National Academy of Sciences. Biosolids Applied to Land:
Advancing Standards and Practices

Chapter 5. Evaluation of EPA's Approach to Setting Chemicals Standards [abridged]

Pharmaceuticals

Since the early 1980s, there have been increasingly frequent reports of pharmaceuticals
detected in wastewater treatment effluent or surface water in trace concentrations
(typically in nanograms per liter) (Daughton and Ternes 1999; Ayscough et al. 2000).
These reports have become more frequent as analytical techniques have improved to
enable identification of very low concentrations of these chemicals in complex mixtures.
Many of these chemicals are produced in very high volumes, and they or their metabolites are added directly to wastewater after use. Most of the concern regarding the potential effects of these chemicals, particularly the potential endocrine-disrupting effects
of hormones, has been for the impact on aquatic receptors. The majority of drugs
are water soluble, and metabolism after ingestion generally increases the solubility
further. Consequently, most drugs and their metabolites are unlikely to be present
in significant quantities in biosolids. Nevertheless, more lipophilic compounds
will have a greater tendency to partition to biosolids.

Since 1969, the National Environmental Policy Act has required the assessment of
risk to the environment from use of drugs. Environmental assessments are part of
the registration procedure for new human pharmaceuticals (PDA 1985; Eirkson 1987).
The procedure in place since 1995 calls for estimation of an expected introductory
concentration (EIC) based on dividing the expected annual production volume by the
number of liters of wastewater entering publicly owned treatment works per year
(U.S. Center for Drug Evaluation and Research 1995). When the predicted EIC in wastewater effluent is less than 1 mg/liter, a detailed environmental assessment is not needed.

Active pharmaceutical compounds and a wide variety of metabolites enter wastewater
after personal use at home and work (Ayscough et al. 2000). A somewhat different
spectrum of chemicals will enter wastewater after use in hospitals and medical centers.
The parent compounds may also be disposed of directly to wastewater. These chemicals
may be further degraded or biodegraded in wastewater and during treatment at wastewater treatment plants. Analytical methods to characterize the resulting complex mixtures of chemicals are useful for research but are not currently adequate for routine
screening (Daughton and Ternes 1999). Standard reference materials are often not
readily available, and many of these substances are not included in environmentally
oriented mass spectral libraries.

The efficiency of removal of drugs in wastewater treatment plants has mainly been
determined by measuring influent and effluent concentrations. Removal efficiency
varies greatly among different pharmaceuticals and varies over time at any single
treatment plant (Daughton and Ternes 1999). Removal of a drug could reflect either
degradation and biodegradation or sequestration in biosolids; no data on drug concentrations in sewage sludge or biosolids were identified for this review. Partition coefficients between organic matter and water vary up to 500-fold for different drugs (Tolls 2001). Since thousands of drugs are approved for use, any attempt to determine whether drugs are routinely present in biosolids would require a carefully focused approach, perhaps looking for the highest volume drugs that have lipophilic properties and are not predominantly metabolized to water-soluble forms.

Toxicity studies have been conducted for most drugs, but the results of such studies
are often not reported in the peer-reviewed literature. If drugs are detected in
biosolids, approaches for evaluating potential adverse health effects will need
to be considered. Typically, effects of toxicity would be limited to doses exceeding
the therapeutic doses. However, therapeutic dose effects in a non-target population
might be considered adverse effects. Therefore, health-based screening could rely
on toxicity values that are a specific fraction of therapeutic dose levels.

In summary, pharmaceuticals and personal care products are produced in high volumes,
and they and their metabolites are excreted directly to wastewater, where they have
been detected in very low (generally, nanograms per liter) concentrations. The potential
for most of these chemicals to partition to biosolids is limited by their generally
high water solubility; however, some drugs may be sufficiently lipophilic to partition
preferentially to biosolids. At present, there is not adequate evidence that pharmaceuticals
are likely to occur in biosolids at concentrations sufficient to warrant their inclusion
in a biosolids risk assessment; however, EPA should continue to monitor research
in this area.

