developmental exposure to low-dose of bisphenol a alters maternal behaviour in rats

1
S294 Abstracts / Toxicology Letters 205S (2011) S180–S300 of carbon. It is about the species Aeromonas hydrophila. This bacte- rial strain shows an hydrophobicity strong as well as an emulsifying power and consequently metabolic capacities to this pesticide. doi:10.1016/j.toxlet.2011.05.992 P2369 Developmental exposure to low-dose of bisphenol A alters maternal behaviour in rats S. Boudalia , L. Decocq, R. Berges, M. Canivenclavier Umr1324 Inra, Centre des Sciences du Goût et de l’Alimentation, Dijon, France Maternal behaviour is a biomarker of neurotoxicity that is used in the safety evaluation of chemical substances. The objective of this study was to determine the effects on the F0 and F1 mater- nal behaviour of gestation/lactation exposure of Wistar rats dams (F0) with a low dose of bisphenol A consistent with human expo- sure. Bisphenol A was administered daily to pregnant rats by gavage (5 g/kg body weight) from the first day of gestation (G1) to wean- ing (PND 21) and then to the female offspring’s until their mating at the adulthood (F1). For each generation, assessments of mater- nal behaviour were carried out within two hours of the beginning of the light cycle from the parturition to PND 8 by observing presence/absence of the following behaviours: Nursing (Arched, blanket and passive position); Resting (Inside the nest or outside the nest); Anogenital licking; Self grooming; Pup licking; Pup car- rying; Feeding; Drinking; Exploration; Rearing; Nest building. We show a significant decrease in the percentage of dams nursing, rest- ing inside the nest, nest building, and pup carrying in both BPA treated mothers F0 and their F1 offspring (p < 0.05). Nevertheless, there was no significant interaction between BPA treatment, gen- eration and percentage of dams observed drinking, feeding, self grooming, exploring, anogenital and pup licking or rearing. The present findings indicate that both an early exposure (F1) and an adult exposure (F0) to a low-dose of BPA lead to significant effect on maternal behaviour. doi:10.1016/j.toxlet.2011.05.993 P2370 Experience with local lymph node assay performance standards using standard radioactivity and non-radioactive cell count measurements E.J. Fabian 1,, D. Basketter 1 , S. Kolle 2 , A. Schrage 3 , B. van Ravenzwaay 1 , R. Landsiedel 1 1 Experimental Toxicology and Ecology, BASF SE, Ludwigshafen, Germany, 2 Experimental Toxicology and Ecology, Ludwigshafen, Germany, 3 MatTek In Vitro Life Science Laboratories, Bratislava, Slovak Republic Purpose: The local lymph node assay (LLNA) is the preferred test for predictive identification of skin sensitizing substances by measuring the incorporation of radioactive thymidine in the lymph node. To facilitate the acceptance of non-radioactive vari- ants, validation authorities have published a harmonised set of minimum performance standards (PS) which the alternative end- point assay must meet. Methods: In the present study, the LLNA performance standards were applied to a variant of the LLNA based on lymph node cell counts (LNCC) run in parallel as a control with the standard LLNA with radioactivity measurements. Results: Of the 22 PS chemicals tested in this study, 21 yielded the same results from radioactive and cell count measurements; only 2- mercaptobenzothiazole was positive by LLNA but negative by LNCC. Of the 16 PS positives, 15 were positive by LLNA and 14 by LNCC; methylmethacrylate was not identified as sensitizer by either of the measurements. Two of the 6 PS negatives tested negative by both LLNA and LNCC. Of the 4 PS negatives which tested posi- tive in our study, chlorobenzene and methyl salicylate were tested at higher concentrations than the published PS whereas the cor- responding concentrations resulted in consistent positive results. Methylmethacrylate and nickel chloride tested positive within the concentration range used for the published PS. The results indi- cate that cell counts and radioactive measurements are in good accordance using the 22 PS as test substances. Comparisons with the published PS results may, however, require a balanced analysis rather than a simple checklist approach. doi:10.1016/j.toxlet.2011.05.994 P2371 The Spanish group of toxicologists from the industry N. Fabre Preclinical Development, Noscira SA, Tres Cantos, Spain Mateu Orfila (Maó, 1787 – Paris, 1853) is considered to be one of the founders of the modern toxicology. His books Traité des Poi- sons (later Toxicologie Générale) and Éléments de Chimie Médicale were key for the establishment of the current approaches to experi- mental toxicology. Currently, and despite this illustrious precedent, industrial toxicology in Spain is relatively not fully developed, probably due to a limited industrial tissue requiring this science. Toxicology is becoming every day a most complicated science. In the industry, it is not only important to define a safe dose, but to understand the mechanism of toxicity, its relevance to man, and, finally, to generate very educated risk assessments. Spanish indus- tries are relatively small and academic toxicologists are far from the industrial needs. Thus, several toxicologists, initially from the Spanish drug industry, have established the Spanish Group of Tox- icologists from the Industry. At the moment is mainly formed by representatives of the main Spanish pharmaceutical companies and CROs. It aims to exchange information between members of the group to facilitate the resolution of problems; at the same time, the group will interact with the Spanish Medicines Agency to become a reference point for new regulation development. The group is not yet a legal entity and it is to be considered as a Club. The group wishes to expand its membership to other Spanish industries from other fields: Agrochemistry, Cosmetics, Chemistry, Veterinary, etc. The group also welcomes Spanish toxicologists working in indus- tries outside of Spain. For information contact Nicolas Fabre. doi:10.1016/j.toxlet.2011.05.995 P2372 Pathological study of different brain areas in fatal head injuries M.A. Gheat Forensic Medicine, Forensic Medicine Institute, Cairo, Egypt Head injuries are not only the most common and most impor- tant in forensic practice, but also the commonest cause of death amongst young adults. This study was carried out on fatal head injury cases representing all selected cases of criminally suspected

