1-chloro-2-nitrobenzene

Endpoint summary

Additional information

Several in vitro genotoxicity studies were performed with 1 -chloro-2-nitrobenzene.

The mutagenic potential of 1 -chloro-2-nitrobenzene was investigated in a bacterial gene mutation assay conducted simliar to OECD-guideline 471. The preincubation assay was performed with Salmonella typhimurium TA98, TA1538, TA1537, TA100, TA1535 and in E. coli strain WP2uvrA both in presence and absence of a metabolic activator (Aroclor1254-induced rat liver S9) at 0, 4, 20, 100, 500, 2500 µg and additionally in TA100 with S9 -Mix 2000 µg 1 -chloro-2 -nitrobenzene per plate.

In the absence of the metabolic activation system, the test compound induced a relatively small but dose dependent increase of revertants with the bacterial strain TA1538 (2.4 times the control value). 1 -chloro-2 -nitrobenzene induced mutations in presence of the metabolic activator in the strains TA98 and TA100 (Hoechst, 1984).

In other reverse gene mutations assays with multiple strains of Salmonella typhimuriumperformed with methods compliant or comparable to the OECD guideline 471, 1 -chloro-2 -nitrobenzene showed also a mutagenic potential (4 times the control value) in TA 100 in the presence of metabolic activation (Herbold, Bayer AG, 1987).

Therefore 1 -chloro-2 -nitrobenezene is a weak mutagen in bacterial test systems

In genetic toxicity tests with mammalian cells 1 -chloro-2 -nitrobenzene showed no mutagenic effects.

O-chloronitrobenzol (ONCB) was tested in vitro to determine whether it would cause chromosomal aberrations in a mammalian cell line derived form Chinese hamster ovary tissue. The cells were incubated with 3 different ONCB concentrations. With rat S9 -mix with 0, 25, 125, 250 ug/ml and without S9-mix with 0, 10, 50, 100 ug/ml ONCB. The cell cycle time for CHO cells is 13 hours. To assess the effect of the test compound at all stages of the cell cycle 3 harvest times (8h, 12h and 21h) were utilised in the presence of metabolic activation. In absence of metabolic activation, where the compound is in contact with the cells for the entire cell cycle, a single harvest time (21h after initiation of treatment) is sufficient. A preliminary toxicity test was carried out to assess the effect of the compound on the mitotic index (top dose level of 100µg/ml without S9 and 250µg/ml top dose level with S9). No concentration of ONCB tested caused any significant increase in the proportion of metaphase figures containing chromosomal aberrations at any harvest time in either the presence or absence of metabolic activation, in either of two analyses. Therefore under these conditions o-chloronitrobenzol has shown no evidence of clastogenic activity in this test system (Brooker, Huntingdon Research Centre, 1988).

Also in HGPRT test which was performed with Chinese hamster V79 lung cells according to OECD guideline 476 1chloro-2 -nitrobenzene does not induce gene mutations (TNO, 1989). An additional HGPRT study with Chinese hamster ovary cells comparable to OECD guideline 476 supports this result (Monsanto, 1984).

Short description of key information:
The weight of evidence suggests that 1-chloro-2-nitrobenzene is not genotoxic

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Ames tests showed positive results, but chromosome aberration tests and HGPRT tests in mammalian cells showed no genotoxic potential of 1 -chloro-2 -nitrobenzene. Therefore 1 -chloro-2 -nitrobenzene has not to be classified according to DSD and GHS.