Reproductive toxicity and toxicokinetics of lindane in the male offspring of rats exposed during lactation

Dalsenter, Paulo Roberto; As, Faqi; Webb, Jessie; Hj, Merker; Chahoud, Ibrahim

doi:10.1177/096032719701600303

Cited by 62 publications

(34 citation statements)

References 31 publications

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“…Testicular damage, reduced sperm counts (Dalsenter et al, 1996), prolongation of the estrous cycle, and delayed vaginal opening (Uphouse and Williams, 1989;Chadwick et al, 1988;Cooper et al, 1989) have also been reported in rats. In addition, there have been descriptions of testicular damage and reduced sperm counts in F1 male rats after administration to lactating dams (Dalsenter et al, 1997). The present two-generation reproduction toxicity study in rats adding extra endpoints to detect endocrine disrupting activity, including AGD, nipple development, sexual maturation, estrous cycle, spermatogenesis, sex organ weights, and blood hormone concentrations, was performed to assess comparative utility.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a Two-Generation Reproduction Toxicity Study Adding Endopoints to Detect Endocrine Disrupting Activity Using Lindane

et al. 2005

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-A two-generation reproduction toxicity study in rats adding extra endpoints to detect endocrine disrupting activity was conducted using lindane by dietary administration at 0, 10, 60, and 300 ppm, for investigation of its utility. The extra endpoints included anogenital distance (AGD), nipple development, sexual maturation (vaginal opening and preputial separation), estrous cycle, spermatogenesis, sex organ weights, and blood hormone concentrations (thyroid and sex hormones). F1 offspring were examined for emotionality (open field test), motor coordination (rotarod test), as well as learning and memory (pole-climbing test). Hepatic drug-metabolizing enzyme activities were also measured. The results revealed general toxicological effects on parental animals, influence on reproductive function, and altered development of offspring; however, they did not demonstrate any distinct changes in the extra endpoints for detection of endocrine disrupting activity. Adult toxicity was observed in both F0 and F1 animals, including suppressed body weight gain and reduced food consumption in both sexes, and deaths of females at 300 ppm. Convulsions and irritability were observed during the perinatal period in pregnant F1 females given 300 ppm. Pathological examination revealed increased liver weights and centrilobular hepatocellular hypertrophy in both sexes and generations at 10 or 60 ppm and above; in addition, increased kidney weights and increased hyaline droplets in the proximal tubule epithelium, and basophilic renal tubules in males were noted at 10 ppm and above. Pituitary weights were decreased in F0 females and in F1 males and females and adrenal weights were increased in F1 males and females at 300 ppm; however, no histological changes were observed, and manifestations suggesting endocrine disrupting activity related to these changes were lacking. Hypertrophy of the thyroid follicular epithelium in F0 females at 300 ppm and in F1 males at 60 and 300 ppm, and decreases in T3 and/or T4 in both sexes and generations at 300 ppm were presumed to be secondary changes associated with the induction of hepatic drug-metabolizing enzymes. Blood hormone analysis revealed no changes in sex hormones attributable to lindane in males or females. Hepatic drug-metabolizing enzyme activities were increased dose-dependently from 10 ppm in both sexes and generations, with the rise in BROD activity being the most prominent. There were also increases in MROD, EROD, T-6β-OH, and T4-UDP-GT activities (BROD >> EROD > MROD, T-6β-OH, T4-UDP-GT). This suggests that while lindane most strongly induces CYP2B, it also upregulates a number of other drug metabolizing enzymes, such as CYP1A, CYP3A, and UDP-GT. As for effects on reproductive function, lack of maternal behavior, including lactation and retrieval behavior, and consequent total litter loss were observed in F1 dams at 300 ppm. There were no effects of lindane on the estrous cycle, spermatogenesis, mating, fertility, pregnancy, or parturition. Neonatal toxicity was observed in bot...

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Section: Introductionmentioning

confidence: 99%

Evaluation of a Two-Generation Reproduction Toxicity Study Adding Endopoints to Detect Endocrine Disrupting Activity Using Lindane

et al. 2005

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“…Lindane had a toxic effect on the reproductive system at the dose of 5 mg/kg/bw/day and higher doses in rodents (Dalsenter et al 1997;FAO/WHO 2002). In previous studies, lindane was used at the doses of 1-30 mg/kg/bw in 30-90-day-old male rats and degenerative changes were reported (Chowdhury et al 1987;Srinivasan et al 1988;Dalsenter et al 1996;Dalsenter et al 1997;Walsh and Stocco 2000;Samanta and Chainy 2002).…”

mentioning

confidence: 99%

“…It causes damage to the male reproduction tract either acting directly on the testes or indirectly through endocrine regulation of the testes (Dalsenter et al 1996;Dalsenter et al 1997).…”

