NCEA-C-1340
ERASC-003
June 2003
NON-DIOXIN-LIKE PCBs: EFFECTS AND CONSIDERATION IN
ECOLOGICAL RISK ASSESSMENT
by
Tala R. Henry and Michael J. DeVito
United States Environmental Protection Agency
Experimental Toxicology Division
National Health and Environmental Effects Research Laboratory
Office of Research and Development
Ecological Risk Assessment Support Center
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH
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ACKNOWLEDGMENTS
This document was prepared by Tala Henry and Michael DeVito of EPA's National
Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and
Development (ORD) in response to a request received by ORD's Ecological Risk Assessment
Support Center (ERASC) from the Ecological Risk Assessment Forum (ERAF). EPA peer
review of the document was conducted by Philip Cook, Mike Hornung, and Linda Birnbaum of
NHEERL, and Deborah Rice, formerly with ORD's National Center for Environmental
Assessment (NCEA). External peer review of the document was conducted by Richard T.
DiGiulio of the Nicholas School of the Environment and Earth Sciences, Duke University, North
Carolina, and Sean Kennedy, EcoToxicology Consulting, Ontario, Canada. Programmatic
review was conducted by the Trichairs of EPA's Ecological Risk Assessment Forum: Susan
Roddy, EPA Region 6; Gina Ferreira, EPA Region 2; and Dale Matey, Office of Solid Waste and
Emergency Response, Office of Emergency and Remedial Response (OSWER/OERR). Finally,
we would like to acknowledge the efforts of Bruce Duncan, EPA Region 10, in initiating the
original request.
n
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TABLE OF CONTENTS
Pag
1. Introduction 1
1.1 Issue 1
1.2 Purpose of this Report 1
1.3 ERASC Request & Response 2
2. Chemical Characterization 3
2.1 Chemical Structure 3
2.2 Nomenclature 3
2.3 Physical-Chemical Characteristics 4
2.4 Dioxin-Like PCB Congeners 5
2.5 Non-Dioxin-Like Congeners 6
3. Detection, Transport and Disposition of PCBs in the Environment 7
3.1 Analytical Methods for Detection of PCBs 7
3.2 Fate, Transport and Disposition in the Environment 8
3.3 Disposition in the Environment: Media 8
3.4 Disposition in the Environment: Biota 9
4. Biological Effects of Non-Dioxin-Like PCBs 10
4.1 Toxicity Pathways 11
4.1.1 Narcosis 12
4.1.2 Liver Effects 13
4.1.3 Endocrine / Neuroendocrine Function 15
4.1.4 Neurochemical / Neurobehavioral Function 21
4.1.5 Immune Function 23
4.2 Relative Toxicity of Non-Dioxin-Like vs. Dioxin-Like PCBs 24
4.2.1 Mammals 25
4.2.2 Birds 26
4.2.3 Fish 26
4.2.4 Invertebrates 26
5. Consideration of Non-Dioxin-Like PCBs in Ecological Risk Assessment 27
5.1 Non-Dioxin-Like Effects Endpoints 27
5.2 Relative Contribution of Dioxin-Like and Non-Dioxin-Like PCBs 27
5.2.1. Exposure 27
5.2.2. Effects 28
5.2.3. Risk 28
111
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6. References 30
APPENDIX 1: Nomenclature & Log Kows 45
APPENDIX 2: ERASC Request 49
IV
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1. Introduction
1.1 Issue
An estimated one million metric tons of commercial mixtures of poly chlorinated
biphenyls (PCBs), such as Aroclors (USA), Kanechlors (Japan) and Clophens
(Germany), were manufactured (WHO, 1993) and used worldwide as dielectric fluids in
capacitors and transformers, heat transfer fluids, hydraulic fluids, lubricating oils, and as
additives in pesticides, paints, copy paper, adhesives and plastics during the 1930s
through the mid-1970s. PCBs have entered the environment during both use and disposal
and have been shown to be ubiquitous contaminants, occurring in most environmental
media as well as biota.
Historically, analyses of environmental media and associated risk assessments have been
conducted using approaches that consider the PCB mixtures as a whole, i.e., "Total
PCBs" or Aroclors. Subsequently, it has been shown that the fate of various congeners in
the environment varies, such that the PCB congener profiles in environmental media may
change significantly from the original commercial mixtures. Likewise, individual PCB
congeners have been found to vary significantly in their uptake, distribution, metabolism,
and elimination within biological systems such that the congener profile in biological
tissues can be quite different from both the original commercial PCB mixture and
environmental media. Toxicological effects and dose-response relationships within
biological systems can also vary among the different PCB congeners.
As a result, the consensus within the scientific community is that "Total PCB"- and/or
Aroclor-based risk analyses may not adequately characterize risks posed by PCB mixtures
(WHO, 2001). Those PCB congeners that elicit dioxin-like toxicity have been defined
and a toxicity equivalence approach for use in both human health and ecological risk
assessment has been developed (U.S. EPA, 2000, 2001, 2003). However, the dioxin-like
PCB congeners represent only 12 of the 209 possible congeners. To assess risks posed by
the remaining 197 congeners, information on the fate and effects of the non-dioxin-like
congeners is required.
1.2 Purpose of this Report
4 To provide ecological risk assessors with a concise summary of the state-of-the-
science regarding the biological effects of non-dioxin-like PCBs.
4 To provide ecological risk assessors with a compilation of references describing
the biological effects of non-dioxin-like PCBs. The list of references is comprised
primarily of books, reports, and review articles to provide risk assessors with
sources from which they may acquire a thorough overview of the topics at hand.
These materials should be used as a source for primary literature references.
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1.3 ERASC Request & Response
The issues addressed in this report are those specifically requested in the Ecological Risk
Assessment Support Center Request Form (Appendix 2). These issues are listed below
along with the section(s) of the report where the information addressing each issue can be
located.
4 Describe the mode of action of non-dioxin-like compounds and types of effects in
receptors (i.e., those congeners that "travel" with the listed dioxins, furans, and
PCBs but just don't act via the Ah receptor)
Addressed in Section 4.
4 Discuss n-d-1 toxicity relative to congener characteristics (something like a QSAR
discussion of planes and rings and big chlorines)
Addressed in Sections 2 & 4.
4 Discuss which congeners are of greatest concern (potency) for n-d-1 toxicity
(dose/response type information in the narcotic range of effects)
Addressed in Sections 3 & 4.
4 Recommend how this scientific info on action, effects, and toxicity should be used
in eco risk assessment where PCBs are present (preferred use of the data,
considerations for site-specific application, etc.)
Addressed in Section 5.
4 Discuss whether a general narcosis model can or should be used to evaluate n-d-1
effects (as a function of range of contaminant concentration typically seen at low,
medium, and highly contaminated sites)
Addressed in Sections 4 & 5.
4 Provide an interactive video-conference on this topic and the one related to
congener analytical methodology
This portion of the request requires another process.
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2. Chemical Characterization
A brief overview of PCB nomenclature and chemical properties is provided in this
section. Several detailed compilations of PCB chemistry and nomenclature have been
compiled previously for all PCBs (Erickson, 1997, 2001; ATSDR, 2000) and for non-
dioxin-like PCBs (Hansen, 1999).
2.1 Chemical Structure
3'
5' 6' 65
Polychlorinated biphenyls (PCBs)
Figure 1. Structure PCBs.
2.2 Nomenclature
Polychlorinated biphenyls (PCBs) are a class of chemicals characterized by a common
biphenyl molecular framework to which 2 to 10 chlorine atoms maybe attached (Figure
1). Although technically not /»o/ychlorinated, mono-chlorinated biphenyls are generally
included when referring to PCBs collectively.
Congener - one of 209 possible PCB structures having the formula, C12H 10.BCln, where n
= 1-10. Each of the 209 PCB congeners can be specifically defined by standard chemical
nomenclature rules in which the number and position of chlorines on the biphenyl ring(s)
are designated. Each PCB congener has also been assigned a number, between 1 and 209,
by the International Union of Pure and Applied Chemists (IUPAC). The IUPAC numbers
provide a convenient shorthand system, but do not provide information as to the specific
chemical identity of the congener. A list of all 209 PCB congeners, including IUPAC
name, IUPAC # and CAS # are provided in Appendix 1.
Homolog - a subset of PCB congeners defined by the degree of chlorination, i.e.,
monochlorobiphenyls through decachlorobiphenyls (Table 1). PCBs within a homolog
group have the same molecular weight and number of chlorines attached to the biphenyl
ring, but the pattern of chlorination varies among the individual isomers within the
homolog group. A list of all PCB homolog groups, including IUPAC name and CAS #
are provided in Appendix 1.
