Sodium dibutyldithiocarbamate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium dibutyldithiocarbamate

EC Number:

205-238-0

EC Name:

Sodium dibutyldithiocarbamate

Cas Number:

136-30-1

Molecular formula:

C9H19NS2.Na

IUPAC Name:

sodium (dibutylcarbamothioyl)sulfanide

Details on test material:

- Name of test material (as cited in study report): Sodium dibutyldithiocarbamate (perkacit SDBC liq-w47%)
- Physical state: clear light yellow liquid
- Analytical purity: 46.20% (concentrated aqueous solution)
- Expiration date of the lot/batch: 19 April 2011 (allocated by NOTOX, 1 year after receipt of the test substance)
- Stability under test conditions: stable
- Storage condition of test material: at room temperature in the dark under nitrogen

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 8-12 weeks old
- Weight at study initiation: +/- 20% of the sex mean
- Fasting period before study: overnight
- Housing: group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom)
- Diet: pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.6 – 21.5
- Humidity (%): 38 - 75
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 46.20%
- Amount of vehicle: 1.887 mL/kg bw (2000 mg/kg bw) and 0.283 mL/kg bw (300 mg/kg bw)
- Justification for choice of vehicle: substance as manufactured and marketed

Doses:

300 and 2000 mg/kw bw

No. of animals per sex per dose:

6 females/dose (in two groups of 3 females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed twice daily for mortality. Body weights were determined at Days 1 (pre-administration), 8 and 15 and at death (if found dead after Day 1).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 1000 mg/kg body weight. The value is determined for 46.2% solution of the substance; recalculated for pure substance it corresponds to LD50 of 141-940 mg/kg bw.

Mortality:

In the first group, treated with 2000 mg/kg bw test substance, 1 female died. In the second group administered the same dose all 3 animals died. Deaths occurred at days 1 or 2 post-treatment.

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

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.

Gross pathology:

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. Cannibalism and beginning autolysis were noted for one of these animals at necropsy. Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

This is applicable for the 47% aqueous solution of SDMC.

Executive summary:

No data on acute toxicity of pure SDBC are available. The acute oral toxicity studies with SDBC as a 46% solution in water were used. In an OECD 423, GLP study in rats (Notox 2010), SDBC was given orally by gavage at 300 and 2000 mg/kg bw. In the first group, treated with 2000 mg/kg bw, 1 female died. In the second group administered the same dose all 3 animals died. Deaths occurred at days 1 or 2 post-treatment. Lethargy, tremor of the head, general muscle twitching, hunched posture, uncoordinated movements, piloerection and ptosis were observed. 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. 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. Cannibalism and beginning autolysis were noted for one of these animals at necropsy. Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities. The LD50 values were between 300 and 2000 mg/kg bw. 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. The LD50 cut-off value was considered to be 1000 mg/kg bw. 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.