Human exposure through the environment 2010

1 Human environmental exposure Martin van den Berg Institute for Risk Assessment Sciences Utrecht University Primary routes of human exposure to chemicals ! In the ambient environment:   Dust and vapor inhalation   Dermal contact with contaminated soil or dust   Ingestion of contaminated food, water, dust or soil ! In the workplace environment:   Predominant route is inhalation or dermal contact   Minor dust ingestion and hand to mouth contact 2 The environmental pathways to human exposure (Paustenbach 2002) Concepts of exposure and dose !   Actual contact of the organism !   Actual entry of the chemical (crossing a boundary) !   Degree of absorption leads to (bio) availibility and amount of chemical that is toxicological relevant !   This is internal or target tissue dose influenced by body distribution factors 3 Crossing the boundary from the “outside to the inside” ! Intake:   Physical movement from the chemical by inhalation, eating or drinking   Chemical contained in medium such as food, soil, dust or water ! Uptake:   Physical uptake and transport across a boundary in the body (e.g. skin or GI-tract) that is a cell layer   Transport medium is usually not absorped with same rate as the chemical Bioavailability Lipophilicity Concept of applied, potential and internal dose ! Applied dose:   Amount of chemical available at the absorption barrier (e.g. lung, GI tract,skin) ! Potential and internal dose:   This is the difference with applied dose   This is the toxicological relevant parameter after body distribution has been taken into account Biological relevant dose (BED) is ultimate goal for exposure assessment ! Xeno-estrogens and kinetics 4 Integrated exposure Area under the curve (AUC) !   Identification of:   Duration and periodicity of exposure   Amount of peak exposure   Shape of the area under the time concentration curve   (Ref. Paustenbach et al 2002) Determining (Lifetime) Average Daily Dose (LADD and ADD) 5 Time weighted average dose (Lifetime) average daily dose (L)ADD 6 Quantifying Exposure ! Direct measurement   Integrating exposure concentration and time of contact ! Exposure scenario   Hypothetical exposure, but realistic ! Biomonitoring Data   Using internal indicators: biomarkers, excretion levels, body burden Gasses Occup exposure Worst case Types of biomonitoring sampling !   Method !   Breath !   Blood !   Adipose !   Nails, Hair !   Urine !   Blood, urine, hair !   Example !   Volatile organics, alcohol; !   Lead, pesticides, heavy metals !   Chlorinated pesticides, dioxins !   Heavy metals !   Tetra/trichloro-ethylene !   Drugs, pharmaceuticals 7 Obtaining Uptake and Intake data !   Large number of variables e.g.:   Drinkingwater consumption   Consumption fruit, vegetables, beef, dairy etc   Consumption recreation caught fish   Incidental soil ingestion rate   Effective surface area of the body Hormones Lipophilic compounds Pesticides Lipophilic compounds Some standard assumptions for exposure (EPA 1996) 8 Direct and indirect exposure pathways An example Municipal Incinerators (D. Paustenbach et al, 2002) Dioxins and heavy metals Bioavailibility Breastmilk Dioxins in foodstuff in the Netherlands and effect of lifestyle (Liem and Theelen, 1997) Dutch Turks General Dutch population 1 % or more of Turks exceeds 10 times the WHO TDI 9 Percentage of Dutch population exceeding the TDI of dioxin in The NL (Liem and Theelen 1997) > 80% exceeds WHO TDI 1-1.5% exceeds 10x WHO TDI More than 150.000 people Infant Influence of animal (dairy) products on the exceedence in the Dutch population (Liem and Theelen,1997) Aslight increase e.g. from 4 to 5 pg TEQs/ g fat means a few % of the Dutch population exceeds TDI and involves easily more than 100.000 people 10 What are background levels? !   “Pristine” levels: Not similar to background levels as areas without anthropogenic influence do not exist anymore on this planet !   “Normal” levels: Average levels that are found e.g. in rural areas without significant influence of industry, traffic or geochemical anomalies !   “Historically polluted regions”: E.g. densely populated regions that have been polluted by e.g. industry, mining and traffic !   Geochemical variation: Background “natural” levels of toxic elements (e.g. heavy metals) may vary with regions due to geochemical variations (e.g. arsenic in the US) Dermal transport of chemicals !   Major determinants: solubility (Kow) and matrix/medium (bioavailability) !   Transport inverse function of molecular weight and volume Consequence: hydrophobic agents with low MW permeate better than hydrophilic agents with high MW. For small molecules hydrophobicity major factor dermal penetration !   