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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1977/12/13 - 1977/12/30
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: 2c: comparable to guideline study with acceptable restrictions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
4-methylthiosemicarbazide
EC Number:
229-563-2
EC Name:
4-methylthiosemicarbazide
Cas Number:
6610-29-3
Molecular formula:
C2H7N3S
IUPAC Name:
1-amino-3-methylthiourea
Details on test material:
-Source: no data
-Batch n°: 7-25-0155K
-Purity: no data

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Holtzman Co. Madison Wisconsin.
- Age: no data
- Weight at study initiation: 256 to 386 g for males 178 to 250 g for females.
-Housing: five per cage
-Diet : Purina lab chow, ad libitum
-Water : ad libitum
-Fasting : yes, 18-hours

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
MTSC is soluble in water and is dissolved in 50 ml of distilled water.
Doses:
4, 8, 12, 16, 23 and 32 mg/kg.
No. of animals per sex per dose:
10 rats/ sex/dose
Control animals:
no
Details on study design:
EXAMINATIONS:
- Clinical signs: yes
- Mortality: was analyzed by the method of Carrol S. Weil , Biometrics.
- Body weight: were taken on days 0, 7 and 14.
- Necropsy: . Macroscopic examination of the main organs: yes
- Microscopic examination: no

- Post dose observation period: 14 days
Statistics:
none

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
16 mg/kg bw
95% CL:
> 13 - < 20
Sex:
female
Dose descriptor:
LD50
Effect level:
14 mg/kg bw
95% CL:
> 11 - < 17
Mortality:
No mortality was observed at 4 and 8 mg/kg bw in female and male rats.
5/10 males and 8/10 females died at 16 mg/kg bw.
10/10 males and 9/10 females died at 32 mg/kg bw.
Clinical signs:
Signs of toxicity for males were the following: diarrhea, salivation, tremors, increased activity, decreased activity, rough coat, and increased aggressiveness. At the level of 4 and 12 mg/kg, the onset of observable diarrhea was delayed to days 7 and 8 respectively. The level of 8 mg/kg showed no observable signs of toxicity throughout the 14-day period. The increased aggressiveness (seen only at the two highest dose levels) included vicious attacks on other rats in the cage.
During the first four hours following administration of this test material, males and females at the levels of 12, 16, 23 and 32 mg/kg generally reacted according to the following pattern: 1. decreased activity; sluggish 2. squealing; paralytic-like stance 3. increased activity; sometimes increased aggressiveness 4. tetanic convulsions; squealing.
Body weight:
See table of results enclosed
Gross pathology:
Necropsies at the time of death or on day 14 showed: only congested lungs at the two lowest levels; animals also had lung adhesions not believed to be related to the test material. Congested lungs, dark liver, hemorrhagic enteritis and evidence of diarrhea and salivation were seen in the next three dose levels; also one rat in the 32 mg/kg level had lung adhesions and abscesses not necessarily compound related. For females, also at the lowest two levels, only congested lungs were observer at gross necropsy. Other gross finding were: congested lungs, congested or dark liver, dark spleen, evidence of diarrhea and salivation, and hemorrhagic enteritis.

Any other information on results incl. tables

Table 1: MTSC Acute oral rat

 

sex

Dose (mg/kg)

Observa-ions (no. death/ no. exposed)

Signs

Time of death within (hour)

Average body weights (g)

LD50 (95% confidence limits) (mg/kg)

Begin within (hour)

End within (hour)

Day 0

Day 7

Day 14

males

4

0/10

Day 7

Day 8

-

317

343

382

 

16

(13 to 20)

8

0/10

-

-

-

309

345

286

12

5/10

3

3*

3

305

340

374

16

5/10

2

2

18

320

350

388

23

10/10

1

3

4

324

-

-

32

10/10

1

2

18

306

-

-

females

4

0/10

-

-

-

237

266

274

14

(11 to 17)

8

0/10

2

2

-

223

251

258

12

4/10

1

3

18

204

240

257

16

8/10

2

3

18

230

268

278

23

10/10

1

4

18

215

-

-

32

9/10

1

2

18

224

231

266

 

* Signs of toxicity also seen on Day 18

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category II
Remarks:
Migrated information Criteria used for interpretation of results: other: Regulation EC n°1272/2008 (CLP)
Conclusions:
The acute oral LD50 values for male and female rats were 14 and 16 mg/kg bw.
Executive summary:

The purpose of this study was to determine the acute oral toxicity of MTSC when administered to male and female rats.

Rats were exposed by gavage at 4, 8, 16 and 32 mg/kg bw. Mortality, clinical signs, body weight were observed during 14 days after administration. Mortalities were observed at 16 and 32 mg/kg in male and females rats. This study also reported neurobehavioral signs such as salivation, tremors, increased activity, aggressiveness and tetanic convulsions.

Under the conditions of this study, the acute oral LD50 values for male and female rats were 14 and 16 mg/kg bw respectively.