BASIC HAZARDOUS WASTE MANAGEMENT - CHAPTER 4 pot

• Be able to locate appropriate data on the toxicology of the chemical constituents of hazardous wastes.. All chemicals are toxic, but the concentration, route of entry, and time of expo

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Toxicology and the Standard-Setting Processes

OBJECTIVES

At completion of this chapter, the student should:

• Understand the basic mechanisms of human exposure

• Be able to relate the exposure mechanisms to the pathways overviewed

in Chapter 3 and to the common release mechanisms

• Be able to locate appropriate data on the toxicology of the chemical constituents of hazardous wastes

• Know the components of the general risk assessment process and under-stand their relationship to each other

• Understand how toxicological and human health considerations have been addressed in RCRA and how RCRA measures, regulates, and attempts to minimize toxic and health impacts of hazardous wastes

INTRODUCTION

Living organisms are composed of cells, and all cells must accommodate and facilitate a variety of chemical reactions to maintain themselves and perform their functions Introduction of a foreign chemical into a cell may interfere with one or more of these cellular reactions, leading to impaired cell function or viability All chemicals are toxic, but the concentration, route of entry, and time of exposure are factors that determine the degree of toxic effect.

Toxicology is the study of how specific chemicals cause injury to living cells and whole organisms Such studies are performed to determine how easily the chemical enters the organism, how it behaves inside the organism, how rapidly it is removed from the organism, what cells are affected by the chemical, and what cell functions are impaired A risk assessment process is used to derive a reliable estimate of the amount of chemical exposure which is considered acceptable for humans or other organisms Risk-based exposure limits are then rationalized in the form of risk-based standards The alternative form of exposure limits is the technology-based standard,

in which the goal is to minimize exposure by the imposition of control technologies

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In recent years, important advances have been achieved in toxicology and in the research methods that are employed by toxicologists Nevertheless, for many chem-icals, current toxicological knowledge is insufficient to provide the basis for quan-titative toxicity assessments Similarly, analytical techniques for risk assessment have been evolving toward attainment of greater sophistication and precision, but nonrepresentiveness, inconsistency, uncertainty, and/or absence of input data1 con-tinue to limit the utility of these techniques (see: Johnson and DeRosa, 1997, Tables

3 and 4 and discussion) It is these very limitations that cause the standards-setting process to be exceedingly lengthy and/or seemingly endless

P UBLIC H EALTH I MPACTS Toxicity Hazard

In the hazardous waste context, toxicity is the ability of a chemical constituent or combination of constituents in a waste to produce injury upon contact with a sus-ceptible site in or on the body of a living organism Toxicity hazard is the risk that injury will be caused by the manner in which a waste is handled

within hours, days, or no more than 2 weeks after a single exposure or multiple brief acute exposures, within a short time, to a chemical agent

Chronic Toxicity: Adverse effects manifested after a lengthy period of uptake

of small quantities of the toxicant The dose is so small that no acute effects are manifested and the time period is frequently a significant part of the normal lifetime of the organism

(Adapted from Hodgson and Levi 1987, pp 357, 360.)

Chemical constituents of wastes may be acutely or chronically hazardous to plants or animals via a number of routes of administration Phytotoxic wastes can damage plants when present in the soil, atmosphere, or irrigation water Phytotoxicity

is the result of a reduction of chlorophyll production capability, overall growth retardation, or some specific chemical interference mechanism

Chemical components that are acutely toxic to mammals may be injurious when inhaled, ingested, and/or contacted with the skin Symptoms resulting from acute exposures usually occur during or shortly after exposure to a sufficiently high concentration of a contaminant The concentration required to produce such effects varies widely from chemical to chemical Data pertinent to a single route of admin-istration may not be applicable to alternative routes For example, asbestos dust is

and Liability Act (CERCLA), and a focus of the Agency for Toxic Substances and Disease Registry (ATSDR) and the EPA, which are jointly tasked by CERCLA with elimination of the data gaps The topic is discussed later in this chapter.