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confidence: 99%

Effects of Hexachlorocyclohexane (HCH-γ-Isomer, Lindane) Intoxication on the Proliferation and Apoptosis in Rat Testes

et al. 2009

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In this study, experimentally lindane-induced histopathological changes and proliferation and/or apoptosis in germ cells in the rat testes were investigated. A total of 40 healthy fertile 3-month-old male rats were used. Animals were divided into 4 groups, each containing 10 rats. Group 1 (control) was given only pure olive oil, Groups 2, 3 and 4 were administered lindane at 10, 20 and 40 mg/kg/bw, respectively, by gastric gavage for 30 days. Microscopically, degenerative changes were observed in the lindane-treated groups. For proliferative activity PCNA immunolabelling and for germ cells apoptosis TUNEL methods were performed. Although a strong PCNA positivity in the control group was observed, a gradual decrease was noted in the lindane-treated groups especially at higher doses. Significant increases of apoptosis were seen in the lindane-treated groups compared to the control group. A decrease in testosterone concentrations was observed in lindane-treated groups compared to the control group. The study indicates that high-dose lindane intoxication contributes to the suppression of spermatogenesis through a reduction of germ cell proliferation and an increase of germ cell death in rat testes.

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“…Livers and one of the two testes were fixed in a 10% neutral buffered formalin solution for routine histological processing and light microscopic evaluation of sections stained with hematoxylin-eosin. The number of spermatozoa in the remaining testis and cauda epididymis was counted as described elsewhere (15) …”

Section: Evaluation Of the Animalsmentioning

confidence: 99%

Study of the effects of ß-myrcene on rat fertility and general reproductive performance

Paumgartten

De-Carvalho

Souza

et al. 1998

Braz J Med Biol Res

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Abstractß-Myrcene (MYR) is a monoterpene found in the oils of a variety of aromatic plants including lemongrass, verbena, hop, bay, and others. MYR and essential oils containing this terpenoid compound are used in cosmetics, household products, and as flavoring food additives. This study was undertaken to investigate the effects of MYR on fertility and general reproductive performance in the rat. MYR (0, 100, 300 and 500 mg/kg) in peanut oil was given by gavage to male Wistar rats (15 per dose group) for 91 days prior to mating and during the mating period, as well as to females (45 per dose group) continuously for 21 days before mating, during mating and pregnancy, and throughout the period of lactation up to postnatal day 21. On day 21 of pregnancy one-third of the females of each group were submitted to cesarean section. Resorption, implantation, as well as dead and live fetuses were counted. All fetuses were examined for external malformations, weighed, and cleared and stained with Alizarin Red S for skeleton evaluation. The remaining dams were allowed to give birth to their offspring. The progeny was examined at birth and subsequently up to postnatal day 21. Mortality, weight gain and physical signs of postnatal development were evaluated. Except for an increase in liver and kidney weights, no other sign of toxicity was noted in male and female rats exposed to MYR. MYR did not affect the mating index (proportion of females impregnated by males) or the pregnancy index (ratio of pregnant to sperm-positive females). No sign of maternal toxicity and no increase in externally visible malformations were observed at any dose level. Only at the highest dose tested (500 mg/kg) did MYR induce an increase in the resorption rate and a higher frequency of fetal skeleton anomalies. No adverse effect of MYR on postnatal weight gain was noted but days of appearance of primary coat, incisor eruption and eye opening were slightly delayed in the exposed offspring. On the basis of the data presented in this paper the no-observed-adverse-effect level (NOAEL) for toxic effects on fertility and general reproductive performance can be set at 300 mg of ß-myrcene/kg body weight by the oral route.

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Reproductive toxicity and toxicokinetics of lindane in the male offspring of rats exposed during lactation

Cited by 62 publications

References 31 publications

Evaluation of a Two-Generation Reproduction Toxicity Study Adding Endopoints to Detect Endocrine Disrupting Activity Using Lindane

Evaluation of a Two-Generation Reproduction Toxicity Study Adding Endopoints to Detect Endocrine Disrupting Activity Using Lindane

Effects of Hexachlorocyclohexane (HCH-γ-Isomer, Lindane) Intoxication on the Proliferation and Apoptosis in Rat Testes

Study of the effects of ß-myrcene on rat fertility and general reproductive performance

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