Chapter 9: Environmental Health & Toxicology

In this chapter we will cover the following topics:

I. Types of Environmental Health Hazards

II. Movement, Distribution, and Fate of Toxins

III. Mechanisms for Minimizing Toxic Effects

IV. Measuring Toxicity

V. Risk Assessment and Acceptance

VI. Establishing Public Policy

Types of Environmental Health Hazards

The World Health OrganizationUnder U.N. agreement, the World Health Organization (WHO) was founded in 1946, with roots that extend back into choleraepidemics of the 1830's. The WHO publishes an annual report on global health status. .

Infectious Organisms

• Infectious disease is 43% of all disease deaths annually • Adults: infections of respiratory tract represent highest mortality • Children: diarrhea represents highest mortality • AIDS: 30 million people infected worldwide, too expensive ($10,000/year) to treat in poor countries • Eradication: smallpox 1977, polio by year 2000 • Immunizations: in transgenic crops which would reach more people

Table 9.1 -- Leading Causes of Death Worldwide

Disease Millions of deaths / year

Cardiovascular disease 9.7Cancers 6.0Chronic lung disease 5.5Acute lung diseases 4.1Injuries 4.0Perinatal conditions 3.2 Diarrhea 3.0HIV/AIDS 2.3Malaria 2.0Vaccine-preventable infections 1.7Other known diseases 3.6Unknown 5.9

Total 51.0 Source: World Health Organization, 1997

Morbidity and Quality of Life

• DALY - disability-adjusted life year: attempt to measure other health factors besides death

• 90% of losses measured by DALY occur in developing countries • preventable measures: malnutrition, sanitation, clean water,

childhood inoculations could reduce infections • parasitic diseases contribute to poor health; combated by donations

of drugs e.g., ivermectin for riverblindness

Table 9.2 -- Annual Disease Burden in Poor Households Disease Group Main Source DALY Burden* Feasible Reduction (millions/year) (%) ---------------------------------------------------------------------------------------- Respiratory infections Indoor Air pollution, 119 15

crowding

Diarrhea Water supply, sanitation 99 40

Tuberculosis Crowding, malnutrition 46 10

Chronic respiratory Indoor air pollution, 45 10 diseases & cancer crowding

Parasites, worms Garbage disposal, 26 30 sanitation

Trachoma Water supply, hygiene 8 10 ---------------------------------------------------------------------------------------------------------- *Disability Adjusted Life Years = years lost from premature death and disability Source: World Bank, World Development Report 1998

Emergent diseases and environmental change

• Emergent Disease: disease never known before or one that has been absent for at least 20 years. - e.g., Ebola• High population density combined with loss of ecosystem components that normally control disease vectors, allows forappearance and spread of contagious diseases. - e.g., Hanta virus in U.S. - ecological change supports high

deer mouse (vector) populations• High travel rates help spread disease organisms all over the globe, especially dormant species that can breakout when moved to new location

Antibiotic and pesticide resistance

• Malaria - mostly Africa, both vector and disease protozoan are resistant to control measures

• Natural selection: repeated low-level exposures selectively produce resistant organisms

• Resistant strains: Tuberculosis, Staphylococcus A

• Reasons: indiscriminant use of antibiotics and pesticides

Toxic Chemicals

• Hazardous: dangerous - flammables, explosives, irritants, sensitizers, acids, and caustics

• Toxins: poisonous - react with specific cellular components to kill cells - Allergens and antigens: activate immune response - Immune depressants, unclear how these act on bodily function - Neurotoxins, fast acting - Mutagens, alter DNA - Teratogens: embryo disruptions, thalidomide, alcohol - Carcinogens: mortality decreasing over last 30 years

Table 9.3 -- Toxic Chemicals in the United States Causing the Greatest Risk to Human Health ---------------------------------------------------------------------------------------- Benzene Mercury Cadmium Methyl ethyl ketone Carbon tetrachloride Methyl isobutyl ketone Chloroform Nickel Chromium Tetrachloroethylene Cyanides Toluene Dichloromethane Trichloroethane Lead Trichloroethylene

Xylene(s) ---------------------------------------------------------------------------------------- Source: Data from Environmental Protection Agency.

