Disulfiram

PBT assessment

PBT assessment: overall result

Reference

Reference 1

Name:

disulfiram

Type of composition:

boundary composition of the substance

State / form:

solid: particulate/powder

Reference substance:

disulfiram

Reference 2

Name:

disulfiram

Type of composition:

legal entity composition of the substance

State / form:

solid: particulate/powder

Reference substance:

disulfiram

PBT status:

the substance is not PBT / vPvB

Justification:

The PBT Assessment is based on the criteria set out in the “Guidance on information requirements and chemical safety assessment, Chapter R.11: PBT Assessment” (ECHA, 2017).

 

Persistence (P) Assessment

 

Data on Disulfiram (CAS No. 97-77-8) to investigate the persistency of the substance is not complete. However data on the analogue substance tetramethylthiuram disulfide (CAS No. 137-26-8) are available.

 

Hydrolysis, predicted by HYDROWIN v2.00 is expected to contribute slightly to the overall degradation of disulfiram in the environment (DT50 hydrolysis = several days to several weeks as a function of pH).

 

In a prolonged study according to OECD Guideline No. 301 the substance did not reach the biodegradation pass level of 60% within 60 d (58% after 60 d) and is therefore not readily biodegradable. However, the study showed a high extent of mineralization of the substance within 60 d. In fact, a plateau of biodegradation was not reached after 60 days, showing that the substance has further potential for biodegradation. Several higher tier studies investigating the degradation of the analogue substance tetramethylthiuram disulfide (CAS No.137-26-8) in water column, sediment/water and soil compartments were therefore considered in a weight of evidence approach.

 

Under aerobic conditions in soil (OECD 307), the analogue substance tetramethylthiuram disulfide (CAS No.137-26-8) (applied at 12.8 mg/kg soil dw) reached maximum mean mineralization (CO2 and CS2) of 53.58% AR after 30 days, 54.28% AR after 39 days, 38.69% AR after 45 days and 49.58% AR after 120 days in four different soils. Further supporting simulation studies with the analogue substance in soil also resulted into mineralization rates of clearly > 50% of AR within 120 d. Thus, on the basis of the criteria set out in the Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.11: PBT/vPvB assessment (2017), the analogue substance and therefore also the target substance can be considered as not persistent and not very persistent in soil since its presumed mineralization half-life was reached within 120 d (presumed mineralization DT50 < 120 days).

The key water simulation study (OECD 309) with the read across substance tetramethylthiuram disulfide (CAS No.137-26-8) resulted into DT50 values in natural river water, treated with 2 and 10 µg/L, of 0.13 - 0.14 days and 0.14 – 0.16 days (0.28 – 0.3 and 0.3 – 0.34 days, recalculated to 12 °C), respectively. Mean recoveries of samples for the HPLC analysis were low and laid at 84.3% AR (2 µg/L sample) and 64.3% AR (10 µg/L) after 62 days. Direct volatile radioactivity (14CO2 and 14CS2) for the 2 µg/L and 10 µg/L treatments accounted for a maximum of 13% AR after 6 days (n.d. after 62 d) and a maximum of 10.4% AR after 6 days (5.4% after 62 d). Since the recoveries were below the validity criteria of the study, one additional sample was connected to a catalytic converter in order to improve the system and minimize losses. The mass balance for this sample was 80.4% AR after 62 days and the 14CO2 accounted for 42.4% AR. In terms of mineralization, the sum of CO2 and CS2 rate was 58% after 62d. Unfortunately, although these data show that mineralization occurs, it is not possible to know at which duration of the study the 50% of mineralization was met. Moreover, due to methodological deficiencies of the study (low recoveries), the study leaves doubts regarding the persistency behavior of the substance in freshwater and no unequivocal conclusion can be drawn regarding P criterion in water, as set out in the Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.11: PBT/vPvB assessment (2017).

