Thiosemicarbazide

Endpoint summary

Description of key information

Acute toxicity: Oral route
The acute oral median lethal dose (LD50) for the test compound thiosemicarbazide is found to be 94.0 mg/kg in deer mice.
Acute toxicity: Inhalation
In accordance with column 2 of Annex VIII of the REACH regulation, inhalation is not the most likely route of exposure considering the vapour pressure and particle size of the chemical thiosemicarbazide and hence this end point was considered for waiver. Thus acute toxicity by the inhaltion route is unlikely.
Acute toxicity: Dermal route
The acute dermal median lethal dose (LD50) for the ) for the test compound thiosemicarbazide is found to be 2200 mg/kg with 95% confidence limit of 1240-2760 mg/Kg.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from publication

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

An acute oral toxicity study was conducted to evaluate toxicity of Thiosemicarbazide in deer mice

GLP compliance:

not specified

Test type:

other: No data available

Limit test:

yes

Species:

mouse

Strain:

other: Peromyscus maniculatus

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Wild-trapped house and deer mice
or domestically bred house mice were used
- Age at study initiation: No data available
- Weight at study initiation: 20 g
- Fasting period before study: No data available
- Housing: No data available
- Diet (e.g. ad libitum): Wheat seeds
- Water (e.g. ad libitum): No data available
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%): No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available

IN-LIFE DATES: From: To: No data available

Route of administration:

oral: gavage

Vehicle:

other: Water, corn oil, or 1.0% carbopol

Details on oral exposure:

No detailed data about vehicle available

Doses:

Dosing details not available

No. of animals per sex per dose:

6 animals

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 3 days
- Frequency of observations and weighing: No data available
- Necropsy of survivors performed: No data available
- Other examinations performed: Mortality was observed

Statistics:

Method of Thompson (1948) and Thompson and Weil (1952)

Sex:

not specified

Dose descriptor:

LD50

Effect level:

94 mg/kg bw

Based on:

test mat.

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) for the test compound thiosemicarbazide is found to be 94.0 mg/kg in deer mice.

Executive summary:

An acute oral toxicity study was conducted to evaluate toxicity ofThiosemicarbazidein deer mice.

 

The chemical was administered by gavage using water, corn oil, or 1.0% carbopol as carriers, followed by 3-days of observations for mortality.

 

The acute oral median lethal dose (LD50) for the test compound thiosemicarbazide is found to be 94.0 mg/kg.

 

According to the publication, the test materialThiosemicarbazide classifies as an acute oral toxicant Category 3 chemical.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

94 mg/kg bw

Quality of whole database:

Data is from peer reviewed publication

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Data is from NTRL report

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Acute dermal toxicity study of Thiosemicarbazide was carried out in New Zealand White rabbit.

GLP compliance:

not specified

Test type:

other: No data

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Marland Breeding Farms, Inc., Hewitt. N.J
- Age at study initiation: No data available
- Weight at study initiation: 2.5-3.5 kg
- Fasting period before study: No data available
- Housing: No data available
- Diet (e.g. ad libitum): No data available
- Water (e.g. ad libitum): No data available
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%): No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available

IN-LIFE DATES: From: To: No data available

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: trunk
- % coverage: 10% of the body surface area
- Type of wrap if used: The test material was held in contact with the skin by an 8-ply gauze wrapping which was moistened with physiological saline. At the 1.4 g/kg dose level, 5.0 ml of saline was used per animal. At the 2.0, 2.8, and 4.0 g/kg dose levels. 10.0 ml of saline was used per animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The exposed area was wiped free of excess test material.
- Time after start of exposure:24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.4, 2.0, 2.8, 4 g/kg (1400, 2000, 2800, 4000mg/kg)
- Concentration (if solution): Not applicable
- Constant volume or concentration used: yes
- For solids, paste formed: no

Additional information:
The hair of each rabbit was clipped from the trunk so as to expose at least 10% of the body surface area. The skin of half the animals (4 males, 4
females) was abraded longitudinally every 2 or 3 centimeters so as to penetrate the stratum corneum but not so deep as to disturb the derma or produce bleeding.

