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Speciation of manganese in drinking water
S120
Abstracts / Toxicology Letters 229S (2014) S40–S252
accepted by regulators, but is seldom used in the field of nutritional regulation. http://dx.doi.org/10.1016/j.toxlet.2014.06.429 P-2.84 Evaluating developmental toxicity in the rat as a basis for human risk assessment for cleft palate Laura Vicario 1,∗ , Jill Dixon 1 , Magnus Rattray 1 , Emma Barnes 2 , Jayne Wright 2 , Michael Dixon 1 1 Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK, 2 Syngenta, Jealott’s Hill International Research Centre, Bracknell, UK
Cleft palate is a craniofacial birth defect that affects one in every 700 new-borns worldwide. This defect results from a disruption in the development of the secondary palate (palatogenesis) which can be caused by several genetic and environmental factors. Morphologically, palatogenesis in mice, rats and humans consists of the same steps: Palatal Shelves (PS) development and growth, elevation, contact and fusion. However, whereas the mouse is the most commonly used species for the study of palatogenesis, the rat is the species used in human risk assessment studies. Although it is assumed that the molecular pathways underlying palatogenesis in mice, rats and humans are similar, this assumption has not been verified. The aim of this project is to identify the pathways underlying palatogenesis in the mouse and rat to verify species similarities. With that purpose, the gene expression patterns of the rat palate during eight stages of palatogenesis were obtained through RNAseq analysis; and the results corresponding to a subset of genes with a known essential role in mouse palatogenesis were compared with their mouse orthologues. This initial analysis indicated similar expression patterns between mice and rats, which suggests that the principal pathways underlying palatogenesis are conserved in both species. Further analysis are expected to secure the reliability of these results and to provide more information about the molecular pathways that are relevant for palatogenesis in mice, rats and humans. http://dx.doi.org/10.1016/j.toxlet.2014.06.430 P-2.85 Speciation of manganese in drinking water Paul Rumsby 1 , Leon Rockett 1,∗ , Helen Clegg 1 , Jorgen Jonsson 1 , Victoria Benson 1 , Mark Harman 1 , Tom Doyle 1 , Lesley Rushton 2 , David Wilkinson 3 , Peter Warwick 3 1
National Centre for Environmental Toxicology, WRc, Swindon, UK, Imperial College Consultants, Imperial College, London, UK, 3 Enviras, Loughborough University, Loughborough, UK 2
Although manganese (Mn) is an essential element, neurotoxicity by inhalation has been widely described, particularly in workers and miners, where exposure is relatively high. Recently, there have been a number of studies suggesting that oral exposure to manganese in drinking water may have adverse effects on neurological development in children. WRc has undertaken a study for the Drinking Water Inspectorate reviewing data on the potential neurotoxicity of oral manganese exposure and conducting four seasonal monitoring surveys in final drinking water at 20 sites, which measured total and soluble man-
ganese to estimate the concentration of the more biologically available Mn(II), and Mn(IV). The review of the literature on studies in experimental animals, suggests that there is a biologically plausible hypothesis for an adverse effect on neurological development of oral exposure to manganese. There is an accumulation of manganese in the same areas of the brain which accompanies neurotoxicity following inhalation of manganese, together with behavioural and locomotor effects. The human epidemiological studies, particularly on children, are suggestive of effects on intellectual and cognitive development. However, the types of studies conducted have limitations and are not the most appropriate for measuring the longer-term effects, such as those which may occur after accumulation of manganese in the brain. The sampling exercises indicated that public water supplies had low levels of manganese (majority below 5 g/l), and levels of the Mn(II) form were approximately 50% of total manganese. However, two private boreholes had higher levels of Mn, all in the Mn(II) form. http://dx.doi.org/10.1016/j.toxlet.2014.06.431 P-2.86 Science and policy in risk-based occupational exposure limits Linda Schenk 1,2,∗ , Qian Ding 1 , Sven Ove Hansson 1 1
KTH-Royal Institute of Technology, Stockholm, Sweden, 2 Karolinska Institutet, Stockholm, Sweden Risk-based occupational exposure limits (OEL) provide an opportunity to study how differences in the exposure limits set by different regulators are influenced by differences in the scientific judgment (what is the risk at different exposures?) and in the policy judgment (how large risks are accepted?). In a broad search seven regulators were identified that had set at least one OEL to which risk-levels were associated, four of these also identified two risk different risk levels: a tolerable risk (that should not be exceeded) and acceptable risk (below which exposure is considered negligible). For ten substances two or three risk-based OEL have been derived. For benzene such data was available from six regulators. The highest tolerable risk level was 4 times higher than the lowest, and the highest accepted risk 10 times higher than the lowest. These values are related to policy-based concerns. The differences in estimates of the risk/exposure relationship, i.e. the scientific judgement, were for most substances in within the same range. The largest differences were found for refractory ceramic fibres (a factor of 56) and for benzene (a factor of 13). For refractory ceramic fibres the database is less developed than many other substances in our selection, also there was a 15-year time difference between the newest and oldest OELs. For benzene the difference is explained by variation in exposure estimates for the Pliofilm cohort. We conclude that the science factor and the policy factor both contribute about equally to differences in risk-based OELs for carcinogens. http://dx.doi.org/10.1016/j.toxlet.2014.06.432
