Thiosemicarbazide

Endpoint summary

Description of key information

Weight of evidence: According the several handbooks and the well documented publications the test item has the following LD values: LD50 oral value of 9.2 mg/kg/ for rats (Enviromental data on Organic chemicals) and 13 mg/kg/bw for rats (Merck Index). The ALD of 94 mg/kg for deer mouse (Archives of Environmental Contamination and Toxicology) and LD100 of 20 mg/kg for mice (Sage Journal). The LD50 of 10 mg/kg/bw for dog, LD50 of 20 mg/kg/bw for cat and LD50 of 94 mg/kg/bw for mouse were evaluated according the handbook of Envirnmental data on organic chemicals. In the summary, the different LD50 values are between 9.2 - 20 mg/kg for species (rats,mouse, cat and dog).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Principles of method if other than guideline:

Data from handbook

GLP compliance:

not specified

Remarks:

Handbook data

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 9.2 mg/kg bw

Based on:

not specified

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

The test item has an LD50 oral value of 9.2 mg/kg/bw for rats.

Executive summary:

According the handbook of Enviromental data on Organic chemicals, the test item has an LD50 oral value of 9.2 mg/kg/bw for rats.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Principles of method if other than guideline:

Data from handbook

GLP compliance:

not specified

Remarks:

Handbook data

Species:

rat

Strain:

Brown Norway

Sex:

not specified

Route of administration:

oral: unspecified

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 13 mg/kg bw

Based on:

not specified

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

The test item has an LD50 oral value of 13 mg/kg/bw for rat.

Executive summary:

According the Merck index, the test item has an LD50 oral value of 13 mg/kg/bw for rat.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

No data on method. No data on GLP.

Qualifier:

no guideline followed

Principles of method if other than guideline:

In the present publication of Archives of Environmental Contamination and Toxicology, 6 animals (20 g) were used. Animals were administrated in gradualy dosage scale by gavage using water, corn oil, or 1.0% carbopol as carriers, followed by 3-days of observations for mortality.

GLP compliance:

not specified

Test type:

other: Not specified

Species:

mouse

Strain:

other: Deer mice

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 20 g

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Corn oil, or 1.0% carbopol as carriers

Details on oral exposure:

DOSAGE PREPARATION (if unusual) :Graduated dosage scale.

MAXIMUM DOSE VOLUME APPLIED: Using this single animal per level method, each succeeding treatment was 50% higher than the preceding level and continued until mortality occurred.

No. of animals per sex per dose:

6 animals

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: Three days of observation for mortality.
- Frequency of observations and weighing: Daily
- Necropsy of survivors performed: No specified

Statistics:

The final set of toxicity data was derived from the FR value, the known average weight of individual wheat seeds (50 mg) and the known average weight of each individual deer mouse (20 gm). This calculated value LDfr represented the average amount of chemical, in mg/kg/ day, that was ingested by each animal over the 3-day test period without killing more than 50% of the test animals.

Key result

Sex:

not specified

Dose descriptor:

other: ALD

Effect level:

ca. 94 mg/kg bw

Based on:

not specified

Key result

Sex:

not specified

Dose descriptor:

other: LDfr

Effect level:

ca. 317 mg/kg bw

Based on:

not specified

Remarks on result:

other: Amount of test substance ingested during the FR test which killed or did not kill more than 50% of the test mice

Mortality:

Not specified

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The test item has an acute oral ALD (approximate lethal dose) value of 94 mg/kg to deer mice and the LDfr value was evaluated as 371 mg/kg/day .

Executive summary:

According the present publication,test item was tested for acute oral toxicity to deer mice. Based on the data from repellency test, the food reduction value, FR value, of thiosemicarbazide was evaluated between 74.7-88.0 %. In the test for acute oral toxicity, 6 animals were used. Animals were administrated by gavage using water, corn oil or 1.0 carbopol, followed by 3 days of observations for mortality.The result value of the acute oral toxicity approximate lethal dose ALD is 94 mg/kg and LDfr was evaluated as 317 mg/kg/bw.

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

No data on method. No data on GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

GLP compliance:

not specified

Species:

mouse

Strain:

C57BL

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 18-20 g

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1 ml
Doses were administrated by a syringe with an attached blunted, curved 15-gauge hypodermic needle which was introduced into the esophagus

Control animals:

not specified

Details on study design:

- Frequency of observations and weighing: Closely 4 hours and again at 12- and 24-hour intervals

Key result

Sex:

not specified

Dose descriptor:

LD100

Effect level:

ca. 20 mg/kg bw

Based on:

not specified

Mortality:

Yes - in all animals tested. The great majority of deaths occurred within the first 4 hours.

Interpretation of results:

study cannot be used for classification

Conclusions:

The test item caused fatal convulsions in the dose 20mg/kg/bw.

Executive summary:

According the present study test item was tested for acute oral toxicity in black mice. Animals were observed closely for 4 hours and again at 12 and 24 hour interval.The majority of death occurred within first 4 hours. As the fatal convulsion occurred in all tested animals (810), the LD100 of 20 mg/kg/bw was evaluated.

Reference 5

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Principles of method if other than guideline:

Data from handbook

GLP compliance:

not specified

Remarks:

Handbook data

Species:

cat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 20 mg/kg bw

Based on:

not specified

Interpretation of results:

study cannot be used for classification

Conclusions:

The test item has an LD50 oral value of 20 mg/kg/bw for cats.

Executive summary:

According the handbook of Enviromental data on Organic chemicals, the test item has an LD50 oral value of 20 mg/kg/bw for cats.

Reference 6

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Principles of method if other than guideline:

Data from handbook

GLP compliance:

not specified

Remarks:

Handbook data

Species:

dog

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 10 mg/kg bw

Based on:

not specified

Interpretation of results:

study cannot be used for classification

Conclusions:

The test item has an LD50 oral of 10mg/kg/bw for dog.

Executive summary:

According the handbook of Enviromental data on Organic chemicals, the test item has an LD50 oral value of 10mg/kg/bw for dog.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

9.2 mg/kg bw

Quality of whole database:

Diverse oral-DL50 from handbooks and publications are taken as a weight of evidence. The results of the whole database lead to the same classification of the substance according to CLP regulation, the oral-LD50 is in accordance with the doses used in repeated dose toxicity studies.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Weight of evidence: Several secondary source and publications of Klimisch 3 and 4 (no data on the method) is available for Thiosemicarbazide. This results range from 9.2-20 mg/kg bw in different species (mouse, rat, cat dog). The most sensitive specie seems to be the rat with a LD50 of 9.2 mg/kg. This information leads to the classification of the substance as Acute oral toxicity Category 2, H302 according to CLP Regulation (EC) no. 1272/2008.

Justification for classification or non-classification

Based on the available data, the test item Thiosemicarbazide is classified according to CLP Regulation (EC) no. 1272/2008 as acutely toxic, Category 2 according the Lethal dose LD50 of 9.2 mg/kg/bw rat.