Volatile Emissions and Odorants

The chemical selection process used for the Part 503 rule risk assessment included
consideration of volatile organic chemicals (VOCs) that are priority pollutants.
These VOCs are generally limited to chlorinated and aromatic volatiles, which might
be present in biosolids as a result of industrial or other discharges to sewer systems.
Because the majority of these VOCs will be released to the air during wastewater
processing, VOCs were ruled out as chemicals of concern for land application of
biosolids.

Sewage sludge also emits many VOCs not included in the EPA priority pollutant list.
These VOCs include sulfur and nitrogen-containing chemicals that are strong odorants,
as well as acids, aldehydes, and ketones that are also odorants. A review by Gostelow
et al. (2001) provides an overview of odorant generation during wastewater treatment
and describes measurement methods. Many of these chemicals are generated during
the biodegradation of wastewater and sewage-sludge components, and the protein breakdown contributes to the generation of sulfur and nitrogen-containing compounds (Gostelow et al. 2001). Sufonates from detergents are additional sources of sulfur, and urine and amino acids contribute to formation of nitrogen-containing compounds. Carbohydrate fermentation during anaerobic sewage sludge treatment contributes to the formation of volatile fatty acids, aldehydes, alcohols, and ketones.

The mixture of odorants in biosolids will differ from that in sewage sludge, and
the relative concentrations will differ between the two mixtures for odorants present
in both. Table 5–14 lists odorants associated with wastewater treatment, their characteristic odors, and their odor thresholds. As noted in the table, many of these odorants have been detected in biosolids.

Although hydrogen disulfide is the predominant odorant associated with wastewater
treatment, it is less of a factor in the odors of biosolids (Striebig 1999). In
an unpublished laboratory study, the predominant odorants varied, depending on treatment methods used to reduce pathogens in the biosolids. Overall odor increased with lime treatment and increasing temperature (Striebig 1999). Additional studies are needed
to provide a more robust database of odorants released from biosolids. Potential
risks associated with odorants cannot be properly assessed until such a database
is developed.

Noxious odors are one of the primary causes of complaints from the public about
land application of biosolids. Odor perception consists of two steps: physiological
reception and psychological interpretation (Gostelow et al. 2001). Although odorants
may cause toxic effects, perception of an odor as noxious is not directly linked
to toxicity. Perception of sewage odors as unpleasant might be due to an association
with decaying material that needs to be avoided. As noted by Schiffman et al. (2000),
foul environmental odors frequently engender concerns for safety. Odor perception
has been shown to affect mood, in eluding levels of tension, depression, anger,
fatigue, and confusion (Schiffman et al. 1995). Mood impairments and stress can
potentially lead to physiological and biochemical changes with subsequent health
consequences (Shusterman et al. 1991; Cohen and Herbert 1986). In addition, conditioned responses (behavioral and physiological) can be developed to odors perceived to be associated with health symptoms (Bolla-Wilson et al. 1988; Shusterman et al. 1988).

Odors associated with biosolids are due to complex mixtures of odorous chemicals
that vary greatly in toxicity and in odor thresholds. The olfactory system processes
stimuli from the chemicals in these mixtures, perceiving one overall odor. There
are two primary approaches to measuring odors: analytical measurements of individual
odorants in a mixture and sensory studies in which human subjects provide subjective
evaluations of odors (reviewed in Gostelow et al. 2001). Fully characterizing an
odor requires the use of both approaches. Although analytical measurements allow
for identification of the chemicals present, sensory studies may provide assessments
of the intensity, character, and hedonic tone (pleasantness or unpleasantness) of
an odor. Analytical measurements are crucial for an assessment of the potential
toxicity of odorous chemicals, because toxicity thresholds often do not correlate
with odor thresholds.

