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

OECD SIDS o-TOLUIDINE
3.1.2 Acute Toxicity
Studies in Animals
Inhalation
Groups of ten male rats were exposed head-only to o-toluidine-vapor/aerosol for 4 hours in
concentrations ranging from 492 up to 1000 ppm (corresponding to 2184 - 4440 mg/m 3 ). Death
occurred at 722 ppm (3206 mg/m 3 ) in 1/10 rats on day 3 post exposure and the concentration of
1000 ppm (4440 mg/m 3 ) was lethal to all animals within 24 hours post exposure. Major treatmentrelated
clinical signs included cyanosis, labored breathing, lethargy, prostration, reddish-brown
nasal discharge and stained wet perinea. In this study no histopathological investigations were
performed. The calculated LC50 value is 862 ppm (3827 mg/m 3 , DuPont Chem, 1981).
Dermal
Dermal application of 2010 - 5250 ml/kg bw over a period of 24 hours followed by a 14-day
observation period yielded a LD50 value of 3250 mg/kg bw using groups of 4 male rabbits and the
one-day cuff method of Draize (Smyth et al., 1962). Signs of toxicity and individual animal data
were not reported. In a further study with female Wistar rats single dermal application of 0.75, 1, or
1.25 % o-toluidine-solution (dosing volume not mentioned) resulted in dose-related increase in
methemoglobinemia up to 8 - 10 % (Senczuk and Rucinska 1984).
Oral
There are no studies according to the current OECD Test Guidelines, but there is one study, which
is adequately documented and is considered of sufficient quality to allow an evaluation of this
endpoint. In male Wistar rats (n = 10) dosed with 0.6, 0.65, 0.7, 0.8 or 0.9 ml/kg bw (app. 600, 650,
700, 800 or 900 mg/kg bw) undiluted o-toluidine deaths occurred at dose levels of ≥ 0.65 ml/kg bw
within 2 - 5 days after application. In moribund animals anesthesia, increased diurese, cyanosis,
bloody eyes were observed. No necropsy and no histopathological examinations were performed.
From this study a LD50 value of 0.75 ml/kg bw (corresponding to 750 mg/kg bw) was derived
(Bayer AG, 1978).
Oral administration of 50 mg/kg bw o-toluidine to 2 cats per sex resulted in 59.6 to 71.7 % methemoglobin
within 4 hours after administration, lateral position, tachypnea, cyanosis mydriasis,
apathy, salivation and the death of one cat. During the 14 day-observation period, one cat was in
poor condition and 2 cats recovered (BASF AG, 1979).
Studies in Humans
Cases of poisoning of workers with o-toluidine following acute exposure are described e.g. by
Stark, 1892, cited in Greim (1997), who reported of a worker who inhaled vapor of toluidine
(isomer not specified) during the transfer from one open vessel to another one. He lost
consciousness, was cyanotic, exhaled levels of toluidine and suffered from strangury and blood was
detected in the urine. Full recovery required 5 weeks. In another case, during repair of machines, a
fitter was accidentally exposed against o-toluidine (exposure route probably: inhalation, concentration
not given). Treatment with tolonium chloride reduced methemoglobinemia from 39.6 %
to 2.6 % (BASF AG, 1989). Goldblatt (1955), reported in a survey article that concentrations of
40 ppm (176 mg/m 3 ) toluidine (isomere not specified) in the atmosphere for more than 60 minutes
caused severe toxic effects in workers, 10 ppm (44 mg/m 3 ) lead to symptoms of illness and
concentration in the atmosphere greater than 5 ppm (22 mg/m 3 ) indicate unsatisfactory conditions
(no further details included). In the recent open literature no further cases of acute poisoning are
reported.
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