Registration Dossier

Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted prior to GLP on the registered substance itself. The method is to be considered scientifically reasonable to determine the toxicity of the substance upon ip injection with minor deficiencies in documentation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974
Report Date:
1974

Materials and methods

Principles of method if other than guideline:
The test item was emulsified in polyethylene glycol 400 and injected in various doses into the abdominal cavity of male and female rats. After the application, the animals were observed 14 days long for symptoms of poisoning.
GLP compliance:
no
Remarks:
test conducted prior to GLP implementation
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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:
intraperitoneal
Vehicle:
polyethylene glycol
Remarks:
400
Doses:
5, 10, 25, 50, 100, 200, 250, 300, 400 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:
291 mg/kg bw
Based on:
test mat.
95% CL:
266 - 318
Sex:
female
Dose descriptor:
LD50
Effect level:
253 mg/kg bw
Based on:
test mat.
95% CL:
233 - 274
Mortality:
See 'Any other information on results incl. tables'
Cases of death occurred within the first 24 hours after the application.
Clinical signs:
Symptoms of poisoning:
Symptoms of poisoning in the form of reduced general well-being, difficult breathing, lying on the stomach and cramps began 1 minute to 2 hours after the application with the rats. Lying on the stomach and cramps lasted up to 24 hours. The difficult breathing was to be observed up to 6 days and the general well-being was reduced up to 12 days.
Gross pathology:
When the dead animals were sectioned, the livers, spleens and kidneys exhibited a pale colour. Local bleeding was observed on the surface of the kidneys.

Any other information on results incl. tables

Table 1: Results

Dose / mg/kg

Conc. in vehicle / %

Toxicol. Results after 14d*

Symptoms of Poisoning

Occurrence after Death

Start

End

Male rats

5

0.1

0/0/15

-

-

-

10

0.2

0/15/15

2 h

1 d

-

25

0.5

0/15/15

1 h

3 d

-

50

1.0

0/15/15

9 min

4 d

-

100

2.0

0/15/15

5 min

4 d

-

200

4.0

0/15/15

4 min

7 d

-

250

5.0

3/15/15

3 min

9 d

4 – 24 h

300

6.0

11/15/15

1 min

9 d

3 – 24 h

400

8.0

14/15/15

1 min

10 d

2 – 24 h

Female rats

5

0.1

0/0/15

-

-

-

10

0.2

0/15/15

1 h

2 d

-

25

0.5

0/15/15

50 min

4 d

-

50

1.0

0/15/15

14 min

4 d

-

100

2.0

0/15/15

5 min

6 d

-

200

4.0

1/15/15

5 min

7 d

-

250

5.0

8/15/15

2 min

10 d

4 – 24 h

300

6.0

12/15/15

1 min

12 d

3 – 24 h

400

8.0

15/15/15

1 min

-

2 – 24 h

*1stNumber = Number of dead animals

2ndNumber = Number of animals with symptoms

3rdNumber = Number of animals used

 

Highest dose without finding (m/f): 5 mg/kg

Lowest lethal dose (m): 250 mg/kg

Lowest lethal dose (f): 200 mg/kg

Applicant's summary and conclusion

Conclusions:
The study conducted prior to GLP on the registered substance itself. The method is to be considered scientifically reasonable to determine the toxicity of the substance upon ip injection with minor deficiencies in documentation. Hence, the results can be considered as sufficiently reliable to assess the acute ip toxicity in rats. The determined LD50 values are 291 mg/kg bw (males) resp. 253 mg/kg bw (females). Nevertheless the route of administration is not relevant for humans and less suitable to assess the systemic toxicity as it does not regard a possible degradation in the stomach or other possible metabolism after e.g. accidental ingestion. Furthermore, Regulation (EC) No. 1272/2008 does not foresee the classification of a substance after ip injection, making this study only suitable as supporting information, which is not relevant for classification.
Executive summary:

In an acute intraperitoneal toxicity study, groups of Wistar-II rats (15/sex/dose) were given a single injection into the abdominal cavity of N-Methyl-2-thion-thiazolidine in polyethylene glycol 400 at doses of 5, 10, 25, 50, 100, 200, 250, 300, 400 mg/kg and observed for 14 days. The following ip LD50 were determined:

 

Males = 291 mg/kg bw (95% C.I. 266 - 318)

Females = 253 mg/kg bw (95% C.I. 233 - 274)

 

Symptoms of poisoning were a reduction of the general well-being, difficult breathing and cramps. Death occurred within 24 hours after the application.