thiourea; thiocarbamide

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

November 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

reliabel with respect to excretion of thiourea in urine; not adequate to quantify dermal absorption

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The absorption of thiourea was estimated by determination of the amount of unchanged Thiourea excreted in the urine.

GLP compliance:

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

Details on test material:

- Name of test material (as cited in study report): Thioharnstoff
- Substance type: organic
- Physical state: white, crystalline powder

Radiolabelling:

no

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 3.2 kg
- Fasting period before study: the night before treatment the animal had free access to tap water and standard laborytory diet. At the day of the experiment the rabbit was kept in the restraining box for the next 24 h under deprivation of water and feed.
- Housing: restraining box
- Individual metabolism cages: no
- Diet (e.g. ad libitum): see above
- Water (e.g. ad libitum): see above
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Duration of exposure:

24 h

Doses:

- Nominal doses: 25 % (w/v) solution of Thiourea corresponding to 2 g Thiourea/kg body weight
- Dose volume: 26 mL

No. of animals per group:

1

Control animals:

no

Details on study design:

DOSE PREPARATION
- Method for preparation of dose suspensions: Thiourea was disolved in demineralized water in a concentration of 25 %(w/v)
- Method of storage: no data

APPLICATION OF DOSE: 26 ml of the 25 % (w/v) thiourea solution were injected through the polyethylene foil onto the cellulose sheet; the adminsitered volume corresponded to a dose of 2g thiourea/kg body weight

VEHICLE
- Amount(s) applied (volume or weight with unit): 26 mL
- Concentration (if solution): 25 % (w/v)
- Lot/batch no. (if required): no data
- Purity: demineralized water

TEST SITE
- Preparation of test site: Part of the trunk of the animal was freed from hair by the day before the start of the experiment using electric clippers
- Area of exposure: trunk of rabbit
- % coverage: 20 % of total body surface
- Type of cover / wrap if used: cellulose sheet and polyethylene foil
- Time intervals for shavings or clipplings: the hair was removed once, the day before application of the test substance

SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: no

REMOVAL OF TEST SUBSTANCE
- Removal of protecting device: no
- Washing procedures and type of cleansing agent: no
- Time after start of exposure: no

SAMPLE COLLECTION
- Collection of blood: no
- Collection of urine and faeces: the bladder was emptied by means of a catheter
- Collection of expired air: no
- Terminal procedure: no
- Analysis of organs: no

SAMPLE PREPARATION
- Storage procedure: samples which could not be analysed within one hour were stored in a refigerator and analysed within 18 h after catheterization
- Preparation details: The urine samples were analysed either diluted (4 x with demineralized water) or undiluted.

ANALYSIS
- Method type(s) for identification: Technicon AutoAnalyzer technique of J.A. Gerfast (Anal.Biochem. 15 (1969)358); using Grote's reagent

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

not examined

Percutaneous absorption

Key result

Dose:

2g/kg bw

Parameter:

percentage

Absorption:

3.76 %

Remarks on result:

other: 24 h

Remarks:

treatment with aqueous solution of thiourea; absorption extrapolated from 3,76 % excretion in urine

Conversion factor human vs. animal skin:

no data

Any other information on results incl. tables

Table 1: urinary excretion of dermally applied thiourea by a female rabbit

Period	Volume of catheterized urine	Amount of thiourea excreted per time interval	Amount in % of administered dose (6.5 g)	Rate of urinary excretion of unchanged thiourea
0-2 h	26 ml	1 mg	0.02 %	0.4 mg/h
2-4 h	18 ml	10 mg	0.15 %	5 mg/h
4-6 h	9 ml	16 mg	0.25 %	8 mg/h
6-8 h	8 ml	27 mg	0.41 %	13 mg/h
8-14 h	50	95 mg	1.46 %	16 mg/h
14-24 h	96 ml	96 mg	1.48 %	10 mg/h
Total 0-24 h	207 ml	245 mg	3.77 %

 

Applicant's summary and conclusion

Conclusions:

3,76 % of the dermally administered dose of Thiourea was excreted in the urine after 24h.

Executive summary:

In a study on percutaneous absorption of Thiourea one female rabbit (New Zealand White) was used. A 25% (w/v) solution Thiourea, corresponding to 2 g Thiourea/kg body weight was applied to the trunk of the rabbit. The urine was analysed regarding its Thiourea content. It was shown that 3.76 % of the dermally administered Thiourea was excreted unchanged in the urine within 24 h. This represents the minimum amount of urea percutanously absorbed by the rabbit.

There are no data on possible accumulation of Thiourea in the body. Furthermore the study was only conducted with one animal.