Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

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:
other: comparable to guideline study with acceptable restriction

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
aerosol dispenser: not specified
Remarks:
migrated information: aerosol
Details on test material:
- Name of test material (as cited in study report): Thioharnstoff
- Substance type: 10 % solution in water
- Physical state: Liquid
- Composition of test material, percentage of components: 10 % solution in water

Test animals

Species:
rat
Strain:
other: SPF-reared (Cpb; WU, Wistar random)
Sex:
male/female
Details on test animals 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 (if applicable): Water
- Concentration of test material in vehicle (if applicable): 10 % solution
- Justification of choice of vehicle: Substance was provided by the sponsor as a 10 % solution in water

TEST ATMOSPHERE (if not tabulated)
- 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
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

01)

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:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
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).