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Tobacco smoke causes changes of oxytocin levels, which may be associated with less milk production
Abstracts / Toxicology Letters 258S (2016) S62–S324
dose not exceeding the Minimal Erythema Dose. Skin reactions were assessed up to 72 h after irradiation. Sparfloxacin showed a higher skin response in the pigmented model compared to the non-pigmented model. 8-Methoxypsoralen showed comparable skin responses in both models. Nalidixc Acid showed a higher response in the non-pigmented model. No response was seen for Pirfenidone. Overall, the results indicate that both the pigmented and non-pigmented strain are suitable models for the assessment of phototoxicity. Based on these current results, we recommend to select the pigmented model for compounds showing an in vitro melanin binding capacity exceeding 75%. http://dx.doi.org/10.1016/j.toxlet.2016.06.1719 P10-053 Tobacco smoke causes changes of oxytocin levels, which may be associated with less milk production M. Napierala 1,∗ , T.A. Merritt 2 , J. Mazela 3 , E. Florek 1 1
Laboratory of Environmental Research, Department of Toxicology, Poznan University of Medical Sciences, Poznan, Poland 2 Children’s Hospital, School of Medicine, Loma Linda University, Loma Linda, California, USA 3 Department of Neonatal Infections, Poznan University of Medical Sciences, Poznan, Poland Oxidative processes, naturally enhanced in gestation period, can be additionally intensified by the use of drugs, such as alcohol or cigarettes, which is particularly hazardous for both the mother and foetus. Moreover, women who smoked during pregnancy breastfeed their children less frequently than non-smoking. The objective of the research was to assess the impact of tobacco smoke exposure on oxytocin levels and biochemical oxidative stress parameters during pregnancy and after birth in experimental model. 72 female Wistar rats were enrolled in the study. Exposure to tobacco smoke was performed in toxicological chamber for 5 days a week, 6 h a day, during 3 weeks, throughout whole pregnancy. On scheduled days of experiment dissection was performed. Plasma was subsequently obtained and frozen in −80 ◦ C for further analysis. A reliable biomarker of exposure (cotinine) was used in the process and it was determined by means of high performance liquid chromatography with diode array detection. Determination of oxytocin was performed by means of ELISA enzyme immunoassay. The levels of selected biochemical parameters: uric acid, protein S-nitrosylation, lipid peroxidation and trolox equivalent antioxidant capacity were measured by spectrophotometric methods. By disturbance of oxidoreductive balance, tobacco smoking affects the endocrine system of the female, which may result in oxytocin fluctuations. This was manifested especially during lactation period in this study. Oxytocin concentration determined among rats from group exposed to tobacco smoke compared to non-exposed group demonstrated a 45.71% decrease. Therefore, women who smoke during pregnancy may breastfeed their children for a shorter period after delivery. http://dx.doi.org/10.1016/j.toxlet.2016.06.1720
S197
P10-054 Interactions of developmental toxicity from four environmental agents W. Lee ∗ , Z. Lee Department of Bioscience Technology, Chang Jung Christian University, Tainan, Taiwan Many environmental agents can interrupt the endocrine system, and affect development, behavior, and reproductive function. There have accumulated a large number of toxicological studies on individual agents. As environmental agents are rarely present alone, most of these studies are not applicable to the real world. Therefore, we developed an in vivo assay system to investigate the interaction of developmental toxicity from four common environmental agents: caffeine (0.5 mM), saccharin (0.05 mM), a cigarette butt leachate (0.2 piece cigarette butt/L), and an electromagnetic field (3.2 kHz, 50 T). The GnRH-GFP transgenic medaka embryo (Oryzias latipes) was used because the gonadotropin-releasing hormone (GnRH) is at the top of the reproductive axis for many vertebrates and also a neuromodulator for embryonic development. In this transgenic medaka, the 5 -region of the GnRH gene is