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Table 1. Chemical Groupings of Polychlorinated Biphenyls
Number of
Chlorines
0
1
2
3
4
5
6
7
8
9
10
Homolog
Group
biphenyl
mono-CB
di-CB
tri-CB
tetra-CB
penta-CB
hexa-CB
hepta-CB
octa-CB
nona-CB
deca-CB
Molecular
Formula
Ci2H10
C12H9C1
C12HgCl2
C12H7C13
Ci2H6Cl4
C12H5C15
C12H4C16
C12H3C17
C12H2Clg
C12HC19
C C1
^-'12^-'i10
Molecular
Weight
154.1
188.0
222.0
256.0
289.9
323.9
357.8
391.8
425.8
459.7
493.7
Number of
Isomers
1
3
12
24
42
46
42
24
12
3
1
Isomer - biphenyls within the same homolog group (i.e., same molecular weight and
molecular formula) with different substitution patterns. Specific isomers are defined by
the position(s) of the chlorine atoms on the biphenyl rings (e.g., 3,3',4,4',5-
pentachlorobiphenyl).
2.3 Physical-Chemical Characteristics
Most pure PCB congeners are colorless, odorless crystals under ambient conditions
(Erickson, 2001). Commercial PCB mixtures (e.g. Aroclors) are clear, viscous liquids,
with viscosity increasing with degree of chlorination. Generally, PCBs have high boiling
points (>200°C), low vapor pressures, low water solubilities (ppm to ppt), moderate to
high log Kows (--4 to 8), high bio concentration factors (BCFs) and do not degrade readily,
which all contribute to their persistence in the environment. These physical-chemical
properties may vary widely between the individual congeners. A summary of these
properties, presented as averages for homolog group (Erickson, 2001) and for individual
congeners (Hansen, 1999), have been compiled. High quality Log Kow values for all 209
PCB congeners, as determined by Hawker and Connell (1988), are provided in Appendix
1 for reference. Primary sources of information on specific congener properties are
referenced within these summaries.
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2.4 Dioxin-Like PCB Congeners
The 12 PCBs listed in Table 2 act through the aryl hydrocarbon receptor (AHR) to cause
the full range of toxic responses elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Hence,
these PCB congeners are referred to as the dioxin-like PCBs. The structure-activity
relationships underlying the distinction of dioxin-like PCBs from the other PCBs have
been characterized. The dioxin-like PCBs have chlorines in a minimum of four of the
lateral positions (i.e., 3, 3', 4, 4', 5, 5') and none (non-) or only one (mono-) of the ortho
positions (i.e., 2, 2', 6, or 6') of the biphenyl. The PCBs without ortho substituted
chlorines are often referred to as co-planar PCBs, but this terminology is not technically
appropriate since these PCBs do not easily assume a planar conformation similar to that
of the dioxins and furans (WHO, 2001). The non-ortho dioxin-like PCBs (i.e., PCBs 77,
81, 126 & 169) bind the AHR and cause dioxin-like toxicity in fish, birds and mammals.
The mono-ortho chlorinated dioxin-like PCBs are also able to bind the AHR and cause
dioxin-like toxicity in birds and mammals, but generally do not cause dioxin-like
responses in fish. The toxicological effects which may occur, as a result of exposure to
dioxin-like PCBs in fish, birds and mammals, have been well characterized relative to the
other PCBs. Dioxin-like toxicity in ecological receptors has been summarized in the
scientific literature and in numerous EPA reports (Peterson et al., 1993; Walker and
Peterson, 1994; Niimi, 1996; Hoffman et al., 1996; Rice et al., 2002; ATSDR, 2000; U.S.
EPA, 1993, 1995a,b, 2001) and will not be discussed in detail further in this report.
Table 2. Dioxin-Like PCBs
IUPAC #
Homolog Group
Substitution Group
IUPAC Name
non-ortho substituted PCBs
77
81
126
169
tetra-CB
tetra-CB
penta-CB
hexa-CB
non-ortho
non-ortho
non-ortho
non-ortho
3,3',4,4'-tetra-CB
3,4,4',5-tetra-CB
3,3',4,4',5-penta-CB
3,3',4,4',5,5'-hexa-CB
mono-ortho substituted PCBs
105
114
118
123
156
157
167
189
penta-CB
penta-CB
penta-CB
penta-CB
hexa-CB
hexa-CB
hexa-CB
hepta-CB
mono-ortho
mono-ortho
mono-ortho
mono-ortho
mono-ortho
mono-ortho
mono-ortho
mono-ortho
2,3,3',4,4'-penta-CB
2,3,4,4',5-penta-CB
2,3',4,4',5-penta-CB
2,3',4,4',5-penta-CB
2,3,3',4,4',5-hexa-CB
2,3,3',4,4',5'-hexa-CB
2,3',4,4',5,5'-hexa-CB
2,3,3',4,4I,5,5'-hepta-
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In ecological risk assessments, the dioxin-like PCBs should be included in a cumulative
assessment with all other chemicals that act via the same mechanism of action (i.e., AHR
agonists such as polychlorinated dibenzo dioxins (PCDDs) and furans (PCDFs)).
Presently, the most credible approach for assessing mixtures of dioxin-like chemicals is
to apply a toxicity equivalence approach in which the concentrations of the individual
dioxin-like congeners are converted to TCDD toxicity equivalence concentrations (TEC)
using a toxicity equivalence factor (TEF) or a relative potency factor (RPF). Guidance
for applying the toxicity equivalence approach in ecological risk assessment is currently
being prepared by EPA's Risk Assessment Forum (U.S. EPA, 2003). For complementary
information on applying the toxicity equivalence approach for assessment of PCDDs,
PCDFs and dioxin-like PCBs, see van den Berg et al. (1998) and U.S. EPA (2000, 2001).
Certain dioxin-like PCBs may act via multiple toxicity pathways. Hence, while the 12
dioxin-like PCBs are known to cause dioxin-like toxicity via the AHR, the 8 mono-ortho
dioxin-like congeners may also act via non-AHR mechanisms to cause additional effects.
As other toxic pathways for PCBs are elucidated, it is possible that dioxin-like PCBs may
be found to cause adverse effects on additional ecologically-relevant endpoints. At this
time, information about the mechanisms of action and dose-response relationships in
ecological receptors is insufficient to allow assessment of dioxin-like PCBs on the basis
of non-AHR mediated pathways. However, a number of studies of effects of PCB
mixtures in wildlife species (including both laboratory and field exposure scenarios) have
shown that most, if not all, toxicity caused by the mixtures (e.g. Aroclors) can be
attributed to the TCDD equivalence concentration (TEC) of the mixture (Walker et al.,
1996; Tillitt et al., 1996; Tillitt and Wright, 1997; Giesy and Kannan, 1998).
2.5 Non-Dioxin-Like Congeners
The 197 PCB congeners which were not discussed in the previous section are currently
referred to collectively as "non-dioxin-like" congeners. These congeners are also often
referred to as the "non-coplanar" or "o7t/zo-substituted" congeners. However, experts
attending an international World Health Organization Consultation in 2001 established
preference for the biologically-based term "non-dioxin-like" for several reasons, the most
compelling being that even the non-ortho substituted PCBs are not strictly planar in
configuration and some O7t/zo-substituted PCB congeners have both dioxin-like and non-
dioxin-like activity (WHO, 2001). As more research is conducted on these congeners it is
likely that they will be classified more specifically into additional subsets based on
toxicological effects endpoints (e.g., endocrine active PCBs; neurotoxic PCBs,
immunotoxic PCBs; etc.) and/or mechanisms of action (estrogen receptor
agonists/antagonists; serotonin biosynthesis inhibitors; etc.). Current knowledge of non-
AHR-mediated effects of PCBs are the subject of Part 4 of this report.
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3. Detection, Transport and Disposition of PCBs in the Environment
3.1 Analytical Methods for Detection of PCBs
The various congener-specific analytical methods have been reviewed in detail elsewhere;
several recent reviews are summarized here. The second edition of a book dedicated to
this topic, Analytical Chemistry of PCBs, was published in 1997 (Erickson, 1997).
Analytical methods are reviewed more briefly in a recent compilation of papers presented
at a PCB workshop held in 2000 (Robertsen and Hansen, 2001). Frame (2001) presents a
concise overview of various analytical methods for quantifying PCBs, dedicating most of
the text to "the ultimate PCB mixture analytical procedure" he refers to as
Comprehensive, Quantitative, Congener-Specific (CQCS) PCB Analysis. EPA's Method
1668A is highlighted and is predicted to become the "gold standard" of CQCS PCB
analysis. A more pragmatic presentation of congener-specific methods is provided by
Beliveau (2001) of EPA's Region 1. Beliveau also provides an examination of Aroclor
and partial congener analyses as well as full references for the various EPA methods for
analysis of PCBs in various environmental matrices. Hansen (1999) has compiled
important details to consider in interpreting and presenting congener-specific data. U.S.
EPA Region 9's Biological Technical Assistance Group has also reviewed various
analytical methods for routine congener-specific analysis and report that methods
currently available are adequate and cost-effective (Valoppi et al., 1999). This report also
presents a phased approach for PCB congener-specific analysis specifically for use within
the context of performing site-specific ecological risk assessments.
