3-chlorophenyl isocyanate

Endpoint summary

Additional information

In vitro, the test substance was investigated using the Salmonella/ microsome test for point mutagenic effects in doses up to 5000 µg per plate on four Salmonella typhimurium LT2 mutants. These comprised the histidine-auxotrophic strains TA 1535, TA 100, TA 1537 and TA 98.

Doses up to and including 8 µg per plate did not cause any bacteriotoxic effects: Total bacteria counts remained unchanged and no inhibition of growth was observed. At higher doses, the substance had a strong, strain-specific and S9 -dependent bacteriotoxic effect, so that this range could only be used to a limited extent up to 200 µg per plate (without S9 mix) and 1000 µg per plate (with S9 mix) for assessment purposes. Substance precipitation occured at 1000 µg per plate and above.

The positive controls sodium azide, nitrofurantoin, 4 -nitro-1,2 -phenylene diamine and 2 -aminoanthracene had a marked mutagenic effect, as was seen by a biologically relevant increase in mutant colonies compared to the corresponding negative controls.

Evidence of mutagenic activity of the test substance was not seen.

No biologically relevant increase in the mutant count, in comparison with the negative controls, was observed. Therefore the test substance was considered to be non-mutagenic without and with S9 mix in the Salmonella/ microsome test (Herbold, 1990).

In vivo, the micronucleus test was employed to investigate the test substance in male and female mice for a possible clastogenic effect on the chromosomes of bone-marrow erythroblasts. The known clastogen and cytostatic agent, cyclophosphamide, served as control.

The treated animals received a single intraperitoneal administration of either the test substance or cyclophosphamide. The femoral marrow of groups treated with the test substance was prepared 16, 24 and 48 hours after administration. All negative and positive control animals were sacrificed after 24 hours. The doses of the test substance and the positive control, cyclophosphamide, were 50 and 20 mg/kg body weight, respectively.

The animals treated with the test substance showed symptoms of toxicity after administration. Two of fourty animals died before the end of the test due to the acute intraperitoneal toxicity of 50 mg/kg test substance.

There was an altered ratio between polychromatic and normochromatic erythrocytes.

Cyclophosphamide, the positive control, had a clear clastogenic effect, as is shown by the biologicaly relevant increase in polychromatic to normochromatic erythrocytes was not altered.

No indications of a clastogenic effect of the test substance were found after a single intraperitoneal treatment with 50 mg/kg body weight (Herbold, 1991).

Short description of key information:
in vitro:
Ames test: negative
Cytogenetic assay: no data
mammalian cell gene mutation test: no data

in vivo:
Micronucleus test: negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

No classification required.