2,2-dimethylpropanethioamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April - Jul 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,2-dimethylpropanethioamide

EC Number:

677-829-5

Cas Number:

630-22-8

Molecular formula:

C5H11NS

IUPAC Name:

2,2-dimethylpropanethioamide

Test material form:

solid: crystalline

Details on test material:

Purity or Composition 100.0 %

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Han

Sex:

female

Details on test animals or test system and environmental conditions:

Female Wistar (RccHan™:WIST) strain rats were supplied by Harlan Laboratories U.K. Ltd., Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals were eight to twelve weeks of age. The bodyweight variation did not exceed ± 20% of the initial mean bodyweight of any previously dosed animal(s).
The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (2014 Teklad Global Rodent diet supplied by Harlan Laboratories U.K. Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose level to confirm the survival of the previously dosed animals.

Doses:

300 mg/kg

No. of animals per sex per dose:

2000 mg/kg

Control animals:

no

Details on study design:

A single animal was treated as follows:
Dose Level Concentration Dose Volume Number of Rats
(mg/kg) (mg/ml) (ml/kg) Female
300 30 10 1

In the absence of toxicity at a dose level of 300 mg/kg, an additional animal was treated as follows:
Dose Level Concentration Dose Volume Number of Rats
(mg/kg) (mg/ml) (ml/kg) Female
2000 200 10 1

Due to mortality and signs of systemic toxicity at a dose level of 2000 mg/kg, an additional group of animals was treated as follows:
Dose Level Concentration Dose Volume Number of Rats
(mg/kg) (mg/ml) (ml/kg) Female
300 30 10 4

A total of five animals were therefore treated at a dose level of 300 mg/kg in the study.

Clinical observations were made ½, 1, 2, and 4 hours after dosing and then daily for up to fourteen days. Morbidity and mortality checks were made twice daily.
Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14 or at death.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Dose Level - 2000 mg/kg
Comatose.
Animal killed for humane reasons due to the occurrence of clinical signs of toxicity that exceeded the moderate severity limit set forth in the UK Home Office Project Licence

Clinical signs:

other: Dose Level - 2000 mg/kg

Gross pathology:

Dose Level - 2000 mg/kg

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Han Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg bodyweight (Globally Harmonised Classification System − Category 4).