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toxic at very low levels when present in air, but asbestos particles in water are believed to pose no ingestive threat at low concentrations

“Acute exposure” traditionally refers to exposure to “high” concentrations of a contaminant and/or short periods of time “Chronic exposure” generally refers to exposure to “low” concentrations of a contaminant over a longer period Chemical contaminants may be chronically toxic to mammals if they contain materials that (1) are bioaccumulated or concentrated in the food chain or (2) cause irreversible damage that builds gradually to a final, unacceptable level Heavy metals and halo-genated aromatic compounds are classic examples of chronic toxicants (HHS 1985,

p 2-1; Dawson and Mercer 1986, p 62; Kamrin 1989, p 134; Manahan 1994, Chapters 22 and 23)

The U.S Environmental Protection Agency (EPA) has classified some 35,000 chemicals as either definitely or potentially harmful to human health A number of them, including some heavy metals (cadmium, arsenic) and certain organic com-pounds (carbon tetrachloride, toluene), are carcinogenic Others, like mercury, are mutagenic and may tend to induce brain and bone damage (mercury, copper, lead), kidney disease (cadmium), neurological damage, and many other problems Multiple exposures can be additive or synergistic, but in many cases, the risk resulting from simultaneous exposure to more than one of these substances is not known

A wide variety of reference materials are available which provide basic toxicity data on specific chemicals The Registry of Toxic Effects of Chemical Substances (RTECS) has been widely used and quoted (HHS 1975) In recent years, the “Health Assessment Guidance Manual,” published by the Agency for Toxic Substances and Disease Registry (ATSDR) has become widely accepted among toxicologists and related practitioners (HHS 1990) Moreover, ATSDR is preparing individual toxico-logical profiles for 275 hazardous substances found at Superfund sites A 1997 publication states that the agency is concentrating on filling 194 data gaps for 50 top-ranked CERCLA hazardous substances (Johnson and DeRosa 1997) These profiles may be obtained from NTIS2 as they become available A Textbook of Modern

provides a wealth of references on individual topics The Handbook of Toxic and

authoritative source The NIOSH “Pocket Guide to Chemical Hazards” is a handy, quick-reference guide to chemical hazards (HHS 1997) The American Conference

of Governmental Industrial Hygienists (ACGIH 1997) publishes a handbook of Threshold Limit Values (TLVs) and Biological Exposure Indices (BEIs) for a variety

of chemical substances and physical agents The EPA operates a database — “Inte-grated Risk Information System” (IRIS)3 — containing up-to-date health risk and EPA regulatory information pertaining to numerous chemicals Other new databases, with current toxicology data and search capabilities, are becoming available For a chemical to exert a toxic effect on an organism, it must first gain access

to the cells and tissues of that organism In humans, the major routes by which toxic chemicals enter the body are through ingestion, inhalation, and dermal absorption

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The absorptive surfaces of the tissues involved in these three routes of exposure (gastrointestinal tract, lungs, and skin) differ from each other with respect to rates

at which chemicals move across them

gas-trointestinal (GI) tract The normal function of the tract is the absorption of foods and fluids that are ingested, but the GI tract is also effective in absorbing toxic chemicals that are contained in the food or water The degree of absorption generally depends upon the hydrophilic (easily soluble in water) or lipophilic (easily soluble

in organic solvents or fats) nature of the ingested chemical Lipophilic compounds (e.g., organic solvents) are usually well absorbed, since the chemical can easily diffuse across the membranes of the cells lining the GI tract Hydrophilic compounds (e.g., metal ions) cannot cross the cell lining in this way and must be “carried” across by a transport system(s) in the cells The extent to which the transport occurs depends upon the efficiency of the transport system and upon the resemblance of the chemical to normally transported compounds