linked to the green fluorescent protein (GFP) cDNA, rendering the GnRH neurons fluorescent. Due to the exceptional optical clarity of the embryo, the fluorescent GnRH neurons and other aspects of development can be easily observed and recorded. Our previous studies have found that embryonic development and larval behavior can be altered by each of these environmental agents. Here we exposed medaka embryos (<5 h post fertilization) to individual or combinations of the agents continually until hatching, and observed their development. We found that not only individual but also the combinations of the agents affected embryonic development. In addition, interactions of developmental toxicity existed among these agents when they were combined. http://dx.doi.org/10.1016/j.toxlet.2016.06.1721 P10-055 Method for identification of low soluble, biopersistent dusts (GBS) O. Creutzenberg ∗ , T. Hansen, S. Sven, T. Thomas, K. Jan Fraunhofer Institute for Toxicology and Experimental Medicine, Hanover, Germany Respirable biopersistent granular dusts (GBS) show a negligible solubility in physiological lung fluid and do not exhibit a specific surface chemistry-related toxicity at volumetric non-overload conditions in lungs. The German MAK Commission proposed a TLV of 0.3 mg/m3 for GBS excluding any adverse lung effects upon chronic exposure (no volumetric lung overload). OBJECTIVES: Determination of a value of ‘low solubility’ and analysis of the inflammatory response in lungs including micro-/nanoscaled dusts. For TiO2 (rutile-micro), TiO2 (anatase-nano), Eu2 O3 (micro-nano mixed), BaSO4 (micro), ZrO2 (micro) and amorphous SiO2 (nano) the solubility (day 3, 28 and 90) and inflammation (day 3 and 28) after intratracheal instillation in rats was analysed. Two doses of 0.5 (non-overload) and 1.5 l (moderate overload) were administered. The differential cell count showed only slight inflammatory cell levels after treatment with TiO2 (rutile) and BaSO4 . In contrast, the TiO2 (anatase) showed a stronger response. The rare earth Eu2 O3 dust showed the strongest effect including a red-coloured lung lavage fluid. ZrO2 and amorphous SiO2 showed a strong acute response after 3 days, however, recovered mostly completely
dose not exceeding the Minimal Erythema Dose. Skin reactions were assessed up to 72 h after irradiation. Sparfloxacin showed a higher skin response in the pigmented model compared to the non-pigmented model. 8-Methoxypsoralen showed comparable skin responses in both models. Nalidixc Acid showed a higher response in the non-pigmented model. No response was seen for Pirfenidone. Overall, the results indicate that both the pigmented and non-pigmented strain are suitable models for the assessment of phototoxicity. Based on these current results, we recommend to select the pigmented model for compounds showing an in vitro melanin binding capacity exceeding 75%. http://dx.doi.org/10.1016/j.toxlet.2016.06.1719 P10-053 Tobacco smoke causes changes of oxytocin levels, which may be associated with less milk production M. Napierala 1,∗ , T.A. Merritt 2 , J. Mazela 3 , E. Florek 1 1
Laboratory of Environmental Research, Department of Toxicology, Poznan University of Medical Sciences, Poznan, Poland 2 Children’s Hospital, School of Medicine, Loma Linda University, Loma Linda, California, USA 3 Department of Neonatal Infections, Poznan University of Medical Sciences, Poznan, Poland Oxidative processes, naturally enhanced in gestation period, can be additionally intensified by the use of drugs, such as alcohol or cigarettes, which is particularly hazardous for both the mother and foetus. Moreover, women who smoked during pregnancy breastfeed their children less frequently than non-smoking. The objective of the research was to assess the impact of tobacco smoke exposure on oxytocin levels and biochemical oxidative stress parameters during pregnancy and after birth in experimental model. 