Duration of exposure:

24 hours

Doses:

1.4, 2.0, 2.8, 4 g/kg (1400, 2000, 2800, 4000mg/kg)

No. of animals per sex per dose:

Total 16
1400 mg/Kg: 3 + 1 (additional 1 animal removed during the Day 2 of study due to broken back)
2000 mg/Kg: 4
2800 mg/Kg: 3 + 1 (additional 1 animal removed during the Day 2 of study due to broken back)
4000 mg/Kg: 4

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality and overt signs of effect were made a 0-2 and 4-6 hours and daily thereafter for fourteen days.
Body weights were recorded initially on Day 7 and terminally (Day 14).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, and histopathology.

Statistics:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 200 mg/kg bw

Based on:

test mat.

95% CL:

1 240 - 2 760

Mortality:

Mortality observed at all dose group

Clinical signs:

At the twenty-four hour dermal observation none or very slight erythema accompanied by none or very slight edema was noted in all surviving animals.
Commonly Observed Signs: Nasal Discharge, Piloerection, Motor Activity Decrease, Motor Activity Increase, Ocular Discharge.

Body weight:

The majority of the surviving animals at all dose levels exhibited a net body weight gain. At the 2000, 2800 and 4000 mg/kg dose levels, one animal per dose level showed a net loss of body weight.

Gross pathology:

Gross abnormalities were observed in lungs, eyes, kidney

Mortality:

Dose level (mg/kg)	Mortality
1400	3/3
2000	2/4
2800	2/3
4000	2/4

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethal dose (LD50) for the ) for the test compound thiosemicarbazide is found to be 2200 mg/kg with 95% confidence limit of 1240-2760 mg/Kg.

Executive summary:

Acute dermal toxicity study of Thiosemicarbazide was carried out in New Zealand White rabbit. The rats were treated at a dose level of 1400, 2000, 2800, 4000 mg/kg.

 

The hair of each rabbit was clipped from the trunk so as to expose at least 10% of the body surface area. The test material was held in contact with the skin by an 8-ply gauze wrapping which was moistened with physiological saline.

 

On the basis of observation made, the acute dermal median lethal dose (LD50) for thefor the test compound thiosemicarbazide is found to be 2200 mg/kg with 95% confidence limit of 1240-2760 mg/Kg.

 

In accordance with the CLP classification, the test material does not classify as an acute dermal toxicant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 200 mg/kg bw

Quality of whole database:

Data is from NTRL report

Additional information

Acute toxicity: Oral route

The acute oral median lethal dose (LD50) for the test compound thiosemicarbazide is found to be 94.0 mg/kg in deer mice.

The supporting studies also indicate the test substance to be toxic by oral route.

Acute toxicity: Inhalation

In accordance with column 2 of Annex VIII of the REACH regulation, inhalation is not the most likely route of exposure considering the vapour pressure and particle size of the chemical thiosemicarbazide and hence this end point was considered for waiver. Thus acute toxicity by the inhaltion route is unlikely.

Acute toxicity: Dermal route

The acute dermal median lethal dose (LD50) for the ) for the test compound thiosemicarbazide is found to be 2200 mg/kg with 95% confidence limit of 1240-2760 mg/kg.

Justification for selection of acute toxicity – oral endpoint
The acute oral median lethal dose (LD50) for the test compound thiosemicarbazide is found to be 94.0 mg/kg in deer mice.

Justification for selection of acute toxicity – inhalation endpoint
In accordance with column 2 of Annex VIII of the REACH regulation, inhalation is not the most likely route of exposure considering the vapour pressure and particle size of the chemical thiosemicarbazide and hence this end point was considered for waiver. Thus acute toxicity by the inhaltion route is unlikely.

Justification for selection of acute toxicity – dermal endpoint
The acute dermal median lethal dose (LD50) for the ) for the test compound thiosemicarbazide is found to be 2200 mg/kg with 95% confidence limit of 1240-2760 mg/Kg.