As European and U.S. regulatory agencies move away from "Total PCB" and Aroclor
analyses, it has been recognized that analysis of all possible PCB congeners may not be
necessary, possible or practical on a routine basis (WHO, 2001). The analysis of subsets
of PCB "indicator-congeners", selected based on abundance, prevalence and distribution
in the environment, has been proposed as an approach for hazard identification,
estimating exposure, and prioritizing risk assessment activities (WHO, 2001). It should
be noted that the WHO expert panel did not support the use of "indicator congeners" for
measures of toxicity however, due to the limited data available on the effects of non-
dioxin-like congeners (WHO, 2001). Hence, while it has been recognized that a full 209
congener-specific analysis may not be necessary for all phases or tiers of risk assessment
and efforts are underway to identify subsets of congeners to measure for particular
applications (e.g. hazard identification, screening, remedial monitoring, etc.),
characterization of the relative contribution of non-dioxin-like PCB congeners to PCB
mixture toxicity remains a significant data gap. Several different lists of potential
indicator congeners have emerged from various sources (WHO, 2001; Frame, 2001;
Valoppi et al., 1999; NOAA, 1993; McFarland and Clarke, 1989). To date, EPA has not
established a definitive list of "indicator congeners", standardized an approach for
analyzing PCBs nor has any of EPA's programs promulgated a congener-specific method
(Beliveau, 2001).
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3.2 Fate, Transport and Disposition in the Environment
Historically (1930s-1970s), commercial mixtures of PCBs were used worldwide as
dielectric fluids in capacitors and transformers, heat transfer fluids, hydraulic fluids,
lubricating oils, and additives in pesticides, paints, copy paper, adhesives and plastics
(ATSDR, 2000; Hansen, 1999). PCBs have been released into the environment as a
consequence of historical use and disposal; releases of newly manufactured PCBs having
been stopped within the U.S. since banning of the manufacture and use of PCBs in
commerce in the 1970s. Examples of primary sources include landfills, hazardous waste
sites, incineration of PCB-containing wastes, leakage from old electrical equipment and
improper disposal or spills (ATSDR, 2000).
The fate of individual PCB congeners is determined by both environmental processes and
the physical-chemical properties of individual congeners. In general, PCB congeners that
are more highly chlorinated and have fewer ortho substitutions are less volatile, less
water soluble, bind more readily to organic particulate matter and are more amenable to
anaerobic dechlorination processes (typically in buried sediments). Thus, these congeners
are more prominent in soils and sediments, less prominent in water and in the
atmosphere, and have higher bioaccumulation factors (BAFs). Congeners that are less
chlorinated and have more ortho substitutions are more volatile, more water soluble and
are much more readily metabolized in mammals. Consequently, these congeners are
more prominent in the atmosphere, surface waters and in fish from temperate waters
(Hansen, 1999). Hydrophobicity is the most important chemical property that controls
bioavailability from water, sediment or soils. Hydrophobicity can be estimated by the
octanol-water partition coefficient, Kow. Generally, log Kows for PCBs increase from
approximately 3 to 9 as degree of chlorination increases (Hansen, 1999). Hence, lower
chlorinated PCBs having lower Kows are more bioavailable than higher chlorinated
congeners having higher Kows. PCBs that are highly hydrophobic are difficult to measure
in water because of the very small concentrations in solution. Conversely, concentrations
in surficial sediments or soils are often measurable and can be used effectively to
reference each PCB congener's distribution to abiotic and biotic components of the
ecosystem. In aquatic ecosystems, concentrations measured in surficial sediments can be
used to estimate average concentrations in water.
Specifics regarding non-dioxin-like PCB congener disposition in environmental
compartments and transfers among them are detailed by Hansen (1999). A detailed
discussion of the dynamics and interplay between these processes is beyond the scope of
this document, but have been presented in detail elsewhere for PCBs generally (ATSDR,
2000; Robertson and Hansen, 2001) and for non-dioxin-like congeners specifically
(Hansen, 1999).
3.3 Disposition in the Environment: Media
Due to historical releases and redistribution among environmental compartments, PCBs
are widely distributed in environmental media and biota. Of the 209 possible congeners,
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-113 are found in environmental media and/or biota (McFarland and Clarke, 1989).
Reports of PCBs, either measured as total PCBs or Aroclors, in environmental media and
biota are abundant in the literature. Fewer congener-specific characterizations are found,
especially in the older literature. In the environment, PCBs are always found as mixtures
of both dioxin-like and non-dioxin-like PCB congeners. Hansen (1999) provides a more
recent summary of the disposition of PCBs in the environment, with special emphasis on
the non-dioxin-like congeners. Hansen points out that global disposition may not be
relevant to site-specific assessment, but there will always be an atmospherically derived
background PCB concentration which will often be regionally similar. While it is
possible to generalize about specific congener fate, transport and disposition based on
physical-chemical properties of PCBs, ultimately the congener profile of interest for a
site-specific ecological risk assessment will be dependent upon the specific congeners
present in the source material (e.g., which Aroclors were used/disposed of) and the
physical and/or chemical processes relevant for the location. For example, the congener
profile present in media and biota at a site where only a single Aroclor mixture was ever
used/disposed may be quite different from the profile found at a manufacturing plant
which produced the full spectrum of PCB products. The literature is also replete with
reports of PCBs in environmental media and organisms from numerous sites around the
world. Physical, chemical and ecological similarities (e.g., sources, transport pathways,
biological systems - lentic vs. lotic, etc.) between sites may serve as a basis for
extrapolating congener profiles.
3.4 Disposition in the Environment: Biota
PCB toxicity cannot be determined simply by examining the environmental
concentrations of the congeners. Differential rates of uptake, metabolism and elimination
will influence the congener profile to which target tissues are ultimately exposed.
Detailed discussions of the disposition of PCBs in various taxa and the role of various
toxicokinetic factors that influence the bioaccumulation of PCB congeners is beyond the
scope of this report, but have been summarized elsewhere (Hansen, 1999; Robertson and
Hansen, 2001; ATSDR, 2000). Some generalizations can be made however. Aquatic
invertebrates serve as a major source of PCBs in food chains and seem to retain polar
metabolites of metabolizable PCBs, which then biomagnify in the food chain. Uptake of
PCBs in fish and invertebrates occurs via contact with media (i.e., respiration of water;
contact with sediment), but food chain transfer is a major contributor for predatory
organisms. Uptake of PCBs in piscivorous mammals and birds is primarily from
ingestion offish. As a class of compounds, PCBs are relatively resistant to metabolism
by animals and the resistence to metabolism increases with degree of chlorination. Most
congeners are metabolized to some extent and differential or selective metabolism among
species appears to have the greatest influence on net PCB accumulation (Hansen, 1999).
PCB congener profiles in mammals are generally similar, but species-specific differences
in absorption, disposition and metabolism certainly exist. The PCB congener profiles in
fish differ considerably from birds and mammals and consistently include greater
proportions of congeners that are more labile in mammals. For example, measurements
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of biota-sediment accumulation factors (BSAFs) for fish clearly demonstrate that very
few PCB congeners are significantly metabolized, but that PCB 77 is a notable exception
(Endicott and Cook, 1994; U.S. EPA, 1995c).
Overviews of dose-, congener-, species- and time-dependent PCB profiles in aquatic and
marine food chains is presented by Hansen (1999). McFarland and Clarke (1989) provide
a congener-specific summary of the occurrence and abundance of all 209 PCBs found in
several classes of animals from various trophic levels collected from several different
sites world-wide. Although this paper presents only a "snapshot" of PCB profiles for
organisms from specific sites, it provides a template of the sort of data one might desire
to collect for an ecological risk assessment. The literature pertaining to bioaccumulation
and biotransformation of PCBs in birds has been reviewed by Barren et al. (1995).
Bioaccumulation and clearance of 42 individual PCB congeners following exposure of
American kestrels to a mixture of Aroclors has been characterized by Drouillard et al.
(2001). Congener-specific bioaccumulation of a number of individual PCB congeners in
three trophic levels of an aquatic food web has been described and biotransfer factors for
four water bird species determined (Zimmermann et al., 1997). Numerous reports
document PCB profiles in higher trophic level birds collected from the field (e.g., Custer
et al., 2002; Herzke et al., 2002; Elliot et al., 2001; van den Brink and Bosveld, 2001).
Information on the PCB profiles present in aquatic and avian species will also serve as a
basis for examining exposure of wildlife mammals via ingestion of such species.
4. Biological Effects of Non-Dioxin-Like PCBs
Some non-dioxin-like PCBs have been shown to elicit different types of responses than
the dioxin-like PCBs, including neurological, neuroendocrine, endocrine, immunological
and carcinogenic effects. These effects occur via multiple toxicity pathways, not
involving the AHR. Currently, only a small number of individual non-dioxin-like PCBs
have been linked to any one of these effects and it should be realized that a single
congener may act through one or more pathways. Likewise, some weak dioxin-like
congeners, or their metabolites (i.e., mono-ortho chlorinated congeners), may also initiate
toxicity via these pathways, independent of the AHR. However, in order to assess risks
posed via these toxicity pathways, the pathways must be demonstrated to be active in a
particular organism or class of organisms. Furthermore, dose-response relationships for
toxicity elicited via these other pathways must be characterized to determine whether
effects of non-dioxin-like PCBs are occurring at concentrations less than those elicited by
dioxin-like PCBs that are always found in the environment along with the non-dioxin-like
PCBs.
