Reaction products of diazotized 2-amino-4-(methylsulfonyl)-phenol with 2-(3-Chlorophenyl)-2,4-dihydro-5-methyl-3H-pyrazol-3-one and Methyl-7-hydroxy-1-naphthylcarbamate – and chromium (III) 2:1, salted by ammonium, sodium and acid

Endpoint summary

Description of key information

LD50, oral, RAI rat: 3350 mg/kg bw (equivalent to OECD TG 401, adopted 1981) (CIBA, 1972) 

Additional information

Oral exposure route:

In an acute toxicity study 5 RAI rats per sex and per dose were treated (oral, gavage) with 500, 1000, 3000, 5000, 10000 mg test substance/kg bw (CIBA, 1972; testing laboratory: Pathology/Toxicology, CIBA-Geigy Ltd.). The key study was in accordance with OECD TG 401 (adopted 1981), with the restriction that the observation period was 8 instead of 14 days. In the two lowest dose groups no mortality occured. After treatment with 3000 mg/kg bw 2/5 male and 3/5 females died, while treatment with 5000 mg/kg bw led to 3/5 male and 5/5 female deaths. In the high dose group all animals died within 8 days after treatment. The LD50 was deduced to be 3350 mg/kg bw. Similar clinical signs were seen in dose groups from 3000 mg/kg bw on, that were ataxia, sedation, piloerection. In addition diarrhoea was observed in the 5000 and 10000 mg/kg bw group. Ventricumbency and muscular weakness was observed in the high dose group, only.

A second acute toxicity study is available for Orasol Brown 2GL (CIBA, 1965; testing laboratory: Industrial Biology Lab.). The study was in accordance with OECD TG 401 (adopted 1981), with the restriction that only 5 animals were used and the sex was not specified. Furthermore, no data about clinical signs or other observations were available.

5 Sherman-Wistar rats per dose were treated (oral, gavage) with 400, 800, 1600, 3200, 6400 mg test substance/kg bw. In the two lowest dose groups no mortality occured. After treatment with 1600 mg/kg bw 3/5 animals died, while treatment with 3200 mg/kg bw led to 4/5 deaths. In the high dose group all animals died within 2 days after treatment. The LD50 was deduced to be 1700 mg/kg bw.

In conclusion an LD50 of 3350 mg/kg bw for oral toxicity of the test substance from the key study was chosen as basis for classification and labelling. Although the key study and the supporting study were based on a similar methodological basis, the supporting study had two restrictions compared to the key study. No clinical signs, general observations or sex of the test animals were reported and only 5 instead of 10 animals were used per dose. Thus, the LD50 of the key study more accurately reflects the actual LD50 due to more statistical power, which was achieved by doubling the number of animals. All things considered, the older study shows substantial deficiencies in quality concerning study design and documentation.

 

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for acute oral toxicity under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC.

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute oral toxicity under Regulation (EC) No. 1272/2008, as amended for the second time in Directive (EC 286/2011).