thiourea; thiocarbamide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979-10-17 to 1979-10-31

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Thiourea

EC Number:

200-543-5

EC Name:

Thiourea

Cas Number:

62-56-6

Molecular formula:

CH4N2S

IUPAC Name:

thiourea

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

other: SPF-reared (Cpb; WU, Wistar random)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Central insitute for the breeding of laboratory animals TNO, Zeist, The Netherlands
- Age at study initiation: No data
- Weight at study initiation: females mean weight: 142 g; males mean weight: 175 g
- Fasting period before study: No data
- Housing: Groupwise (5 per cage)
- Diet: Ad libitum (during exposure no access to food)
- Water: Ad libitum(during exposure no access to water)
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 1°C
- Humidity (%): 50-60%

Administration / exposure

Route of administration:

other: dispersion of 10 % thiourea to a fine mist

Type of inhalation exposure:

whole body

Vehicle:

not specified

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 1.5 m³
- Method of holding animals in test chamber: Individually in wire-screen cages to prevent crowding and minimize filtration of the inspired air by animals fur
- Source and rate of air: Airflow rate of nebulizer: 0.9 m³/h; the mist was passed through the exposure chamber with a total airflow of 1.1 m³/h
- System of generating particulates/aerosols: Stainless steel/glass aerodynamic nozzle nebulizer
- Method of particle size determination: Particle Size determination with cascade Impactor (aerosol diameter < 3.3 µm)

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetrically by passing a measured quantity of the test atmosphere through a Cambridge glass fibre filter;
- Samples taken from breathing zone: No

VEHICLE
- Composition of vehicle: Water
- Concentration of test material in vehicle: 10 % solution
- Justification of choice of vehicle: Substance was provided by the sponsor as a 10 % solution in water

TEST ATMOSPHERE
- Particle size distribution: 100 % of particle counts have a diameter of less than 3.3 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): No data

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetrically; Cambridge glass fibre filter

Duration of exposure:

ca. 4 h

Concentrations:

10 % solution

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Frequently (body weight determination at day 0, 1, 2, 4, 7 and 14)
- Necropsy of survivors performed: No
- Other examinations performed: Clinical signs, body weight

Statistics:

No statistics

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 195 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: highest attainable concentration

Mortality:

One male died on the first day of the observation period.

Clinical signs:

other: During the first 30 min restlessness; thereafter motionless, eyes half-closed; after exposure the rats were slow in their movement, but otherwise looked normal.

Body weight:

During first day both males and females lost body weight; thereafter body weight gain again.

Gross pathology:

None

Other findings:

None

Any other information on results incl. tables

Table 1: Individual and mean body weights (g) of rats exposed to an aerosol of a 10 % solution of “Thioharnstoff” in rats

Animal code earmarks	0^1)	1	2	4	7	14
Males
Z	176	-	-	-	-	-
R1	176	167	171	183	190	226
R2	166	156	163	172	182	208
L1	180	173	176	186	196	218
L2	176	169	172	182	198	232
Mean body weight	175	166	171	181	192	221
Females
Z	140	130	129	--^2)	140	149
R1	148	141	143	--	152	163
R2	130	126	130	--	139	152
L1	142	133	132	--	144	156
L2	149	143	143	--	151	161
Mean body weight	142	135	135	--	145	156

1)     Day 0: day of exposure

2)     data omitted because unreliable

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The 4 h LC50 of thiourea in rats was higher than 195 mg/m³ air. Higher concentrations could not be attained.

Executive summary:

In an acute inhalation toxicity study one dose group (5 males, 5 females) of SPF-reared rats (Cpb; WU, Wistar random) were exposed (whole body) to a fine mist of 10 % thiourea in water for 4 hours. Animals were then observed for 14 days.

One male died on the first day of the observation period. During the first 30 min restlessness was observed. Thereafter the rats were motionless and their eyes were half-closed. After the exposure the rats were slow in their movement, but otherwise looked normal.

The LC₅₀ was determined to be higher than 195 mg/m³ (maximum attainable concentration).