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Description of key information

No data on acute toxicity of isolated (anhydrous) sodium dibutyldithiocarbamate are available. However, the substance is solely manufactured and marketed by the registrant as a saturated aqueous solution (ca. % 45.5%-47.5% w/w) and it is not expected that exposure to pure substance is possible. Therefore for the risk assessment it is considered to be acceptable and in fact more relevant to use acute toxicity data on the substance as manufactured. 
The acute oral toxicity studies with sodium dibutyldithiocarbamate as a 46.20% solution in water (SDBC is manufactured as a 45.5-47.5% solution) showed LD50 values between 300 and 2000 mg/kg bw. Calculated for the isolated (anhydrous) substance, this corresponds to LD50 of 141-940 mg/kg bw. In the earlier acute oral toxicity study with rats using 47.5% aqueous solution of SDBC, LD50 of 1430 and 1330 mg/kg bw was established for males and females, respectively; recalculated for the isolated (anhydrous) substance, this corresponds to LD50 of 672 and 625 mg/kg bw for males and females, respectively.
In the acute dermal toxicity study in which 3 female rats were treated with 1000 mg/kg bw sodium dibutyldithiocarbamate as 46.20% solution in water one animals died and two animals were killed at day 8 in extremis, showing that the LD50 value is around or slightly below 1000 mg/kg bw.
No data on acute inhalation toxicity are available; however, in accordance with REACH Annex VIII, the study does not need to be conducted as data on two other routes of exposure are available.

Key value for chemical safety assessment

Additional information

No data on acute toxicity of isolated (anhydrous) sodium dibutyldithiocarbamate are available. However, the substance is solely manufactured and marketed as a saturated aqueous solution (ca.45.5%-47.5% w/w) by the registrant and it is not expected that exposure to pure substance is possible. Therefore for the risk assessment it is considered to be acceptable and in fact more relevant to use acute toxicity data on the substance as manufactured.

Acute oral toxicity of sodium dibutyldithiocarbamate (SDBC) as 46.20% solution was studied in a GLP-compliant guideline study with rats, using acute toxic class method (Notox, 2010a). Two groups of 3 female rats were administered the test substance as received by oral gavage at dose level 2000 mg/kg bw. 1 out of 3 animals of the first set and 3 out of 3 animals of the second set were found dead. Therefore the next dose level of 300 mg/kg bw was administered to the next two groups of 3 females each. All animals survived the treatment. All animals at 2000 mg/kg showed a combination of the following clinical signs on Day 1: lethargy, tremor of the head, general muscle twitching, hunched posture, uncoordinated movements, piloerection and ptosis. The surviving animals at 2000 mg/kg had fully recovered from the symptoms by Day 3. Hunched posture and/or piloerection were also noted among the animals at 300 mg/kg which had fully recovered from the symptoms by Day 3. The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. Upon macroscopic post mortem examination, several reddish or many dark red foci were found in the stomach glandular mucosa of all animals at 2000 mg/kg that were found dead during the study. Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities.

The oral LD50 value of SDBC in its manufactured form in Wistar rats was established to be within the range of 300-2000 mg/kg body weight (for 46.20% solution). The average of 2 dead animals per set of 3 treated animals at 2000 mg/kg was used for the assessment of the LD50 cut-off value. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 1000 mg/kg body weight. Calculated for the isolated (anhydrous) substance, this corresponds to LD50 of 141-940 mg/kg bw. However, the lower limit of this range is meaningless for classification and labeling purposes for the pure substance.

Acute oral toxicity of sodium dibutyldithiocarbamate (SDBC) as 47.5% aqueous solution was also investigated in the study with rats (Sumimoto Chemical Co., 1977), in which 10 male and 10 female rats per dose were administered the test substance at doses 100, 250, 500, 750, 1000, 1500, 2000 and 2500 mg/kg bw. At dose levels of 750 mg/kg bw and above, death occurred mostly 4-16 hours after treatment. No toxic signs were found at the lowest dose level, while at 250 and 500 mg/kg about 1 hour after administration decrease of spontaneous motor activity, piloerection and irregular respiration were developed, and disappeared in 1-2 days. At higher dose levels, also dyspnea, diarrhea and ataxia in hind limbs or whole body were observed. Toxic symptoms of surviving animals disappeared in 4-7 days. Necropsy findings did not reveal any remarkable findings in any test group. Based on the results of the studies LD50 for 47.5% solution of SDBC for males was calculated to be 1430 mg/kg bw (95% CI = 1100 -1860 mg/kg bw) and for females 1330 mg/kg bw (95% CI = 961 -1840 mg/kg bw). Calculated for the isolated (anhydrous) substance, this corresponds to LD50 of 672 and 625 mg/kg bw for males and females, respectively.