While PCBs have been shown to affect various physiological system(s) in some classes of
organisms, this is not necessarily the case for all taxa. Table 3 summarizes the toxicity
pathways that have, to date, been shown to be affected by non-dioxin-like PCBs and those
organisms in which PCBs have elicited effects attributable to those toxicity pathways.
10
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The following sections summarize what is currently known regarding the toxicity
pathways activated by non-dioxin-like PCBs in different biological systems. The
congener-specific data provided represents the data that currently exists in the literature
(i.e., only a very small number of individual congeners have been examined for activity
through the various non-dioxin-like toxicity pathways). Lack of mention of a particular
congener in association with a toxicity pathway does not imply that the congener does not
act through this pathway, rather that the congener has not been tested for activity via the
pathway. The data presented here should not be interpreted to be all-inclusive, as
characterization of non-AHR-mediated effects of PCBs is an active area of research and
new data appear in the literature daily.
Table 3. Toxicity Pathways Documented for Non-Dioxin-Like PCBs
Toxicity Pathway
Narcosis
Liver Effects
Neurochemical / behavioral
Endocrine / Neuroendocrine
Immunological
Organism Class
Invertebrate
X
N/A
7
7
X
Fish
X
7
7
hydroxyPCBs
7
Birds
X
7
7
7
7
Mammals
X
X
X
X
X
4.1 Toxicity Pathways
Narcosis is a non-specific mechanism of toxicity that may be elicited in any organism by
any organic compound, including non-dioxin-like PCBs, at sufficiently high
concentrations. Other potential toxicity pathways, such as endocrine/neuroendocrine
disruption, neurotoxicity, and immunotoxicity, of non-dioxin-like PCBs are currently
being studied in all classes of organisms and as they are elucidated, some toxic effects of
non-dioxin-like PCBs observed in any of these classes of organisms maybe attributable
to them. Non-dioxin-like PCB toxicity occurring via other toxicity pathways has been
established for mammals. Although evidence for non-dioxin-like PCB activity via other
toxicity pathways in birds, fish and invertebrates is mounting, the majority of information
on PCB toxicity has not focused on measures of effects associated with these toxicity
pathways. Hence, most PCB toxicity data for birds characterize dioxin-like toxicity and
those for fish characterize either narcosis (acute exposures; high concentrations) or
dioxin-like toxicity (early life stage toxicity; low concentrations). The bulk of existing
data for invertebrates describe their general insensitivity to PCBs, with toxicity observed
at high concentrations, consistent with narcosis as the mode of action. It is assumed that
non-dioxin-like PCB toxicity that occurs via any of the more specific toxicity pathways
will occur at concentrations lower than those which induce narcosis (Carey et al., 1998).
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4.1.1 Narcosis
Narcosis, also referred to as "baseline toxicity" or "anesthesia", is elicited by organic
chemicals in all organisms given sufficient exposure and assuming a more potent toxicity
pathway is not initiated at a lower dose. Narcosis is thought to be initiated through
chemical-mediated perturbations of membrane-bound proteins, either through direct
interactions or modification of the protein-membrane lipid interface or micro-
environment. Narcotic effects are generally considered to be reversible until death
occurs. For aquatic organisms, narcosis has been characterized in laboratory toxicity
tests, and relationships between octanol/water partition coefficients, lethality and critical
body residues are well established. The common toxicity pathway and established
concentration-residue-response relationships allow mixtures of chemicals (including
PCBs) to be assessed cumulatively using additivity approaches (DiToro and McGrath,
2000; DiToro et al., 2000; Van Leeuwen et al., 1992). Narcotic mode of action and
toxicity are summarized concisely by Carey et al. (1998) and presented in detail in
numerous reviews (DiToro and McGrath, 2000; DiToro et al., 2000; Bradbury et al.,
1989).
Mammals & Birds - Examples of PCB-induced narcosis in laboratory studies for
mammals and birds are generally not available because sufficiently high steady-state
blood concentrations of PCBs can not be attained through oral exposures. Under chronic
exposure scenarios with lower doses, effects of PCBs via AHR-mediated toxicity
pathways have been well documented. Likewise, effects that maybe found to occur via
non-dioxin-like toxicity pathways as described in the following sections would also be
expected to occur at concentrations below those which cause toxicity via narcosis (Carey
et al., 1998). Therefore, for most ecological risk assessment scenarios, mammalian and
avian assessment endpoints should be based on toxicity endpoints other than narcosis.
Fish - Lethality of PCB mixtures (e.g., Aroclors) and individual non-dioxin-like PCBs in
fish following acute aqueous exposures are generally attributed to narcosis. For example,
there are numerous reports of Aroclor-induced lethality in fish (see ECOTOX/AQUIRE
database: www.epa.gov/ECOTOX). The symptomology observed in these tests shows
responses characteristic of narcosis and the toxicity can be accurately described using
related QSARs (Van Leeuwen et al., 1992; Veith et al., 1983). Other toxic effects of non-
dioxin-like PCBs that occur at lower concentrations/doses and through longer exposures,
which are elicited through other toxicity pathways (e.g. endocrine disruption), are
beginning to be elucidated as described in the following sections. It is anticipated that
effects occurring via these more specific toxicity pathways would occur at concentrations
below those which cause toxicity via narcosis (Carey et al., 1998).
Invertebrates - Distinction between dioxin-like and non-dioxin-like PCBs in reference to
invertebrate toxicity is obviated due to the apparent lack of an AHR-mediated toxicity
pathway in this class of organisms. Although AHR homo logs have been identified in a
variety of invertebrate species (Hahn, 1998) they apparently lack the ability to bind the
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prototypical AHR ligands, 2,3,7,8-TCDD and p-naphthoflavone (Butler et al, 2001).
Hence, all toxicity elicited by PCB in invertebrates is considered to occur via non-dioxin-
like toxicity pathways. Several studies are of particular interest in evaluating the toxicity
of individual congeners to invertebrates. These studies include Borgmann et al. (1990;
PCB 52 inHyalella azteca), Dillon et al. (1990; PCBs 52, 101, 118, 138, 153, 180 in
Daphnia magna), Dillon and Burton (1991; PCBs 18, 116, 128, 153, 171, 194 mDaphnia
magna), Fisher et al. (1999; PCBs 1, 15, 47, 153 mLubriculus variegatus), Smith and
Johnston (1992; PCB 15 in shrimp, Crangon crangon) and Schweitzer et al. (1997; PCBs
47 and 153 in purple sea urchin, Stongylocentrotus prupuratus). The PCB concentrations
used in these studies were very high (often exceeding water solubility) and the
invertebrates were most often found to be unaffected by the PCBs. A report by Hwang et
al. (2001; PCB 153 in Chironomus riparius) is a recent addition to the database of effects
of PCBs on invertebrate fecundity and development. Comprehensive summaries of toxic
effects caused by PCB mixtures and individual PCB congeners in a variety of
invertebrates are provided byNiimi (1996) and Jarvinen and Ankley (1999). In those
cases where toxicity was observed in these studies, it occurred at relatively high
concentrations and was consistent with narcosis (West et al., 1997; Fisher et al., 1999).
Many of these studies have been summarized and evaluated by the U.S. EPA for their
potential utility for deriving wildlife criteria values (U.S. EPA, 2002).
4.1.2 Liver Effects
Hepatotoxicity of commercial mixtures of PCBs in mammals is well documented and
includes a number of endpoints including increased liver weight, biochemical changes
(e.g., enzyme induction, porphyrin accumulation), histopathology, and tumors as
compiled recently by ATSDR (2000). However, congener-specific effects data,
generally, and non-dioxin-like congener effects data, specifically, are quite limited.
Furthermore, such endpoints are typically not used as measurement endpoints in
ecological risk assessments because it is often difficult to clearly link these effects to
adverse outcomes on either individuals or populations of ecological receptors. Although
not necessarily useful for ecological risk assessment, a brief summary of reports of liver
effects, particularly those that may be useful in distinguishing dioxin-like effects from
non-dioxin-like effects, is provided.
A few studies utilizing various mammalian models have examined effects of specific
congeners on liver endpoints. The general trend is for the endpoints examined to be
responsive to dioxin-like PCBs, but not non-dioxin-like PCBs (reviewed in ATSDR,
2000). Structure-activity relationships for PCB-induced biochemical and
histopathological responses are not well established, but have been reviewed previously
(Safe, 1994; Marks, 1985). Liver effects in birds and fish have largely been described
within the context of dioxin-like effects, or lack thereof. Hence, several non-dioxin-like
congeners have been assessed for their ability to cause non-specific liver lesions (e.g.,
weight changes, protein concentration changes) and/or induce CYP1A, but effects
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specific to non-dioxin-like congeners have not been established. These data for
mammals, birds and fish are summarized below.
