4-methylthiosemicarbazide

Acute Toxicity: oral

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

Test material information

Constituent 1

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 levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

16 mg/kg bw

95% CL:

> 13 - < 20

Effect levels 2

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:

other: 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

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.