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An extended one-generation reproductive toxicity study of plant protection product containing glyphosate on rats – Androgen- and estrogen-dependent endpoints
Abstracts / Toxicology Letters 280S (2017) S162–S165
state was evaluated on the 20th pregnancy day in the exposed rats mated with intact rats. Thereby the number of corpora lutea in the ovaries, the number of alive, dead and resorbed fetuses and embryos, the fetus weight, the total weight of litters, the occurrence of malformations were registered. The reproductive indexes were taking into account. According to the results of the studies: C1 and C2 in dose of 2 mg/kg/bw have sign of gonadotoxcitcity (antiandrogenic activity). However, C1 in this dose showed the general toxic effect on males and females rats in exposing period. Adverse effects in dose 0.2 mg/kg/bw of C1 and C2 have no observed in both sexes Wistar Han rats. http://dx.doi.org/10.1016/j.toxlet.2017.07.455 P-04-10-04 An extended one-generation reproductive toxicity study of plant protection product containing glyphosate on rats – Androgen- and estrogen-dependent endpoints Inga Mrzyk, Aleksandra Szewczyk, Robert Sornat, Katarzyna Gruszka, Aneta Kropidlo, Malgorzata Przybyla, Patrycja Florek, Agnieszka Drzewiecka Department of Toxicological Studies, Institute of Industrial Organic Chemistry Branch Pszczyna, Pszczyna, Poland The aim of an extended one-generation reproductive toxicity study are an evaluation of the pre- and postnatal effects of chemicals on the development as well as an evaluation of systemic toxicity in pregnant, lactating females and offspring. The study provides information about the effects of a test substance on the integrity and performance of the adult male and female reproductive systems. A plant protection product containing glyphosate (360 g/L) was assessed for androgen- and estrogen- endpoints. The product at two doses was administered continuously to groups of sexually mature males and females. The rats (25/sex/dose) were exposed to 0, 3000 and 9000 ppm in diet. The parents were dosed during premating and mating periods. The parental females were further treated during pregnancy and lactation periods until the weaning of litters. The F1 offspring were exposed to the test product from weaning to adulthood. The F1 offspring were examined for survival, development and reproductive toxicity. Androgen- and estrogendependent endpoints were evaluated. Androgen-sensitive endpoints such as AGD, nipple retention, preputial separation, male reproductive organ weights, histopathology, sperm parameters were not altered in any of the exposed groups. Estrogen-sensitive endpoints, which included estrus cyclicity, reproductive indices, organ weights, pathology, were not altered. There were no exposure-related effects on the age and body weights of young females on the day of vaginal opening. These data suggest that the plant protection product containing 360 g /L glyphosate showed no adverse effects on androgen- and estrogen-dependent endpoints. http://dx.doi.org/10.1016/j.toxlet.2017.07.456
S163
P-04-10-05 Extended OECD 422 screening study for the evaluation of substances with suspected reproductive toxicity and/or endocrine activity Lawrence Segal 1 , Lourdes Canut 2 , David Myers 3 , Silvia García 2 , Mark Blee 3 , John Butala 4 1
Penman Consulting BVBA, Brussels, Belgium Envigo, Barcelona, Spain 3 Envigo, Eye, United Kingdom 4 Toxicology Consultants, Inc., Gisbonia, United States 2
OECD TG 422 is often used as a screening to assess the potential systemic, developmental and reproductive toxicity of chemicals. The standard OECD 422 design may be refined by including thyroid hormone analysis and extending the postnatal phase to sexual maturity of the F1 pups. Groups of F0 rats (12 rats/sex/group), are exposed to a chemical for two weeks before mating through 28 days for males and until day 20 postpartum for females. F1 pups to be evaluated for sexual maturation were dosed from PND 21 until sexual maturation on PND 70. Although direct treatment starts soon after weaning, all offspring have potential indirect exposure in utero and during lactation. The remaining pups were sacrificed on PND 4 or 13 and are not dosed, but received potential indirect exposure in utero and during lactation. On PND 13, three male and female F1 pups are randomly selected for the sexual maturation phase (size of each litter adjusted by eliminating extra pups). Male pups were examined daily from PND 38 for the completion of balano-preputial separation and bw was recorded on the day of completion of separation. Female pups were examined daily from PND 25 until vaginal opening occurs, with bw recorded on the day of vaginal opening. Blood samples were taken for T4 and TSH analysis from at least two pups/litter on PND 4 and PND13, from all adult males at termination, from all dams on day 21 postpartum, and from F1 pups on PND 7. http://dx.doi.org/10.1016/j.toxlet.2017.07.457 P-04-10-06 Early gestational intermittent hypoxia in rats induces delayed changes in immune and redox homeostasis with lasting perivascular placental edema 1 , L’udovít ˇ Eduard Ujhazy 1 , Lucia Raˇcková 1 , Martin Skandík Danihel 2 , Ingrid Brucknerová 3 , Mojmír Mach 1 1
Department of Developmental and Behavioral Toxicology, Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia 2 Institute of Pathological Anatomy, Faculty of Medicine, Comenius University, Bratislava, Slovakia 3 Neonatal Department of Intensive Medicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia Early markers of hypoxic insult during gestation are vital aid for future therapy (pharmacological or behavioral) and improvement of delayed hypoxia-mediated complications. The aim of this study was to assess markers of early gestational intermittent hypoxia (eGIH) in placenta and amniotic fluid as well as to evaluate developmental outcomes of eGIH by means of teratological examination. Pregnant animals were exposed to 10.5% O2 during sensitive stages of development for 8 h or 12 h respectively. Heme oxygenase-1 and the levels of IgG in amniotic fluid, histological changes in placenta and teratological examination were assessed on day 21 of gesta-