Abstracts / Toxicology Letters 229S (2014) S40–S252
accepted by regulators, but is seldom used in the field of nutritional regulation. http://dx.doi.org/10.1016/j.toxlet.2014.06.429 P-2.84 Evaluating developmental toxicity in the rat as a basis for human risk assessment for cleft palate Laura Vicario 1,∗ , Jill Dixon 1 , Magnus Rattray 1 , Emma Barnes 2 , Jayne Wright 2 , Michael Dixon 1 1 Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK, 2 Syngenta, Jealott’s Hill International Research Centre, Bracknell, UK
Cleft palate is a craniofacial birth defect that affects one in every 700 new-borns worldwide. This defect results from a disruption in the development of the secondary palate (palatogenesis) which can be caused by several genetic and environmental factors. Morphologically, palatogenesis in mice, rats and humans consists of the same steps: Palatal Shelves (PS) development and growth, elevation, contact and fusion. However, whereas the mouse is the most commonly used species for the study of palatogenesis, the rat is the species used in human risk assessment studies. Although it is assumed that the molecular pathways underlying palatogenesis in mice, rats and humans are similar, this assumption has not been verified. The aim of this project is to identify the pathways underlying palatogenesis in the mouse and rat to verify species similarities. With that purpose, the gene expression patterns of the rat palate during eight stages of palatogenesis were obtained through RNAseq analysis; and the results corresponding to a subset of genes with a known essential role in mouse palatogenesis were compared with their mouse orthologues. This initial analysis indicated similar expression patterns between mice and rats, which suggests that the principal pathways underlying palatogenesis are conserved in both species. Further analysis are expected to secure the reliability of these results and to provide more information about the molecular pathways that are relevant for palatogenesis in mice, rats and humans. http://dx.doi.org/10.1016/j.toxlet.2014.06.430 P-2.85 Speciation of manganese in drinking water Paul Rumsby 1 , Leon Rockett 1,∗ , Helen Clegg 1 , Jorgen Jonsson 1 , Victoria Benson 1 , Mark Harman 1 , Tom Doyle 1 , Lesley Rushton 2 , David Wilkinson 3 , Peter Warwick 3 1
National Centre for Environmental Toxicology, WRc, Swindon, UK, Imperial College Consultants, Imperial College, London, UK, 3 Enviras, Loughborough University, Loughborough, UK 2
Although manganese (Mn) is an essential element, neurotoxicity by inhalation has been widely described, particularly in workers and miners, where exposure is relatively high. Recently, there have been a number of studies suggesting that oral exposure to manganese in drinking water may have adverse effects on neurological development in children. WRc has undertaken a study for the Drinking Water Inspectorate reviewing data on the potential neurotoxicity of oral manganese exposure and conducting four seasonal monitoring surveys in final drinking water at 20 sites, which measured total and soluble man-
ganese to estimate the concentration of the more biologically available Mn(II), and Mn(IV). The review of the literature on studies in experimental animals, suggests that there is a biologically plausible hypothesis for an adverse effect on neurological development of oral exposure to manganese. There is an accumulation of manganese in the same areas of the brain which accompanies neurotoxicity following inhalation of manganese, together with behavioural and locomotor effects. The human epidemiological studies, particularly on children, are suggestive of effects on intellectual and cognitive development. However, the types of studies conducted have limitations and are not the most appropriate for measuring the longer-term effects, such as those which may occur after accumulation of manganese in the brain. The sampling exercises indicated that public water supplies had low levels of manganese (majority below 5 g/l), and levels of the Mn(II) form were approximately 50% of total manganese. However, two private boreholes had higher levels of Mn, all in the Mn(II) form. http://dx.doi.org/10.1016/j.toxlet.2014.06.431 P-2.86 Science and policy in risk-based occupational exposure limits Linda Schenk 1,2,∗ , Qian Ding 1 , Sven Ove Hansson 1 1
KTH-Royal Institute of Technology, Stockholm, Sweden, 2 Karolinska Institutet, Stockholm, Sweden Risk-based occupational exposure limits (OEL) provide an opportunity to study how differences in the exposure limits set by different regulators are influenced by differences in the scientific judgment (what is the risk at different exposures?) and in the policy judgment (how large risks are accepted?). In a broad search seven regulators were identified that had set at least one OEL to which risk-levels were associated, four of these also identified two risk different risk levels: a tolerable risk (that should not be exceeded) and acceptable risk (below which exposure is considered negligible). For ten substances two or three risk-based OEL have been derived. For benzene such data was available from six regulators. The highest tolerable risk level was 4 times higher than the lowest, and the highest accepted risk 10 times higher than the lowest. These values are related to policy-based concerns. The differences in estimates of the risk/exposure relationship, i.e. the scientific judgement, were for most substances in within the same range. The largest differences were found for refractory ceramic fibres (a factor of 56) and for benzene (a factor of 13). For refractory ceramic fibres the database is less developed than many other substances in our selection, also there was a 15-year time difference between the newest and oldest OELs. For benzene the difference is explained by variation in exposure estimates for the Pliofilm cohort. We conclude that the science factor and the policy factor both contribute about equally to differences in risk-based OELs for carcinogens. http://dx.doi.org/10.1016/j.toxlet.2014.06.432