Course: BIS 105 Environmental Biology

Unit 9 Learning Module

Risk Assessment

Risk Assessment

Risk assessment is a scientific process used by federal agencies and risk management decision-makers to make informed decisions about actions that may be taken to protect human health by ascertaining potential human health risks or health hazard associated with exposure to chemicals in the environment.

Some of the real-world examples of risk assessment includes: establishment of national ambient air quality and drinking water standards for protection of public health (e.g. ozone, particulate matter in outdoor air; chromium, chloroform or benzene in water); establishment of clean-up levels for hazardous waste site remediation; development of fish consumption advisories for pregnant women and general population (e.g. PCBs, mercury); assessment of risks and benefits of different alternative fuels for sound energy policy development (e.g. oxygenated gasoline, biodiesel); and estimation of health risks associated with pesticide residues in food. The regulatory risk assessment follows a four-step paradigm using qualitative and/or quantitative approaches. In quantitative risk assessment using either deterministic or probabilistic approaches, the risk estimates pertaining to an exposure scenario is particularly useful when comparing a number of exposure or risk reduction measures among one another as an optimization protocol to determine the best economically viable option for protection of public health and the environment. With environmental sustainability and life-cycle analysis in the forefront of green technological innovation, energy, and economic savings in the 21^st Century, risk assessment will pay a pivotal role in discerning the option(s) with the most benefit in health protection and, thus, will be an integral part of any environmentally sustainability analysis. Such comparative risk assessment can be performed for traditional approaches vs. environmentally sustainable approaches. They can also be performed among different environmentally sustainable options for an environmental pollution problem such hazardous waste site remediation and redevelopment, air quality management in urban areas, pest management practices, agricultural health and safety, alternative energy sources for transportation sources and among others.

The four steps of risk assessment are i) hazard identification; ii) toxicity (or dose-response) assessment; iii) exposure assessment; and iv) risk characterization, which are described below in detail. The emphasis is given in documenting the resources necessary to successfully perform each step.

Hazard Identification

In the hazard identification step, a scientific weight of evidence analysis is performed to determine whether a particular substance or chemical is or is not causally linked to any particular health effect at environmentally relevant concentrations. Hazard identification is performed to determine whether, and to what degree, toxic effects in one setting will occur in other settings. For example, is a chemical that is shown to cause carcinogenicity (cancer) in animal test species (e.g. rat, mouse) likely to be a carcinogen in exposed humans? In order to assess the weight of evidence for adverse health effects, risk analysts follow the following steps (EPA, 1993): (1) Compile and analyze all the available toxicology data on the substance of interest; (2) Weigh the evidence that the substance causes a toxic effect (cancer of non-cancer health end-points); and (3) Assess whether adverse health effect (or toxicity) could occur from human exposure in a real-life setting.

In the first task of hazard identification, risk analyst examines the toxicity literature using the following analytical tools in the order of importance:

- Epidemiological studies
- Controlled human exposure chamber experiments
- In-vivo animal bioassays
- In-vitro cell and tissue culture bioassays
- Quantitative Structure –Activity Relationship Analysis (QSAR)

Among these, in-vivo animal bioassays are, by far, the most utilized source of information for hazard identification for chemicals and, on rare instances, for chemical mixtures (e.g. diesel). When available, well-conducted epidemiological studies are regarded as the most valuable source of human health hazard identification information since they provide direct human evidence for potential health effects. Epidemiology is the study of the occurrence and distribution of a disease or physiological condition in human populations and of the factors that influence this distribution. The advantages of epidemiological studies for hazard identification are: animal-to-human extrapolation is not necessary, real exposure conditions, and a wide range of subjects with different genetic and life-style patterns. However, epidemiological studies have a number of shortcomings, which limit their usefulness in hazard identification. Some of these disadvantages include difficulty in recruiting and maintaining a control group; having no control over some of the non-statistical variables related to exposures, lifestyles, co-exposure to other chemicals, etc.; absence of actual exposure measurements along with memory bias for retrospective studies; lengthy latency periods for chronic health effects such as cancer; and poor sensitivity and inability to determine cause-effect relationships conclusively.

