Registration Dossier

Administrative data

Endpoint:
specific investigations: other studies
Type of information:
experimental study
Adequacy of study:
key study
Study period:
5 April 1978 - 10 April 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report date:
1979

Materials and methods

GLP compliance:
not specified
Type of method:
in vivo
Endpoint addressed:
other: organ toxicity

Test material

Constituent 1
Chemical structure
Reference substance name:
1,3-dihydro-5-methoxy-2H-benzimidazole-2-thione
EC Number:
253-326-2
EC Name:
1,3-dihydro-5-methoxy-2H-benzimidazole-2-thione
Cas Number:
37052-78-1
Molecular formula:
C8H8N2OS
IUPAC Name:
5-methoxy-1,3-dihydro-2H-benzimidazole-2-thione
Specific details on test material used for the study:
Batch numer 70620

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
The rats were during the trial housed 6 to a cage with free access to food and water. The temperature in the animal room was + 21°C
± 1°C and the relative humidity was 55-60 %.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.7 % w/v Methocel®
Details on exposure:
The suspended test compounds were administered orally by use of a gastric tube. The desired dose was given in a volume of 10 ml/kg body mass. The animals were dosed on two separate occasions, between which there was an interval of 5 days
Analytical verification of doses or concentrations:
not specified
Frequency of treatment:
The animals were dosed on two separate occasions, between which there was an interval of 5 days
No. of animals per sex per dose:
6
Control animals:
yes, concurrent vehicle

Examinations

Examinations:
Clinical observations:
Food consumption was recorded at the end of the five day period, and the mean daily consumption per rat was calculated.
Body masses were recorded at the beginning and end of the trial.

Iodide uptake in the thyroid:
One hour after the second occasion of drug administration and 4 hours before sacrifice 178 kBq 125I- in 0.50 ml NaCl (155 mmol/1) was injected intraperitoneally into all the rats. The thyroid glands were placed in vials for gamma counting.

Pathology:
The thymus glands were weighed. No histologic investigation was carried out.

Results and discussion

Details on results:
Food consumption: There was no marked difference in food consumption between the treated and control animals.
Body weight: There was no marked difference between the treated rats and control rats.

Iodide uptake in the thyroid: The amount of radioactivity in the thyroids of treated and control animals, expressed as ratio of the group mean values (treated to controls) and as depression of iodide uptake. There was 93% depression of the iodide uptake in the group treated with metmercazole.

Pathology, Thymus masses: The substance evoked a significant decrease of the thymus mass in the rats.The relative thymus weight was significantly lower in the metmercazole group compared to control (61% of control).

Applicant's summary and conclusion

Conclusions:
Expsure to Metmercazol effects the thymus.
Classification: Specific target organ toxicity, single exposure, category 1. Target organ: Thymus
Executive summary:

The effect of metmercazole on the thymus have been investigated. Metmercazole was given orally using a dose of 72mg/kg. The animals were dosed on two separate occasions with 5 days in between. The last dose was given 5 hours before termination. Thymus weight and iodine uptake in the thymus was measured. Not histological examination of the thymuses was carried out. Exposure to metmercazole significantly decreased the iodine uptake (93% reduction). The relative thymus weight was significantly lower in the metmercazole group compared to control (61% of control).Target organ is the thymus based on the clear effect on weight and the supporting information regard the reduced iodine uptake in the thymus. The mechanism behind the reduced iodine uptake and reduced thymus weight is unknown.