Acute dermal toxicity of SDBC as 46.20% solution was studied in a GLP-compliant guideline study with rats (Notox, 2010b). Initially, the test substance was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight (corresponding to 940 mg/kg bw pure substance) for 2-4 hours after which the animals were found dead or killedin extremis. Based on the mortality at 2000 mg/kg, an additional group of 3 females was treated at 1000 mg/kg bw (corresponding to 490 mg/kg bw pure substance) for 24 hours. The animals at 1000 mg/kg were subjected to daily observations and weekly determination of body weight. Macroscopic examination of all animals was performed within 24 hours after death.

One female at 1000 mg/kg was found dead on Day 1 and the remaining two females at 1000 mg/kg were killed in extremison Day 8. Individual animals at 2000 mg/kg showed general muscle twitching or lethargy at two hours post-treatment. The animal at 1000 mg/kg that died on Day 1 showed lethargy, hunched posture, uncoordinated movements, shallow respiration, piloerection, chromodacryorrhoea and ptosis prior to death. Similar clinical signs were observed between Days 1 and 8 for the two animals at 1000 mg/kg that were killedin extremison Day 8. In addition, these two animals showed focal erythema, necrosis, scabs, a wound and/or a thickened area in the treated skin-area between Days 2 and 8.

The two females at 1000 mg/kg that were killedin extremison Day 8 showed changes in bodyweight gain over the first week post-treatment which were within the range expected for rats used in this type of study.

The two females at 1000 mg/kg that were killed in extremison Day 8 showed isolated or several scab formations in the dorso-lumbar region of the skin at macroscopic post mortem examination. No abnormalities were found at macroscopic post mortem examination of the animals at 2000 mg/kg and 1000 mg/kg that were found dead or killedin extremison Day 1. The dermal LD50 value of SDBC in Wistar rats is considered to be around or slightlybelow 1000 mg/kg body weightfor 46.2% aqueous solution of the substance (470 mg/kg bw for pure substance).

The treated skin of the two animals at 1000 mg/kg that were killedin extremisshowed severe effects such as necrosis and a wound and these animals were hypersensitive to touch of the treated skin. These signs suggest that treatment with the test substance caused marked pain and distress due to corrosive or irritating properties of the test substance. According to the test guidelines, further testing of the test substance need not be carried out based on these findings.

The toxic effects are separate from the corrosive effects: Toxic effects are central nervous system related and appear quite rapidly, whereas local effects show up in surviving animals later on. So there is a clear separation between 'systemic' and 'local' effects.

Based on the observations reported in the study report the systemic dermal LD50 is considered to be around 1.000 mg/kg. Therefore, an assumption that the LD50 for dermal exposure is in the range of 200-1000 mg/kg appears to be justified and in line with the precautionary principle.

The classification and labeling of the test substance for acute dermal toxicity is based on the weight of evidence applied to systemic vs. local effects at 1000 mg/kg bw.

Justification for classification or non-classification

Based on LD50 between 300 and 2000 mg/kg bw established in the acute oral toxicity study, according to the Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures, sodium dibutyldithiocarbamate (SDBC) in its manufactured and marketed form (as 45.5 -47.5% aqueous solution) should be classified as Category 4 and should be labeled as H302: Harmful if swallowed. According to the EU Directive 67/548/EEC it should be labeled as harmful if swallowed (Xn, R22).

The study of Sumimoto Chemical Co., 1977, in which the exact value of LD50 was determined for 47.5% solution of sodium dibutyldithiocarbamate rather than a range, allows calculation of the exact value of LD50 (672 and 625 mg/kg bw for males and females) for pure (anhydrous) sodium dibutyldithiocarbamate. Based on this value, according to the Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures, pure (anhydrous) sodium dibutyldithiocarbamate (SDBC) should also be classified as Category 4 and should be labeled as H302: Harmful if swallowed. According to the EU Directive 67/548/EEC it should be labeled as harmful if swallowed (Xn, R22).

Based on the results of acute dermal toxicity study and a careful separation of systemic and local effects and from a precautionary point of view, sodium dibuthyldithiocarbamate (SDBC) in its manufactured and marketed form should be classified according to the Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures as Category 3 and should be labeled as H311: Toxic in contact with skin. According to the EU Directive 67/548/EEC it should be labeled as: toxic in contact with skin (T, R24). Since the bioavailability of the pure substances is considered to be limited by the maximum aqueous concentration of 47% solution, it is considered to be acceptable to apply the same classification for the pure substance as for the 47% solution.