Animal bioassays remedy some of the weaknesses of epidemiological studies by allowing for greater control over the experiment and are deemed to be reliable measurement of toxic effects, although they require "high dose in animals-to low dose in humans" extrapolation. The selection of design parameters of animal bioassays is critically important in observing or missing an actual hazard. These parameters include: animal species selected for the experiment (rat, mouse); strain of the test species; age/sex of the test species; magnitude of exposure concentrations/doses applied or administered; number of dose levels studied; duration of exposure; controls selected; and route of exposure. Animal studies are characterized as acute (a single dose or exposures of short duration), chronic (exposures for full lifetimes of test species – about two years in rats/mice) and sub-chronic (usually 90 days) based on the exposure duration. In the hazard identification step, the following measures of toxicity are commonly compiled:

- LD_50 / LC_50 / EC_50: The lethal dose (LD) or lethal concentration (LC) in a toxicity study at which 50 percent mortality in test species was observed. The EC_50 is the effective concentration causing adverse effects or impairment in 50% of the test species.

- NOAEL (No Observable Adverse Effect Level): The highest dose or concentration in a toxicity study at which no adverse effect was observed.

- LOAEL (Lowest Observable Adverse Effect Level): The lowest dose or concentration in a toxicity study at which an adverse effect was observed.

- MTD (Maximum Tolerated Dose): The largest dose a test animal can receive for most of its lifetime without demonstrating adverse health effects other than carcinogenicity.

Risk scientists rely on a number of reputable sources to gather, compile, and analyze hazard identification information to be able to perform weight of evidence analysis and to conclude whether a chemical may cause a health effect in humans. Some of these sources are:

- Hazardous Substances Data Bank (HSDB) maintained by the National Library of Medicine: This scientifically peer-reviewed data bank provides human and animal toxicity data for about 5,000 chemicals and can be accessed via http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB

- ChemIDplus Advanced database maintained by the National Library of Medicine http://chem.sis.nlm.nih.gov/chemidplus/

- National Toxicology Program (NTP) of the Department of Health and Human Services:
  - Report of Carcinogens (RoC): The RoC is an informational scientific and public health document that identifies and discusses agents, substances, mixtures, or exposure circumstances that may pose a hazard to human health by virtue of their carcinogenicity. The link to the most recent version of the RoC can be accessed via http://ntp.niehs.nih.gov/?objectid=BD1A20B5-F1F6-975E-7CF8CBFACF0FC7EF

  - NTP Toxicity Testing Study Results and Research Areas: NTP tests chemicals for their toxicity in human and animal systems. http://ntp.niehs.nih.gov/index.cfm?objectid=720160DB-BDB7-CEBA-F7CC2DE0A230C920

- National Institute of Occupational and Safety Health (NIOSH) Hazard Identification Databases: The following NIOSH website houses a multitude of databases and information for chemicals and their hazards under a single umbrella, including NIOSH's "Pocket Guide to Chemical Hazards": http://www.cdc.gov/niosh/database.html

- Agency for Toxic Substances and Disease Registry (ATSDR) Toxicological Profiles and Public Health Statements: ATSDR produces "toxicological profiles" for hazardous substances found at National Priorities List (NPL) Superfund sites. About 300 toxicological profiles have so far been published or are under development. The chemical-specific toxicological profiles can be accessed via http://www.atsdr.cdc.gov/toxprofiles/index.asp

- World Health Organization (WHO) International Programme of Chemical Safety (IPCS): ICPS publishes "Environmental Health Criteria" (EHC) for chemical substances, which provide critical reviews on the effects of chemicals or combinations of chemicals and physical and biological agents on human health and the environment. The IPCS site can be accessed via http://www.who.int/ipcs/assessment/en/

- Material Safety Data Sheets (MSDS): MSDS are invaluable resource to obtain compositional data for products and mixtures.

Toxicity (Dose-Response Assessment)

Dose-response assessment takes the toxicity data gathered in the hazard identification step from animal studies and exposed human population studies and describes the quantitative relationship between the amount of exposure to a chemical (or dose) and the extent of toxic injury or disease (or response). Generally, as the dose of a chemical increases, the toxic response increases either in the severity of the injury or in the incidence of response in the affected population. In toxicity-assessment step, the relationship between the magnitude of the administered, applied, or absorbed dose and the probability of occurrence and magnitude of health effect(s) (e.g. tumor incidence in the case of cancer) is determined.

Dose-response assessment for carcinogens and non-carcinogens differ in toxicity values use and how these toxicity values are derived. In general, toxicity values provide a measure of toxic potency of the chemical in question. These toxicity values are:

- Reference Dose (RfD) for oral/dermal pathways or Reference Concentration (RfC) for inhalation pathway – Noncarcinogens: A chronic RfD is defined as an estimate (with uncertainty spanning perhaps an order of magnitude or greater) of a daily exposure level for the human population, including sensitive subpopulations, that is likely to be without an appreciable risk of deleterious effects during a lifetime. It has the unit of mg of pollutant per kg of body weight per day (mg/kg-day). Chronic RfDs are specifically developed to be protective for long-term exposure to a chemical, usually, for exposure periods between seven years (approximately 10 percent of a human lifetime) and a lifetime.

