine.
3.1.5 Repeated Dose Toxicity
Studies in Animals
Oral
A sub-acute (14 days) feeding study in male and female Fischer rats (n = 5 per sex and group) with
doses of 0, 500, 3000, 6000 ppm (corresponding to an estimated substance intake of 40.4, 238, 449
or 43.5, 251, 481 mg/kg bw/day of males or females, respectively, not adjusted to the test substance
stability: 58.6 % (500 ppm), 68 % (3000 ppm) and 66.8 % (6000 ppm)) was performed to
investigate the urinary bladder toxicity by histopathological evaluation as well as by quantitative
determination of the urinary metabolite N-acetyl-4-amino-m-cresol (NAAC) and the level of
methemoglobinemia as potential biological exposure indices (DuPont, 1994). Additional 5 - 10 rats
per sex and group were used to perform an UDS test (see chapter 3.1.6). No mortality and no
compound-related clinical findings were reported, except for wet and stained perineum in female
rats at 6000 ppm after one week. Slight but statistically significantly decreased body weights were
observed in the high dose groups (males: 218 g versus 233 g of controls; females: 142 g versus
151 g of controls). Body weight gain was decreased in high dosed males (30.0 g versus 43.5 g of
controls) and in all dose groups of females (low, mid and high dose: 19.2 g, 18.6 g and 15.4 g
versus 23.5 g of controls). Urothelial hyperplasia was described to be mild in the high dosed
females, and in males, thickening of the urothelial layer was minimal (detailed data were not given).
Urinary bladder epithelial cell proliferation, characterized by labeling indices, increased with
increasing dosage of o-toluidine but was significant only in the 6000 ppm dosed males (1.42 versus
0.47 of controls) and in the 6000 and 3000 ppm dosed females (2.55 and 0.38 versus 0.08 of
controls). Urinary excretion of NAAC was positively correlated with the cell proliferation in both
male and female rats, according to the author, indicating that NAAC may be a useful urinary
biomonitor for o-toluidine exposure. Statistically significant and dose-related increase in
methemoglobin production was determined in all treated animals (males: 4.2 %, 10.7 %, and 14.9 %
versus 0.6 % in controls; females: 6.2 %, 14.5 %, and 19.0 % versus 0.5 % in controls). Therefore a
NOAEL could not be established. The LOAEL based on methemoglobinemia (male and females)
and decreased body weight gain (females) was 500 ppm (adjusted to the test substance stability:
app. 23.7 mg/kg bw/day for males and app. 25.5 mg/kg bw/day for females) (DuPont, 1994).
In subchronic feeding studies, o-toluidine hydrochloride was administered to three groups of male
Fisher 344 rats (n = 20) for 13 weeks (group one and two) and for 26 weeks (group three) at a
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