If the ingested chemical is a weak organic acid or base, it will tend to be absorbed

by diffusion in the part of the GI tract in which it exists in its most lipid-soluble (least ionized or polar) form Since gastric juice in the stomach is acidic and the intestinal contents are nearly neutral, the polarity of a chemical can differ markedly

in these two areas of the GI tract A weak organic acid is in its least polar form while in the stomach and therefore tends to be absorbed through the stomach A weak organic base is in its least polar form while in the intestine and therefore tends

to be absorbed through the intestine Some caustics can cause acute reactions within the GI tract

Another important determinant of absorption from the GI tract is the interaction

of the chemical with gastric or intestinal contents Many chemicals tend to bind to food, and so a chemical ingested in food is often not absorbed as efficiently as when

it is ingested in water Additionally, some chemicals may not be stable in the strongly acidic environment of the stomach and others may be altered by digestive enzymes

or intestinal bacteria to yield different chemicals with altered toxicological proper-ties For example, intestinal bacteria can reduce aromatic nitro groups to aromatic amines, which may be carcinogenic (ICAIR 1985, pp 4-1, 4-3) Irrespective of the route of absorption, once the chemical enters the bloodstream, it is then delivered

to the target organ

The ingestion route of exposure is seldom a factor in industrial situations, with the exception of the inadvertent incident For example, workers eating lunch in a battery factory might ingest lead with their sandwiches (Beaulieu and Beaulieu

1985, p 12) Ingestion gains importance with long-term intake of contaminants in water supplies

chemicals are gases (e.g., carbon monoxide) or vapors of volatile liquids (e.g., trichloroethylene) Absorption in the lung is usually great because the surface area

is large and blood vessels are in close proximity to the exposed surface area Gases cross the cell membranes of the lung via simple diffusion, with the rate of absorption dependent upon the solubility of the toxic agent in blood If the gas has a low solubility (e.g., ethylene), the rate of absorption is limited by the rate of blood flow

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through the lung, whereas the absorption of readily soluble gases (e.g., chloroform)

is limited only by the rate and depth of respiration

Chemicals may also be inhaled in solid or liquid form as dusts or aerosols Liquid aerosols, if lipid-soluble, will readily cross the cell membranes by passive diffusion The absorption of solid particulate matter is highly dependent upon the size and chemical nature of the particles The rate of absorption of particulates from the alveoli4 is determined by the compound’s solubility in lung fluids, with poorly soluble compounds being absorbed at a slower rate than readily soluble compounds Small insoluble particles may remain in the alveoli indefinitely Larger particles (2

to 5 µm) are deposited in the trachea or bronchial (upper) regions of the lungs where they may be cleared by coughing or sneezing or they may be swallowed and deposited in the GI tract Particles of 5 µm or larger are usually deposited in the nasal passages or the pharynx where they are subsequently expelled or swallowed (ICAIR 1985, p 4-3) A chronic effect on the lung can be caused if the defense mechanisms are overwhelmed with particles from smoke, coal dust, etc

Inhalation of air contaminants is probably the most important route of entry of chemicals to the body in industrial situations A worker exposed to 1000 parts per million (ppm) of toluene vapor, over an 8-hr work shift, could be expected to show dramatic symptoms of eye and respiratory irritation and depression of the central nervous system (CNS) This response to toluene demonstrates local effects (at the point of entry — eye, lung) and systemic effects where the chemical was absorbed into the bloodstream and affected the CNS

Some chemicals do not provide “warning properties” in the gaseous or vapor state For example, carbon monoxide (CO) is odorless and colorless and can inflict serious toxic effects to the unsuspecting victim Other chemicals may have the property of desensitizing the receptor For example, hydrogen sulfide (H2S) has the prominent “rotten egg” odor at low concentrations However, at high concentrations the olfactory senses become paralyzed and the exposed individual can be quickly overcome with the toxic effect (Beaulieu and Beaulieu 1985, p 14) High concen-trations of H2S can also cause respiratory arrest

