Barbital sodium

Toxicity to reproduction

Administrative data

Endpoint:

reproductive toxicity, other

Type of information:

experimental study

Adequacy of study:

other information

Study period:

1965

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: documentation not sufficient, key information missing

Data source

Reference

Reference Type:

publication

Title:

Effect of barbital sodium on male reproductive organs of albino rats

Author:

D'Souza M. E.-A., Appaswamy Rao M.

Year:

1965

Bibliographic source:

Current Science. No. 20 Oct. 20, 1965, Pg. 584

Materials and methods

Test guideline

Qualifier:

no guideline followed

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Barbital sodium

EC Number:

205-613-9

EC Name:

Barbital sodium

Cas Number:

144-02-5

Molecular formula:

C8H11N2O3.Na

IUPAC Name:

sodium 5,5-diethyl-4,6-dioxo-1,4,5,6-tetrahydropyrimidin-2-olate

Test material form:

not specified

Specific details on test material used for the study:

purchased from Merck

Test animals

Species:

rat

Strain:

Wistar

Details on species / strain selection:

CFTRI inbred Wistar strain

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CFTRI

- Age at study initiation: 40 days old
- Weight at study initiation: Males: 80-90 g
- Fasting period before study: no information
- Housing: no information
- Diet: CFTRI rat feed ad libitum
- Water: ad libitum
- Acclimation period: no information

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 26±1°C
- Humidity (%): no information
- Air changes (per hr): no information
- Photoperiod (hrs dark / hrs light): no information
IN-LIFE DATES: From: To: no information

Administration / exposure

Route of administration:

subcutaneous

Vehicle:

water

Details on exposure:

Barbital sodium in a dose of 15 mg/100 g body weight in 1 mL of distilled water was administered subcutaneously. The controls received 1 mL of distilled water.

Details on mating procedure:

no mating procedure

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

20 days

Frequency of treatment:

twice a day

Doses / concentrations

Dose / conc.:

300 mg/kg bw/day

Remarks:

2 x 150 mg/kg bw

No. of animals per sex per dose:

controls: 10 male rats
barbital sodium treatment: 15 male rats

Control animals:

yes, concurrent no treatment

Examinations

Parental animals: Observations and examinations:

Initial and final body weight was observed. The animals were autopsied without anaesthesia on 21st day of the study.

Postmortem examinations (parental animals):

Male reproductory organs of albino rats were examined. Testes, epididymis, vas deferens, seminal vesicle, ventral prostate, adrenal and thymus were dissected out, weighted to the nearest mg, fixed in Bouin's fluid, sectioned at 10 µm thick and stained in Harris' haematoxylin-eosin, Heidenhain's iron haematoxylin and Mallory's triple stains.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

not examined

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Description (incidence and severity):

Barbital sodium treatment did not affect the body weight.

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Barbital sodium treatment affects the structure of the testis, but not its weight. In the controls, the seminiferous tubules are large, and closely packed with many sperms in their lumen. The seminiferous epithelium exhibits various stages of meiosis and spermiosis. In the barbital sodium-treated animals, the seminiferous tubules shrink considerably and are lined by highly vacuolated degenerating seminiferous epithelium with pycnotic nuclei. The sperms are still present in their lumen. The intertubular spaces are wide with well-developed Leydig cells.

Effect levels (P0)

Dose descriptor:

dose level:

Effect level:

6 000 mg/kg bw (total dose)

Based on:

test mat.

Sex:

male

Basis for effect level:

organ weights and organ / body weight ratios

histopathology: non-neoplastic

Applicant's summary and conclusion

Conclusions:

The barbital sodium treatment causes degeneration of seminiferous epithelium of the testis without affecting the Leydig cells or the accessory organs. The direct toxic effect of barbital sodium on the testis is not proved here.

Executive summary:

The effect of barbital sodium on male reproductive organs was examined in Wistar rats. Barbital sodium in a dose of 15 mg/100 g body weight in 1 mL of distilled water was administered subcutaneously. The controls received 1 mL of distilled water.

Initial and final body weight was examined. The animals were autopsied without anaesthesia on 21st day of the study. Male reproductory organs of albino rats were examined. Testes, epididymis, vas deferens, seminal vesicle, ventral prostate, adrenal and thymus were dissected out, weighted to the nearest mg, fixed in Bouin's fluid, sectioned at 10 µm thick and stained in Harris' haematoxylin-eosin, Heidenhain's iron haematoxylin and Mallory's triple stains.

Barbital sodium treatment did not affect the body weight. In the barbital sodium-treated rats, there was significant increase (P=<0.01) in the weights of seminal vesicles and ventral prostate. There is no change in the weight of adrenals and testes. There is increase in the weight of epididymis and vas deferens, which is not significant. There is decrease in the weight of thymus, which is also not significant.

Barbital sodium treatment affects the structure of the testis, but not its weight. In the controls, the seminiferous tubules are large, and closely packed with many sperms in their lumen. The seminiferous epithelium exhibits various stages of meiosis and spermiosis. In the barbital sodium-treated animals, the seminiferous tubules shrink considerably and are lined by highly vacuolated degenerating seminiferous epithelium with pycnotic nuclei. The sperms are still present in their lumen. The intertubular spaces are wide with well-developed Leydig cells.