1
S48 Abstracts / Toxicology Letters 196S (2010) S37–S351 postnatal month as well as the maximum concentration reached during the first 14 months. Mothers enrolled in this cohort had a median blood concentration (5–95th percentiles) of 34 (7–76), 41 (7–125) and 119 (42–518) ng/g lipids for PCB-153, HCB and DDE, respectively. Median cord blood levels were slightly lower than median maternal levels. Infant maximum blood concentrations were on average two-fold higher than maternal levels with median values (5–95th percentiles) of 66 (15–199), 72 (13–250) and 227 (55–1258) ng/g lipids for PCB-153, HCB and DDE, respectively. The infant toxicokinetic profiles simulated using PBPK modeling will be used to thoroughly investigate associations between internal levels during different postnatal time windows and neurodevelop- ment measurements. This approach will be applied to the six other Spanish longitudinal birth cohorts involved in the INMA project. doi:10.1016/j.toxlet.2010.03.194 P102-011 Modeling the impact of short-term variations in trihalomethane drinking water levels on internal exposure C. Catto 1 , M. Rodriguez 2 , J. Lavoué 1 , G. Charest-Tardif 1 , R. Tardif 1 1 Université de Montréal, Canada, 2 Université Laval à Québec, Canada The variability in trihalomethane (THM) levels in drinking water raises the question as whether or not the short-term vari- ations (within-day) should be accounted for when assessing exposure to those contaminants suspected for carcinogenicity and reprotoxicity. This work aims at determining the magni- tude of the impact on the predicted biological levels of THMs (internal doses) exerted by within-day variations of THMs in drink- ing water. A database, excerpted from a campaign in Quebec city’s distribution system, allowed producing 81, 79 and 64 con- centration profiles for the three most abundant THMs, namely chloroform (TCM), dichlorobromomethane (DCBM) and dibro- mochloromethane (DBCM), respectively. Using a physiologically based toxicokinetic (PBTK) modeling approach, we simulated expo- sures (1,5 L water/day and a 10-min shower) based on each of these profiles and predicted, for 2000 individuals (Monte-Carlo), the maximum blood concentrations (C max ), the areas under the time versus blood concentrations curve (24 h-AUCcv) and the absorbed doses (AD). Three different hypotheses were tested: (A) assuming a constant THM concentration in water (e.g., mean value of a day); (B) accounting for within-day variations in THM levels; and (C) a worst-case scenario assuming within-day vari- ations and showering while THM levels are maximal. For each exposure profile, exposure indicator and individual, we calculated the ratios of values obtained according to each hypothesis (e.g., C max B/C max A and C max C/C max A) and the values corresponding to the 5th and 95th of these ratios. The more these percentiles are close to the value of 1, the less is the error of assuming constant THM concentrations rather than their actual variability. Results showed that the minimal gap between these percentiles was for TCM-ADB/TCM-ADA (5th; 95th = 0.91; 1.08) whereas the maximal was for CDBM-C max C/CDBM-C max A (5th; 95th = 0.50; 3.40). Overall, TCM and AD were the ones less affected (TCM < DCBM < DBCM and AD < AUCcv < Cmax). (Supported by RRSE, FRSQ) doi:10.1016/j.toxlet.2010.03.195 P102-012 Data harmonization: Comparative study of four poison centres using INTOX data management system software J.C. Rios Bustamante 1 , L. Fruchtengarten 2 , C. Meneses 3 , A.M. Lynch 4 , J. Tempowski 5 , M. Bettini 1 , J.J. Mieres 1 , A. Zucollo 2 , E. Paris 1 1 Centro de Información Toxicológica de la Facultad de Medicina, Pontificia Universidad Católica de Chile, Chile, 2 Poison Control Centre of Sao Paulo, Brazil, 3 Centro de Informacion y Asesoramiento Toxicológico, Ecuador, 4 Western Australian Poisons Information Centre, Australia, 5 WHO IPCS International Programme on Safety, Geneva, Switzerland The INTOX data management system (INTOX-DMS) is a multilin- gual data collection tool using controlled and defined terminology, developed by WHO to register cases in poison centers. The pur- pose of this study was to evaluate the usefulness of the software to compare data from four different centers: Poison Information Center of the Catholic University (CITUC), Chile; Poison Control Centre of Sao Paulo (CCI-SP), Brazil; Centro de Información y Aseso- ramiento Toxicológico (CIATOX), Ecuador; and Western Australian Poisons Information Centre (WAPIC). All calls received in 2008 were compared. Data were recovered using a report tool included in the software, or by Microsoft Access ® queries (WAPIC). All cen- ters successfully produced reports on: total number and type of communications, number of communications per month, cases of human exposure by agent category and circumstance, cases of human exposure by agent category, age group and gender. In total, there were 63,599 cases: WAPIC 30,277, CITUC 25,037, CCI-SP 7807 and CIATOX 478. Adult (20–75 years) cases were distributed as follows: CITUC 42.7%, CCI-SP 37.8%, CIATOX 59.0% and WAPIC 36.6%, while children younger than 5-years were: CITUC 32.3%, CCI-SP 40.7%, CIATOX 7.3% and WAPIC 47.5%. Pharmaceutical prod- ucts were the main agent involved CCI-SP (46.4%), CITUC (55.9%), WAPIC (43.8%), except for Ecuador where pesticides predominated (31.2%). Gender was evenly distributed except for Chile where women comprised over 60% of exposures. These results show that the INTOX-DMS is a useful tool for comparative data collection between different poisons centres working in different languages. In conclusion, data recovered from the INTOX-DMS from different parts in the world could assist in creating an international toxi- covigilance network. This registry would be useful to plan global as well as local strategies to prevent poisonings. doi:10.1016/j.toxlet.2010.03.196 P102-013 Global DNA methylation in relation to DDT exposure and genetical susceptibility among pregnant women in Morelos, Mexico R. Ruiz-Ramos 1 , L. Torres-Sanchez 2 , M. La Merrill 3 , L. López-Carrillob 2 , J. Chen 3 , M.E. Cebrián 1 1 CINVESTAV-IPN, 2 INSP, 3 Mount Sinai School of Medicine DNA hypermethylation is associated with gene silencing in contrast to hypomethylation that is related to gene expression; both events may be induced by genetic such as one-carbon metabolic genes, and environmental factors, such as DDT and folate. Methylenete- trahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA methylation. Mexico has one of the highest prevalence of the variant allele of the MTHFR 677C > T

