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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009-11-10 to 2009-12-09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: valid without restriction; GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Thiourea
- Molecular formula (if other than submission substance): CH4N2S
- Substance type: White odourless solid
- Physical state: Solid
- Analytical purity: 99.8 %
- Composition of test material, percentage of components: 0.1 % H2O, 0.1 % sulfated ash
- Purity test date: 6.10.2009
- Lot/batch No.: 905423
- Stability under test conditions: Stable
- Storage condition of test material: Room temperature
- Other: Density 1.405 g/cm³ (20 °C), solubility in water 137 g/L (20 °C), pH 5-7 (50 g/l, 20° C), melting range 171-184 °C

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, D-97633 Sulzfeld
- Age at study initiation: Approx. 8 weeks at the time of administration
- Weight at study initiation: Mean 189.7 to 194.0 g
- Fasting period before study: Overnight
- Housing: Individual
- Diet: Ad libitum except fasting period
- Water: Ad libitum
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 12 per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
test substance is soluble in water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 300 mg and 2000 mg per kg body weight
- Amount of vehicle (if gavage): 20 ml per kg body weight
- Justification for choice of vehicle: Thiourea is soluble in water

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: No prior information on the toxicity of the test substance was available; starting dose 300 mg/kg body weight was chosen.
Doses:
300 mg per kg bw, 2000 mg per kg bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0-0.5, 0.5-1, 1-2, 2-4 and 4-6 hours after administration and at least once a day for a total of 2 weeks
- Necropsy of survivors performed: Ces
- Other examinations performed: Clinical signs, body weight
Statistics:
None

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 - < 2 500 mg/kg bw
Based on:
test mat.
Mortality:
1/3 animals died 1 day after the administration (300 mg/kg bw)
1/3 animals died 1 day after the administration (2000 mg/kg bw)
Clinical signs:
All animals were affected; earliest onset shortly after the administration, lasting until death or up to a maximum of 2 d p.a. in the surviving animals:
- Retention of faeces
- Signs of reduced well-being (sedation, apathy, piloerection, hunched posture, closed eyes)
Body weight:
All surviving animals gained weight in both weeks p.a.
Gross pathology:
Abnormal findings in deceased animals: Hydrothorax
Other findings:
None

Any other information on results incl. tables

Table 1: Synopsis of results

Dose mg/kg

Step No.

Animal No.

Numbers of animals

exposed

affected

deceased

300

1

11, 12, 13

3

3

0

300

2

14, 15, 16

3

3

1

2000

3

21, 22, 23

3

3

1

2000

4

24, 25, 26

3

3

0

Table 2: Time of death

Dose mg/kg

Step No.

Animal No.

Time of death (p.a.)

300

1

11, 12, 13

All survived

300

2

14, 15, 16

No. 16 died at day 1

2000

3

21, 22, 23

No. 21 died at day 1

2000

4

24, 25, 26

All survived

Table 3: Body weights and body weight gain

Dose mg/kg

Animal No.

Body weight (g)

Body weight gain (g)

 

 

Before administration

7 days p.a.

14 days p.a.

death

0-7 days p.a.

7-14 days p.a.

300 (1)

11

189

205

213

-

19

8

12

190

219

227

-

29

8

13

193

217

218

-

24

1

Mean

SD

189.7

3.5

213.7

7.6

219.3

7.1

-

24

5

5.7

4

300 (2)

14

199

226

231

-

27

5

15

179

195

209

-

16

14

16

191

a

a

188

a

a

Mean

SD

189.7

10.1

210.5

21.9

220

15.6

-

21.5

7.8

9.5

6.4

2000 (3)

21

192

a

a

195

a

a

22

195

226

229

-

31

3

23

195

226

237

-

31

11

Mean

SD

194.0

1.7

226

0

233

5.7

-

31

0

7

5.7

2000 (4)

24

183

212

242

-

29

30

 

25

202

236

251

-

34

15

 

26

185

219

237

-

34

18

 

Mean

SD

190.0

10.4

222.3

12.3

243.3

7.1

-

32.3

2.9

21

7.9

a)     animal died spontaneously

 

Due to unspecific symptoms in life no specific mode of action of the test substance could be identified. Circulatory failure may have been the cause of death.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 of thiourea in rats was estimated to be between 2000 and 2500 mg/kg body weight.
Executive summary:

In an acute oral toxicity study, groups (12 females) of Crl:CD(SD) rats, (approx. 8 weeks, mean weight 189.7 to 194 g) were given a single oral dose of thiourea in deionised water of 300 and 2000 mg/kg bw. Animals were then observed for 14 days.

Oral LD50 (females) = 2000-2500 mg/kg bw.

Thiourea is practically non-toxic.

All surviving animals gained body weight in both weeks p.a. In each case (300 and 2000 mg/kg bw dose) one of three animals died at the first day p.a. All animals were affected. The findings were retention of faeces and signs of reduced well-being, like sedation, apathy, piloerection, hunched posture or closed eyes. Abnormal findings (hydrothorax) were present only in deceased animals.

This acute oral study is considered to be reliable. It does satisfy the guideline requirement for an acute oral study OECD 423 in the rat.