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Description of key information

The acute inhalative toxicity is moderate: LC50 (rat) ca. 3200 mg/m³ (= 495 ppm, vapor/aerosol mixture) for 4 hours. Cyanotic appearance was the predominant symptom.
The acute dermal toxicity is moderate (LD50 (rat, male) = 655 mg/kg bw, LD50 (rat, female) = 1320 mg/kg bw; LD50(rabbit) = 400 mg/kg bw (male: 445 mg/kg bw, female: 355 mg/kg bw)). Cyanotic appearance was the predominant symptom.
After single oral application 1-chloro-2-nitrobenzene is toxic to moderate toxic (LD50, oral: rat, male: 144, 251 or 560 mg/kg bw; rat, female: 263 or 560 mg/kg bw). Cyanotic appearance was the predominant symptom.

Key value for chemical safety assessment

Additional information

Inhalation

There are no studies according to the current OECD guideline but there are study reports with rats which give sufficient information to evaluate this endpoint: (Haskell Laboratory, 1992) LC50 ca. 3200 mg/m3 for 4 hours (= 495 ppm, vapor/aerosol mixture). Signs of intoxication during exposure were lethargy, slight to moderate cyanosis, slight to moderate corneal opacity, semi-prostration or prostration, reddish brown nasal discharge and tachypnoe. Signs of intoxication post exposure were pallor, reddish brown nasal discharge, semi-prostration and lethargy, corneal opacity. Death occurred within 7 days but not dose-dependently. Thus LC50 value was calculated from statistically not significant regression.

Dermal

There are no studies according to the current OECD guideline but there are study reports with rats and rabbits which give sufficient information to evaluate this endpoint: (Bayer 1976): The dermal LD50 following a 24-hour occlusive application of the test material to the skin of rats is determined to be 1320 mg/kg bw in females and 655 mg/kg bw in males. The test material was applied as emulsion with the vehicle polyethylene glycole 400. Reduced general condition, difficulties in breathing and cyanotic appearance were the signs of intoxication starting 18 hours post application. Skin irritation was not reported. Deaths occurred within 4 days (males), and 7 days (females), respectively. A section was not performed. In rabbits (2/sex/dose, undissolved substance but warmed to make suitable for dosing, no further information on application procedure, 5 doses, exposure time: 24 hours, observation time: 14 d; Younger Labs. Inc. 1992) the LD50 was 400 mg/kg bw (male: 445 mg/kg bw; female: 355 mg/kg bw). Lethargy for up to three days, increasing weakness, collapse and deaths were reported. At gross autopsy, decedents showed haemorrhagic areas in the lungs, liver-, kidneys- and spleen-discoloration, gastrointestinal inflammation and enlarged gall bladder whereas in survivors the viscera appeared normal. A further investigation on acute dermal toxicity with rabbits yielded a similar result (LD50 = 450 mg/kg bw, 5/dose). The sex of the animals used was not mentioned and a section was not performed (United States Testing Company 1976).

Oral

There are no studies according to the current OECD guideline but there are study reports with rats which give sufficient information to evaluate this endpoint: (Bayer, 1982 a; b) LD50 (Wistar, male) 251 mg/kg bw; LD50 (Wistar, female) 263 mg/kg bw. As signs of intoxication rats displayed reduced general condition, cyanotic appearance, rough fur, sedation, narcosis and females showed paralysis of the hind limb. Death occurred within 3 days. No macroscopic findings were recorded from decedents and from survivors 14 days post application. In another study the LD50 of male and female Sprague-Dawley rats was determined to be 560 mg/kg bw (Younger Labs 1991). As signs of intoxication reduced appetite and reduced activity (in survivors for at least 2-3 days), increasing weakness, ocular discharge, collapse and death were noted. Death occurred within one to four days post application of 1-chloro-2-nitrobenzene, with most death within 2 days. Hemorrhagic lungs, jaundiced liver, darkened kidneys and spleen and gastrointestinal inflammation were seen at gross autopsy of decedents. From survivors 7 days post application, lung congestion and darkened kidneys and spleen were reported. An older study on male Wistar rats (Hoechst 1975) yielded an LD50 of 144 mg/kg bw. As signs of intoxication rats showed imbalance, tremor, rough fur and diarrhea. Section of the rats, that had died, could not be performed because of ongoing autolytic changes.

Justification for classification or non-classification

Based on LC50 of 3.2 mg/L for aerosol/vapour mixture, the substance needs to be classified as Category 3, H331 according to EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 and as Xn, R20 according to EU Directive 67/548/EEC.

The reported oral LD50 values vary between 144 mg/kg bw and 560 mg/kg bw. Using a precautionary principle, based on the lowest LD50, classitication of the test substance as Category 3, H301 according to EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008and T, R25 according to EU Directive 67/548/EEC is suggested.

The reported dermal LD50 values were 655 -1796 mg/kg bw in rats and 355 -450 mg/kg bw in rabbits. Based on these values, classification of the substance as Category 3, H311 is suggested according to EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. Although one of the reported values in rabbits is lower than the limit of 400 mg/kg bw for classification as Harmful according to EU Directive 67/548/EEC, all other values are above the cut-off; therefore classification as Xn, R21 is suggested according to EU Directive 67/548/EEC.