Mammals - Both dioxin-like and non-dioxin-like PCBs are hepatic tumor promoters in
rodents. In two-year bioassays of Aroclors 1016, 1242, 1254 and 1260, all of these
mixtures were considered carcinogenic, particularly in female rat livers. When the doses
of these mixtures were expressed on a TEC basis (i.e., dioxin-like PCBs only), the dose-
response relationship for Aroclor-induced tumors in female rat liver is similar to that
observed for TCDD, except for the Aroclor 1016 mixture. The Aroclor 1016 mixture
contains the lower chlorinated PCBs and has little dioxin-like activity and the
carcinogenic effect of this mixture may be attributed to the non-dioxin-like PCBs present.
Unlike TCDD, liver tumors were observed in the male rats receiving Aroclor 1260,
suggesting that these effects are mediated through pathways other than the Ah receptor.
Other liver effects, including increased liver weight, biochemical changes (e.g., enzyme
induction, porphyrin accumulation) were also observed in the aforementioned studies.
Similar to the carcinogenic effects, the female rats were more sensitive than the males and
Aroclor 1016 was much less potent than the other mixtures. These studies suggest that
the hepatic toxicity of mixtures of PCBs are largely due to the dioxin-like congeners in
these mixtures (ATSDR, 2000). In mammals, induction of liver enzymes distinct from
cytochrome P4501A, namely cytochrome P450s 2A and 3B (CYP2A/3B), have been
linked to non-dioxin-like PCBs (reviewed by Bandiera, 2001). Although the molecular
mechanism(s) underlying CYP2B/3A induction has not been elucidated, this endpoint, in
the absence of CYP1A induction, could be used as a biomarker of non-dioxin-like PCB
exposure and/or effects (WHO, 2001; Bandiera, 2001).
Liver porphyrin accumulation in response to PCB exposure, both PCB mixtures and
individual PCB congeners, has been studied in several mammalian species (see ATSDR,
2000 for review). Dioxin-like PCB congeners 105, 128 and 126, but not 77, cause
porphyrin accumulation in rats (ATSDR, 2000; van Birgelen et al., 1996). In contrast,
non-dioxin-like PCB congeners 28, 118, 153 and 156 reportedly are not porphyrinogenic
in rats. While a strong association between AHR responsiveness and porphyrinogenic
responses indicates that the porphyrinogenic response in mammals is largely AHR-
mediated (ATSDR, 2000), non-dioxin-like PCBs have been reported to greatly enhance
AHR-mediated porphyrin accumulation. It appears that both dioxin-like and non-dioxin-
like PCBs may affect the heme biosynthetic pathway via different molecular mechanisms
(van Birgelen et al., 1996; Marks, 1985).
Birds - While induction of cytochrome P450s isozymes other than 1A1 have been
associated with exposure to non-dioxin-like PCBs in mammals, this relationship has not
been established in birds. Kennedy et al. (1996) have reported induction of EROD
activity in chicken embryo hepatocytes treated with the non-dioxin-like congeners #2, 12,
35, 37, 78, 79, 80, 66, 70, 110, 122, 128, 138, 139, 167, 170, 180, and 194. Lorenzen et
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al. (1997) report that PCBs 52, 54, 101, 136 and 153 failed to induce EROD activity or
CYP1A protein in chicken embryo hepatocytes, but were able to induce porphyrin
accumulation at high concentrations. Quail exposed to PCB 153 displayed increased liver
weights, but the occurrence of porphyria and CYP1A induction caused the authors to
suspect that the PCB was contaminated with dioxin-like congeners, which was confirmed
by chemical analysis (Elliot et al., 1997). In ovo exposure of chicken eggs to PCB 153
failed to cause liver lesions and other early life stage effects associated with exposure to
dioxin-like congeners (Zhao et al., 1997).
Like the CYP1A induction response, the porphyrinogenic response to PCB exposure in
birds is not clearly associated with only the dioxin-like PCB congeners. Several studies
using chick embryo liver cells show that although dioxin-like PCB congeners are more
potent porphyrinogenic agents, certain non-dioxin-like congeners (e.g., 66, 128, 153, 155,
(non-dioxin-like) also possess porphyrinogenic activity, albeit much weaker (Goldstein et
al., 1976; Kawanishi et al., 1978; Marks, 1985; Sassa et al., 1986). Similarly, Miranda et
al. (1987) have reported porphyrinogenic responses in Japanese quail exposed to both
PCB 77 (dioxin-like) and 47 (non-dioxin-like). Sassa et al. (1986) have used the chick
embryo liver data to demonstrate that porphyrinogenic potency is correlated with chlorine
substitution patterns that convey planarity of the PCB molecule. Hence, while the
structural determinants for porphyrinogenic potency of dioxin-like PCBs are the same as
those which determine AHR responsiveness, it remains to be determined whether non-
dioxin-like PCBs may act on the heme biosynthetic pathway via other mechanisms as has
been postulated to occur in mammals (van Birgelen et al., 1996).
Fish - While induction of cytochrome P450s isozymes other than 1A1 have been
associated with exposure to non-dioxin-like PCBs in mammals, this relationship has not
been established in fish. The ability of a few non-dioxin-like PCB congeners to induce
CYP1A protein and/or EROD activity has been assessed. PCBs 128 and 138 were tested
in scup (Stenotomus chrysops) in vivo (Gooch et al., 1989); PCBs 128, 138, 153 and 170
were tested in a zebrafish (Danio rerio) liver cell line (Henry et al., 2001) and PCB 153
was tested in a topminnow (Poeciliopsis lucidd) hepatoma cell line (Bruschweiler et al.,
1996). None of the non-dioxin-like congeners tested were effective at inducing fish
CYP1A. These data do not provide evidence linking non-dioxin-like PCB exposure in
fish tissues to an enzyme induction biomarker as has been established in mammals, but
they do reinforce the association of CYP1A induction as an effect that is specific to
dioxin-like congeners in fish.
4.1.3 Endocrine / Neuroendocrine Function
A broad range of xenobiotics, including PCBs, may have the potential to alter endocrine
function. Endocrine disrupting activity is of concern for ecological risk assessment
because most physiological, developmental and reproductive processes in both
invertebrates and vertebrates are controlled by one or more endocrine systems. Endocrine
disrupters may directly or indirectly mimic or inhibit the production or action of a variety
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of steroids including estrogens, progestins, androgens, adrenal steroids and thyroid
hormones. Individual PCB congeners may act through one or more endocrine pathways
to cause effects and individual congeners in a mixture may have opposing activities (e.g.,
estrogenic and anti-estrogenic). These actions may occur via a variety of molecular or
biochemical events in a number of cells, tissues or organs within a given endocrine
system (e.g., hypothalamus, pituitary, gonad, thyroid, adrenal, steroid metabolism, etc.).
Characterizing the effects of PCBs on the various endocrine systems is further
complicated by the fact that the concentrations, actions and potencies of steroids and
other endocrine active compounds can vary considerably during different life stages and
reproductive cycles. Thus, the potential for PCBs to disrupt endocrine activity will need
to be determined on a congener-specific basis to establish structure-activity relationships
for specific endocrine effects and subsequently the means to assess cumulative effects of
mixtures of environmental congeners.
It is well established that PCBs, including both dioxin-like and non-dioxin-like congeners
and hydroxylated metabolites of some congeners (i.e., hydroxylated PCBs) may affect
endocrine systems in vertebrates (Cooke et al., 2001). Issues related to the
characterization of endocrine-related effects of PCBs have been reviewed in detail
elsewhere (Brouwer et al., 1998; ATSDR, 2000; Cooke et al., 2001). PCB-induced
endocrine effects are summarized below for mammals, birds fish and invertebrates. The
summaries provided focus on effects that have been attributed specifically to non-dioxin-
like PCB congeners, but Aroclor effects data are presented if they are the only data
available that demonstrates the potential for PCB-induced endocrine effects for a class of
organisms.
Mammals - Reports of the effects of PCBs on various endocrine systems in mammals
following exposure to Aroclors are abundant and have been reviewed elsewhere
(ATSDR, 2000; Brouwer et al., 1998). These reports provided the impetus for further
investigating the mechanisms underlying such effects and for determining specific PCB
congeners that elicit effects through a common pathway. The Aroclor studies will not be
discussed further here. The remainder of this section will focus on describing
endocrine/neuroendocrine effects for which causality has been unambiguously linked to
non-dioxin-like PCB congeners.
Reproductive - Effects of non-dioxin-like PCBs in a variety of mammalian endocrine
systems have been described (Cooke et al., 2001; Fischer et al., 1998). Much of the
individual congener data has been collected from in vitro model systems in an attempt to
elucidate the means by which disruption of endocrine pathways can be initiated. For
example, several studies have demonstrated that hydroxylated PCBs bind to the estrogen
receptor (Layton et al., 2002; Yoon et al., 2001; Matthews and Zacharewski, 2000;
Kuiper et al., 1998). Other studies have demonstrated that hydroxylated PCBs inhibit
estrogen sulfation that may result in increases in target tissue concentrations of estradiol
(Kester et al., 2000). Congener specific data from in vivo studies are limited.
