Applying Toxicology Data to the Environment

1
Applying Toxicology Data to the Environment

• Jennifer Lowry, MD
• Medical Director,
• Mid-America Poison Control Center
• University of Kansas Medical Center

2
Complications of Assessing the Environment

• Different species react differently to same
  toxin
  
• Pollutants may occur in more than one form or may
  be changed in the environment prior to exposure
  
• Toxic chemicals may be mutually additive,
  synergistic, or antagonistic
  
• Indirect effects of toxic chemical may be as
  important or more important than direct effects
  
• no mortality
• but, causes reproductive problems

3
Environmental Toxicology

• Requires an understanding of how chemicals can
  affect individuals, populations, communities, and
  ecosystems.
  
• Environmental toxicology testing attempts to
  evaluate cause-and-effect relationships at higher
  levels of organization (populations)
  
• integration of laboratory and field research
• critical to understanding the complex set of
  parameters that an organism must deal in order to
  reproduce or survive after exposure
  
• Increase in interest in relationship of
  environment and potential environmental stressors
  in human implications

4
Chemical Movement, Fate and Exposure

• Must measure a chemical in different
  environmental compartments
  
• air, soil, water and biological systems
• Understand the movement and transport of the
  chemical within and among those compartments
  
• Follow the chemical as it is metabolized,
  degraded, stored, or concentrated in each
  compartment

5
Chemical Behaviors

• Once chemical in environment, it is acted on by
  natural forces such as temperature, wind,
  water-flow, solar radiation, atmospheric pressure
  and humidity
• Different concentrations in air, water, soil, and
  living organisms
  
• movement of chemical concentrations (high
  concentration to low concentration)
  
• air evaporation, stack emissions, other
• water direct application, spills, wet and dry
  deposition and interphase movement
  
• soil similar to water. Effect depends on type
  of soil.
  

6
Bioavailability in Environment

• Only portion of total is potentially available
  for uptake by organisms.
  
• Water
• related to water solubility
• settle into sediments
• physical, chemical and biologic processes may
  change the chemical form
  
• Soil
• tight sorption or sequestration of contaminants
  with increasing residence time in soil may reduce
  fraction of the contaminant available to soil
  organisms.

7
Biomarkers

• Relating the presence of a chemical in the
  environment to a valid prediction of the hazard
  to potential biological receptors
  
• Biomarker of exposure
• detect presence of chemical. Can predict dose?
• Biomarker of effect
• biochemical, physiologic, behavioral, or other
  alterations in organism recognized as disease
  
• Biomarker of susceptibility
• endpoints indicative of biological state that may
  predispose person to effects later in life
  
• Biomarker interpretation
• caution needed (esp. species to species)

8
Endocrine Disruptors

• Compounds that cause alterations in endocrine
  system
  
• May have significant effects on pregnancy, sexual
  differentiation and development, and male-female
  behavioral patterns
  
• Initially observed in wildlife species
• Important tool in determining the risk posed by
  the environment
  
• Examples
• American bald eagle eggshell thinning, brain
  asymmetry
  
• african clawed frog sexual imprinting (100
  females)

9
Toxicity Tests

• Designed to determine the short- and long-term
  effects of chemical exposure on a variety of
  endpoints
  
• Provides a critical foundation for evaluating the
  exposures and effects encountered in the field
  and for linking cause and effect
  
• Results can be used to determine
• pathologic effects of contaminants
• provide data necessary to analyze effects
  discovered in field tests
  
• identify potential effects to be aware of
• provide dose-response data for comparison to
  exposure levels in the field

10
Population and Community Effects

• Determine the effects of environmental
  contamination on density, abundance, or biomass
  of indigenous organisms
  
• Chemical interactions and natural stressors
• Effects on populations can be predicted using
  mathematical models
  
• abundance, age distribution, age-specific
  mortality and fecundity
  
• Changes in communities
• direct mortality or decreased reproduction
• indirect eg. loss of food supply, loss of home

11
Terrestial Testing

• Exposed through ingestion, inhalation, and skin
• Toxicity testing
• oral dosing primarily
• measure LD50, LC50, ED50,, EC50 , and
  reproductive tests (fertility, egg hatchability,
  neonate survival)
  
• Field testing
• testing in natural environment
• conducted in complex ecological systems where
  plants and animals are affected by natural
  stressors and contaminants
  
• compare contaminated sites to noncontaminated
  sites

12
Aquatic Testing

• Certain chemicals are not volatile in air but are
  soluble in water (eg. Metals) and others will not
  degrade over time due to lack of aerobic
  conditions.
• Toxicity testing
• used to measure the toxic effects of chemicals or
  contaminated water collected from the field
  
• enviromental monitoring and verifying compliance
• Sublethal effects
• tumors or infections and parasitic infestations
• can have effect on population levels

13
Aquatic Testing

• Field Testing
• manipulative or observational
• endpoints are assessed by exposing caged
  organisms to contaminated water, sediment, or
  both
  
• monitor for mortality and reproductive
  impairments
  
• difficult to assess overt toxicity except in
  massive mortality resulting in morbidity results
  more common
  
• other assessments
• chemical bioavailability to aquatic animals
• possible health risks to humans who might consume
  organisms
  
• modeling accumulation and effects in organisms at
  higher trophic levels

14
Risk Assessment

• Need to assess and quantify the impact of toxic
  chemicals on organisms, their populations, and
  communities
  
• determine potential pathways and species that may
  be affected by the toxic substance using routes
  of exposure, the organisms of concern, and
  anticipated endpoints
• use exposure data and toxic effects of chemical
  of interest to determine risk
  
• consider other issues such as sublethal effects
  and population/community impacts

15
Problems to be addressed

• Need well designed systems for summarizing and
  analyzing the existing tox information and
  assembling database to assess trends in toxic
  agents in environment
• ATSDR - Toxicological Profiles
• EPA - Toxics Release Inventory
• CDC - National Report on Human Exposure to
  Environmental Chemicals
  
• Need uniform system for classifying the risk of
  toxic exposures
  

16
Human versus Wildlife

• Four steps of risk assessment
• hazard identification
• dose-response assessment
• exposure assessment
• risk management
• Links serve as premise for extrapolation in risk
  assessment
  
• share some cellular and subcellular mechanisms
• overlap in physical environment
• difficulty due to shorter life span of animal
• reversible versus irreversible

17
The interconnections between ecological health
and human health should not be overlooked. The
indirect effects of environmental pollution may
in the end be more important than the direct
effects for human health. The environment is
thought to act as a buffer for both toxicants and
disease. However, even a buffer has its limits.
RJ Kendall et al. Ecotoxicology
Essentials of Toxicology. 2003