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Additional information

In vitro

Ames test

The test item was tested according to the guidelines for bacterial mutagenicity testing published by the major Japanese Regulatory Authorities including MITI, MHW, MOL and MAFF, and is reliable with restrictions as analytical purity of the test substance is not reported. The test substance was tested in 4 Salmonella and 1 E.coli strains at dose levels of 8 -5000 µg/plate. No increase in the number of revertants over background was detected in any strain with and without metabolic activation. No cytotoxic effect was observed. (Safepharm, 1989)

A second study was conducted comparable to the OECD Guideline 471 and is reliable with acceptable restrictions (only 4 strains tested). The test substance was tested in the standard plate test and pre-incubation test with and without metabolic activation in S. typhimurium TA98, TA100, TA1535 and TA1537 at dose levels of 20 -5000 µg/plate. No increase in the number of revertants was detected in any strain with and without metabolic activation. No bacteriotoxic effect was observed.(BASF, 1988).

A third test according to guideline 471 with four Salmonella strains (TA98, 100, 1535, 1537) and E.coli WP2uvrA also showed that the test substance does not induce gene mutations in bacteria (Covance Laboratories, 2005). The assay was conducted in both the presence and absence of S9 mix along with concurrent vehicle and positive controls using three plates per dose. The results of the' initial mutagenicity assay were confirmed in an independent experiment. The doses tested in the initial and confirmatory mutagenicity assays with all tester strains were 33.3,

100, 333, 1000, 3330, and 5000 ug per plate in the presence and absence of S9 mix. No cytotoxicity was observed with either tester strain in the presence of S9 mix, or with WP2uvrA in the absence ofS9 mix, as evidenced by no dose-related decreases in the number of revertants per plate and

normal bacterial background lawns. A reduced bacterial background lawn and a slight decrease in revertants was observed with TA 100 in the absence of S9 mix at 5000 ug per plate. The test article did not cause a positive increase in the mean number of revertants per plate with any of the tester strains either in the presence or absence of metabolic activation.

HPRT test

In a mammalian cell gene mutation assay (HPRT), Chinese Hamster V79 cells cultured in vitro were exposed to N-Vinylcaprolactam dissolved in deionised water, at concentrations of 0, 87.5, 175, 350 700 and 1400 µg/mL in the presence and absence of mammalian metabolic activation (phenobarbital/beta-naphthoflavone induced rat liver S9-mix).

 

N-Vinylcaprolactam was tested up to the limit concentrations of 1400 µg/mL (10 mM). In both independent experiments of this study (with and without S9 mix) the range of the solvent controls was from 2.8 up to 32.4 mutants per 10E6 cells while the range of the groups treated with N-Vinylcaprolactam was from 7.7 up to 31.8 mutants per 10E6 cells. The positive controls did induce the appropriate response. There was no evidence of induced mutant colonies over background. This study satisfies the requirement for Test Guideline OECD 476 for in vitro mutagenicity (mammalian forward gene mutation) data. 

Chromosome aberration test

A chromosome aberration test was performed with the test item at too high concentrations with significant cytotoxic effects. These high concentrations can not be used for the evaluation of effects of the test substance on structural chromosome aberrations and therefore the study was disregarded. However, according to the authors interpretation of the test results, N-Vinylcaprolactam is considered to be clastogenic to CHL cells in vitro. (BASF, 1989)

In a second mammalian cell cytogenetics assay (Chromosome aberration), V79 cell cultures were exposed to N-Vinylcaprolactam dissolved in deionised water at concentrations of 0, 348, 696 and 1392 µg/mL (4h treatment time) with and 0, 348, 696 and 1392 µg/mL (4h treatment time) and 0, 174, 348 and 696 µg/mL (18h and 28h treatment time) without metabolic activation (phenobarbital/beta-naphthoflavone induced rat liver S9-mix).

N-Vinylcaprolactam was tested up to cytotoxic (696 µg/mL) or limit concentrations (1392 µg/mL). Positive controls induced the appropriate response. There was no evidence of chromosome aberrations induced over background.

This study satisfies the requirement for Test Guideline In vitro mammalian cytogenetics Chromosome Aberration Test OECD 473 for in vitro cytogenetic mutagenicity data.

Justification for selection of genetic toxicity endpoint
No study was selected since all studies were negative.

Short description of key information:
The test substance was not mutagenic in a bacterial reverse mutation assay in Salmonella and E.coli (OECD 471, Ames).
The test substance was non-mutagenic in the HPRT assay (OECD 476, In vitro Mammalian Cell Gene Mutation Test).
The test substance was non-clastogenic in the Chromosome Aberration Test (OECD 473, In vitro Mammalian Chromsome Aberration Test).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the key in vitro study results, N-Vinylcaprolactam is not subject to classification as mutagenic according to the criteria of EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.