In assessing odorants, it is important to distinguish between symptoms or health
complaints due to odor perception and irritant effects and other forms of toxicity.
Participants at a workshop held at Duke University in 1998 defined a set of odor
levels to clarify the intensities associated with potential health impacts (Schiffman
et al. 2000) (see Table 5–15). These levels begin with odor detection and progress
through odor intolerance (defined as physical symptoms occurring at a nonirritant
concentration), irritant effects, and chronic and acute toxicity.

Identification of these levels does not imply that consistent increases in concentrations
trigger each level of response. For example, some odorants might have minimal irritant
effects but produce chronic or acute toxicity. Strong odorants might be detected
at concentrations far less than those that cause toxicity, whereas weak odorants
might cause toxicity at concentrations close to odor detection thresholds. Table
5–16 provides a comparison of odor thresholds and thresholds for toxicity of odorants
detected in biosolids. Toxicity threshold values for airborne chemicals are derived
by a variety of organizations. EPA and the Agency for Toxic Substances and Disease
Registry are the primary sources of toxicity values for evaluating effects of chronic
exposure. EPA is also overseeing the development of acute exposure guideline levels
(AEGLs) to evaluate acute exposures of the general public, and the National Institute
for Occupational Safety Health, the American Conference of Governmental Industrial
Hygienists, and the Occupational Safety and Health Administration derive acute exposure
guidelines for occupational exposures. The divergence of odor threshold and toxicity
is illustrated by comparing values for hydrogen sulfide and carbon disulfide. The
odor thresholds for the two chemicals are similar, but the reference concentrations
suggest that the chronic toxicity of hydrogen sulfide is more than 100 times greater
than that of carbon disulfide.

As can be seen in Table 5–16, toxicity values are available for only a small number
of odorants found in biosolids. Evaluation of risks of exposure to odorants will
depend on the availability of appropriate toxicity values for these chemicals. Appropriate
toxicity values will need to be based on the likely exposure duration (short-term
vs. chronic). Consequently, initial efforts to evaluate the potential hazards of
odorants identified in biosolids should focus on dose-response assessment for exposure
durations likely to occur in the exposed populations. Because many of these chemicals
are structurally similar, quantitative structure activity analysis (QSAR) might
be a useful tool to augment the limited toxicity database. In conclusion, a wide
variety of odorants are present in wastewater effluents, and the chemical compositions
and concentrations of odorants in biosolids vary with the treatment processes as
well as the origin of the effluents. Inhalation is the only exposure pathway of
concern for VOCs, and both acute and chronic exposures should be considered. Additional studies are needed to identify odorants typically released from biosolids and to determine the range of likely air concentrations near biosolids-application sites.
Acute and chronic toxicity values (air concentrations determined to be safe for
specified kinds of exposures) should be developed for the predominant odorants,
and a hazard analysis should be conducted to determine whether air concentrations
generated near application sites are high enough to warrant more detailed risk assessment for this category of chemicals. Research is also needed on the impacts of odors. Particular attention should be paid to the degree to which effective biosolids treatment reduces odorant concentrations and impacts.

NOTE: THE BULK OF CHAPTER 5's MATERIAL IS NOT INCLUDED, JUST THE FOLLOWING FINDINGS AND RECOMMENDATIONS.

FINDINGS AND RECOMMENDATIONS

Finding: In responding to the committee's charge to evaluate the technical basis of the biosolids chemical standards, it is important to distinguish between the appropriate risk-assessment methods at the time the standards were developed versus the most appropriate methods now. The committee did not attempt to determine whether the methods used at that time were appropriate, and the committee's findings and recommendations should not be construed as either criticism or approval of the standards when issued. Instead,
the findings and recommendations focus on how current risk-assessment practices
and current knowledge regarding chemicals in biosolids can be used to update and
strengthen the scientific credibility of EPA's chemical standards.