72 female Wistar rats were enrolled in the study. Exposure to tobacco smoke was performed in toxicological chamber for 5 days a week, 6 h a day, during 3 weeks, throughout whole pregnancy. On scheduled days of experiment dissection was performed. Plasma was subsequently obtained and frozen in −80 ◦ C for further analysis. A reliable biomarker of exposure (cotinine) was used in the process and it was determined by means of high performance liquid chromatography with diode array detection. Determination of oxytocin was performed by means of ELISA enzyme immunoassay. The levels of selected biochemical parameters: uric acid, protein S-nitrosylation, lipid peroxidation and trolox equivalent antioxidant capacity were measured by spectrophotometric methods. By disturbance of oxidoreductive balance, tobacco smoking affects the endocrine system of the female, which may result in oxytocin fluctuations. This was manifested especially during lactation period in this study. Oxytocin concentration determined among rats from group exposed to tobacco smoke compared to non-exposed group demonstrated a 45.71% decrease. Therefore, women who smoke during pregnancy may breastfeed their children for a shorter period after delivery. http://dx.doi.org/10.1016/j.toxlet.2016.06.1720
S197
P10-054 Interactions of developmental toxicity from four environmental agents W. Lee ∗ , Z. Lee Department of Bioscience Technology, Chang Jung Christian University, Tainan, Taiwan Many environmental agents can interrupt the endocrine system, and affect development, behavior, and reproductive function. There have accumulated a large number of toxicological studies on individual agents. As environmental agents are rarely present alone, most of these studies are not applicable to the real world. Therefore, we developed an in vivo assay system to investigate the interaction of developmental toxicity from four common environmental agents: caffeine (0.5 mM), saccharin (0.05 mM), a cigarette butt leachate (0.2 piece cigarette butt/L), and an electromagnetic field (3.2 kHz, 50 T). The GnRH-GFP transgenic medaka embryo (Oryzias latipes) was used because the gonadotropin-releasing hormone (GnRH) is at the top of the reproductive axis for many vertebrates and also a neuromodulator for embryonic development. In this transgenic medaka, the 5 -region of the GnRH gene is linked to the green fluorescent protein (GFP) cDNA, rendering the GnRH neurons fluorescent. Due to the exceptional optical clarity of the embryo, the fluorescent GnRH neurons and other aspects of development can be easily observed and recorded. Our previous studies have found that embryonic development and larval behavior can be altered by each of these environmental agents. Here we exposed medaka embryos (<5 h post fertilization) to individual or combinations of the agents continually until hatching, and observed their development. We found that not only individual but also the combinations of the agents affected embryonic development. In addition, interactions of developmental toxicity existed among these agents when they were combined. http://dx.doi.org/10.1016/j.toxlet.2016.06.1721 P10-055 Method for identification of low soluble, biopersistent dusts (GBS) O. Creutzenberg ∗ , T. Hansen, S. Sven, T. Thomas, K. Jan Fraunhofer Institute for Toxicology and Experimental Medicine, Hanover, Germany Respirable biopersistent granular dusts (GBS) show a negligible solubility in physiological lung fluid and do not exhibit a specific surface chemistry-related toxicity at volumetric non-overload conditions in lungs. The German MAK Commission proposed a TLV of 0.3 mg/m3 for GBS excluding any adverse lung effects upon chronic exposure (no volumetric lung overload). OBJECTIVES: Determination of a value of ‘low solubility’ and analysis of the inflammatory response in lungs including micro-/nanoscaled dusts. For TiO2 (rutile-micro), TiO2 (anatase-nano), Eu2 O3 (micro-nano mixed), BaSO4 (micro), ZrO2 (micro) and amorphous SiO2 (nano) the solubility (day 3, 28 and 90) and inflammation (day 3 and 28) after intratracheal instillation in rats was analysed. Two doses of 0.5 (non-overload) and 1.5 l (moderate overload) were administered. The differential cell count showed only slight inflammatory cell levels after treatment with TiO2 (rutile) and BaSO4 . In contrast, the TiO2 (anatase) showed a stronger response. The rare earth Eu2 O3 dust showed the strongest effect including a red-coloured lung lavage fluid. ZrO2 and amorphous SiO2 showed a strong acute response after 3 days, however, recovered mostly completely