Data harmonization: Comparative study of four poison centres using INTOX data management system software

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Page 1: Data harmonization: Comparative study of four poison centres using INTOX data management system software

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48 Abstracts / Toxicology L

ostnatal month as well as the maximum concentration reacheduring the first 14 months. Mothers enrolled in this cohort had aedian blood concentration (5–95th percentiles) of 34 (7–76), 41

7–125) and 119 (42–518) ng/g lipids for PCB-153, HCB and DDE,espectively. Median cord blood levels were slightly lower thanedian maternal levels. Infant maximum blood concentrationsere on average two-fold higher than maternal levels with median

alues (5–95th percentiles) of 66 (15–199), 72 (13–250) and 22755–1258) ng/g lipids for PCB-153, HCB and DDE, respectively. Thenfant toxicokinetic profiles simulated using PBPK modeling wille used to thoroughly investigate associations between internal

evels during different postnatal time windows and neurodevelop-ent measurements. This approach will be applied to the six other

panish longitudinal birth cohorts involved in the INMA project.

oi:10.1016/j.toxlet.2010.03.194

102-011odeling the impact of short-term variations in

rihalomethane drinking water levels on internal exposure

. Catto 1, M. Rodriguez 2, J. Lavoué 1, G. Charest-Tardif 1, R.ardif 1

Université de Montréal, Canada, 2 Université Laval à Québec,anada

he variability in trihalomethane (THM) levels in drinking wateraises the question as whether or not the short-term vari-tions (within-day) should be accounted for when assessingxposure to those contaminants suspected for carcinogenicitynd reprotoxicity. This work aims at determining the magni-ude of the impact on the predicted biological levels of THMsinternal doses) exerted by within-day variations of THMs in drink-ng water. A database, excerpted from a campaign in Quebecity’s distribution system, allowed producing 81, 79 and 64 con-entration profiles for the three most abundant THMs, namelyhloroform (TCM), dichlorobromomethane (DCBM) and dibro-ochloromethane (DBCM), respectively. Using a physiologically