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Page 1: Developmental exposure to low-dose of bisphenol A alters maternal behaviour in rats

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294 Abstracts / Toxicology Le

f carbon. It is about the species Aeromonas hydrophila. This bacte-ial strain shows an hydrophobicity strong as well as an emulsifyingower and consequently metabolic capacities to this pesticide.

oi:10.1016/j.toxlet.2011.05.992

2369evelopmental exposure to low-dose of bisphenol A altersaternal behaviour in rats

. Boudalia ∗, L. Decocq, R. Berges, M. Canivenclavier

Umr1324 Inra, Centre des Sciences du Goût et de l’Alimentation,ijon, France

Maternal behaviour is a biomarker of neurotoxicity that is usedn the safety evaluation of chemical substances. The objective ofhis study was to determine the effects on the F0 and F1 mater-al behaviour of gestation/lactation exposure of Wistar rats damsF0) with a low dose of bisphenol A consistent with human expo-ure. Bisphenol A was administered daily to pregnant rats by gavage5 �g/kg body weight) from the first day of gestation (G1) to wean-ng (PND 21) and then to the female offspring’s until their matingt the adulthood (F1). For each generation, assessments of mater-al behaviour were carried out within two hours of the beginningf the light cycle from the parturition to PND 8 by observingresence/absence of the following behaviours: Nursing (Arched,lanket and passive position); Resting (Inside the nest or outsidehe nest); Anogenital licking; Self grooming; Pup licking; Pup car-ying; Feeding; Drinking; Exploration; Rearing; Nest building. Wehow a significant decrease in the percentage of dams nursing, rest-ng inside the nest, nest building, and pup carrying in both BPAreated mothers F0 and their F1 offspring (p < 0.05). Nevertheless,here was no significant interaction between BPA treatment, gen-ration and percentage of dams observed drinking, feeding, selfrooming, exploring, anogenital and pup licking or rearing. Theresent findings indicate that both an early exposure (F1) and andult exposure (F0) to a low-dose of BPA lead to significant effectn maternal behaviour.

