Sulfapyridine

Toxicity to reproduction

Administrative data

Endpoint:

toxicity to reproduction

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Scientific research with rational method

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1994

Materials and methods

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sulfasalazine (SASP)

IUPAC Name:

Sulfasalazine (SASP)

Constituent 2

Reference substance name:

Sulfapyridine

EC Number:

205-642-7

EC Name:

Sulfapyridine

Cas Number:

144-83-2

Molecular formula:

C11H11N3O2S

IUPAC Name:

4-amino-N-pyridin-2-ylbenzenesulfonamide

Test material form:

not specified

Details on test material:

No data

Test animals

Species:

rat

Strain:

other: Porton strain

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: The Central Animal House, Panjab University, Chandigarh
- Weight at study initiation: Sexually mature Males: 150-200 g
- Use of restrainers for preventing ingestion (if dermal): yes/no
- Diet: pelleted standard laboratory feed ad libitum
- Water: water ad libitum
- Acclimation period: 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 22°C
- Humidity (%): 40 ± 5%
- Photoperiod: 12 h light, 12 h darkness

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

Sulfasalazine at doses of 125, 250, 500 mg/ kg body weight and sulfapyridine at doses of 60, 120 and 250 mg kg/ body weight suspended in 0.5 mL of corn oil was administered to male rats (six animals in each group) by oral intubation daily for 60 days.

Analytical verification of doses or concentrations:

no

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
125, 250, 500 mg/kg body weight
Basis:
nominal conc.
Sulfasalazine

Doses / concentrations 2

Remarks:

Doses / Concentrations:
60, 120 and 250 mg/kg body weight
Basis:
nominal conc.
sulfapyridine

No. of animals per sex per dose:

6 males per group

Control animals:

yes, concurrent vehicle

Positive control:

No

Examinations

Statistics:

Student’s Mest.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

not specified

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Reproductive function / performance (P0)

Reproductive function: sperm measures:

effects observed, treatment-related

Description (incidence and severity):

sperm motility was reduced significantly at the higher dose levels

Reproductive performance:

not specified

Details on results (P0)

Compared to the controls, sperm motility was reduced significantly at the higher dose levels of sulfasalazine and sulfapyridine. There was no forward progression of spermatozoa, but an increased frequency of abnormal spermatozoa was seen. Significant reductions in sperm reserves were encountered, 46% and 29% in the caput and cauda sperm reserves at 500 mg dose of sulfasalazine. A significant fall (56%) occurred in the cauda of animals given sulfapyridine (250 mg). Total sperm reserves also decreased (28.91% and 34.93%) at the highest dose levels of sulfasalazine and sulfapyridine.
No morphological changes in the histoarchitecture of the testis were discernible and all germinal elements were intact. There was a marginal decrease in the step 19 spermatid: step 7 spermatid ratio in the animals receiving 500 mg of sulfasalazine. No significant changes in tubular diameter or germinal height were observed in sulfasalazine treated animals.
A marginal (3.88%) decrease was seen in germinal height and tubular diameter of the sulfapyridine treated group.

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The study precludes the testis as a site of action of sulfasalazine and sulfapyridine and confirms earlier observations that the effect of these two test substances is post- testicular at the level of the epididymis.

Executive summary:

Sulfasalazine at doses of 125, 250, 500 mg/ kg body weight and sulfapyridine at doses of 60, 120 and 250 mg kg/ body weight suspended in 0.5 mL of corn oil was administered to male rats (six animals in each group) by oral intubation daily for 60 days.

Sperm motility was reduced significantly at the higher dose levels of sulfasalazine and sulfapyridine. An increased frequency of abnormal spermatozoa was seen. Significant reductions in sperm reserves were encountered, 46% and 29% in the caput and cauda sperm reserves at 500 mg dose of sulfasalazine. A significant fall (56%) occurred in the cauda of animals given sulfapyridine (250 mg). Total sperm reserves also decreased (28.91% and 34.93%) at the highest dose levels of sulfasalazine and sulfapyridine. No morphological changes in the histoarchitecture of the testis were discernible and all germinal elements were intact. There was a marginal decrease in the step 19 spermatid: step 7 spermatid ratio in the animals receiving 500 mg of sulfasalazine. No significant changes in tubular diameter or germinal height were observed in sulfasalazine treated animals. A marginal (3.88%) decrease was seen in germinal height and tubular diameter of the sulfapyridine treated group.

Neither of the two test substances, at the dose levels employed, caused major disturbances in the histomorphological profile of the testis as far as the different stages of spermatogenesis are concerned. Histoarchitecture was also retained and comparable with that of the controls.

The two test substances did not affect the earlier stages of spermatogenesis that proceed to form step 19 spermatids.

Thus, this study precluded the testis as a site of action of sulfasalazine and sulfapyridine and confirms earlier observations that the effect of these two test substances was post- testicular at the level of the epididymis.