Experiences with Exposure Models for Estimating the Bioavailability of Lead (Pb) in Children in the EU

Transcription

1 18 September 2012 Experiences with Exposure Models for Estimating the Bioavailability of Lead (Pb) in Children in the EU Dr. Camilla Pease Senior Manager, Eurotox Registered Toxicologist. Human Health Risk Assessment of Pb Health Concerns of Pb Exposure Sources & Pathways of Pb Exposure Estimating Human Systemic Exposure of Pb Risk/Impact Assessment & Policy Making Contexts

2 Health Concerns of Pb Exposure Effects and symptoms vary depending on the individual and the dose/duration of lead exposure Acute Pb poisoning >70 μg/dl blood: Observable clinical symptoms include - abdominal pain, anaemia, confusion, irritability, seizures, coma and death Chronic exposures to Pb non thresholded toxicity from elevated blood and tissue levels (even at <10 μg/dl blood) Renal effects Cardiovascular effects Neurobehavioural effects Children and pregnant women are sensitive subpopulations - irreversible effects of exposure in the developing child Detection of Pb in the blood & bone health surveys Health Concerns of Pb Exposure Neurobehavioural problems in children most sensitive effect non-thresholded Lanphear et al., 2005 Low-Level Environmental Lead Exposure and Children s Intellectual Function: An International Pooled Analysis. Childrens Health, 113, e.g. EFSA 2010 Opinion BMDL 01 = 1.2 μgpb/dl blood Reductions in Intelligence Quotient (I.Q.) [Endpoint = 1point drop in I.Q.]

3 Potential Sources of Pb Exposure in Children Intake Pathways of Pb Exposure in Humans Using exposure scenarios to obtain relevant metrics of human exposure e.g. mg/kg-bw/day mg/m 3 μg/cm 2 μg/dl blood

4 Consumer Product Safety Experience IEUBK model for Pb exposure in children US EPA Integrated Exposure Uptake BioKinetic (IEUBK) model The model and supporting guidance and technical manuals can be accessed via the US EPA website Translates intakes (mg/day) to uptakes as blood Pb levels Uses a set of kinetics algorithms to describe the biokinetics of absorption & elimination The model considers children s exposure to all sources of environmental Pb in Air, Soil & Dust, Water, Food, Alternative. Multiple sources of all environmental Pb exposures combined in a user-defined way Consumer Product Safety Experience IEUBK model parameters Approximately 140 parameters in the model that can be userdefined Background data (including body weights and blood volume data) is from US sources as specified in the technical guidance provided on the EPA website.

5 Screenshots of IEUBK model Consumer Product Safety Example: Toys Children s Body Weight Data Comparison

6 Lead modelling of exposures from soil using IEUBK and default values Action standard withdrawn by JECFA and EA in 2011 ~840 mg Pb/kg soil New CDC May 2012 action standard ~330 mg Pb/kg soil NB. The above soil values are generic and default. Site specific assessments in DQRA may yield higher or lower values in soil leading to the same blood level Lead modelling of exposures from soil using IEUBK and default values CDC May 2012 action standard ~330 mg Pb/kg soil EFSA BMDL value ~20 mg Pb/kg soil NB. The above soil values are generic and default. Site specific assessments in DQRA may yield higher or lower values in soil leading to the same blood level

7 Consumer Product Safety Example Case study: Alternate Source - Children s Toys A) Consider type of toy/material to be assessed e.g. Children s paints Modelling clays Painted toys - flaked off paint B) Seek data on habits & use e.g. RIVM report / Chemicals in Toys Dry powder like material 100mg/day ingestion Liquid sticky material 400 mg/day Painted toys - flaked off paint 8mg/day C) Assume oral ingestion is main route of toy material; inhalation and dermal routes negligible Consumer Product Safety Example Case study: Alternate Source - Children s Toys Estimating blood Pb levels from intake levels: Step 1: Estimate daily oral Intake of substance into the stomach of a child (mg/day) e.g. for dry brittle powder-like material Analysis 13.5 mg migratable Pb/kg toy material (EU Toys Directive - maximum) If a child ingests 100 mg/day of this material then: 13.5 mg Pb/kg toy material is equivalent to 13.5 microgram Pb/g toy material Equals 1.35 microgram Pb/day ingested in 100 mg toy material (= intake/day). (NB. Of this ingested intake, 50% is estimated to be absorbed across the gut into the systemic circulation = 0.7 microgram Pb uptake/day) Step 2: Use of the IEUBK model to calculate blood levels of Pb Step 3: Comparison of i) blood levels with health guidance value/action standards ii) overall impact on total exposure of making changes to specific intakes

8 Consumer Product Safety Experience Modelling alternate exposures (other than environmental sources) All air, soil, dust, water defaults used in model (background exposures) Intakes by Source and Calculated Blood Lead ***************************************** ***************************************** CALCULATED BLOOD LEAD AND LEAD UPTAKES: DEFAULT VALUES CALCULATED BLOOD LEAD AND LEAD UPTAKES: No Change scenario ***************************************** ***************************************** Year Air Diet Alternate Water Year Air Diet Alternate Water (µg/day) (µg/day) (µg/day) (µg/day) (µg/day) (µg/day) (µg/day) (µg/day) The impact of different sources of exposure can be compared Consumer Product Safety Experience Conclusions IEUBK is a useful tool to model the impact of Pb exposures from various sources Represents the best kinetic model available for modelling Pb blood levels in children Relevant for EU children (mean weight ranges) Parameters can be modified with site/scenario specific data

9 Risk/Impact Assessment & Policy Decisions A 40 year history 1970 Centre for Disease Control USA (60 μg/dl action level) 1971 CDC USA (40 μg/dl action level) 1978 CDC USA (30 μg/dl action level) 1985 CDC USA (25 μg/dl action level) 1991 CDC USA/WHO 1995 (10 μg/dl action level) 2002 UK Environment Agency (10 μg/dl action level) May 2012 CDC USA (5 μg/dl action level) 2010 EFSA BMDL01 (1.2 μg/dl) EU status 2012: How to best interpret the new science in a policy context?