 

The aerobic aquatic metabolism of the test substance in two different water/sediment systems (Abbey Lake and Swiss Lake, OECD 308) was investigated in the key study with the read across substance tetramethylthiuram disulfide (CAS No.137-26-8) and resulted into total recoveries for both systems of > 90% at all sampling intervals. The best fit DT50 values based on test material analysis (calculated in a new kinetic assessment in compliance with FOCUS guideline 2006) were 0.14 d at 20 °C (FOMC kinetics, recalculated to 0.3 d for 12 °C) and 0.129 d at 20°C (SFO kinetics, recalculated to 0.27 d for 12 °C) for Abbey Lake and Swiss Lake, respectively. Mineralisation of the substance (CO2 and CS2) reached 24.42% and 37.67% of AR by the end of the incubation period (60 d) in Abbey Lake and Swiss Lake, respectively. Although the data show that the substance mineralizes, due to the low duration of the study (<120 d), the persistence of the substance in sediment cannot be fully assessed based on the criteria set out in the Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.11: PBT/vPvB assessment (2017).

 

In conclusion the substance is not readily biodegradable but shows potential for mineralization as shown in the prolonged study according to OECD Guideline No. 301 (58% biodegradation after 60 d, no biodegradation plateau was reached). Based on simulation studies available for three compartments (water, sediment and soil) the source substance degrades rapidly in the environment through primary degradation. Mineralization behavior, in contrast, leaves some doubts regarding the P criterion evaluation. Indeed, as it can be clearly concluded that the substance is not P/vP in soil, however, even if primary degradation DT50 leads to a not P/vP conclusion in water and sediment compartments, unequivocal conclusion cannot be reached for these compartments regarding mineralization.

 

Bioaccumulation B

Experimental data determining the bioconcentration factor (BCF) of disulfiram in aquatic organisms is available.

 

One study evaluating the bioaccumulation potential of disulfiram (CAS No. 97-77-8) is available (van Leeuwen, 1986). In this test, the bioaccumulation of radio-labeled disulfiram was evaluated in Rainbow trout (Oncorhynchus mykiss) after an exposure of 96 hours, within a static water regime. The results of the study shows that no steady-state conditions were reached for fish exposed to the test substance, and therefore the BCF value in steady-state could not be determined. In order to determine the BCF value, three biotransformation constants were introduced in the equation, leading to an estimated BCF value of 225 L/Kg. According to Regulation (EC) No. 1907/2006, Annex XIII, 1.1.2, a substance only fulfills the bioaccumulation criterion (B) when BCF values are > 2000 L/kg. Since the BCF value obtained for disulfiram is well below the trigger value of 2000 L/kg, this substance is considered to have a low bioaccumulation potential.

 

Additional information on the bioaccumulation of disulfiram in fish species is available. Estimated bioconcentration (BCF) and bioaccumulation (BAF) factors were calculated using the regression and Arnot-Gobas methods (BCFBAF v3.02 program, Estimation Programs Interface Suite™ for Microsoft® Windows v 4.11., US EPA). The resulting BCF/BAF values are in the same order of magnitude than the one from the experimental study (110-182.8 L/kg), thus supporting the assumption of the expected low bioaccumulation potential of disulfiram.

 

Finally, the log Pow of 3.6 leads to the conclusion that the substance will not bioaccumulate in aquatic organisms. According to the screening criteria stated in the “Guidance on information requirements and chemical safety assessment, chapter R.11: PBT assessment” (ECHA, 2008) substances with log Pow values below 4.5 are not considered as B or vB. Based on these information, disulfiram does not meet the B criterion.

 

Toxicity assessment T

According to the criteria stated in Regulation (EC) 1907/2006, Annex XIII, the toxicity of a certain substance can be assessed based on the available toxicity data on aquatic organisms and mammals. The long-term study performed testing the chronic effects on daphnia species resulted in an EC10 value of 2.64 µg a.i./L. Furthermore, this substance is classified as STOT RE Cat. 2 (H373). Thus, the substance is considered to meet the T criterion.

 

Overall conclusion:

Due to the B criterion not fulfilled and the uncertainties around P criterion, the substance is not considered to be PBT or vPvB.