Long-term chronic health effects may be experienced by humans in various situations For example, chronic bronchitis has been convincingly linked to long-term inhalation of sulfur dioxide, one of the more prominent urban air pollutants (Hodgson and Levi 1987, pp 189–190) Emphysema, asbestosis, silicosis, and berylliosis have all been associated with exposure to dusts and/or fumes

skin, and into the bloodstream, is hindered by the densely packed layer of rough, keratinized5 epidermal cells Absorption of chemicals occurs much more readily through scratched or broken skin There are significant differences in skin structure from one region of the body to another (palms of hands vs facial skin), and these differences further influence dermal absorption

carbon dioxide occurs.

structures, such as hair, nails, horns, and hoofs.

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Absorption of chemicals by the skin is roughly proportional to their lipid solu-bility and can be enhanced by application of the chemical in an oily vehicle and rubbing the resulting preparation into the skin Some lipid-soluble compounds can

be absorbed by the skin in quantities sufficient to produce systemic effects For example, carbon tetrachloride can be absorbed by the skin in amounts large enough

to produce liver injury (ICAIR 1985, p 4-3) The NIOSH “Pocket Guide to Chemical Hazards” and the ACGIH handbook of TLVs and BEIs provide guidance regarding dermal exposure to hazardous materials (see also: HHS 1985, p 2-2)

Toxic Actions

Toxic chemicals can be categorized according to their physiological effect upon the exposed species The categories often overlap, but can be (somewhat simplistically) separated into groups of irritants, asphyxiants, CNS depressants, and systemic toxicants

the skin, eyes, respiratory tract, or GI tract are considered irritants, a local effect at the point of entry to the body An example is sodium hydroxide (caustic) dust on perspiration-moist skin The pH of the fluid is quickly increased above normal resulting in irritation Mechanical friction, such as the rubbing of shirt cuffs or collar, compounds the irritating effect The effect may be as simple as a mild stinging sensation to the more serious blistering of the skin Ammonia vapors or spray can irritate the mucous membranes of the respiratory tract, causing tearing and stinging

in the nasal passages and throat

host organism, thereby slowing or halting metabolism Simple, or mechanical, asphyxiants displace the available oxygen in an air space to the point of producing

an atmosphere unable to support life (less than 16% oxygen) Oxygen starvation may occur in a confined space where methane gas (CH4) displaces oxygen to the extent that the oxygen content of the atmosphere falls to less than 16% Conversely, carbon monoxide (CO) is a gas that chemically ties up the hemoglobin in blood after inhalation With hemoglobin unable to transport oxygen to cells and carbon dioxide from the cells, the tissues cannot maintain natural metabolic functions, and death occurs

sol-vent vapors and anesthetic gases, or the introduction of narcotics to the body in the form of alcohol or depressant drugs, causes a deadening of the nervous system A worker who inhales trichloroethylene vapor during a workshift might not have the neuromuscular coordination to safely drive an automobile The appearance of ine-briation can be mistaken for the effects of elevated blood alcohol concentration

their effect dramatically upon a specific organ system and possibly far from the site of entry There is considerable overlap between the systemic toxicants and the other categories For example, the organic solvent carbon tetrachloride (CCl4)

is definitely a CNS depressant as well as an irritant and can cause irreversible liver or kidney damage

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Mercury vapor does not seem to produce irritation upon inhalation, but causes serious impairment to nerve endings Chronic inhalation of mercury vapor can result

in serious disease of the nervous system, including insanity (see also: Manahan

1994, p 677)

An agent that has the potential to induce the abnormal, excessive, and uncoor-dinated proliferation of certain cell types, or the abnormal division of cells, is termed

a carcinogen or potential carcinogen Inhalation of asbestos fibers has been firmly linked to the production of lung cancer and mesothelioma (cancer of the linings of lung tissues)

