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Abstract for RACB20103, RACB20104, RACB20105, RACB20106, and RACB20203

Pubertal Toxicity Study of Vinclozolin, Flutamide and Phenobarbital in Male Sprague Dawley Rats and Methoxychlor, Ethinyl Estradiol and Phenobarbital in Female Sprague Dawley Rats when Administered in Corn Oil by Oral Gavage


  • Vinclozolin (CASRN 50471-44-8)
  • Flutamide (CASRN 13311-84-7)
  • Phenobarbital (CASRN 50-06-6)
  • Methoxychlor (CASRN 72-43-5)
  • Ethinyl Estradiol (CASRN 57-63-6)

Report Date: May 2004


The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings were not evaluated in accordance with the levels of evidence for reproductive or developmental criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.


The purpose of this study was to examine the sensitivity of the pubertal assay to an estrogen (Methoxychlor), anti-androgen (Vinclozolin and Flutamide), and a thyroid-active agent (Phenobarbital) in intact juvenile/peripubertal male and female rats. Fifty-five time-mated female (F0) Sprague Dawley Rats were received from Charles River Laboratories and allowed to litter at TherImmune. After weaning on Postnatal Day (PND) 21, 135 F1 males and 135 F1 females were assigned to male and female cohort studies, respectively. The F1 males were dosed with corn oil (0 mg/kg), or the test articles: Phenobarbital (25, 50, and 100 mg/kg/day), Vinclozolin (10, 30, and 100 mg/kg/day), or Flutamide (25 and 50 mg/kg/day), once daily via oral gavage from PND 23-53/54. The F1 females were dosed with corn oil (0 mg/kg), or the test articles: Ethinyl Estradiol (0.0025 and 0.0050 mg/kg/day), Methoxychlor (12.5, 25, and 50 mg/kg/day), or Phenobarbital (25, 50 and 100 mg/kg/day), once daily via oral gavage from PND 22-42/43.

Parameters evaluated include mortality and clinical observations, body weights, day of preputial separation, day of vaginal opening, estrous cyclicity, gross pathology, organ weights and histopathology.

Test Article Concentration
Age of Preputial
Organ Weights Histology
Phenobarbital 25 - - ⇑liver -
  50 - - ⇑liver -
  100 ⇑liver
Vinclozolin 10 - - -
  30 - ⇓repro. organs
⇑ testis,
  100 - ⇓repro. organs
⇑ testis
Flutamide 25 - ⇓repro. organs
⇑ testis,
⇓ kidneys
  50 - ⇓repro. organs
⇑ testis,
⇓ kidneys,
⇑adrenal glands
testis lesions

- = no effect; ⇑ = higher than control means; ⇓ = lower than control means
repro. = reproductive

Test Article Concentration
Age at Vaginal
Age at First
Estrous Cycles
Phenobarbital 25 - - - ⇑liver
⇑ adrenal
  50 - - - ⇑ liver
⇑ adrenal
  100 - - ⇑ liver
⇑ adrenal
⇓ thyroid
Methoxychlor 12.5 - -
  25 X -
  50 X ⇓ liver
⇓ ovary
⇓ pituitary
0.0025 - - - ⇑adrenal
  0.005 X ⇑adrenal

- = no effect; ⇑ = higher than control means; ⇓ = lower than control means; X =present
repro. = reproductive

The lowest observable effect level (LOEL) for an endocrine effect was 25 mg/kg/day for Flutamide, 10 mg/kg/day for Vinclozolin, 100 mg/kg/day for Phenobarbital, 12.5 mg/kg/day for Methoxychlor, and 0.005 mg/kg/day for Ethinyl Estradiol.

NTIS # PB2004-105924