Disulfiram

Biodegradation in water and sediment: simulation tests

Description of key information

-       DT50 of parent substance in surface water: 0.13 – 0.16 days at 20 °C based on test material analysis (recalculated to 0.28 – 0.34 d at 12°C, aerobic, OECD 309, natural river water).

-       58% of AR mineralization after 62 d (only in sample connected to a catalytic converter, however low recoveries).

 

-       DT50 of parent substance in water/sediment: 0.129 – 0.14 days at 20 °C based on test material analysis (recalculated to 0.27 – 0.3 d at 12°C, aerobic, BBA Part IV Section 5-1, natural water/sediment system)

-       24.42 and 37.67% of AR mineralization after 60 days.

Additional information

No higher tier biodegradation data are available for disulfiram. Several studies investigating the transformation of the analogue substance tetramethylthiuram disulfide (thiram) (CAS No. 137-26-8) in natural water and water/sediment systems are available.

 

In the first study (2015), the degradation and metabolism of the analogue substance was investigated in a simulation study performed according to the OECD Guideline No. 309 and GLP. The degradation of 2.0 and 10.0 µg/L radiolabeled parent substance was investigated in natural river water incubated for 62 d in the dark under aerobic conditions at a temperature of 20 °C. Duplicate vessels were analysed for test substance and degradation products by HPLC. Treated samples were additionally used for the direct measurement of volatile degradation products and were incubated in air flow systems for 62 d. 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. The surface water samples at the 2 µg/L nominal concentration, where volatile radioactivity (14CO2 and 14CS2) was stripped off, showed a decline in total radioactivity in solution over the time course from 87.6% AR at 2 hours to a mean of 15.5% AR after 62 days. Direct volatile radioactivity (14CO2 and 14CS2) accounted for a maximum of 13% AR after 6 days (n.d. after 62 d). The surface water samples at the 10 µg/L nominal concentration, where volatile radioactivity (14CO2 and 14CS2) was stripped off, showed a decline in total radioactivity in solution over the time course from 88.1% AR at 2 hours to a mean of 21.2% AR after 62 days. Direct volatile radioactivity (14CO2 and 14CS2) accounted for a maximum of 10.4% AR after 6 days (5.4% after 62 d). Since the recoveries were low one sample was connected to a catalytic converter in order to improve the system. The mass balance for this sample was 80.4% AR after 62 days and the 14CO2 accounting for 42.4% AR. This suggests that mineralisation to CO2 does occur. The disappearance times (DT50 and DT90) of the analogue substance thiram in surface water were calculated by nonlinear regression and the best fits were based on the Simple First Order kinetic model and the Double First Order in Parallel model. Based on test material analysis, of the analogue sutbstance thiram in surface water treated at 2 µg/L and 10 µg/L degraded rapidly under aerobic conditions with DT50 values 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. CS2 and CO2 were the major degradants. The proposed pathway for the biotransformation of the analogue substance thiram in surface water is that the substance transforms to CS2 directly and to CO2 through unstable degradates.

 

In the second study (2014), the aerobic aquatic metabolism of the analogue substance was investigated in two different water/sediment systems (Abbey Lake and Swiss Lake) according to the OECD guideline 308 and GLP. The test was conducted in flow-through systems, in the dark at 20 ± 2 °C. The water/sediment systems were sampled in duplicates at day 0 and also after 0.04, 0.08, 0.21, 1, 6, 13, 39 and 60 days of incubation. Samples were analysed by LS and by HPLC. In order to confirm the identity of the test substance and metabolites, representative extracts were analysed using LC/MS and HPLC methods. The total recovery for both systems was > 90% at all sampling intervals. DMCS was the major metabolite identified for both systems in the water phase, accounting for a maximum of 36.1 % and 58.8 % of AR 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 (60 d) in Abbey Lake and Swiss Lake, respectively. Sediment-bound residues (non-extractables) for Abbey Lake increased throughout the study, reaching a mean maximum of 61.9 % at day 39 and declined by day 60, whereas non-extractables for Swiss Lake increased permanently reaching a mean maximum of 45.2 % at day 60. The study shows that the analogue substance degrades rapidly to the major metabolite DMCS, converts partly to bound residues, and ultimately mineralises to carbon dioxide. The DT50 values were calculated in a new kinetic assessment in compliance with FOCUS kinetic (2006). The study resulted into the best fit DT50 values based on test material analysis of 0.14 d at 20°C (FOMC kinetics, recalculated to 0.3 d for 12°C) and 0.129 d at °C (SFO kinetics, recalculated to 0.27 d for 12°C) for Abbey Lake and Swiss Lake, respectively. The results and methodology of this study in water/sediment system is of better quality compared to the ones that follow.

 

In a further study (1995), the degradation and metabolism of the analogue substance tetramethylthiuram disulfide (CAS No. 137-26-8) in a natural water/sediment system (river Rhine) was investigated according to the German BBA Guidelines, Part IV, Section 5-1 and GLP conditions. Based on experience from previous studies a lower application rate of 16.26 µg/L was chosen. This study focused on the fate of the very polar radioactive fractions (MW1 to 9) detected by HPLC within the first several minutes of the HPLC-run and therefore the duration of the study was only 10 d. The radiolabeled test compound was incubated under aerobic conditions in 530 mL water and 300 g sediment (wet) at 20 °C for 10 days in the dark. The mean recovery of the radioactivity was 94.9±2.9%. Thiram degraded fast to 0.5% on Day 10 resulting in a DT50 of 0.7 d (1.5 days, recalculated to 12 °C). Within the first days the analogue substance thiram may be hydrolysed to a small extent to CS2, but mineralization started very soon to achieve ca. 25% within 10 days of incubation.

 

In a further study (1992), the biodegradation of the analogue substance in water/sediment systems (from a pond and a river) and aerobic conditions was investigated. The study resulted into half-lives ranging from 0.14 to 1.9 days (0.30 - 4.03 days, recalculated to 12 °C). The recoveries of the test item were between 87.8 – 90.7% AR after 101 d. 14C-thiram was degraded mainly to 14CO2 and 14CS2, which reached 65.8% and 60.8% of the applied RA for river and pond systems, respectively, over the incubation period of 101 days. However, the oxygen concentrations were in several cases very low (1.9 – 4.7 mg/L) and the aerobic conditions were not always met during the study. Therefore, the results of this study should be considered with caution.

 

The aerobic/anaerobic and anaerobic degradation of the analogue substance tetramethylthiuram disulfide in water/sediment was investigated in one more simulation study, resulting in degradation half-life of 4.25 days (9.02 days, recalculated to 12 °C). The main metabolite was CS2, which appeared very fast mainly within the first 14 days and then reached 77.5 % applied radioactivity after 252 days.

In a weight of evidence approach the results from the above described water and sediment studies show that the analogue substance mineralizes in the environment. Anaerobic conditions might favor mineralization of the substance, as shown by the respective study. Due to structural similarity as justified in the read across justification, a similar biodegradation behavior is expected by the target substance disulfiram.