3-methylthiazolidine-2-thione

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted prior to GLP similar to OECD guideline 401 on the registered substance itself. The method is to be considered scientifically reasonable with minor deficiencies in documentation.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1974

Report date:

1974

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not applicable

GLP compliance:

no

Remarks:

test conducted prior to GLP implementation

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-methylthiazolidine-2-thione

EC Number:

217-614-1

EC Name:

3-methylthiazolidine-2-thione

Cas Number:

1908-87-8

Molecular formula:

C4H7NS2

IUPAC Name:

3-methyl-1,3-thiazolidine-2-thione

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Substance type: pure substance
- Analytical purity: chemically pure

Test animals

Species:

rat

Strain:

other: Wistar-II

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann animal breeder (Kirchborchen, Paderborn district) and Gierlich animal breeder (Bochum)
- Weight at study initiation: 160-210g
- Housing: macrolon cages, Type III
- Diet (e.g. ad libitum): Altromin R Standard diets (Altromin GmbH, Lage/Lippe) ad libitum
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:

oral: gavage

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 1, 2, 5, 10 , 20, 24, 30, 40%
- Amount of vehicle (if gavage): 0.5ml / 100 g bw

Doses:

50, 100, 250, 500, 1000, 1200, 1500, 2000 mg/kg (males; females only 50-1500 mg/kg)

No. of animals per sex per dose:

15

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

The determination of the average lethal dose (LD50) was made using a Probit analysis (FINK und HUND, Arzneimittelforschung 15, 624, 1965).

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

1 218 mg/kg bw

Based on:

test mat.

95% CL:

1 098 - 1 337

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

1 203 mg/kg bw

Based on:

test mat.

95% CL:

1 086 - 1 331

Mortality:

See 'Any other information on results incl. tables'

Clinical signs:

other: Appearance of poisoning: Symptoms of poisoning in the form of reduced general well-being, difficult breathing, reduced reflexes and lying on the stomach began 2 minutes to 24 hours after the application with the rats. The difficult breathing lasted up to

Gross pathology:

The livers of the dead animals exhibited a spotty appearance when sectioned.

Any other information on results incl. tables

Table 1: Results

Dose / mg/kg	Conc. in vehicle / %	Toxicol. Results after 14 d*	Symptoms of poisoning		Occurence of Death after
			Start	End
Male Rats
50	1	0/0/15	-	-	-
100	2	0/15/15	24 h	2 d	-
250	5	0/15/15	24 h	4 d	-
500	10	0/15/15	1 h	9 d	-
1000	20	3/15/15	16 min	9 d	1 – 6 d
1200	24	7/15/15	10 min	10 d	1 – 2 d
1500	30	12/15/15	4 min	12 d	1 – 2 d
2000	40	15/15/15	2 min	-	1 – 2 d
Female Rats
50	1	0/0/15	-	-	-
100	2	0/15/15	24 h	2 d	-
250	5	0/15/15	24 h	3 d	-
500	10	0/15/15	1.5 h	9 d	-
1000	20	3/15/15	20 min	7 d	1 – 2 d
1200	24	7/15/15	15 min	7 d	1 – 2 d
1500	30	13/15/15	15 min	9 d	1 – 2 d

*1^stNumber = Number of dead animals

2^ndNumber = Number of animals with symptoms

3^rdNumber = Number of animals used

 

Highest dose without finding (m/f): 50 mg/kg

Lowest lethal dose (m/f): 1000 mg/kg

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The study was conducted prior to GLP similar to OECD guideline 401 on the registered substance itself. The method is to be considered scientifically reasonable with minor deficiencies in documentation. Hence, the results can be considered as sufficiently reliable to assess the acute oral toxicity in rats. The determined LD50 values are 1218 mg/kg bw (males) resp. 1203 mg/kg bw (females). The results for both sexes are hence consistant and suitable to determine the classification of N-Methyl-2-thion-thiazolidine. According to Regulation (EC) No. 1272/2008, the substance needs to be classified as acute toxic cat. IV.

Executive summary:

In an acute oral toxicity study similar to OECD guideline 401, groups of Wistar-II rats (15/sex/dose) were given a single oral dose N-Methyl-2-thion-thiazolidine in polyethylene glycol 400 at doses of 50, 100, 250, 500, 1000, 1200, 1500, 2000 mg/kg (males; females only 50-1500 mg/kg) and observed for 14 days. The following oral LD50 were determined:

 

Males = 1218 mg/kg bw (95% C.I. 1098 - 1337)

Females = 1203 mg/kg bw (95% C.I. 1086 - 1331)

 

Symptoms of poisoning were a significant reduction of the general well-being, difficult breathing and reduction of the reflexes. Mortality occurred after 8 minutes to 6 days.

 

N-Methyl-2-thion-thiazolidine is of slight toxicity based on the LD50 in females, leading to the classification as acute toxic Cat. IV according to Regulation (EC) No. 1272/2008.