Natural and Synthetic Toxins

• Concept of chemical warfare among plants and animals leads to powerful natural toxins

• Many more natural pesticides in diet than synthetic • Must not underestimate the actual danger of both synthetic and

natural toxins

Physical Agents, Trauma, and Stress

• Radiation, noise, other electromagnetic energy • Trauma: a principle cause of death e.g., car accidents • Stress: physical, chemical, or emotional

Diet

High fat, salt diet associated with disease; low protein, high fiber diet associated with longevity

Movement, Distribution, and Fate of Toxins

Routes of toxin introduction determines effects

Solubility

Is a chemical oil or water soluble?

• Oil soluble chemical more likely to enter a cell and stay in body

Bioaccumulation and Biomagnification

1.Bioaccumulation: selective absorption 2.Biomagnification: movement of toxin from prey into predator

Persistence

Plastics, pesticides (DDT) are used because they "stay around" but also better chance of interaction with unintended organism

Chemical Interactions

Antagonistic, additive, synergistic

Table 9.5 Factors in Environmental Toxicity Factors Related to the Toxic Agent

1.Chemical composition and reactivity 2.Physical characteristics (such as solubility, state) 3.Presence of impurities or contaminants 4.Stability and storage characteristics of toxic agent 5.Availability of vehicle (such as solvent) to carry agent 6.Movement of agent through environment and into cells Factors Related to Exposure

1.Dose (concentration and volume of exposure) 2.Route, rate, and site of exposure 3.Duration and frequency of exposure 4.Time of exposure (time of day, season, year)

Factors Related to Organism

1.Resistance to uptake, storage, or cell permeability of agent 2.Ability to metabolize, inactivate, sequester, or eliminate agent 3.Tendency to activate or alter nontoxic substances so they become toxic 4.Concurrent infections or physical or chemical stress 5.Species and genetic characteristics of organism 6.Nutritional status of subject 7.Age, sex, body weight, immunological status, and maturity

Mechanisms for Minimizing Toxic Effects

Every substance is toxic at some dose--

"What is there that is not poison? All things are poison and nothing [is] without poison. Solely the dose determines

that a thing is not a poison."

-- Paracelsus (1493-1541)

Metabolic Degradation and Excretion

• Liver: enzyme systems detoxify and help excretion out of body, can also convert substances into carcinogens

• Excretion: bladder and kidney can be exposed to the toxins intended for removal

Repair Mechanisms

• DNA, protein, cells all have repair mechanisms to replace worn or damaged parts

• Tissues with high level of cell growth and replacement can be a site of unregulated growth if under stress (cancer)

Measuring Toxicity

Dose and route of exposure

Animal Testing

• Time consuming, expensive • Not all animals are sensitive to same dose, not all human• individuals have same sensitivity • Description: LD50

Toxicity Ratings

Many carcinogens may be toxic at doses below direct toxicity measuring techniques

Table 9.6 -- Acute lethal does for some toxic organic chemicals. Chemical Exposure LD50 -----------------------------------------------------------------------------------Ricin (castor bean) Ivn-mus 3ng/kg Orl-rat 100 mg/kg Botulism toxin Ipr-mus 160 ng/kg

Dioxin (tetrachlorodioxin) Orl-gpg 600 ng/kg Orl-hmstr 3 mg/kg Muscarine (mushroom poison) Ivn-mus 250 ug/kg

Parathion (insecticide) Ipr-rat 1.5 mg/kg

Aflatoxin (fungal toxin) rl-mky 1.75 mg/kg Nicotine Ivn-cat 2 mg/kg

Orl-rat 53 mg/kg

DDT Orl-hum 50 mg/kg Toxaphene Orl-rat 60 mg/kg 2,4-D Orl-hum 80 mg/kg

Source: Data from Registry of Toxic Effects of Chemical Substances, National Institute for Occupational Safety and Health, 1985

