1,3-diethyl-2-thiourea

Specific investigations: other studies

Administrative data

Endpoint:

endocrine system modulation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Data source

Reference

Reference Type:

publication

Title:

Further studies on the chemical nature of compound which inhibit the function of the thyroid gland

Author:

Astwood E.B., Bissell A., Hughes A.M.

Year:

1945

Bibliographic source:

Endocrinology, 37: 456-481.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

DETU was tested in rats for capacity to interfere with the endocrine function of the thyroid gland. Each substance was administered to young rats by mixing it with the drinking water in various concentrations. At the end of ten days the thyroid glands were examined grossly and microscopically for evidence of hypertrophy and hyperplasia, and the relative activities of the compounds were then roughly compared on the basis on the minimal dose required to produce a noticeable effect.

GLP compliance:

not specified

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

1,3-diethyl-2-thiourea

EC Number:

203-308-5

EC Name:

1,3-diethyl-2-thiourea

Cas Number:

105-55-5

Molecular formula:

C5H12N2S

IUPAC Name:

1,3-diethyl-2-thiourea

Details on test material:

no data

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: no data
- Age: "young"
- Weight at study initiation: 40-80 g

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Details on exposure:

- Test substance was mixed with food.
- Thiouracil was used as a standard of reference and was considered to have an activity of 1.

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

10 day(s)

Frequency of treatment:

in the food

Doses / concentrations

Remarks:

Doses / Concentrations:
37 mg/kg of body weight per day
Basis:

No. of animals per sex per dose:

3

Control animals:

other: thiouracile as standard of reference

Details on study design:

Type: other: Thyroidotoxicity
Observation period: no data

Examinations

Examinations:

- Body weight gain: recorded every two days, during the 10-day feeding period (average gain in g per day)
- Total food consumption: globally measured for the 3 animals in order to calculate the average food daily intake per 100g of body weight.
- Organ weight: thyroid glands were weighed at necropsy (in mg per 100g of body weight)
- Biological analysis: thyroid glands of the three rats were pooled and iodine concentration was determined in this pool (in mg per 100 g of fresh tissue).

Results and discussion

Details on results:

CONTROL VALUES (Thiouracile):
. Daily body weight gain = 3.6 g
. Thyroid weight = 8.06 mg per 100 g of body weight
. Thyroid iodine concentration = 73.1 mg per 100 g of wet tissue.

RESULTS WITH TEST SUBSTANCE:
. Daily body weight gain = 4.0 g (not significantly different from control values)
. Thyroid weight = 12.1 mg per 100 g of body weight (increased compared to control)
. Thyroid iodine concentration = 3.3 mg per 100 g of wet tissue. Activity was estimated to 0.4 according to thiouracyl values (thiouracyl activity considered as equal to 1). The test substance was found to possess significant antithyroid activity.

Applicant's summary and conclusion

Conclusions:

An antithyroid activity of DETU was observed in this study.

Executive summary:

DETU was tested in rats for capacity to interfere with the endocrine function of the thyroid gland. Test substance was administered to young rats by mixing it with the food at 37 mg/kg bw. At the end of ten days the thyroid glands were examined grossly and microscopically for evidence of hypertrophy and hyperplasia, and the relative activities of the compounds were then roughly compared on the basis on the minimal dose required to produce a noticeable effect.

The weight of thyroid was increased in rat treated with DETU compared to control rats. Thyroid iodine concentration in treated rats was smaller than concentration of control rats. Therefore, an antithyroid activity of DETU was observed in the rats treated with DETU compared to the control rats (treated with thiouracil).