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Uterotrophic effects of PCB 153 have been observed in immature female rats
(Soontornchat et al., 1994). In addition, developmental exposures to a mixture of PCBs
has induced feminization of male behavior in rats (Kaya et al., 2002). However, it is
possible that these effects are mediated through the actions of dioxin-like PCBs present in
these mixtures. While there are limited in vivo studies on individual non-dioxin-like
PCBs, it is possible that alterations in the developing reproductive and neurological
systems from in utero and lactational exposure to PCBs is due, in part, to these effects on
estrogen catabolism and receptor interactions.
Initial studies indicated that PCB 138 has an antagonistic effect on androgen receptor
activity in transiently co-transfected Chinese Hamster ovary cells (Bonefeld-Jorgensen et
al., 2001). Portigal et al. (2002) demonstrated in an in vitro system that Aroclors 1260,
1254, 1248, and 1242 antagonize androgen receptor-mediated gene transcription induced
by dihydrotestosterone. Three individual congeners lacking dioxin-like activity
(congeners 42, 128 and 138) have been tested and were also anti-androgenic in this
system (Portigal et al., 2002). A number of studies have demonstrated that either
mixtures of PCBs or individual congeners inhibit rat testicular steroid biosynthesis and
the authors of the studies suggest this effect is not mediated through the AHR (Kovacevic
et al., 1995; Andric et al., 2000a,b). However, the importance of these mechanisms in the
reproductive and developmental effects of PCBs is uncertain.
Thyroid - A number of studies have demonstrated that both dioxin-like and non-dioxin-
like PCBs decrease serum thyroid hormone concentrations. The non-dioxin-like PCBs,
while much less potent than the dioxin-like PCBs, produce greater than a 90% decrease in
serum thyroxine concentrations. In comparison, the dioxin-like PCBs are much more
potent, but only produce a 40-50% decrease in serum thryoxine (Craft et al., 2002). Two
different mechanisms have been proposed for the decreases in serum thyroid hormones by
PCBs. A number of studies have demonstrated that PCB mixtures or individual
congeners increase hepatic thyroxine glucuronidation by inducing UDPGT isoforms
(Craft et al., 2002; Hood and Klaassen, 2000). The induction of thryoxine
glucuronidation increases the biliary elimination of thyroid hormones (Vansell and
Klaassen, 2002a,b). A second mechanism maybe the interaction of PCBs with
transthyretin (Chauhan et al., 2000). Transthyretin is a serum transport protein for thyroid
hormones and certain non-dioxin-like PCBs can displace thyroid hormones from binding
to this site and potentially increasing their hepatic uptake and elimination (Chauhan et al.,
2000). However, while a number of non-dioxin-like congeners have this activity, so do
some dioxin-like congeners (Chauhan et al., 2000). Other potential mechanisms may
involve alterations in thyroid hormone sulfation pathways by PCBs (Kester et al., 2000).
Thyroid hormones are critical in the development of the central nervous system. Perinatal
exposures to PCBs that result in decreases in thyroid hormones in neonatal rats is
associated with decreases in ototoxicity (Goldey et al., 1995). The ototoxicity can be
ameliorated by administration of exogenous thyroxine, suggesting the ototoxicity is due
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to the hypothyroxinemia (Goldey and Crofton, 1998). In humans, background exposures
to PCBs have been associated with decreases in serum thyroid hormones in infants
(Koopman-Esseboom et al., 1994). While these changes are also associated with
neurological developmental delays (Koopman-Esseboom et al., 1997), it is uncertain
whether these associations are causal. Once again, few studies have examined individual
non-dioxin-like PCBs for these developmental effects and the role of the dioxin-like
chemicals present in these mixtures remains a confounder in ascribing these effects solely
to the non-dioxin-like PCBs.
Birds - Effects of PCBs on endocrine endpoints in birds is actively being explored, but
currently available studies are largely limited to Aroclor or field exposures. No studies
describing endocrine effects attributable specifically by non-dioxin-like PCBs in birds
have been reported.
Reproductive - Plasma androgen and estrogen concentrations were unaffected in
American kestrels (Falco sparverius) exposed to a mixture of Aroclors 1248, 1254 and
1260 although the altered courtship behaviors, reproduction and fertility was attributed to
non-persistent, non-dioxin-like congeners, based on bioaccumulation and clearance rates
measured for individual PCB congeners (Fisher et al., 2001; Fernie et al., 2001a,b;
Drouillard et al., 2001). No correlations were found between steroid hormone
concentrations and PCB concentrations in common tern eggs collected from the field
(French et al., 2001; Nisbet et al., 1996). However, common tern embryos collected from
a site contaminated with an unusual mixture of congeners comprised predominantly of
less chlorinated congeners displayed ovarian morphology indicative of feminization.
While correlations between feminization and individual PCB congeners measured in the
embryos were not statistically significant, the authors noted that the strongest correlation
was found between concentrations of PCB 29, which is structurally similar to PCBs 30
and 61. The hydroxylated metabolites of these two congeners are strongly estrogenic
(Korach et al., 1988). The authors also report that extracts of these tern eggs were found
to be estrogenic in an estrogen receptor binding assay (Hart et al., 1998).
Thyroid - The role of thyroid hormones in normal behavior and development in wildlife
and the evidence supporting potential disruption of this pathway by xenobiotics have
been reviewed recently (Colborn, 2002; Brucker-Davis, 1998). Abnormal thyroid gland
development and aberrant thyroid hormone levels have been widely reported in birds;
however, clear association between such endpoints and ecologically relevant adverse
effects and specific environmental contaminants are lacking (Colborn, 2002).
Association between thyroid effects and PCB exposure is further complicated by the fact
that thyroid disruption maybe mediated via both AHR- and non-AHR-mechanisms.
In ovo exposure of chicken embryos to Aroclors 1242 and 1254 decrease plasma
thyroxine concentrations and reduce activity of hepatic type I monodeiodinase, an enzyme
responsible for thyroid hormone homeostasis (Gould et al., 1999; Quinn et al., 2002).
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Neither PCB 54 or PCB 80 (non-dioxin-like) caused similar effects; however, the authors
propose that the effects are mediated via a non-dioxin-like mechanism because PCB 77
(dioxin-like) also did not produce the effects. Aroclor 1254 has also been reported to
decrease plasma thyroid hormone (T3; triiodothyronine) and increase thyroid gland
weight in adult mallards (Fowles et al., 1997).
The use of Aroclor mixtures in all the studies described above does not allow a clear
causal relationship between exposure to non-dioxin-like PCB congeners and endocrine
effects in birds to be established at this time. However, Janz and Bellward (1996a,b)
have provided a body of evidence demonstrating that in ovo exposure of birds to TCDD
had no effect on plasma thyroid hormone concentrations, plasma sex hormone
concentrations or hepatic estrogen receptors in several species of birds (chicken, pigeon,
great blue heron). Taken together, these data implicate non-dioxin-like congeners in the
etiology of endocrine effects observed in birds exposed to Aroclors.
Fish - A variety of xenobiotics cause endocrine disruption in fish, but data regarding
endocrine activity of PCBs are generally limited and the majority of existing data are for
Aroclors.
Reproductive - In Atlantic salmon the non-dioxin-like PCB congeners 58, 104, 112 and
188 were not estrogenic as measured by induction of the egg yolk protein vitellogenin, a
hallmark for estrogenic activity in oviparous animals. However, the authors note that the
route of exposure that was used (intraperitoneal) may not have provided an accurate
assessment (Norrgren et al., 1999). Hydroxylated metabolites of PCB 9, 15, 18 and 61
have been tested for their ability to bind to Atlantic croaker estrogen receptor, but only
hydroxylated PCB 61 displayed affinity (Loomis and Thomas, 1999). Hydroxylated PCB
30 also has affinity for Atlantic croaker progestogen receptor (Thomas et al., 1998).
Hydroxylated PCBs, OH-30, OH-50, OH-72 and OH-112 were found to induce
vitellogenin in rainbow trout hepatocytes in vitro and OH-30 was more active than the
other congeners (Andersson, et al., 1999). Hydroxylated metabolites of PCB 30 and PCB
61 were estrogenic in vivo, as measured by vitellogenin induction, in rainbow trout
(Oncorhynchus mykiss) with OH-PCB 30 approximately 100-fold more potent than
OH-PCB 61 (Carlson and Williams, 2001).
Thomas and co-workers have tested several Aroclor mixtures for their ability to bind
progesterone, estrogen and androgen receptors from the marine fishes, spotted seatrout
(Cynoscion nebulosus) and Atlantic croaker (Micropogonias undulatus) (Thomas, 2000;
Sperry and Thomas, 1999; Loomis and Thomas, 1999; Pinter and Thomas, 1997).
Overall, the Aroclors tested (1210 and 1254) either showed no or very low binding
affinity toward these fish receptors (Thomas, 2000). Aroclor 1254 bound to a small
degree to carp estrogen receptor, but the affinity was so low that incomplete binding
curves were not obtainable (Kloas et al., 2000). Thomas and co-workers have also
complemented these binding studies with in vivo studies that demonstrate that Aroclor
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1254 interferes with the neuroendocrine system in fish at the level of the hypothalamus
and results in effects throughout the brain-pituitary-gonadal axis of Atlantic croaker
(Khan et al, 2001; Khan and Thomas, 2001, 2000, 1996). These studies with Aroclors
serve well as screens for potential endocrine activity within the mixture of PCB
congeners, but do not allow an assessment of the activity of specific non-dioxin-like
congeners.