oi:10.1016/j.toxlet.2011.05.993

2370xperience with local lymph node assay performancetandards using standard radioactivity and non-radioactiveell count measurements

.J. Fabian 1,∗, D. Basketter 1, S. Kolle 2, A. Schrage 3, B. vanavenzwaay 1, R. Landsiedel 1

Experimental Toxicology and Ecology, BASF SE, Ludwigshafen,ermany, 2 Experimental Toxicology and Ecology, Ludwigshafen,ermany, 3 MatTek In Vitro Life Science Laboratories, Bratislava,lovak Republic

Purpose: The local lymph node assay (LLNA) is the preferredest for predictive identification of skin sensitizing substancesy measuring the incorporation of radioactive thymidine in the

ymph node. To facilitate the acceptance of non-radioactive vari-nts, validation authorities have published a harmonised set ofinimum performance standards (PS) which the alternative end-

oint assay must meet. Methods: In the present study, the LLNAerformance standards were applied to a variant of the LLNA basedn lymph node cell counts (LNCC) run in parallel as a controlith the standard LLNA with radioactivity measurements. Results:

05S (2011) S180–S300

Of the 22 PS chemicals tested in this study, 21 yielded the sameresults from radioactive and cell count measurements; only 2-mercaptobenzothiazole was positive by LLNA but negative by LNCC.Of the 16 PS positives, 15 were positive by LLNA and 14 by LNCC;methylmethacrylate was not identified as sensitizer by either ofthe measurements. Two of the 6 PS negatives tested negative byboth LLNA and LNCC. Of the 4 PS negatives which tested posi-tive in our study, chlorobenzene and methyl salicylate were testedat higher concentrations than the published PS whereas the cor-responding concentrations resulted in consistent positive results.Methylmethacrylate and nickel chloride tested positive within theconcentration range used for the published PS. The results indi-cate that cell counts and radioactive measurements are in goodaccordance using the 22 PS as test substances. Comparisons withthe published PS results may, however, require a balanced analysisrather than a simple checklist approach.

doi:10.1016/j.toxlet.2011.05.994

P2371The Spanish group of toxicologists from the industry

N. Fabre

Preclinical Development, Noscira SA, Tres Cantos, Spain

Mateu Orfila (Maó, 1787 – Paris, 1853) is considered to be oneof the founders of the modern toxicology. His books Traité des Poi-sons (later Toxicologie Générale) and Éléments de Chimie Médicalewere key for the establishment of the current approaches to experi-mental toxicology. Currently, and despite this illustrious precedent,industrial toxicology in Spain is relatively not fully developed,probably due to a limited industrial tissue requiring this science.Toxicology is becoming every day a most complicated science. Inthe industry, it is not only important to define a safe dose, but tounderstand the mechanism of toxicity, its relevance to man, and,finally, to generate very educated risk assessments. Spanish indus-tries are relatively small and academic toxicologists are far fromthe industrial needs. Thus, several toxicologists, initially from theSpanish drug industry, have established the Spanish Group of Tox-icologists from the Industry. At the moment is mainly formed byrepresentatives of the main Spanish pharmaceutical companies andCROs. It aims to exchange information between members of thegroup to facilitate the resolution of problems; at the same time, thegroup will interact with the Spanish Medicines Agency to becomea reference point for new regulation development. The group is notyet a legal entity and it is to be considered as a Club. The groupwishes to expand its membership to other Spanish industries fromother fields: Agrochemistry, Cosmetics, Chemistry, Veterinary, etc.The group also welcomes Spanish toxicologists working in indus-tries outside of Spain. For information contact Nicolas Fabre.

doi:10.1016/j.toxlet.2011.05.995

P2372Pathological study of different brain areas in fatal head injuries

M.A. Gheat

Forensic Medicine, Forensic Medicine Institute, Cairo, Egypt

Head injuries are not only the most common and most impor-tant in forensic practice, but also the commonest cause of deathamongst young adults. This study was carried out on fatal headinjury cases representing all selected cases of criminally suspected