Thiosemicarbazide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: based upon the physic-chemical properties and available toxicity data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from authoritative database

Data source

Reference

Reference Type:

publication

Title:

Estimation of toxicokinetic potential of 1-amino-2-thiourea

Author:

U.S. National Library of Medicine

Year:

2015

Bibliographic source:

HSDB, U.S. National Library of Medicine, Toxicological data network, Toxnet

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Evaluating the toxicokinetic potential of the chemical 1-amino-2-thiourea based upon its physico-chemical properties

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Thiosemicarbazide

EC Number:

201-184-7

EC Name:

Thiosemicarbazide

Cas Number:

79-19-6

Molecular formula:

CH5N3S

IUPAC Name:

hydrazinecarbothioamide

Constituent 2

Reference substance name:

1-amino-2-thiourea

IUPAC Name:

1-amino-2-thiourea

Test material form:

other: white crystalline powder or long needles

Details on test material:

CAS No: 79-19-6
Chemical Name: 1-amino-2-thiourea
Nature of chemical: Organic

Radiolabelling:

no

Test animals

Species:

other: Not applicable

Strain:

other: Not applicable

Sex:

not specified

Administration / exposure

Route of administration:

other: Not applicable

Vehicle:

other: Not applicable

Details on exposure:

Not applicable

Duration and frequency of treatment / exposure:

Not applicable

No. of animals per sex per dose / concentration:

Not applicable

Control animals:

no

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

The chemical is likely to be absorbed via the skin, inhalation of particles and the gastrointestinal tract upon oral ingestion.

Main ADME results 2

Type:

distribution

Results:

Considering the high water solubility of the chemical (1X10+4 mg/L at 20 deg C) and low octanol/water partition co-efficient value (log Kow = -1.67 (est), the chemical is likely to be distributed to various parts of the living system via the blood.

Main ADME results 3

Type:

metabolism

Results:

The low octanol/water partition co-efficient will result in reduced bio-availability of the chemical for metabolism within the living system.

Main ADME results 4

Type:

excretion

Results:

Some of the ingested chemical is likely to be excreted out of the living system via urine. BCFs of 3.8-4.2 and <39 in carp (Cyprinus carpio) suggest bioconcentration in aquatic organisms is low.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Not applicable

Details on distribution in tissues:

Not applicable

Details on excretion:

Not applicable

Metabolite characterisation studies

Metabolites identified:

no

Details on metabolites:

Not applicable

Any other information on results incl. tables

1-Amino-2-thiourea is an odorless white crystalline powder or long needles from water. It is an intermediate for pesticides, especially herbicides, and pharmaceuticals; used in certain photographic and dye applications and used as a reagent for the detection of metals. Occupational exposure to 1-amino-2-thiourea may occur through inhalation of dust and dermal contact with this compound at workplaces where 1-amino-2-thiourea is produced or used.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
This report suggests that when ingested, thiosemicarbazide may cause goiter, bone marrow depression, and vomiting. Thiosemicarbazide was evaluated in range-finding study for acute oral toxicity in male CD rats administered single doses (0.5% Methocel dispersion, 10 mL/kg) of 0, 5, and 50 mg/kg by gavage. All rats of a 50 mg/kg dose were dead upon 2-hour observation, having shown no overt signs of toxicity one hour post-gavage. Terminal necropsy disclosed wet and/or tan or red-stained muzzles and darkened livers. No apparent toxicity was reported among rats of a 5 mg/kg dose and the study authors assigned an acute oral LD50 between 1 and 50 mg/kg. In an acute dermal study, prior to death, the decedent rats unanimously exhibited convulsions, tremors, salivation, aggressiveness, and red-stained muzzle.
In humans, this chemical was found to be mutagenic in human HeLa cells. DNA damage was also observed in human tissue.
Thus, considering the above inforamtion and also since no toxico-kinetic data is available for the chemical Thiosemicarbazide (Synonym: 1-amino-2-thiourea), the bio-accumulation potential cannot be judged. Minimum lethal human exposure is unknown.

Executive summary:

This report suggests that when ingested, thiosemicarbazide may cause goiter, bone marrow depression, and vomiting.Thiosemicarbazide was evaluated in range-finding study for acute oral toxicity in male CD rats administered single doses (0.5% Methocel dispersion, 10 mL/kg) of 0, 5, and 50 mg/kg by gavage. All rats of a 50 mg/kg dose were dead upon 2-hour observation, having shown no overt signs of toxicity one hour post-gavage. Terminal necropsy disclosed wet and/or tan or red-stained muzzles and darkened livers. No apparent toxicity was reported among rats of a 5 mg/kg dose and the study authors assigned an acute oral LD50 between 1 and 50 mg/kg. In an acute dermal study, prior to death, the decedent rats unanimously exhibited convulsions, tremors, salivation, aggressiveness, and red-stained muzzle.

In humans, this chemical was found to be mutagenic in human HeLa cells. DNA damage was also observed in human tissue.

Minimum lethal human exposure is unknown.

Thus, considering the above inforamtion and also since no toxico-kinetic data is available for the chemicalThiosemicarbazide (Synonym: 1-amino-2-thiourea), the bio-accumulation potential cannot be judged.