       Document 0936
 DOCN  M9620936
 TI    Short-term male reproductive toxicity study with sulfasalazine in the
       rat.
 DT    9602
 AU    Hoyt JA; Fisher LF; Swisher DK; Toxicology Research Laboratories, Eli
       Lilly and Company,; Greenfield, IN 46140, USA.
 SO    Reprod Toxicol. 1995 May-Jun;9(3):315-26. Unique Identifier : AIDSLINE
       MED/96089907
 AB    Sulfasalazine (2-hydroxy-5-[[4-[(2-pyridinylamino) sulfonyl]
       phenyl]azo]benzoic acid; SASP) was administered to rats in a short-term
       male reproductive toxicity study to further examine the utility of this
       grouping of techniques and to generate reference data with a substance
       that is known to cause reversible infertility in men. Adult male CD rats
       (10/group) were orally administered 0, 150, 300, or 600 mg SASP/kg body
       weight in divided doses for 14 d followed by a 2-week period without
       treatment. Males were killed on test day (TD) 15 or 29. At each time
       point, the reproductive system was evaluated by comparing testicular and
       epididymal weights, DNA ploidy distributions of testicular cell
       suspensions, testicular and epididymal histopathology, and epididymal
       sperm concentrations, motion, morphology, and breakage. Adding time as a
       factor in the protocol aids in distinguishing testicular from
       posttesticular effects. Changes in sperm quality after 2 weeks of test
       article administration (TD 15) predominantly reflect effects that
       occurred after the sperm entered the epididymis, while testicular
       effects predominated on TD 29. Beginning on TD 14, males to be killed on
       TD 29 were cohabited with untreated females (1:2). Females were killed
       at midgestation and examined for pregnancy status. Body weight gain was
       depressed in all SASP groups during the first 3 d of test article
       administration. Food consumption was depressed at the 300- and 600-mg/kg
       dose levels. No changes were seen in testicular weight, but epididymal
       weight was depressed at the 600-mg/kg dose level. DNA ploidy
       distributions determined by flow cytometry did not indicate that the
       kinetics of spermatogenesis were disturbed. However, alterations in
       sperm release, which have not previously been reported, were seen at all
       SASP dose levels. On TD 29, the percentage of progressively motile sperm
       was depressed and beat/cross frequency was increased at the 600-mg/kg
       dose level. No changes were observed in sperm morphology or breakage.
       Fertility was slightly depressed at the 600-mg/kg dose level. In this
       study, testicular histopathology provided the most sensitive endpoint
       for reproductive toxicity. The impairment of fertility immediately after
       treatment was stopped, when no changes were apparent in sperm release or
       sperm motion, suggested that decreased sperm concentrations and altered
       motility, while contributory, may not be the primary causes of
       SASP-mediated infertility.
 DE    Animal  DNA/DRUG EFFECTS  Fertility/*DRUG EFFECTS  Flow Cytometry  Male
       Rats  Rats, Sprague-Dawley  Sperm Count/DRUG EFFECTS  Sperm
       Motility/DRUG EFFECTS  Sulfasalazine/*TOXICITY  Testis/*DRUG
       EFFECTS/PATHOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

