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An ability of sodium dibutyldithiocarbamate (SDBC) in its manufactured form (as 47.5% aqueous solution) to induce gene mutations in bacteria was studied in Ames test with Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 at test concentrations 50, 158, 500, 1580 and 5000 µg per plate (corresponding to 23.75, 75.05, 237.5, 750.5 and 2375 µg per plate for pure (anhydrous) substance), in the presence and absence of metabolic activation (Life Science Research Ltd, 1990). The study was performed in accordance with OECD Guideline 471 and EPA OTS 798.5265 and under GLP. The lowest level of SDBC causing visible thinning of the background lawn of non-revertant cells was 5000 µg/plate. The substance did not induce a statistically significant increase in the number of revertants in any strain, both with and without metabolic activation, indicating that sodium dibutyldithiocarbamate (SDBC) is not mutagenic in Ames test.

No data on the ability of sodium dibutyldithiocarbamate (SDBC) to induce chromosome aberrations or gene mutations in mammalian cells were available for assessment. However, Article 13 of the REACH legislation states that, in case no appropriate animal studies are available for assessment, information should be generated whenever possible by means other than vertebrate animal tests, i.e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across.

Two in vitro guideline studies on gene mutations and chromosome aberrations in mammalian cells were available for the structural analogue of sodium dibutyldithiocarbamate (SDBC), zinc bis(dibutyldithiocarbamate) (ZDBC) (Tinkler, 1998). In the first one, mouse lymphoma L5178Y cells were treated with the test substance at concentration levels up to 15.0 µg/ml, with and without metabolic activation, using DMSO as a vehicle. Although isolated cases of increased mutant colony numbers in test cultures were seen, neither these numbers nor the calculated mutation frequencies showed clear or reproducible increases after any ZDBC treatment. Based on the results of the study, the substance was concluded to be negative in mouse lymphoma assay in vitro.

The ability of zinc bis(dibutyldithiocarbamate) (ZDBC) to induce chromosome aberrations in vitro was studied in human lymphocytes, using DMSO as a vehicle. The cells were harvested 24 and 48 hr after the treatment and the test concentrations were up to 20 µg/ml in experiments without metabolic activation for both harvesting times, up to 50 µg/ml with metabolic activation for 24 hr harvesting time and up to 100 µg/ml with metabolic activation for 48 hr harvesting time. Statistically significant increases in aberrant cell frequency were seen following ZDBC exposure in cells harvested at 24 hr, both with and without S9-mix. These increases were small; in some cases not sufficiently large to exceed the historical solvent control range of the testing laboratory (0-5% excluding gaps). At the 48-hr harvest, the single case of statistically significant increase in the frequency of aberrant cells (ZDBC at 10 µg/ml) was not considered biologically significant. When gap-type aberrations were taken into account, a generally similar pattern of small increases over control values was seen. The reproducibility of the effect seen in the presence of S-9 mix at the 24-hr harvest time was considered evidence of weak clastogenic activity.

An apparent increase in the incidence of polyploidy and endoreduplication in ZDBC-treated cultures was observed, since these effects were not determined quantitatively, no further conclusion can be drawn. Overall, it was concluded that ZDBC showed weak clastogenicity in this assay, at exposure levels which reduced cell division (mitotic index) by some 0-60%.

In addition, two reliable in vivo studies with zinc bis(dibutyldithiocarbamate) (ZDBC), liver UDS test with rats and micronucleous test with mice, were available for assessment (Tinkler, 1998). In the first study, 4 male rats were orally administered the test substance at doses 1000, 1500 and 2000 mg/kg. Two experiments were performed, with rats killed 2 and 16 hours post-dosing. Rats dosed with ZDBC showed no adverse reactions to treatment. Hepatocyte viabilities were generally high among control rats and those dosed at 1000 or 1500 mg/kg bw (73-93%); in rats dosed at 2000 mg/kg bw they appeared slightly lower (69-78%). Statistical analysis revealed no significant differences between test and control groups for nuclear grain count (NG), net nuclear grain count (NNG) or % IR. No individual test animal gave an NNG value greater than 0 on both slide preparations scored for grain counts. It was concluded that ZDBC gave negative results in this in vivo liver UDS assay.

In the micronucleous test, conducted in accordance with OECD Guideline 474 with zinc bis(dibutyldithiocarbamate) (ZDBC), 5 CD-1 mice of each sex received 200, 1000 or 5000 mg/kg of the test substance in corn oil by oral gavage. Post-exopsure period was 24 hours for low and mid-level groups, and 24, 48 and 72 hours for high dose and control test groups. No significant adverse reactions were observed at any dose, there was no evidence of effect in the bone marrow. However, the maximum dose tested was both high and the maximum normally employed in studies of this type. No significant difference in frequency of micronucleated polychromatic erythrocytes between test and vehicle control animals was found at any of the dosages or times. In conclusion, zinc bis(dibutyldithiocarbamate) (ZDBC) was concluded to be negative in in vivo micronucleous test. Overall, based on the results of available in vivo studies, the substance is considered to be non-genotoxic in vivo.

Based on these results, sodium dibutyldithiocarbamate (SDBC) is also concluded to be non-genotoxic in vivo.

Short description of key information:
Sodium dibutyldithiocarbamate (SDBC) in its manufactured form (as 47.5% aqueous solution) was not mutagenic in Ames test with and without metabolic activation up to dose levels of 5000 µg per plate (2375 µg per plate for pure substance). No data on its ability to induce gene mutations and chromosome aberrations in mammalian cells were available; however, based on the read-across with its structural analogue zinc bis(dibutyldithiocarbamate) (ZDBC), which is not genotoxic, SDBC is concluded not to have a genotoxic potential.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the negative results in the Ames test with sodium dibutyldithiocarbamate (SDBC) and negative in vivo studies with a structural analogue, zinc bis(dibutyldithiocarbamate) (ZDBC) the substance should not be classified as genotoxic, according to the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.