Orl= oral, ivn = intravenous, ipr = intraperitoneal, mus = mouse; mky = monkey, hmstr = hamster, hum = human, gpg = guinea pig Nanogram (ng) = 1 X10-9 g; Microgram (ug) = 1 X 10-6 g; Milligram (mg) = 1 X 10-3 g

Acute versus Chronic Doses and Effects

• Acute = single dose causes some health effect • Chronic = long term effects from single or repeated exposure • Delaney Clause 1958, No Reasonable Harm 1996

Detection Limits

Technology allow detection of chemicals at levels that may or may not indicate more prevalence than in past

Risk Assessment and Acceptance

• Risk = probability of harm X probability of exposure

Assessing Risks

Relative risk and perceptions

1. De-emphasize risk of activities we enjoy 2. Understanding "chance in 100" type assessments 3. Personal experience plays a role in perceived risk 4. Ability to control our own fate is over estimated 5. News media accounts of risk are not always "real" 6. Familiarity (or lack thereof) affects perception of risk

Accepting Risks

Reaction to emotion is more persuasive than statistics: more peoplewilling to accept an activity (automobile driving) that is much more dangerous than nuclear energy and other high emotion, butlow risk encounters

Establishing Public Policy

• Scientific results may not provide enough information for establishing public health risks (saccharin, aspartame)

• Standard setting needs to consider: 1.Combined effects from different sources 2.Sensitivities 3.Chronic and acute exposures

• Difficult to find line between repair mechanisms maintaining healthy status and risk of bodily damage

• Policy decisions need to consider ecological impacts (EPA)

Table 9.7 -- Activities Estimated to Increase Your Chances of Dying in any Given Year by 1

in 1 Million Activity Resulting Death Risk ---------------------------------------------------------------------------------------------- Smoking 1.4 cigarettes Cancer, heart disease Dinking 0.5 liter of wine Cirrhosis of the liver Spending 1 hour in a coal mine Black lung disease Living 2 days in New York or Boston Air pollutionTraveling 6 minutes by canoe AccidentTraveling 10 miles by bicycle AccidentTraveling 150 miles by car Accident Flying 1000 miles by jet Accident Flying 6000 miles by jet Cancer caused by cosmic radiation Living 2 months in Denver Cancer caused by cosmic radiation Living 2 months in a stone or brick building Cancer caused by natural radioactivity One chest X ray Cancer caused by radiation Living 2 months with a cigarette smoker Cancer, heart disease Eating 40 tablespoons of peanut butter Cancer from aflatoxin Living 5 years at the site boundary of a Cancer caused by radiation from routine leaks typical nuclear power plant Living 50 years 5 miles from a nuclear Cancer caused by accidental radiation releasepower plant Eating 100 charcoal-broiled steaks Cancer from benzopyrene ------------------------------------------------------------------------------------------------ From William Allman, "Staying Alive in the Twentieth Century," Science 85, 5(6): 31 October 1985.Used by permission of the author

Table 9.8 -- Relative Risks to human welfare Relatively High-Risk Problems • Habitat alteration and destruction • Species extinction and loss of biological diversity • Stratospheric ozone depletion • Global climate change Relatively Medium-Risk Problems

• Herbicides/pesticides • Toxics and pollutants in surface waters • Acid deposition • Airborne toxics

Relatively Low-Risk Problems• Oil spills • Groundwater pollution • Radionuclides • Thermal pollutionSource: Data from Environmental Protection Agency

Summary

• Health a state of physical, mental, social well-being, not just absence of disease

• Most important health threats: pathogenic organisms (especially emergent and resistant microorganisms)

• Stress, diet, and lifestyle: important health factors • Dose of toxic exposure can be difficult to equate with health risk • Distribution of materials in environment depend on may factors:

physical, chemical, transport in and out of organisms • Forced to use estimators of actual risk; leads to many questions

regarding health