Lipophilic compounds tend to accumulate in stratum corneum !   Decreasing Permeability: foot/sole > palm > scrotum > forehead > abdomen [...]... products with synthetic foam •  Continuation fumigation food products and “close contact” consumer producten use a sticker for consumer warning about possible risks Bijv: This product is fumigated and possibly damages your health and the environment •  The use of fumigation of pharmaceutical never allowed! SO –  Risk of damaging the quality of the reactive part of the pharmaceutical by the methylbromide... molecular and biochemical techniques (e.g genomics and proteomics) more identification of biomarkers, but how relevant are these effects with respect to the real observed adverse dose response relationships 19 L L A definite must for the risk assessment! Human and Ecological Risk Assessment Theory and Practice By Dennis J Paustenbach (Wiley-Interscience, New York, 2002) 20 ...Estimation of uptake via the skin (Fick’s law of diffusion at steady state) !   Partition parameter Kp is key parameter and be approached with Kow Key factors that influence dermal uptake of xenobiotics from the environment !   Bioavailability: large impact on uptake and depends on the organic content soil !   Skin surface area: use rule of “nines” 9 percent... or lymphatics Direct penetration small particles epithelial membranes -> blood or lymphatics 16 Degree of response Methylbromide/Dichloorethaan in containers: Interpretation measurements ZfAM (Germany/Netherlands) Increasing exposition Safety standard air/product No effect animal ? Lowest effect Safety margin 100 1/10 inter humans * 1/10 animals -> humans Harbor personel (not protected) Wharehouse personel... percent for each lower limb Front of back of the trunk also each 18 percent US EPA estimates exposed area of 2900, 3400 and 2940 cm2 for children from 0-2 and 2-6 years, and adults !   Actual soil loading on the skin: 0.5-6 mg/cm2 and 0.2 to 2.8 mg/ cm2 for adults and children 11 Calculation of dermal uptake of chemical in gaseous or aqueous media (Paustenbach 2002) Human cutaneous permeability coefficients... damage, strong neurological and behavioral effects kidney/stomach effects L T RA N human University of Utrecht Institute for Risk Assessment Sciences Prof dr Martin van den Berg 17 L L Degree of response Dichloorethaan: Exposure and Effects Increasing exposition Safety standard air/product No effect animal ? Lowest effect human Veiligheids marge Most important for sensitive unprotected consumers Chronic... coefficients (cm/h) in aqueous medium (From Paustenbach 2002) 12 Representative surface area’s of the male human body (Paustenbach 2002) US-EPA suggested method for percutanous absorption from soil: An example: Skin uptake of a chemical from water (from Paustenbach 2002) 13 !   Soil ingestion !   Indoor and outdoor exposure !   Varies strongly with age, most significant between 2 and 7 years !   Uptakes varies... Sciences Prof dr Martin van den Berg Some significant issues in exposure assessment !   Bioavailability – relevant for food, soil and airborne particles !   Chemical fate – (bio)degradation e.g by sunlight, oxidation, hydroxylation and microorganisms !   Biomarkers and molecular epidemiology – e.g Proteins, RNA, DNA and their adducts !   What is the toxicological relevance? !   With increasing molecular... unit/kg bw – day) Lifestyle is major uncertainty in determining actual uptake for the population Lipophilic contaminants mostly via dairy, meat and fish Uptake pesticides also through vegetables and fruit (Table from Paustenbach 2002) 14 !   Breast milk – a special situation !   TDI or ADI not applicable (no life time exposure) !   Accumulation of lipophilic compounds (e.g PCBs, dioxins) and drugs !... Wharehouse personel (not protected) Consumers OS SO L VS I V ST I T RA N Institute for Risk Assessment Sciences Prof dr Martin van den Berg University of Utrecht T IÆ I L L Degree of response Methylbromide: Exposure and Effects Increasing exposition Safety standard air/product No effect animal ? Safety margin Most important for unprotected consumers Chronic– low: Irritation lungs (inhalation) and GI tract(oral), . 1 Human environmental exposure Martin van den Berg Institute for Risk Assessment Sciences Utrecht University Primary routes of human exposure to chemicals ! In the ambient environment: . soil ! In the workplace environment:   Predominant route is inhalation or dermal contact   Minor dust ingestion and hand to mouth contact 2 The environmental pathways to human exposure. –  Risk of damaging the quality of the reactive part of the pharmaceutical by the methylbromide This product is fumigated and possibly damages your health and the environment O S S T I I Æ L L V S T R A N O S L V I I T