thiourea; thiocarbamide

Endpoint summary

Description of key information

Skin:

Five studies are available on skin irritation of thiourea. A study conducted by the CIVO Institute (1983), a study by Korte and Greim (1981) and a publication by Kosova (1970). In all studies thiourea did not induce skin irritation; results from a study on dermal absorption reports slight irritation at a dose of 2.000 mg/kg (TNO 1978).

 

Eye:
Three studies are available on eye irritation of thiourea. Korte and Greim (1981) reported thiourea to be slightly irritating but not subject to classification. In a study by TNO (1983) a 10 % thiourea solution was shown to be not irritating to the eye. The UBA-FB 1982) reports slight, reversible irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

exposure 4h, no reading after 1 h and 48 h; animals are treated on intact and abraded skin

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

abraded

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g undiluted test material

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

12

Details on study design:

TEST SITE
- Area of exposure: 1 inch²
- Type of wrap if used: surgical patch, adhesive tape, impervious material to wrap

SCORING SYSTEM: Draize and CIVO grading

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of the animals with intact skin

Time point:

24 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of the animals with intact skin

Time point:

48 h

Score:

1

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of the animals with intact skin

Time point:

72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 72h

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of the animals with abraded skin

Time point:

24 h

Score:

1.5

Max. score:

2

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: only in one animal very slight scaliness was observed after 72 hours

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

0.2

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

other: one of six animals showed very slight scaliness after 72 hours

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 72h

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Score:

1

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24 h

Score:

1.5

Max. score:

2

Reversibility:

not fully reversible within: 72h

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

48 h

Score:

1

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

72 h

Score:

0.2

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

probability of weak irritation

Other effects:

No other effects were observed

Table 1: Individual and average skin irritation scores of undiluted thiourea

Rabbit number	Intact skin			Rabbit number	Abraded skin
	24 hours		72 hours		24 hours		72 hours
	A	B			A	B
1	1	0	0	7	2	2	1
2	0	0	0	8	2	0	0
3	1	2	0	9	0	0	0
4	1	1	0	10	0	0	0
5	0	0	0	11	1	1	0
6	0	0	0	12	1	0	0
average	1.0		0	average	1.5		0.2

 

Interpretation of results:

GHS criteria not met

Conclusions:

On the basis of the results it is concluded that undiluted thiourea is a very slight to slight primary skin irritant but not relevant for classification.

Executive summary:

In a primary dermal irritation study 12 healthy, adult New Zealand White albino rabbits were dermally exposed to 0.5 g of undiluted thiourea on 1 inch² of the body surface area on the back of the animals. Test sites were covered with an occlusive dressing for 24 hours. Animals were then observed for 72 hours. Irritation was scored by the method of Draize (1944) and the CIVO grading system. After 24 hours dermal effects were observed in seven out of twelve rabbits. These effects consisted of very slight to well-defined erythema with or without very slight or slight oedema. After 72 hours one rabbit treated on the abraded skin showed slight scaliness. No other dermal effects were observed. In this study, thiourea is very slightly to slightly irritatin but not relevant for classification.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

other: Entwurf der Prüfungsvorschrift der OECD "Short term toxicology group, Acute eye irritation/corrosivity" vom 31.12.1979

GLP compliance:

no

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: own breed
- Age at study initiation: no data
- Weight at study initiation: 2.5 to 2.8 kg
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3°C
- Humidity (%): 60% +/- 5%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: the right eye of the animals served as control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 100 mg or 0.1 mL (1 g equates to 1.5 mL)
- Concentration: n.a.

VEHICLE
- Amount applied: no vehicle
- Concentration: n.a.
- Lot/batch no.: n.a.
- Purity: n.a.

Duration of treatment / exposure:

The substance is put into the left eye and kept close for 1 second. The substance was not washed out the eye. The exposure was throughout the observation period.

Observation period (in vivo):

An observation of the animals was done immediatetly after the application and 1, 24, and 72 hours after apllication of the test substance.

Number of animals or in vitro replicates:

6 male Himalayan rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: n.a.

SCORING SYSTEM: The scoring was done after Draize et al. 1944

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

other: There were no individual animal data available.

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

other: There were no individual animal data available.

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not specified

Remarks on result:

other: There were no individual animal data available.

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

not measured/tested

Other effects:

No other effects were reported.

No effects were reported after examination of the eyes following the fluorescein treatment.

Interpretation of results:

GHS criteria not met

Conclusions:

In this study Thiourea is not considered to be irritation to the eye.

Executive summary:

In a primary eye irritation study similar to the OECD guideline 405, 100 mg Thiourea were instilled undiluted without any vehicle into the conjunctival sac of the left eye of 6 male Himalayan rabbits. The eye lids were kept close for 1 second and the application lasted during the whole observation period for 72 hours as the eyes were not washed after application. Animals were observed immediately after application, and 1, 24 and 72 hours after the treatment. Irritation was scored according to Draize et al. (1944). Fluorescein was used to assess the score. The right eye in which 0.1 ml isotonic NaCl were instilled served as control.

A deficiency of the study is that there is no detailled documentation of individual animal data. Due to the fact that thiourea is not considered to be irritating in this eye irritation test and the detailled description of the procedure of the test this fact can be neglected.

The scores were reported as mean. Thiourea is reported to be not irritating to the eye. Nevertheless a with respect to the conjunctiva an irritation score of 1-2 has been reported for swelling and redness.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Thiourea was shown to be non-irritating to the skin and the eyes according to the CLP. A study conducted by the CIVO Institute (1983) showed that undiluted thiourea is a very slight to slight primary skin irritant but scores were below the threshold for classification. In a study by Korte and Greim (1981) no erythema and oedema were observed. In a publication by Kosova (1970) thiourea did not induce skin irritation.

Three studies are available on eye irritation of thiourea. Korte and Greim (1981) reported thiourea to be slighlty irritating to the eyes. In a study by TNO a 10 % thiourea solution was shown to be not irritating to the eye. This study was rated as reliable. Nevertheless it is not adequate as a 10 % solution of Thiourea was tested.

Taken together the results of the studies show that thiourea is slightly irritating to the skin and to the eyes but irritation scores are below the threshold for classification.

Justification for selection of skin irritation / corrosion endpoint:
key study, supported by Korte & Greim, 1981; Kosova 1970; TNO 1978

Justification for selection of eye irritation endpoint:
key study; supported by TNO 1983

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data Thiourea is only very slightly to slightly irritating to the skin with scores below the threshold for classification. The same applies for irritation to the eyes based on the results of appropriate studies. For this reason Thiourea does not need to be classified for skin and eye irritation according to Regulation (EC) No 1272/2008 (CLP), as amended for the seventeenth time in Regulation (EU) No 2021/849.