ased toxicokinetic (PBTK) modeling approach, we simulated expo-ures (1,5 L water/day and a 10-min shower) based on each ofhese profiles and predicted, for 2000 individuals (Monte-Carlo),he maximum blood concentrations (Cmax), the areas under theime versus blood concentrations curve (24 h-AUCcv) and thebsorbed doses (AD). Three different hypotheses were tested:A) assuming a constant THM concentration in water (e.g., meanalue of a day); (B) accounting for within-day variations in THMevels; and (C) a worst-case scenario assuming within-day vari-tions and showering while THM levels are maximal. For eachxposure profile, exposure indicator and individual, we calculatedhe ratios of values obtained according to each hypothesis (e.g.,maxB/CmaxA and CmaxC/CmaxA) and the values corresponding tohe 5th and 95th of these ratios. The more these percentiles arelose to the value of 1, the less is the error of assuming constantHM concentrations rather than their actual variability. Resultshowed that the minimal gap between these percentiles was forCM-ADB/TCM-ADA (5th; 95th = 0.91; 1.08) whereas the maximal

as for CDBM-CmaxC/CDBM-CmaxA (5th; 95th = 0.50; 3.40). Overall,

CM and AD were the ones less affected (TCM < DCBM < DBCM andD < AUCcv < Cmax). (Supported by RRSE, FRSQ)

oi:10.1016/j.toxlet.2010.03.195

196S (2010) S37–S351

P102-012Data harmonization: Comparative study of four poison centresusing INTOX data management system software

J.C. Rios Bustamante 1, L. Fruchtengarten 2, C. Meneses 3, A.M.Lynch 4, J. Tempowski 5, M. Bettini 1, J.J. Mieres 1, A. Zucollo 2, E.Paris 1

1 Centro de Información Toxicológica de la Facultad de Medicina,Pontificia Universidad Católica de Chile, Chile, 2 Poison Control Centreof Sao Paulo, Brazil, 3 Centro de Informacion y AsesoramientoToxicológico, Ecuador, 4 Western Australian Poisons InformationCentre, Australia, 5 WHO IPCS International Programme on Safety,Geneva, Switzerland

The INTOX data management system (INTOX-DMS) is a multilin-gual data collection tool using controlled and defined terminology,developed by WHO to register cases in poison centers. The pur-pose of this study was to evaluate the usefulness of the softwareto compare data from four different centers: Poison InformationCenter of the Catholic University (CITUC), Chile; Poison ControlCentre of Sao Paulo (CCI-SP), Brazil; Centro de Información y Aseso-ramiento Toxicológico (CIATOX), Ecuador; and Western AustralianPoisons Information Centre (WAPIC). All calls received in 2008 werecompared. Data were recovered using a report tool included inthe software, or by Microsoft Access® queries (WAPIC). All cen-ters successfully produced reports on: total number and type ofcommunications, number of communications per month, casesof human exposure by agent category and circumstance, casesof human exposure by agent category, age group and gender. Intotal, there were 63,599 cases: WAPIC 30,277, CITUC 25,037, CCI-SP7807 and CIATOX 478. Adult (20–75 years) cases were distributedas follows: CITUC 42.7%, CCI-SP 37.8%, CIATOX 59.0% and WAPIC36.6%, while children younger than 5-years were: CITUC 32.3%,CCI-SP 40.7%, CIATOX 7.3% and WAPIC 47.5%. Pharmaceutical prod-ucts were the main agent involved CCI-SP (46.4%), CITUC (55.9%),WAPIC (43.8%), except for Ecuador where pesticides predominated(31.2%). Gender was evenly distributed except for Chile wherewomen comprised over 60% of exposures. These results show thatthe INTOX-DMS is a useful tool for comparative data collectionbetween different poisons centres working in different languages.In conclusion, data recovered from the INTOX-DMS from differentparts in the world could assist in creating an international toxi-covigilance network. This registry would be useful to plan global aswell as local strategies to prevent poisonings.

doi:10.1016/j.toxlet.2010.03.196

P102-013Global DNA methylation in relation to DDT exposure andgenetical susceptibility among pregnant women in Morelos,Mexico

R. Ruiz-Ramos 1, L. Torres-Sanchez 2, M. La Merrill 3, L.López-Carrillob 2, J. Chen 3, M.E. Cebrián 1

1 CINVESTAV-IPN, 2 INSP, 3 Mount Sinai School of Medicine

DNA hypermethylation is associated with gene silencing in contrastto hypomethylation that is related to gene expression; both eventsmay be induced by genetic such as one-carbon metabolic genes,

and environmental factors, such as DDT and folate. Methylenete-trahydrofolate reductase (MTHFR) is a critical enzyme in folatemetabolism and is involved in DNA methylation. Mexico has one ofthe highest prevalence of the variant allele of the MTHFR 677C > T