Thiosemicarbazide

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

secondary source

Title:

Initial Submission: Letter from BF Goodrich Submitting Studies with Acetone Thiosemicarbazone Indicating Possible Teratogenic & Neurotoxic Effects

Author:

BF GOODRICH CO

Year:

1992

Bibliographic source:

Company report-OTS0539438, 1992

Materials and methods

Test guideline

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

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

Test material form:

other: Tan powdery crystals

Details on test material:

- Name of test material (as cited in study report): Thiosemicarbazide
- Molecular formula (if other than submission substance): CH5N3S
- Molecular weight (if other than submission substance): 91.14
- Substance type: Organic
- Physical state: Solid
- Analytical purity:99%

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels

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

Any other information on results incl. tables

Mortality:

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

Applicant's summary and conclusion

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.