6-ethyl-2-toluidine

Endpoint summary

Description of key information

The oral LD50 for rats of 2-methyl-6-ethylaniline in these acute oral toxicity studies is found within 885 to 1700 mg/kg body weight.
The LC50 for 2-methyl-6-ethylaniline is 2.6 mg/l/ 4 h in air.
The dermal LD50 is 1290 mg/kg bw in rabbits.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

885 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

LC50

Value:

2 600 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

1 290 mg/kg bw

Additional information

Acute toxicity: oral

The oral toxicity of 2-methyl-6-ethylaniline (MEA) was evaluated in several studies with rats, mice or rabbits. All these studies show restrictions and deficiencies, but are appropriate for a weight of evidence approach. In a study with male Sprague-Dawley rats an oral LD50 of 1180 mg/kg body weight was determined (Jacobson 1972, Durden 1973). In another study with male and female Sprague-Dawley rats a LD50 value of 1150 mg/kg body weight was calculated (ECB 2000). In a publication from Short et al. (1983) an oral LD50 of 885 mg/kg body weight for the rat was published. In addition, Vasilenko (1987) published an oral LD50 value of 1700 mg/kg body weight for the rat and an oral LD50 value of 930 mg/kg body weight for mice. For rabbits an LD50 of 700 mg/kg body weight was published (Vasilenko (1987).

The oral LD50 for 2-methyl-6-ethylaniline as administered in these studies is found within 885 to 1700 mg/kg body weight.

In a special study with male Wistar rats the methemoglobin content was determinate after a single oral application of 2 -methyl-6-ethylaniline (MEA). The methemoglobin was determinate before and 1, 3, 7 and 24 hours post application. No relevant increase in methemoglobin was found in any of the dose groups evaluated. Clinical signs were observed after a single application of 500 mg/kg bw MEA. An increased oral discharge, rough fur, difficulties in breathing, cyanosis and poor general conditions were seen. The clinical signs developed 15 minutes after the application and continued up to 2 days. After 3 days no clinical signs were found anymore; one rat (1/5) of the highest dose group diet after 24 hours after the application. No clinical signs were seen in the 20 mg/kg bw and 100 mg/kg bw dose group. The body weight gain was not affected in any dose group evaluated. The pathological evaluation showed, that one rat (1/5) from the 20 mg/kg bw group had a slightly red mucous membrane of the small intestine. The animals from the 100 mg/kg bw and the 500 mg/kg bw dose group had a red mucous membrane of the small intestine and a change of the liver color (Bomhard 1989).

Acute toxicity: inhalation

The test substance 2 -methyl-6-ethylaniline (MEA) was evaluated in an acute inhalation study (Bechtel 1989). In this study three groups of 5 male and 5 female Sprague-Dawley rats were each exposed for 4 hours to an atmosphere of aerosolized 2-methyl-6-ethylaniline at mean analytical concentrations of 2.1, 2.5, or 3.2 mg per liter in air (whole body exposure). Exposure was followed by a 14-day observation period and subsequent necropsy. At the highest exposure concentration eight rats died, at the 2.5 mg/l level four animals died and at the 2.1 mg/l level two animals died. The calculated LC50 values for both sexes were 2.6 mg/l, for females 2.2 mg/l. and for the males 3.1 mg/l. The observations during exposure showed a visible hypo-activity of the animals and clear nasal discharge. The clinical signs noted immediately after exposure were non-responsiveness, disuse of limbs, labored respiration, clear nasal discharge, and salivation. The observations made during post-exposure day one and four showed non-responsiveness, prostrate, disuse of limbs, respiration difficulties, and ocular opacity. From post-exposure days 5 to 14 the only clinical sign noted was ocular opacity. There was weight loss in all animals by post-exposure day 2. By post-exposure day 14 all animals were gained weight and exceeded their pre-exposure weights. Gross necropsy findings noted in unscheduled deaths were corneal opacity, abnormal discharge/encrustation about eyes, abnormal liver color, fecal stained skin, abnormal color of testis, abnormal contents of urinary bladder. The only necropsy findings noted at the scheduled sacrifices were corneal opacity and hydronephrosis, which is relative common in animals of this strain and age and was not considered test-related.

The LC50 for 2-methyl-6-ethylaniline as administered in this study is 2.6 mg/l/ 4 h in air. As the animals were exposed whole-body there is a potential that dermal penetration added to the overall toxicity. Nevertheless, according to the findings of this study MEA should be classified as harmful by inhalation based on the classification criteria 67/548/EWG and regulation no. 1272/2008 (GHS).

Acute toxicity: dermal

A study with limited documentation and therefore low reliability revealed a LD50 dermal of 1290 mg/kg bw in rabbits (ECB 2000, secondary literature). This is in line with the available data on acute oral toxicity and reflects the good dermal resorption of MEA. In conclusion, MEA should be classified as harmful in contact with skin according to the classification criteria 67/548/EWG and regulation no. 1272/2008 (GHS).

Justification for classification or non-classification

According to the findings of the oral acute toxicity studies, the acute inhalation study and the data from the acute dermal toxicity study, MEA should be classified as harmful based on the classification criteria 67/548/EWG and regulation no.1272/2008 (GHS).