Thyroid - Abnormal thyroid gland development and aberrant thyroid hormone levels have
been widely reported in fish; however, clear association between such endpoints and
ecologically relevant adverse effects and specific environmental contaminants are lacking
(Colborn, 2002). The role of thyroid hormones in normal behavior and development in
wildlife and the evidence supporting potential disruption of this pathway by xenobiotics
have been reviewed recently (Colborn, 2002; Brucker-Davis, 1998). While disruption of
the thyroid hormone system in fish by PCB mixtures (Besselink et al., 1996) and dioxin-
like PCBs (Palace et al., 2001; Adams et al., 2000) has been reported, effects of non-
dioxin-like PCBs are essentially unexplored.
With the exception of a few hydroxylated metabolites, virtually all studies of potential
effects of PCBs on fish endocrine systems have been conducted using Aroclors. The
Aroclor data indicate that PCB mixtures do have endocrine activity in fish, but do not
allow assignment of the activity to either dioxin-like or non-dioxin-like congeners, since
both types of PCBs may act as endocrine disrupters (Cooke et al., 2001). The lack of
congener-specific data on endocrine activity in fish also precludes making informed
cross-species comparisons or extrapolations.
Invertebrates - The vertebrate steroid hormones (e.g., estrogens, androgens, etc.) are
found in some invertebrate phyla. In echinoderms and deuterostomes they perform
essentially the same functions (i.e., sex differentiation and reproduction) as in vertebrates,
but their functions in other invertebrate phyla are not clear. In invertebrates, many
processes and functions controlled by hormones are unique to this class of organisms.
Therefore, any comprehensive assessment of xenobiotics to act as potential endocrine
disrupters, must include studies in these systems. Given that invertebrates do not possess
an AHR that binds prototypical dioxin-like compounds (Butler et al., 2001), it may be
concluded that any endocrine effects observed in invertebrates do not occur via an AHR-
mediated pathway.
Endocrine disruption by environmental contaminants in invertebrates has received less
attention than for vertebrates, hence very little data are available regarding endocrine
disruption in general, and data on the potential endocrine activity of PCBs and/or their
metabolites are even more scarce. To date, studies on endocrine disruption in
invertebrates have focused on disruption of growth and/or developmental processes (e.g.,
molting, metamorphosis and regeneration) and reproduction in insects and crustaceans
which are known to be controlled by hormones. Aroclor 1242 and the non-dioxin-like
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congener, PCB 29, has been reported to increase molting time, a process regulated by
ecdysteroid hormones, in Daphnia magna (Zou and Fingerman, 1997a,b). The authors
hypothesized that this effect occurred as a result of competitively blocking the
endogenous ecdysteroids from binding to the ecdysteroid receptor (EcR). Oberdorster et
al. (1999) tested the ability of Aroclor 1254 to interact with the Drosophila EcR and
activate gene transcription in vitro and found no effect, neither agonistic nor antagonistic,
on the reporter-gene. Aroclors 1242 and 1254 are mixtures of both dioxin-like and non-
dioxin-like congeners, with PCB 29 present in 1242 but not in 1254. Hence both studies
provide some information regarding what PCB congeners may be potential ecdysone
pathway disrupters in invertebrates.
Summary - PCBs have been shown to have the potential to disrupt the endocrine systems
offish, birds and mammals. Conclusive evidence for PCB-induced endocrine effects in
invertebrates is lacking. For fish and birds, endocrine activity cannot currently be
assigned to specific PCB congeners, because virtually all studies of effects on endocrine
endpoints have been conducted using Aroclors. However, hydroxylated metabolites of
certain PCB congeners appear to be consistently estrogenic across animal classes. In
mammals, more data on individual congeners are available and some structure-activity
relationships are emerging, but the total number of congeners that have been assessed for
effects on the various endocrine systems is quite small relative to the number of
congeners present in the environment.
4.1.4 Neurochemical / Neurobehavioral Function
A number of studies have demonstrated associations between PCB exposure and
developmental delays in humans. One of the difficulties in interpreting theses studies is
the co-exposure to dioxins. In experimental animals, both dioxin and non-dioxin-like
PCBs induce developmental neurotoxicity (reviewed in Seegal, 2001; Fischer et al.,
1998). The present data, while suggesting that non-dioxin-like PCBs are developmental
neurotoxicants, do not allow for a rigorous analysis of the role of the non-dioxin-like vs.
dioxin-like PCBs in these effects.
Mammals - Both dioxin-like and non-dioxin-like PCBs have been shown to have
biochemical effects on the central nervous system. A number of in vitro studies have
demonstrated that some of the non-dioxin-like PCBs are neuroactive. Some PCBs
decrease catecholamine concentrations, particularly dopamine, in the central nervous
system (Seegal et al., 1986; Seegal, 2001; Fischer et al., 1998). Structure-activity
relationship studies indicate that the non-dioxin-like PCBs are the more active congeners
(Shain et al., 1991). Others have reported alterations in calcium, protein kinase C, and
phorbol ester signaling in brain tissues by the non-dioxin-like PCBs (Kodavanti and
Tilson, 1997; Fischer et al., 1998). These studies suggest potential mechanisms by which
the non-dioxin-like PCBs could be neurotoxic. However, the available data on the
developmental neurotoxicity of individual PCBs is limited. While qualitative
descriptions of the developmental neurotoxicity of the non-dioxin-like PCBs is possible,
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quantitatively describing these effects following exposure to complex mixtures of PCBs
is currently not possible.
Birds - Neurotoxic effects of non-dioxin-like PCBs in birds have not been reported in the
literature. Aroclor 1254 has been demonstrated to reduce neurotransmitter concentrations
in brains of ring doves, and the author of this study suggests that these biochemical
affects could result in abnormal behaviors (Heinz et al., 1980). Consistent with this
hypothesis, Aroclor exposures have elicited behavioral effects in birds. Male kestrels
exposed to a mixture of Aroclors 1248, 1254 and 1260, exhibited more sexual and flight
behaviors than control animals (Fisher et al., 2001) and Aroclor 1254 affected courting
and nesting behaviors in mourning doves (Tori and Peterle, 1983), but because PCB
mixtures were used in these studies, it is impossible to attribute the effects to any specific
congener(s).
Fish - As mentioned previously, Thomas and co-workers have demonstrated that Aroclor
1254 affects the neuroendocrine system in Atlantic croaker. Endocrine effects have been
linked to specific actions on neural tissues (e.g. hypothalamus) and neurotransmitter
synthesis pathways (Khan et al., 2001; Khan and Thomas, 2001, 2000, 1996). These
studies demonstrate PCBs can affect neural tissues in fish and provide a mechanistic
connection between the neurotoxicity and impaired gonadal growth observed in fish
exposed to Aroclor 1254. However, because these studies were conducted with a PCB
mixture, the neurological effects cannot be attributed specifically to non-dioxin-like PCB
congeners.
Invertebrates - A recent study (Smith et al., 1999) demonstrated that exposure of the
embryonic marine invertebrate, Spisula, to Aroclor 1254 resulted in decreased growth of
serotonergic cells. The effect of Aroclor 1254 was dose-dependent, but it is unknown
whether the effect is attributable to dioxin-like PCBs, non-dioxin-like PCBs, or both.
However, the absence of a functional AHR in invertebrates (Butler et al., 2001) indicates
the effects are likely mediated through non-dioxin-like pathway(s). Regardless of the
PCB congener(s) involved, this biochemical effect has not been linked to adverse
outcomes on either individuals (e.g. mortality) or populations (e.g. fecundity) of
invertebrates, hence the toxicological significance of the effect for this class of organisms
remains to be established.
Summary - Neurotoxic effects of PCB mixtures in mammals have provided much of the
impetus for exploring effects of non-dioxin-like PCB congeners. Neurochemical effects
of several non-dioxin-like congeners have been characterized in a number of mammalian
cells/tissues (Fischer et al., 1998; Seegal, 2001). Neurotoxic effects of PCBs, dioxin-like
or non-dioxin-like, have not been reported in birds. To date, reports of PCB-induced
neurotoxicity in fish and invertebrates are limited to biochemical effects of PCB mixtures
on specific neuroendocrine or neurological cells/tissues.
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4.1.5 Immune Function
Of environmental contaminants studied thus far, PCBs are among the most potent
immunotoxicants (Carey et al., 1998). They have been documented to affect the immune
systems of multiple species of mammals, birds and fish (Tryphonas, 1995). These effects
may include structural alterations of components (e.g., thymus, lymphocytes) or altered
function (e.g., antibody production, hypersensitivity) of the immune system. The
mechanism(s) by which PCBs are thought to cause immunotoxicity are described by
Tryphonas and Feeley (2001). Effects of various Aroclors on several morphologic and
functional endpoints of rodent, guinea pig, rabbit and chicken immune systems are
summarized by Tryphonas and Feely (2001) and reviewed in detail elsewhere
(Tryphonas, 1994).