- Cancer Slope Factor (CSF) for oral/dermal pathway or Unit Risk Factor (URF) for inhalation pathway – Carcinogens: Unlike the noncarcinogens, carcinogens assumed to be non-threshold chemicals based on the Environmental Protection Agency (EPA) assumption that a small number of molecular events can evoke changes in a single cell that can lead to uncontrolled cellular proliferation and eventually to cancer. Toxicity values for carcinogenic effects also can be expressed in terms of risk per unit concentration of the chemical, which are called unit risk factors (URFs).

Exposure Assessment

In the third step of risk assessment, the magnitude of exposure is determined by measuring or estimating the amount of an agent to which humans are exposed (i.e. exposure concentration) and the magnitude of dose (or intake) is estimated by taking the magnitude, frequency, duration, and route of exposure into account. Exposure assessments may consider past, present, and future exposures.

While estimates of past or current exposure concentration/dose can be based on measurements or models of existing conditions, estimates of future exposure concentration/dose can be based on models of future conditions. In the case of inhalation exposures, personal or area monitoring to sample for contaminants in the air can be employed. The sampling data can be augmented with modeling efforts using default and/or site-specific input parameters.

In any exposure assessment, the risk scientists ask a number of questions to hypothesize the exposure scenario pertaining to environmental pollution affecting the population or a sub-group. Some of these are:

- What is the source of pollution at the site? (e.g. underground storage tank leak, emissions from an industrial plant, surface water run-off from agricultural fields)

- Which environmental compartments are likely to be contaminated? (i.e. air, water, sediment, soil, plants, animals, fish)

- What are the chemicals of concern originating from the pollution source?

- What are the fate and transport properties of these chemicals that may inform the aging of the pollution in the environment over time and resultant chemical signature in each environmental medium?

- Who is exposed? (e.g. children, elderly, asthmatics, general population, workers)

- How many people are exposed?

- Where are people exposed? (e.g. home, workplace, outside environment, retirement communities, schools)

- How are people exposed? (i.e. exposure pathway – inhalation, dermal contact or ingestion)

- How often are people exposed? (i.e. exposure frequency)

- How long are people exposed? (i.e. exposure duration)

Answers to these questions frame the problem at hand. In the next step, a number of exposure parameters are integrated into an estimate of daily dose received by an exposed individual via each exposure route (ingestion, dermal contact or skin absorption, and inhalation). The magnitude of human exposures, in general, is dependent on the concentration in the environment, exposure parameters describing human physiology (e.g. ingestion rate, body weight), and population-specific parameters describing exposure behavior (exposure frequency, duration).

Risk Characterization

In the last step, a hazard quotient (HQ) as an indicator of risks associated with health effects are calculated by evaluating data from dose-response and exposure assessments. To account for exposures to multiple chemicals of concern via multiple pathways, individual HQs are summed to provide an overall hazard index (HI).

Conclusion

The improvement in the scientific quality and validity of health risk estimates depends on advancements in our understanding of human exposure to, and toxic effects associated with, chemicals present in environmental and occupational settings. For example, life-cycle of and health risks associated with pharmaceuticals in the environment is poorly understood due to lack of environmental concentration and human exposure data despite extensive toxicological data on drugs. There are many other examples for which either data on exposure or toxicity or both have not yet been developed, preventing quantitative assessment of health risks and development of policies that protect the environment and public health at the same time. Therefore, it is important to continue to develop research data to refine future risk assessments for informed regulatory decision-making in environmental sustainability and to ensure that costs associated with different technological and/or engineering alternatives are scientifically justified and public health-protective. One area that, particularly, requires advancement is the assessment of health risks of chemical mixtures (synergistic effects). Current risk assessment approaches consider one chemical at a time. However, chemicals are present in mixtures in the environment. Furthermore, physical, chemical and biological transformations in the environment and interactions among chemicals in the environment may change the toxic potential of the mixture over time. Thus, risk assessment is an evolving scientific discipline that has many uncertainties in all of the four steps. These uncertainties should be thoroughly documented and discussed and the risk assessment results should be interpreted within the context of these uncertainties.