Sodium diethyldithiocarbamate

Endpoint summary

Description of key information

19.4% sodium diethyldithiocarbamate (SDEC)LD50 > 5000 mg/kg bw

Calculation based on the above:

26% aqueous solution SDEC LD50 > 3654 mg/kg bw

Anhydrous SDEC LD50 > 970 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Principles of method if other than guideline:

The test material was administered orally to a group of 10 males and 10 females in one single dose of 10 to 50 mL per kg body weight without dilution.
After treatment the animals were observed for signs of intoxication during a 14-day period, after which autopsies were carried out on the survivors and LD50 value was calculated.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Shizuoka Agricultural Cooperative Association for Experimental Animals, Shizuoka.
- Age at study initiation: 7-week old
- Weight at study initiation: 230-260 g (males); 180-210 g (females)
- Housing: 10 animals per cage
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ± 1°C
- Humidity (%): 60 ± 10% R.H.

Route of administration:

oral: unspecified

Vehicle:

unchanged (no vehicle)

Doses:

1000, 2000, 3000, 4000 and 5000 mg/kg

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes

Statistics:

No data

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Remarks on result:

other: The value is determined for 19.4% solution of the substance; recalculated for pure SDEC and its 26% aqueous solution it corresponds to LD50 > 970 and >3654 mg/kg bw, respectively.

Mortality:

No death observed.

Clinical signs:

other:

Gross pathology:

No remarkable changes were found in any groups of the test animals.

Other findings:

No sex difference was observed in type, intensity and duration of the toxic symptoms.

Conclusions:

The acute oral LD50 of 19.4% aqueous solution SDEC was calculated to be >5000 mg/kg. This corresponds to >970 and >3654 mg/kg bw for the anhydrous SDEC and it 26% aqueous solution.

Executive summary:

In this acute oral toxicity study, 19.4% aqueous solution of SDEC was administered orally to a group of 10 males and 10 female Sprague Dawley rats (per dose) at levels of 1000, 2000, 3000, 4000 and 5000 mg/kg bw. After treatment the animals were observed for signs of intoxication during a 14-day period, after which autopsies were carried out on the survivors and LD50 value was calculated. No mortality was seen. At 30 to­ 60 minutes after administration (at 2000 mg/kg and above), a decrease of spontaneous motor activity, piloerection, and irregular respiration were developed, and disappeared in 1-2 days. In addition to the above toxic symptoms, hind limb ataxia and dyspnea were noted at the two highest dose levels. After 2-3 days all animals looked quite healthy again. No remarkable changes were observed in any groups of the test animals at the autopsy. The acute oral LD50 was calculated to be >5000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

> 970 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

> 3 654

Additional information

As the substance is manufactured and marketed in amounts 1-10 tonne per year, the requirements of REACH Annex VII apply. Therefore only data on acute toxicity by oral route are required for sodium diethyldithiocarbamate (SDEC).

No data on acute toxicity of isolated (anhydrous) sodium diethyldithiocarbamate are available. However, the substance is solely manufactured and marketed as a saturated aqueous solution (ca. 26% w/w) and it is not expected that exposure to pure substance may occur. 

Acute oral toxicity of sodium diethylcarbamate (SDEC) was tested using its 19.4% aqueous solution. LD50 values varying from 3350 and > 5000 mg/kg in rats and from 2000 to 2300 mg/kg in mouse have been reported in three different sources (Sumimoto Chemical Co., Ltd. 1977, Korablev 1965 and Rhone-Poulenc 1973). The most recent study of Sumimoto Chemical Co., Ltd., 1977 has been chosen as a key study. The test material was administered orally to a group of 10 males and 10 females at dose levels 1000, 2000, 3000, 4000 and 5000 mg/kg bw. After treatment the animals were observed for signs of intoxication during a 14-day period. Afterwards the animals were necropsied and LD50 value was calculated. There were no mortalities. At 1000 mg/kg bw, slight motor ataxia was observed. At 2000-3000 mg/kg bw, decrease of spontaneous motor activity, piloerection and irregular respiration were developed 30-60 minutes after administration and disappeared in 1-2 days. At 4000-5000 mg/kg, in addition to the above toxic symptoms, hind limb ataxia and dyspnea were noted. After 2-3 days all animals looked quite healthy again. The LD50 value for both male and female rats was determined to be > 5000 mg/kg bw. 

Potential risks associated with exposure to either the anhydrous form or the 26% aqueous solution of SDEC were assessed based on the data with the 19.4% solution. Acute oral toxicity of sodium diethyldithiocarbamate was tested using 19.4% aqueous solution of the substance in a study with rats, resulting in the LD50 value of > 5000 mg/kg bw. Recalculated for a 26% solution, this corresponds to LD50 > 3654 mg/kg bw. Recalculated for the anhydrous form this results to an LD50 > 970 mg/kg bw.

No data on acute dermal and inhalation toxicity were available for assessment. However, in accordance with Column 2 of REACH Annex VII, these data are not required, as data on oral route are available.

Justification for classification or non-classification

Based on the acute oral LD50 of > 5000 mg/kg bw of 19.4% aqueous solution of sodium diethyldithiocarbamate, resulting in the calculated LD50 > 3654 mg/kg bw for the 26% solution, classification for the substance in its marketed form (as 26% solution) as hazardous to health after acute oral exposure is not warranted following the (CLP) Regulation (EC) No. 1272/2008. However, as safety precaution the 26% solution will be given the same classification for acute oral toxicity as its anhydrous form. The anhydrous is classified as Acute Tox. 4, H302, based on the recalculation of the LD50 results (> 970 mg/kg bw).