A chemical that causes mutations or changes in the genetic codes of the DNA

in chromosomes is called a mutagen Formaldehyde vapor causes these changes in the bacterial organisms Salmonella sp.This characteristic is the basis for the “Ames test,” a bacterial procedure used for indication of mutagenicity of suspect substances Mutagenic toxins may affect future generations

A teratogen is a toxicant that produces physical defects in unborn offspring A suspect substance may be administered to a test animal to determine if it will cause congenital abnormalities in a fetus produced by the test animal (Beaulieu and Beaulieu 1985, pp 15–17) The birth defects of a teratogen are not passed to future generations (see also: Manahan 1994, p 662)

Risk Assessment and Standards

The EPA and other regulatory agencies have, over the years, frequently opted for risk-based standards because of the court-imposed need to “show harm” when a particular standard is challenged As noted above, CERCLA, in 1980, created ATSDR and tasked the EPA and the new agency with filling data gaps for 275 priority hazardous sub-stances.6 As noted in the “Introduction” to this chapter, this insistence upon a rational basis (i.e., a showing of harm) for environmental or exposure standards has caused the standards-setting process to be time consuming, laborious, and frustrating In 1990 it became apparent that Congress was then steering the EPA back toward more reliance upon technology-based standards (Environment Reporter, 9 March, 1990, pp 1840–1841) The 1990 Clean Air Act Amendments (CAAA) require that the EPA assign maximum achievable control technology (MACT) standards to the newly listed haz-ardous air pollutants Yet Section 303 of the CAAA also establishes a Risk Assessment and Management Commission, which is to “… make a full investigation of the policy implications and appropriate uses of risk assessment and risk management in regulatory programs under various Federal laws to prevent cancer and other chronic human health effects which may result from exposure to hazardous substances” (42 USC 7412) Thus the search continues, on the part of Congress, for approaches to rationalize standards

to protect human health, while continuing reliance upon control technologies The congressional focus upon technology-based standards is an expression of the frustration of that body with the slow pace of the standards-setting process, the endless arguments growing from the “how-clean-is-clean” issues, and the inherent flaws in biological research (conversion of test animal data to human exposure

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application — more on this later in this chapter) Nevertheless, the courts can be expected to lend a sympathetic ear to pleas for rationality in standards As data gaps are filled and as research and analytical techniques advance, risk-based standards will increasingly dominate the regulatory schemes

haz-ards varies, in detail, according to the proclivities, experiences, focus, and/or man-dates of the individual risk assessor, researcher, or regulatory agency However, the general paradigm for risk assessment flows from the 1983 National Research Council (NRC) publication Risk Assessment in the Federal Government. The process usually consists of the following four steps:

• Hazard identification

• Dose-response evaluation

• Exposure assessment

• Risk characterization

Variations on the process for use in Superfund or RCRA site evaluations will be summarized in Chapter 10 EPA methodology for risk assessment is introduced in

an unnumbered Technical Information Package titled “Risk Assessment,” which can

be accessed at <http://www.epa.gov/oiamount/tips/risktip.htm> Much more detail, although in the Superfund site remediation context, is available in the referenced documents (EPA 1990; EPA 1992; see also: LaGoy 1999)

expo-sure standard for an individual chemical, may take the form of a toxicological evaluation, wherein the answer is sought to the the question: “Does the chemical have an adverse effect?” This evaluation may be a “weight-of-evidence” process in which the available scientific data are examined to determine the nature and severity

of actual or potential health hazards associated with exposure to the chemical This step involves a critical evaluation and interpretation of toxicity data from epidemi-ological, clinical, animal, and in vitro7 studies Factors that should be considered during the toxicological evaluation include routes of exposure, types of effects, reliability of data, dose, mixture effects, and evidence of health end-points including developmental toxicity, mutagenicity, neurotoxicity, or reproductive effects The tox-icological evaluation should also identify any known quantitative indices of toxicity such as the threshold level or No Observable Adverse Effect Level (NOAEL), Lowest Observable Adverse Effect Level (LOAEL), carcinogenic risk factors, etc (ICAIR

