Sulfapyridine

Endpoint summary

Additional information

There was one publication(MICHAEL J. IATROPOULOS,et al.)conducted to evaluate the mutagenic potential of Salicylazosulfapyridine (SASP). This study involved 3 genetic endpoints required information for mutagenicity in vitro (ames test, gene mutation test and chromosome aberration test in vitro).

Based on the results of Ames test, test article showed negative mutagenicityfor Salmonella typhimurium and E. coli.This in vitrostudy was performedwith the Salmonella typhimurium(TA 95,TA 100, TA 1535, WP2p and WP2 uvrA-p) at dose levels from 0.4 to 6250 μg/plateboth in the presence and absence of metabolic activationto check the potential of mutagenicity. No mutagenic effect was found.

 Inanotherin vitro gene mutation test, there was consistent result with that of Ames test. The test concentration of 0.22 to 700 μg/ml, 50 to 500 μg/ml of the test substance were administrated to mice lymphoma L51784. No mutagenic effect was observed. Thus,itcanbeconcludethattest substance dose not induce the gene mutation in the test condition.

However,Salicylazosulfapyridine (SASP)has induced sister chromatid exchanges and micronuclei(MN) in cultured human lymphocytes without S9 mix.In the in vitro test, cultured human lymphocytes were applied with test substance of 2.5 to 100 μg/ml. SASP had induced sister chromatid exchanges and micronuclei (MN) in cultured human lymphocytes in the absence of liver activation enzymes and in B6C3F1 mice (but not in rats) MN in bone marrow and peripheral RBC.

Onein vivostudy wasperformed to assess the chromosome aberration of the test substance to rat bone marrow cells.500 mg/kg was applied orally to male and female rats. The rats were killed after 6, 24 and 48 hours later. No chromosome damaging was found. Thus, we can conclude the test substancecannot cause chromosome aberrations in in vivo in rat bone marrow cells.

According to Chapter R.7a: Endpoint specific guidance, table R.7.7-5, row 9, no further tests are required since available data (negative results from in vitro gene mutation in bacteria and cytogenicity study in vivoand in vitro) is sufficient to conclude that test article is non-mutagenicy.

Based on the information as above, Salicylazosulfapyridine (SASP)can be considered to be non-mutagenic agent. However, it is insufficient to conclude whether sulfapyridine can the gene mutation effect.

Justification for selection of genetic toxicity endpoint
Available data resulted from in vivo animal test should be given more weight due to the high reliability and relevance to human.

Short description of key information:
Based on the information as above, Salicylazosulfapyridine (SASP)can be considered to be non-mutagenic agent. However, it is insufficient to conclude whether sulfapyridine can the gene mutation effect.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available data resulted from the existing studies, Salicylazosulfapyridine (SASP) can not show the gene mutation effect. However, it is inclusive to make the classification for sulfapyridine.