state was evaluated on the 20th pregnancy day in the exposed rats mated with intact rats. Thereby the number of corpora lutea in the ovaries, the number of alive, dead and resorbed fetuses and embryos, the fetus weight, the total weight of litters, the occurrence of malformations were registered. The reproductive indexes were taking into account. According to the results of the studies: C1 and C2 in dose of 2 mg/kg/bw have sign of gonadotoxcitcity (antiandrogenic activity). However, C1 in this dose showed the general toxic effect on males and females rats in exposing period. Adverse effects in dose 0.2 mg/kg/bw of C1 and C2 have no observed in both sexes Wistar Han rats. http://dx.doi.org/10.1016/j.toxlet.2017.07.455 P-04-10-04 An extended one-generation reproductive toxicity study of plant protection product containing glyphosate on rats – Androgen- and estrogen-dependent endpoints Inga Mrzyk, Aleksandra Szewczyk, Robert Sornat, Katarzyna Gruszka, Aneta Kropidlo, Malgorzata Przybyla, Patrycja Florek, Agnieszka Drzewiecka Department of Toxicological Studies, Institute of Industrial Organic Chemistry Branch Pszczyna, Pszczyna, Poland The aim of an extended one-generation reproductive toxicity study are an evaluation of the pre- and postnatal effects of chemicals on the development as well as an evaluation of systemic toxicity in pregnant, lactating females and offspring. The study provides information about the effects of a test substance on the integrity and performance of the adult male and female reproductive systems. A plant protection product containing glyphosate (360 g/L) was assessed for androgen- and estrogen- endpoints. The product at two doses was administered continuously to groups of sexually mature males and females. The rats (25/sex/dose) were exposed to 0, 3000 and 9000 ppm in diet. The parents were dosed during premating and mating periods. The parental females were further treated during pregnancy and lactation periods until the weaning of litters. The F1 offspring were exposed to the test product from weaning to adulthood. The F1 offspring were examined for survival, development and reproductive toxicity. Androgen- and estrogendependent endpoints were evaluated. Androgen-sensitive endpoints such as AGD, nipple retention, preputial separation, male reproductive organ weights, histopathology, sperm parameters were not altered in any of the exposed groups. Estrogen-sensitive endpoints, which included estrus cyclicity, reproductive indices, organ weights, pathology, were not altered. There were no exposure-related effects on the age and body weights of young females on the day of vaginal opening. These data suggest that the plant protection product containing 360 g /L glyphosate showed no adverse effects on androgen- and estrogen-dependent endpoints. http://dx.doi.org/10.1016/j.toxlet.2017.07.456
S163
P-04-10-05 Extended OECD 422 screening study for the evaluation of substances with suspected reproductive toxicity and/or endocrine activity Lawrence Segal 1 , Lourdes Canut 2 , David Myers 3 , Silvia García 2 , Mark Blee 3 , John Butala 4 1
Penman Consulting BVBA, Brussels, Belgium Envigo, Barcelona, Spain 3 Envigo, Eye, United Kingdom 4 Toxicology Consultants, Inc., Gisbonia, United States 2
OECD TG 422 is often used as a screening to assess the potential systemic, developmental and reproductive toxicity of chemicals. The standard OECD 422 design may be refined by including thyroid hormone analysis and extending the postnatal phase to sexual maturity of the F1 pups. Groups of F0 rats (12 rats/sex/group), are exposed to a chemical for two weeks before mating through 28 days for males and until day 20 postpartum for females. F1 pups to be evaluated for sexual maturation were dosed from PND 21 until sexual maturation on PND 70. Although direct treatment starts soon after weaning, all offspring have potential indirect exposure in utero and during lactation. The remaining pups were sacrificed on PND 4 or 13 and are not dosed, but received potential indirect exposure in utero and during lactation. On PND 13, three male and female F1 pups are randomly selected for the sexual maturation phase (size of each litter adjusted by eliminating extra pups). Male pups were examined daily from PND 38 for the completion of balano-preputial separation and bw was recorded on the day of completion of separation. Female pups were examined daily from PND 25 until vaginal opening occurs, with bw recorded on the day of vaginal opening. Blood samples were taken for T4 and TSH analysis from at least two pups/litter on PND 4 and PND13, from all adult males at termination, from all dams on day 21 postpartum, and from F1 pups on PND 7. http://dx.doi.org/10.1016/j.toxlet.2017.07.457 P-04-10-06 Early gestational intermittent hypoxia in rats induces delayed changes in immune and redox homeostasis with lasting perivascular placental edema 1 , L’udovít ˇ Eduard Ujhazy 1 , Lucia Raˇcková 1 , Martin Skandík Danihel 2 , Ingrid Brucknerová 3 , Mojmír Mach 1 1
Department of Developmental and Behavioral Toxicology, Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia 2 Institute of Pathological Anatomy, Faculty of Medicine, Comenius University, Bratislava, Slovakia 3 Neonatal Department of Intensive Medicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia Early markers of hypoxic insult during gestation are vital aid for future therapy (pharmacological or behavioral) and improvement of delayed hypoxia-mediated complications. The aim of this study was to assess markers of early gestational intermittent hypoxia (eGIH) in placenta and amniotic fluid as well as to evaluate developmental outcomes of eGIH by means of teratological examination. Pregnant animals were exposed to 10.5% O2 during sensitive stages of development for 8 h or 12 h respectively. Heme oxygenase-1 and the levels of IgG in amniotic fluid, histological changes in placenta and teratological examination were assessed on day 21 of gesta-