Registration Dossier

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

Constituent 1
Chemical structure
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 levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 218 mg/kg bw
Based on:
test mat.
95% CL:
1 098 - 1 337
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:
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 3 days. The reduced reflexes and lying on the stomach were to be observed up to 24 hours and the general well-being was reduced up to 12 days. The occurrence of death took place within 24 hours to 6 days after the application.
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

*1stNumber = Number of dead animals

2ndNumber = Number of animals with symptoms

3rdNumber = 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.