In light of the advances made in risk-assessment methods and the need to update
many of the exposure parameters used in the risk assessment process, the existing
biosolids standards for inorganic pollutants clearly need to be reevaluated. A comparison
of the pollutant limits with risk-based soil screening levels suggests that the
pollutant standards are adequately protective for some exposure pathways (i.e.,
soil/biosolids ingestion), but may need to be reevaluated for others (i.e., ingestion
of homegrown produce grown on biosolids-amended soil, groundwater). Reevaluating
the standards is not the same as saying that the standards should be lower. In fact,
some standards might increase after a reevaluation. A lower standard for a particular
pollutant also would not necessarily indicate the presence of a health risk. The
risk would depend on the actual concentrations of the pollutant in biosolids to
which people were exposed. Nonetheless, the current limits cannot with confidence
be stated to be adequately protective for all of the regulated pollutants. Additionally,
limitations in the chemical selection process apply to inorganic, as well as organic,
pollutants.

Recommendation: A revised multipathway risk assessment should be performed for the
currently regulated pollutants, with particular attention paid to arsenic and to
indirect exposure pathways for cadmium and mercury. In addition, new survey data
should be used to identify any additional inorganic or organic pollutants that might
need to be included in a risk assessment.

Finding: The science and body of knowledge underlying the practice of risk assessment
have evolved substantially since the risk assessment supporting the Part 503 rule
was conducted. Consequently, different approaches and supporting data would be used
if the Part 503 rule risk assessment were conducted again today or in the future.
One important development has been the recognition of the importance of engaging
stakeholders in the risk-assessment process to help characterize potential exposures.
Stakeholders are groups potentially affected by the risk, risk managers, and groups
affected by efforts to manage the source of the risk. Involving stakeholders throughout
the risk-assessment process provides opportunities to bridge gaps in understanding,
language, values, and perspectives and to address concerns of affected communities.

Recommendation: Risk-based standards for land application of biosolids should be
reevaluated on a regular basis to take into account new information regarding the
identity and properties of chemicals present in these mixtures and current approaches
to evaluating the risks of exposure to such mixtures. Stakeholders should be included
in the process, particularly in the development of the exposure assessments.

Finding: The chemical selection process used to identify chemicals of concern for
the risk assessment is now outdated. Data from the NSSS that was used in the selection
process are over a decade old, and there is a need to characterize the concentrations
and distribution of chemicals now present in biosolids. Additional chemicals not
included in the NSSS analyses have now been identified as new concerns. Analytical
methods have improved since the NSSS was conducted.

Recommendation: The committee endorses the recommendation of the previous NRC committee (NRC 1996) that a new national survey of chemicals in biosolids be conducted. It recognises that more recent survey data are available through many state programs and recommends that EPA consider those databases in the course of designing a new national survey. Other elements that should be included in a new survey are the
following: evaluation of the adequacy of analytical methods and detection limits
to support risk assessment; consideration of categories of chemicals of current
concern that were not previously evaluated (e.g., odorants, surfactants, and pharmaceutical); and assessment of the possible presence of multiple species of mercury, arsenic, and other metals that have different toxic end points.

Finding: EPA's decision to eliminate all chemicals detected at less than 5% or
10% frequency in the NSSS is unjustified. Data gaps may now be filled for toxicity
and fate and transport characteristics that were previously used to eliminate chemicals
from the risk assessment. In addition, uncertainties associated with the chemical
selection process have not been adequately evaluated.

Recommendation: Selected persistent, bioaccumulative, and highly toxic chemicals
should be retained in the risk assessment even if they are detected relatively infrequently
or if some chemical-specific fate and transport parameters are missing. An uncertainty
assessment should be performed to evaluate the significance of eliminating chemicals
from the risk assessment because of lack of toxicity data or other parameters.

Finding: The Part 503 rule risk assessment focused on agricultural land-application
scenarios. Conceptual site models documenting the exposure pathways judged to be
major and minor are not available for the scenarios evaluated. Consequently, it
is difficult to determine whether all relevant pathways were identified. Although
the pathways evaluated are likely to be the major exposure pathways for chronic
exposures in agricultural scenarios, there might be differences in the significance
of pathways for short-term exposures and for different scenarios.

