thiourea; thiocarbamide

Acute Toxicity: oral

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:

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

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

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:

Crj: CD(SD)

Sex:

female

Details on test animals or test system 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

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
- 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

Key result

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:

other: 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,

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

1. 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:

GHS criteria not met

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.