Toxicology and Metabolism Relating to Occupational and Residential Chemical Exposures Robert I. Krieger 1 , Jeffrey H. Driver 2,3 , John H.Ross 2,4 1 Personal Chemical Exposure Program, Dept. of Entomology, University of California, Riverside, 2 infoscientific.com, Inc., Manassas, VA 3 and Carmichael, CA 3
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Toxicology and Metabolism Relating to Occupational and Residential
Chemical Exposures
Robert I. Krieger1, Jeffrey H. Driver2,3, John H.Ross2,4
1Personal Chemical Exposure Program, Dept. of Entomology, University of California, Riverside, 2infoscientific.com, Inc.,
Manassas, VA3 and Carmichael, CA3
Chemical Exposure
Chemical contact with potential absorption• Ingest, inhale, touch• Amount [dose (mg), dosage (mg/kg)]• Time [acute, short term, chronic]• Response [benignNOEL,NOAEL to lethalLD50]
Determinants of quality and longer life include lower incidence of disease, fewer accidental deaths, a safer food supply, and access to improved
pharmaceuticals, pesticides and numerous other chemical technologies.
Age-Adjusted Death Rates by Class of Injury, U.S.A. (1910-2004)
Dea
th R
ates
a
Pesticide and Chemical Human Exposure Classes
• Accidental– Workplace (U.S. National Safety Council)– Home (young children, U.S.A.)
• Unintended– Occupational– Residential
• Unavoidable – Food – Water – Air – Surfaces
Research Strategy PCEP, UCR after Collins, IUPAC
• Commodity chemicals exposures–2,4-D, OPs, chlorpyrifos, malathion, captan–Variety of use conditions (not scenarios)
• Proprietary chemicals stewardship–Speeds product registrations–Uses validated exposure data
Well known safe uses of commodity chemicals, to study generic exposure factors, to promote the registration, stewardship and general knowledge of prorietary products.
Accidental Pesticide Exposures
• Rare (catastrophic)• Short term (seconds, min, hrs, days)• Response: toxicity
– Death (LD50)– Target organ effects (ED50)
• Regulation– Restricted Materials & Engineering Controls– Training for safe use– Personal Protective Equipment
Leading Causes of Death U. S. A., 2004
All causes 2,443,000
Heart disease 697,000
Cancer 557,000
Stroke 163,000
Chronic lung disease 125,000
Unintentional injuries 107,000Diabetes 73,000
Flu 66,000
Deaths, 2004 Total Rate/million
All unintentional injuries 111,000 378Motor vehicle accidents 46,200 157Falls 20,200 69Poisoning 13,300 45Choking 4,900 17Fires and smoke 3,900 13Drowning 3,800 13Suffocation 1,300 4Heat or cold 1,200 4
All others 16,200 55
Accidental U. S. Deaths, National Safety Council, 2005-2006
Estimated Chlorpyrifos Exposure from Indoor Broadcast Use
Study Estimated Dosage (ug/kg)
Berteau et al. (1989) 2700Nafzigger (1985) 38Fenske et al. (1990) 75-160Vacaro et al. (1990) 21-31Ross et al. (1990) 7-25Gurunathan (1998) 64-356Krieger et al. (2001) 1-3
How Can There Be 1,000-Fold Difference for One Chemical?
• Regulatory concern mandates overestimates• Hypothesized importance of a particular exposure route• Use of non-validated models vs. measurements from
individuals• Use of methods never quantitatively related to human
exposure• Structured activity vs. Situational biomonitoring
Biomonitoring Is a Gold Standardfor Model Validation
Biomonitoring MODEL Env Monitoring⎯ →⎯⎯⎯⎯⎯⎯ ← ⎯⎯⎯⎯⎯⎯⎯⎯
The Case for Biomonitoring and Aggregate Exposure Estimates
• Cumulative estimates require adding aggregates from individual pesticides
• Errors from each aggregate exposure multiply with cumulative estimate
• Best exposure estimates are measured closest to person, not closest to source
Biomonitoring Uncertainties
• Biomarker >> parent in/on food, in water, on foliage or residential surfaces
• Biomarker may be well absorbed dermally• Biomarker is well absorbed orally (from food or hand-to-
mouth)• Biomarker is frequently more environmentally stable
than parent pesticide e.g., CP and TCP or CP and Diethyl phosphate
Dietary DAPs Confound Estimates of OP Exposure Based on Biomonitoring
• 33 Produce types monitored at the farm gate• All samples selected contained measurable OPs• 66% had more DAP biomarker than parent OP• Mole ratio of DAP/OP = 0.1-73• DAPs are less-well absorbed orally, but if DAP>OP, a
large, significant overestimate of OP exposure will occur Zhang and Krieger, 2004
Studying Residential Exposure Structured vs. Situational
Chemical residues, signatures of thriving in the 21st Century
“More and more about less and less”
Demonstrate the power of advanced analytical chemistry and the naiveté of myopic policy-makers and the public.
The persistence issue is an opportunity for teaching and enlightenment!
POPs
CDC Biomonitoring 21st Century Chemical Biomarkers
Ever-present signs of life in blood and urine of the living
“the most comprehensive assessment of chemical contamination in individuals ever performed.”
Environmental Biomonitoring Chemical Inventories
• CDC/March 2001 27 chemicals
• CDC/January 2003 116
• CDC/June 2005 143
• EWG/Mt.Sinai 167 (total, n = 9)
Stimulates media fear-mongering and reports that alarm the chemically naïve public who are then bombarded with scary lists of health hazards; and, finally the sponsors seek more regulation of vanishingly small, benign amounts of chemicals in blood and/or urine.
CDC 3rd Report of 2005, 143 chemicals; promises 300 by 2007 and perhaps 700 by 2011!
Valuable perspective on pesticides, but present metabolite misclassification needs revision. Active ingredients are not that persistent.
U. S. Communicable Disease Center 3rd Report on Chemical Exposure, 2005
• Organochlorine Pesticides
• Organophosphate Pesticide
• Pyrethroids Pesticides (sic)• Carbamate Insecticides• Herbicides• Other Pesticides
• Organochlorine Pesticides and Biomarkers
• Organophosphorous Pesticides and General Biomarkers
• Organophosphorous Pesticides and Specific Biomarkers
• Pyrethroid Pesticide Biomarkers• N-Methyl Carbamate Biomarkers• Herbicidal Pesticides and Biomarkers• Other Pesticides and Biomarkers
Present Misclassification Suggested
Pesticide Use andHuman Chemical Exposureare inseparable at some level...whether Accidental, Unintentional or Unavoidable.
Biomarkers in our chemical world can clarify the significance of trace amounts…
There is a safe level of everything!
Personal Chemical Exposure ProgramDepartment of Entomology
University of California, Riverside, CA 92521Bob Krieger, Ph.D. (951) 827-3724