Recommendation: A new risk assessment should include separate exposure scenarios
that represent substantial differences in exposure potential (e.g., land reclamation
and forestry applications). For each scenario, a conceptual site model approach
should be used to identify major and minor exposure pathways and routes of exposure.
Risks from short-term episodic exposures should also be evaluated for volatile chemicals,
such as odorants.

Finding: The degree of realism varies by exposure pathway. The pathways were not
evaluated in a consistent manner (i.e., it is not apparent that exposure estimates
were comparably conservative for all pathways). Exposures also were not added for
multiple pathways affecting a single receptor. For the indirect pathways, the use
of multiple, highly conservative assumptions could result in unrealistic overestimates
of risk. However, because of the diversity of exposed populations, environmental
conditions, and agricultural practices in the United States, exposure analyses based
on a nationwide range of exposures might not be adequately protective for all cases.

Recommendation: A comparable reasonable maximum exposure (RME) should be evaluated for each exposure pathway in each exposure scenario, and where the same receptor is likely to be exposed to more than one pathway, exposures should be added across pathways. Such considerations are applicable for both deterministic and probabilistic exposure assessment approaches. Multiple highly conservative assumptions should be avoided; however, care should be taken to ensure that the risks are assessed
for the high-end population and that the most sensitive conditions for biosolids
application are considered. For example, for the groundwater infiltration pathway,
if biosolids application is likely to occur in areas of sandy soil or karst topography
with shallow groundwater, those conditions should be used in the risk assessment.

Finding: As described above and in Chapter 4, new scientific data are now available
that could be used to support alternative assumptions for many of the exposure parameters used in the risk assessment. Comprehensive reviews and updated recommendations for many parameters have been compiled in several EPA guidance documents. Fate and transport models used to estimate exposure point concentrations for many pathways have also been updated.

Recommendation: The most recent EPA reviews and new studies reported in the literature should be used to identify updated assumptions for exposure parameters for use in risk assessment. Updated fate and transport models should be used to estimate exposure point concentrations. For each exposure pathway, fate and transport models and exposure parameter assumptions should be selected so that pathway exposures reflect the RME.

Finding: Biosolids are likely to include many categories of chemicals that differ
from the categories of chemicals of concern in industrial discharges. Although it
is impossible to identify all of these pollutants, it is important that EPA continually
think about the types of chemicals released into wastewaters and added during wastewater and sewage-sludge treatment processes as part of its process for updating the Part 503 rule. EPA eliminated certain chemicals of concern from further assessment when there was an absence of data on fate, transport, and toxicity. New data on some
of these chemicals might now be available for determining whether risk assessments
for those chemicals are needed. Because some organic chemicals, such as organochlorines, are persistent in the environment, consideration should be given to their tendency for trophic transfer and biomagnification. EPA has already undertaken such an evaluation for dioxins. Consideration should also be given to toxic end points that might not have been evaluated adequately in the earlier assessment (e.g., potential interactions of chemicals with the endocrine system). Two categories of chemicals deserving special attention are pharmaceuticals and odorants. Considering the amounts discharged to sewage systems, the presence of pharmaceuticals in biosolids has not been adequately investigated. For odorants, the need for further evaluation is driven by the high level of public concern, as well as very limited characterization of the odorants present in biosolids and their toxicity.

Recommendation: In addition to the recommendation above for a new biosolids survey
and chemical selection process, it is recommended that a research program be developed for pharmaceuticals and other chemicals likely to be present in biosolids that are not currently included in routine monitoring programs. This includes chemicals eliminated from Round 1 and Round 2 evaluations because of data gaps. The research program should have the goal of identifying additional chemicals that should be included
in routine biosolids surveys and in future risk assessments. For odorants, research
in needed to identify the odorants present in various kinds of biosolids. For odorants
commonly present in biosolids, EPA should move aggressively to develop acute toxicity
values for use in assessing the risks posed by these chemicals and should support
research on the interaction between these chemicals and pathogens in causing human
disease.