Nitrapyrin

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vivo

Description of key information

Ambiguous results relating to the test items in vitro genetic toxicity are stated in peer reviewed secondary literature sources. In two independent Ames tests, which were not conducted according to current guidelines, a weak positive result was noted for certain strains only in the presence of metabolic activation (Zeiger et al., 1988; Sui et al. 2009). Furthermore, Yano et al. (2008) stated the final outcome of three further Ames tests in which the test item was regarded as non-mutagenic. One of these tests was conducted according to the current guidelines using a set of all required bacterial strains. Moreover, Yano et al. (2008) reported that the test item did not cause a positive result in the in vitro HGPRT test, in the in vitro UDS assay and in two in vivo micronucleus test in mice. Overall, considering all the available results including the negative in vivo test, the test item was regarded as non-genotoxic.

Link to relevant study records

Reference

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Peer reviewed secondary source with dose decriptor provided only.

Principles of method if other than guideline:

Secondary literature source no data about the method was available.

GLP compliance:

not specified

Type of assay:

micronucleus assay

Species:

mouse

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

no data available

Route of administration:

oral: unspecified

Vehicle:

no data available

Details on exposure:

no data available

Duration of treatment / exposure:

no data available

Frequency of treatment:

no data available

Post exposure period:

no data available

Remarks:

Doses / Concentrations:
800 mg/kg
Basis:
no data

No. of animals per sex per dose:

no data available

Positive control(s):

no data available

Tissues and cell types examined:

bone marrow

Details of tissue and slide preparation:

no data available

Evaluation criteria:

no data available

Statistics:

no data available

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

no data available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vivo:

Zeiger et al. (1988) evaluated the mutagenicity of the test item dissolved in DMSO via the preincubation assay using Salmonella typhimurium strains TA97, TA98, TA100, and TA1535. The assay was conducted, with and without metabolic activation using both, Aroclor 1254-induced hamster liver S-9 (HLI) and Aroclor 1254-induced rat liver S-9 (HRI). The test item evaluated at concentrations up to 666 μg/plate. In the absence of metabolic activation, no increase in revertant frequency was observed for all strains tested. An increase in revertants was observed for strains TA 100, TA 97 and TA 98. No increase in the number of revertant was observed for TA 1535 with and without metabolic activation. Consequently, the test item was regarded as mutagenic in the presence of metabolic activation.

Sui et al. (2009) used the test item to compare a new 384 multiwell based high throughput fluctuation Ames test version (Improved FAT) to the standard Ames approach (Ames Test). The test item, dissolved in DMSO, was evaluated in both assays using Salmonella typhimurium strains TA98 and TA100. The assays were conducted, with and without metabolic activation. The test concentrations were not provided. Ambiguously, the test item caused only a weak increase in revertant frequency for strain TA100 in the presence of metabolic activation in "Ames test", while with the "Improved FAT" method only negative results were observed for all strains tested. Hence, for the "Ames test method" the test item was judged to be mutagenic in the presence of metabolic activation only. For the "Improved FAT" method, the test item was regarded as non-mutagenic.

Yano et al. (2008) stated the final outcome of two further ames test in which the test item was regarded as non-mutagenic. One of these tests was conducted according to the current guidelines using a set of all required bacterial strains. Furthermore, Yano et al. (2008) reported that the test item did not cause a positive result in the in vitro HGPRT test, in the in vitro UDS assay and in an in vivo micronucleous test in mice.

Justification for selection of genetic toxicity endpoint
Sole in vivo study available.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under Directive 67/548/EEC. Based on the sum of the available data and according to the harmonised Annex I classification the substance is not considered to be classified for genetic toxicity under Directive 67/548/EEC, as amended for the 31st time in Directive 2009/2/EG.  

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on the sum of the available and according to the harmonised Annex VI classification the substance is not considered to be classified for genetic toxicity under Regulation (EC) No 1272/2008, as amended for the sixth time in Regulation (EC) No 605/2014.