Registration Dossier

Administrative data

Description of key information

- oral: LD50 = 1978 mg/kg bw. (OECD 401)
- dermal: LD50 > 2000 mg/kg bw (OECD 402)
- inhalation: LC50 = 1.80 mg/l air (OECD 403)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
1 978 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
Value:
1 800 mg/m³

Additional information

Oral: The acute toxicity of the test substance was evaluated in rats according to the recommendations of OECD Guideline No. 401. The test substance was administered at the dose levels of 880, 1300 and 2000 mg/kg to 3 groups of 5 males and 5 females in each. The test substance dissolved in corn oil was administered at a volume of 10 ml/kg. All animals were fasted before treatment. The main clinical signs observed after the treatment consisted of hypokinesia and sedation accompanied by dyspnoea. Coma was also noted in a few animals given 1300 or 2000 mg/kg of the test substance. The onset of clinical signs occurred 15 minutes after administration of the test substance. The clinical signs had reversed by day 5. Between days 1 and 5 the body weight gain of the treated males given 1300 and 2000 mg/kg was slightly lower than that of historical controls. The body weight gain returned to normal thereafter. Between days 1 and 15 the body weight gain of the other surviving animals was not affected by the treatment. Deaths were noted within 48 hours post-treatment. The mortality rate was 0%, 0% and 60% in rats at 880, 1300 and 2000 mg/kg respectively. The death rate was lower in males when compared to females. Macroscopic post-mortem examination revealed no abnormalities in the animals found dead during the study or sacrificed at the end of the study. Under our experimental conditions, the acute oral median lethal dose of the test substance in rats was 1978 mg/kg (1519-6369) with 95% confidence interval limits.

Dermal: The potential acute toxicity of the test substance 2,6-dichloro-4 -trifluoromethylaniline (DCPTFMA) was evaluated in rats according to the recomendations of the OECD Guideline No. 402. The test substance in its original form was prepared on a moistened compress at a dose of 2000 mg/kg and then applied to the skin of 10 Sprague-Dawley rats (5 males and 5 females) . After 24 hours under a semi-occlusive dressing. The general behaviour and body weight gain of the animals were not affected by the treatment. No deaths occurred at the dose level of 2000 mg/kg. Macroscopic examination revealed no abnormalities in the animals sacrificed at the end of the study. Under these experimental conditions the LD50 of the test substance 2,6 DCPTFMA when administered by dermal route in rats was higher than 2000mg/kg b.w.. No signs of toxicity were observed at this dose level.

Inhalation: The acute inhalation toxicity o f 2,6 DCPTFMA was investigated by exposing each of four groups of five male and five female CD rats to an atmosphere containing the test material at a concentration of 0.35, 0.94, 2.88 or 5.14 mg per litre of air. Each test group was subjected to a single four-hour, continuous, snout-only exposure. A similarly constituted control group was exposed to compressed air only. All exposures were followed by a 28 day observation period. There were no deaths during the exposures. Four males and two females exposed to 5.14 mg/l died overnight following exposure. Animals that survived the immediate effects of the exposure at this concentration died between day 2 and 15 of the observation period. At 2.88 mg/l four males and four females died between day 2 and 16 of the observation period and one female exposed to 0.94 mg/l died on day 8. During the period of exposure to 2,6 DCPTFMA, reduced respiratory rate and exaggerated respiratory movements were seen for all animals. Wet fur was seen on the head of animals exposed to 0.94 mg/l or more; by the end of the exposures, isolated occurrences of wet fur occurred in females exposed to 0.35 mg/l. Struggling in the restraint tube was seen in animals exposed to 0.94 mg/l and in males exposed to 2.88 or 5.14 mg/l. During the first two hours following exposure, signs seen among animals exposed to 2.88 or 5.14 mg/l included: reduced respiratory rate, exaggerated respiratory movements, rales, gasping, prone posture, hunched posture, lethargy, underactivity, staggering gait, piloerection, wet fur, pigmented staining on the head and hypothermia. Many of these signs were also evident for animals exposed at a concentration of 0.94 mg/l, and increased respiratory rate, shallow respiration, hunched posture and wet fur were seen for animals exposed to 0.35 mg/l. Most of the signs observed during the first two hours after the exposures persisted for several days. Necropsy findings that were attributed to exposure to atmospheres containing 2,6 DCPTFMA were confined to failure of the lungs to collapse when the trachea was cut and pallor of the lung lobes; these findings were apparent for many of the decedents and also for a small number of the animals killed after 28 days of observation. Under the conditions of this study, the median lethal concentrations of 2,6 DCPTFMA for four hours exposure (LC50 4 hours) were 2.45 mg/l for males, 1.61 mg/l for females and, for males and females combined, 1.80 mg/l.

Justification for classification or non-classification

Oral: The available data for 2,6 -dichloro-4 -trifluoromethylaniline (DCPTFMA) indicate a potential for acute toxicity. In an acute oral study, the LD50 was 1978 mg/kg bw for male and female rats. Therefore, 2,6 DCPTFMA has to be classified as Xn; R22 according to Directive 67/548/EEC and as Cat.4; H302 according to Regulation (EC) No. 1272/2008.

Dermal: In a dermal acute study the LD50 was greater than 2000 mg/kg bw for male and female rats. Therefore, 2,6 DCPTFMA does not need to be classified according to Directive 67/548/EEC and according to Regulation (EC) No. 1272/2008 for this

endpoint.

Inhalation: In another acute study, according to OECD TG 403 the inhalative LC50 was determined to be 1.80 mg/l air for male and female rats. Therefore, 2,6 DCPTFMA has to be classified as Xn; R20 according to Directive 67/548/EEC and as Cat.4; H332 according to Regulation (EC) No. 1272/2008.