Reaction product of propargyl chloride and sodium bisulfite

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Ames test: not mutagenic

HPRT assay: not mutagenic

MN test: not chromosome damaging nor aneugenic active

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

In vitro

In a GLP study according OECD TG 471 (1992) the mutagenic potential of the test item was assessed in the Ames test. Standard plate and preincubation tests both with and without metabolic activation (Aroclor-induced rat liver S9-mix) were performed using fours strains of Salmonella typhimurium (TA 1535, TA 1537, TA 100, TA 98). In both, standard plate and incubation test doses of 0, 2500, 5000, 10000, 15000 and 20000 µg/pIate were tested. No bacteriotoxic effect was observed. An increase in the number of revertants was not observed both in the standard plate test and in the preincubation test either without S9-mix or after the addition of a metabolizing system (BASF SE 40M0366/914218; 1992).

In a GLP study according OECD TG 476 the test item was assessed for its potency to induce gene mutations at the HPRT locus in CHO cells in vitro. Two independent experiments were performed, both with and without addition of liver S9 mix from phenobarbital- and β-naphthoflavone induced rats (exogenous metabolic activation). According to an initial range-finding cytotoxicity test for the determination of the experimental doses the following concentrations were tested and evaluated for gene mutations:1st Experiment (with and without S9-mix):0; 1000.0; 2000.0; 4000.0; 8000.0; 16000.0 μg/mL and 2nd Experiment (with and without S9-mix):0; 1250.0; 2500.0; 5000.0; 10000.0; 16000.0 μg/mL. Cells were treated with the test item for 4 hours in the presence and absence of S9-mix. Subsequently, cells were cultured for 6-8 days and then selected in 6-thioguanine-containing medium for another week. Colonies were fixed with methanol and stained with Giemsa. The vehicle controls gave mutant frequencies within the range expected. Both positive control substances, ethyl methanesulfonate and 7,12-dimethylbenz[a]-anthracene led to the expected statistically significant increase in the frequencies of forward mutations. In both experiments in the absence and the presence of metabolic activation no cytotoxicity was observed up to the highest concentrations tested for gene mutations. The test substance did not cause any statistically significant or biologically relevant increase in the mutant frequencies either without S9-mix or after the addition of a metabolizing system in two experiments performed independently of each other. Therefore, under the experimental conditions of this study, the test item is not mutagenic in the HPRT assay in the presence or absence of metabolic activation (BASF SE 50M0178/16M236; 2017).

Further Reaction product of propargylchloride and sodium bisulfite was assessed for its potential to induce micronuclei in TK6 cells in vitro (clastogenic or aneugenic activity) according to OECD 487 guideline under GLP condition (BASF SE 2018, 37M0178/16M239). Three valid, independent experiments were carried out with and without the addition of liver S9 mix from phenobarbital- and β-naphthoflavone induced rats (exogenous metabolic activation). According to an initial range-finding cytotoxicity test, the following concentrations were tested. The top concentration was 16000 mg/mL based on the purity of the test substance (water content 68,3g/100g). A sample of at least 1000 cells for each culture was analyzed for micronuclei, i.e. 2000 cells for each test group. The negative controls gave frequencies of micronucleated cells within our historical negative control data range for TK6 cells. Both positive control substances, mitomycin C (MMC) and cyclophosphamide (CPP), led to the expected increase in the number of cells containing micronuclei. No cytotoxicity indicated by reduced cell count or proliferation index (CBPI) was observed up to the highest applied test substance concentration. On the basis of the results of the present study, the test substance did not cause any biologically relevant increase in the number of cells containing micronuclei either without S9 mix or after adding a metabolizing system. Thus, under the experimental conditions described, Reaction product of propargylchloride and sodium bisulfite, is considered not to have a chromosome-damaging (clastogenic) effect nor to induce numerical chromosomal aberrations (aneugenic activity) under in vitro conditions in human TK6 cells in the absence and the presence of metabolic activation.

Summarising all invitro tests following the ITS are negative, hence the substance is judged as not mutagenic and no further test is proposed.

Justification for classification or non-classification

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

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified for genetic toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.