1985, p 8-2; EPA Science Policy Council 1995; Schoeny et al 1998, Chapter 9)

The dose-response relationship is the most fundamental concept in toxicology The product of the dose-response evaluation is an estimate of the relationship between the dose of a chemical and the incidence of the adverse effect in the human population actually exposed, or in test organisms in the laboratory

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chemical is likely to cause a particular adverse effect, the next step is to determine the potency of the chemical The dose-response curve describes the relationship that exists between degree of exposure to a chemical (dose) and the magnitude of the effect (response) in the exposed organism(s), usually laboratory animals By defini-tion, no response is seen in the absence of the chemical being evaluated At low dose levels, response may not be evident, but as the amount of chemical exposure increases, the response becomes apparent and increases Thus, a steep curve indicates

a highly toxic chemical; a shallow curve indicates a less toxic substance The toxicity values derived from this quantitative dose-response relationship, usually at very high exposure levels, are then extrapolated to estimate the incidence of adverse effects occurring in humans at much lower exposure levels The EPA Integrated Risk Information System (IRIS) is a repository for data needed by the risk assessor in developing the dose-response relationship EPA program offices also maintain pro-gram-specific databases, such as the Office of Solid Waste and Emergency Response (OSWER) Health Effects Assessment Summary Tables (HEAST) The EPA guidance provides a detailed discussion of the data requirements for the dose-response devel-opment (U.S EPA Science Policy Council 1995)

Depending upon the mechanism by which the subject chemical acts, the dose-response curve may rise with or without a threshold Figure 4.1 illustrates the NOAEL and LOAEL described earlier The TD50 and TD100 points indicate the doses associated with 50 and 100% occurrence of the measured toxic effect (see also:

Chastain 1998)

FIGURE 4.1 Hypothetical dose response curves (Adapted from ICAIR Life Systems, Inc.,

Toxicology Handbook, prepared for the U.S Environmental Protection Agency Office of Waste Programs Enforcement, Washington, D.C.)

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Figure 4.2 illustrates threshold and no threshold dose-response curves In both cases, the response normally reaches a maximum after which the dose-response curve becomes flat or nearly so The no-threshold curve coincides with a long-standing EPA assumption that damage to a single cell could trigger a chain reaction

of mutations; therefore there is no “safe” dose of a carcinogen EPA is said to be moderating this position because scientific studies indicate that exposure-caused damage to DNA is not always irreversible In fact, some evidence shows that very high doses (i.e., maximum tolerated dose) and the methods used in dosing test animals may be biasing the results of cancer risk assessments (Chastain, 1998) The dose-response evaluation for noncarcinogenic chemicals provides an esti-mation of the NOAEL or LOAEL The NOAEL may then be assumed to be the basis for establishing an “Acceptable Daily Intake” (ADI) or Reference Dose (RfD)

In practice, the NOAEL is adjusted by safety and uncertainty factors, which are an attempt to account for the “unknowns” involved (Assante-Duah 1993, pp 94–102; Krieger et al 1995, pp 126–128; Chastain, 1998)

Mathematical models of the dose-response relationship for carcinogenic chem-icals are used to derive estimates of the probability or range of probabilities that a carcinogenic effect will occur under the test conditions of exposure Suggested readings providing examples of these models can be found in Assante-Duah 1993,

pp 91–92 and Krieger et al 1995, Chapter 5

specific exposure data to enable estimates of the magnitude of actual and/or potential human exposures, the frequency and duration of these exposures, the pathways by

FIGURE 4.2 Hypothetical dose-response curves (Adapted from ICAIR Life Systems, Inc.,

Toxicology Handbook, prepared for the U.S Environmental Protection Agency Office of Waste Programs Enforcement, Washington, D.C.)

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