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Description of key information

Acute Toxicity:
Oral: LD50:620 mg/kg bw
Inhalative: LC 50: 0.64 mg/L air (1 h exposure)
Dermal: LD50: 890 mg/kg bw

Key value for chemical safety assessment

Additional information

OECD SIDS, 2005

Studies in Animals

There are no animal studies available, which are performed according to the current guidelines. Nevertheless the studies are considered of sufficient good quality to allow the evaluation of this endpoint:

 

Inhalation

In an inhalation hazard test, 6 rats were exposed for one hour against vapor concentrations of approximately 0.64 mg p-toluidine/L. Signs of intoxication during and post exposure included generalized inactivity, rhinitis and lacrimation, which ceased one day post exposure. No animal died during the exposure or during the 14-day observation period. Gross autopsy revealed no significant findings (Industrial Bio-Test Laboratory Inc., 1973).

 

Dermal

Dermal application of 464 - 1470 mg/kg bw moistened p-toluidine (exposure time not mentioned) to 5 rabbits/dose group resulted in an LD50-value of 890 mg/kg bw. Signs of intoxication from day 4 post exposure in the lowest dose group and within 4 hours post exposure in the highest dose group were hypoactivity, muscular weakness, convulsions and vocalisation just prior to death which occurred in all dose groups. Additionally, moderate to severe erythema, mild edema, focal chemical burns and subdermal hemorrhages were seen in the skin of the rabbits. Pathological investigations showed granular livers in the decedents whereas from survivors no significant findings were noted

(Industrial Bio-Test Laboratory Inc., 1973).

Single dermal application of p-toluidine resulted in methemoglobin level up to 20 %, and recovery occurred within 48 hours. Dermal application of 0.5, 0.75, 1, or 1.25 % solution of p-toluidine to rats for 2 - 6 hours (no further details) resulted in dose-related increase in methemoglobin level up to

40 %. As the experimental performances of the tests are described poorly these results are difficult to interpret (Senczuk and Rucinska, 1984).

Oral

To determine LD50 values of p-toluidine, there are 2 studies, which could be taken into account. In the first one 10 male rats per dose received dosages ranging from 100 mg/kg bw up to 900 mg/kg bw dissolved in lutrol (Bayer AG, 1978) Signs of intoxications were hypoactivity, increase of urinary excretion, emaciation, bloody eyes, cyanosis, anorexia and narcosis which led to dose-related death during the 14 day post exposure observation period. The resulting LD50 value is 620 mg/kg bw. This data correspond to another study which was carried out to an earlier timepoint and which is of questionable reliabilty. In that study 5 rats per dose group were treated with up to 1000 mg/kg bw dissolved in corn oil. Hypoactivity, cyanosis, anorexia and death and no significant findings at gross autopsy were reported. The resulting LD50value was 656 mg/kg bw (Industrial Bio-Test Laboratory Inc., 1973;).

Reported in brief and therefore difficult to interpret, single oral application of 200 mg/kg bw p-toluidine to rat (no further details given) resulted in a methemoglobin level (max) of 21.7 % two hours post application (Senczuk and Rucinska, 1984).

 

Studies in Humans

It is reported in an earlier publication that toluidines (isomer not specified) due to methemoglobin formation produce the same symptoms, as does aniline (route and duration of exposure is not specified), with less cyanosis but more strangury and hemoglobinuria (Smyth, 1931). Goldblatt (1955) reported in a survey article that, due to effects of their metabolic products on haemoglobin, concentrations of 40 ppm (176 mg/m3) of toluidine (isomer not specified) in the atmosphere for more than 60 minutes caused severe toxic effects in workers, 10 ppm (44 mg/m3) lead to symptoms of illness and concentrations in the atmosphere greater than 5 ppm (22 mg/m3) indicate unsatisfactory conditions (no further details included). In the recent open literature no cases of acute poisoning were reported.

 

Conclusion

For p-toluidine, the LC50 (inhalative, rat) is > 0.64 mg/l, and LD50 (dermal, rabbit) is 890 mg/kg bw. LD50 (oral, rat) was determined 656 mg/kg bw and 620 mg/kg bw. Signs of intoxication include hypoactivity, muscular weakness, convulsions, cyanosis and narcosis. p-Toluidine is a methemoglobin forming chemical in rats. Levels up to 21.7 % following oral application to rats and up to 40 % following dermal application to rats were measured. p-Toluidine is a methemoglobin forming chemical in humans as it produces the same toxic effects as aniline from 22 mg/m³ onwards with less cyanosis but more stranguria and hemoglobinuria.

 

Justification for classification or non-classification

Taking into account that humans are much more sensitive to methaemoglobin producing substances than rats p-toluidine is classified as T, Toxic and labelled as R 23/24/25, toxic by inhalation, in contact with skin and if swallowed.