p-toluidine

Endpoint summary

Additional information

OECD SIDS 2005

p-Toluidine does not induce point mutations in the vast majority of in-vitro Ames test. In Chinese hamster lung cells p-toluidine is clastogenic in the presence but not in the absence of S9-mix. In vivo, DNA single strand breaks are detected in liver and kidneys of mice using alkaline-elution technique after single intraperitoneal injection of (35 mg/kg bw), therefore it cannot be decided definitely whether the effects occurred due to cytotoxicity or real genotoxic mechanisms.

Overall, there is some indication for clastogenic activity in vitro and some residual suspicion for such action in vivo. In mammalian cell systems (chromosomal aberration) for p-toluidine - but not for m-toluidine - there is some indication for clastogenic activity in vitro

m-Toluidine is not genotoxic because of negative results in bacterial experiments (Salmonella typhimurium TA98, TA100, TA1535, TA 1537, TA1538, G46, C3076, D3052, Escherichia coli WP2 and WP2uvrA with or without an exogenous metabolic activation system) and mammalian in vitro tests according to OECD TG 473 (chromosomal aberration in Chinese hamster lung (CHL) cells) as well as in vivo experiments. The four available in vivo genotoxicity studies could not be adopted as the robust study due to the lack of detailed data. Their types were sister chromatid exchange and inhibition of DNA-synthesis. All results were negative (UNEP, 2003).

Overall conclusion

Both, p- and m-toluidine are not mutagenic to Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and to Escherichia coli strain WP2uvrA with and without addition of rat liver S9 mix.

p-Toluidine was positive in Salmonella typhimurium TA 100 in the presence of hamster liver S9 mix; m-toluidine was inactive under these conditions. In mammalian cell systems (chromosomal aberration) for p-toluidine - but not for m-toluidine - there is some indication for clastogenic activity in vitro

Short description of key information:
OECD-SIDS, 2005

In vitro Studies
In 1996 and 1997 JETOC reported standard Ames-test (preincubation methodology) with p-toluidine using Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and Escherichia coli WP2urA (with and without rat liver S9-mix) and concentrations ranging between 0.0 and 5000 µg/mL with negative results. In 1997 JETOC reported additionally Salmonella typhimurium TA102 and TA104 and Escherichia coli WP2urA/pKM101 (0 - 5000 µg/mL) yielding also negative results. Positive controls were reported to be functional in both publications. Zeiger et al. (1992) did not find mutagenic activity in concentrations ranging between 0 and 3333 µg/plate using Salmonella typhimurium TA97, TA98 and TA1535 without metabolic activation and in the presence of hamster or rat liver S9-mix. Salmonella typhimurium TA100 was tested negative without metabolic activation and in the presence of rat liver S9-mix but was positive in the presence of hamster liver S9-mix. Concurrent positive controls were always functional (Zeiger et al., 1992).
p-Toluidine was tested for clastogenicity in Chinese hamster lung cells in the presence and in the absence of an exogen metabolic activation system. Test concentrations ranged from 12.5 µg/mL up to 50 µg/mL (Ishidate, 1988) and up to 1000 µg/mL (Ishidate, Harnois and Sofuni, 1988), respectively.
Cytotoxicity was determined in preliminary tests with and without S9-mix, in the presence of S9-mix from 25 µg/mL onward (Ishidate, 1988). In both reports induction of chromosomal aberrations were only observed in the presence of S9-mix (from12.5 µg/mL (Ishidate, 1988) and from 500 µg/mL (Ishidate, Harnois and Sofuni, 1988), respectively) but not in the absence of the metabolic activation system.

In vivo Studies
Single intraperitoneal injection of 35 mg/kg bw into male Swiss mice caused significant increases in DNA-single strand breaks in the nuclei of liver and kidney which were prepared 4 hours after application and measured by alkal...

Endpoint Conclusion: No adverse effect observed (negative)