Mammals - Immunotoxic effects of PCBs have been well studied in rodents and
primates. The mammalian evidence indicates that PCBs may have a number of effects on
the immune system and that the immune system is one of the most sensitive targets for
PCB-induced toxicity (Tryphonas and Feely, 2001). Immunotoxicity data has been
collected from studies with Aroclors as well as from individual congeners. In general,
higher chlorinated Aroclors (i.e., 1248, 1254 and 1260) are more immunotoxic than lower
chlorinated Aroclors (i.e., 1016, 1232 and 1248) (Carey et al., 1998). Much of the
congener specific data focus on dioxin-like PCBs. These data are consistent with the
Aroclor data, indicating that the dioxin-like congeners exert their immunotoxic effects via
the AHR and are more potent immunotoxicants than the non-dioxin-like congeners.
While the data on the dioxin-like congeners include measures of functional effects on the
immune system, the data for non-dioxin-like PCBs focus solely on changes in
biochemical parameters of specific immune components and have been observed at high
concentrations of PCBs. For example, Ganey and colleagues (Fischer et al., 1998) have
demonstrated that PCBs alter neutrophil degranulation through a mechanism independent
of the AHR. However, it is uncertain if these changes result in alterations in immune
integrity. In addition, some of the non-dioxin-like congeners appear to antagonize the
immunotoxic effects of dioxin-like congeners, but do so through non-AHR mediated
mechanisms (Tryphonas and Feely, 2001). Smialowicz et al. (1997) demonstrated that
PCB 153 can enhance the immune response to sheep red blood cells as determined in a
plaque forming cell assay. PCB effects on the mammalian immune system have been
reviewed in detail elsewhere (Tryphonas, 1994; Tryphonas and Feely, 2001).
Birds - Effects of PCBs on immunological endpoints in birds is largely unexplored and
existing studies are limited to Aroclor or field exposures. No studies of immunological
effects caused specifically by non-dioxin-like PCBs in birds have been reported. PCB
concentrations in plasma and eggs of field exposed Caspian terns have been correlated
with immunotoxicity measured by T lymphocyte function and antibody production;
however, the changes in the specific endpoints measured also correlated with DDE
concentrations in the terns (Grasman and Fox, 2001). Antibody production was affected
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in kestrels exposed either via food or in ovo, to a mixture of Aroclors 1248, 1254 and
1260 (Smits and Bortolotti, 2001). In contrast, antibody production was not affected in
progeny of chickens fed Aroclors 1232, 1242, 1248 and 1254, although spleen and bursa
weights were found to be decreased by these Aroclors (Harris et al., 1976). Subchronic
exposure of adult male mallards to Aroclor 1254 resulted in no immunotoxic effects, as
measured by a battery of immune endpoints, several of which were the same as those
measured in the tern and kestrel studies (Fowles et al., 1997). Hence, no clear causal
relationship between PCB exposure and immunotoxicity in birds has so far emerged.
Because dioxin and dioxin-like PCB congeners have also been reported to cause immune
effects in birds (Powell et al., 1996a,b; Hoffman et al., 1996; Nikolaidis et al., 1988),
future studies that aim to assess the potential impacts of PCBs on bird immune function
should be designed to discern immunological effects caused by dioxin-like and non-
dioxin-like congeners.
Fish - Effects of PCBs on immune function in fish have not been reported in the
literature.
Invertebrates - Effects of non-dioxin-like PCB 15 on the immune system of the common
shrimp (Crangon crangori) has been described (Smith and Johnston, 1992). In the same
study, dioxin-like PCB 77 also caused the same effect, but this response was considered
equivocal based on the magnitude of the response and dose-response relationship
observed.
Summary - PCB mixtures have been demonstrated to cause immunological effects in
mammals, but effects attributable specifically to non-dioxin-like congeners have not been
clearly delineated. Reports of effects of PCB mixtures on immune endpoints in birds are
mixed and no data are available which describe exposure and/or effects specifically for
non-dioxin-like congeners. PCB-induced immune effects in fish are unstudied. A single
study provides some evidence that non-dioxin-like congeners may have immune effects
in invertebrates.
4.2 Relative Toxicity of Non-Dioxin-Like vs. Dioxin-Like PCBs
As evidenced by the data review provided in the previous section, most studies of the
toxicity of PCBs have focused on either commercial mixtures, concentrated
environmental samples or laboratory defined mixtures. All three of these approaches
result in mixtures that contain both dioxin-like and non-dioxin-like PCBs. In these
studies, it is often difficult to qualitatively determine the relative contribution of dioxin-
like and non-dioxin-like PCBs to the toxic effects observed. Quantitative assessments of
the role of these chemicals is simply not possible using these study designs. Although
PCBs are frequently characterized as dioxin-like and non-dioxin-like, this
characterization is an overly simplified description of a structurally diverse class of
chemicals. The toxicity of a number of the dioxin-like PCBs have been fairly well
characterized. However, these congeners represent just 12 of the 209 possible PCBs.
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The remaining PCBs are structurally diverse and may act via one or more toxicity
pathways; hence from a mode of action perspective, characterizing them as a single class
is inappropriate. Most of the congener-specific toxicity data for these non-dioxin-like
PCBs is focused on less than a dozen congeners. Hence, while a compilation of data
comparing dioxin-like and non-dioxin-like effects levels (e.g., NOAELs, LOAELs,
EC50s, etc.) would be helpful in assessing the relative toxicity of PCB congeners, the
limited amount of congener-specific data currently available severely limits the utility of
such an exercise.
Presently, it is unclear how to apply this limited congener-specific toxicity data to the
assessment of complex mixtures found in environmental samples. In the following
discussion, these limitations are described in greater detail for specific toxicity responses.
One approach taken in these analyses is to examine the contribution of the dioxin-like
effects to the toxic response and determine if the use of the toxicity equivalence
methodology would be protective of wildlife species.
4.2.1 Mammals
Relatively few studies are available that characterize the toxicity of non-dioxin-like PCBs
individually. Studies of the commercial mixtures indicate that the more sensitive effects
described to date are mediated by the dioxin-like chemicals present in these mixtures.
For example two different lots of Aroclor 1254 have been examined in a series of studies
(Burgin et al., 2001; Kodavanti et al., 2001). These two lots differ in the concentrations
of dioxin-like PCB congeners and PCDF contaminants. The toxicity equivalence
methodology adequately predicted some responses that were clearly mediated by the Ah
receptor. However, effects on thyroid hormones, oxidative stress, Ca2+ buffering and
phosphokinase C translocation in brain preparations were not predicted by the toxicity
equivalence methodology. It is uncertain whether these effects are due solely to the non-
dioxin-like chemicals or due to interactions between dioxin-like and the non-dioxin-like
chemicals. The data are presently insufficient to ascribe specific effects solely to the non-
dioxin-like PCBs present in these mixtures.
Using the available data on neurotoxicological endpoints characterized in mammals,
Giesy and Kannan (1998) performed an analysis of the relative toxicity of dioxin-like and
non-dioxin-like PCBs to mink. They concluded that it is unlikely for the neurotoxic
effects caused by non-dioxin-like PCBs to be critical based on 1) the high concentrations
of di-ortho substituted PCB congeners needed to elicit neurotoxic responses; 2) the
propensity for the most neurotoxic congeners to be those that are less chlorinated and
therefore more easily metabolized and excreted and less bioaccumulative; and 3) field
studies indicating that neuroactive congeners do no accumulate to sufficient levels in feral
animals (Giesy and Kannan, 1998).
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4.2.2 Birds
An evaluation of the relative importance of non-dioxin-like PCB congener toxicity in
birds is hindered by lack of data. Evidence from both laboratory and field studies is
sufficient to conclude that PCBs produce a wide spectrum of toxic effects in birds,
including effects that have been associated with non-dioxin-like PCBs in mammals (e.g.,
endocrine disruption, neurotoxicity, immunotoxicity). However, the use of Aroclor or
field exposures in virtually all studies of PCB effects in birds precludes characterizing the
toxicity(ies) that are attributable specifically to non-dioxin-like congeners. Additional
studies are needed to establish that non-dioxin-like congeners are toxic in birds and to
characterize the type(s) of effects endpoints that are affected by these congeners.
Furthermore, it is necessary to demonstrate that non-dioxin-like effects result in whole
organism responses that are ecologically relevant (i.e., adverse effects on survival, growth
or reproduction) and to evaluate the potential for significant ecological outcomes (e.g.
population effects) due to such effects.
4.2.3 Fish
Very few studies are available that characterize toxicity of non-dioxin-like PCB
congeners in a manner sufficient for use in ecological risk assessment. The only
individual non-dioxin-like congeners studied in vivo in fish are PCBs 4, 52, 128, 138 and
170 (Gooch et al., 1989; Zabel et al., 1995). Each of these studies has been summarized
(Jarvinen and Ankley, 1999; U.S. EPA, 2002) and evaluated by the U.S. EPA for their
potential utility for deriving wildlife criteria values (U.S. EPA, 2002). It should be noted
that endpoints evaluated in these studies were those associated with AHR-mediated
(dioxin-like) toxicity (e.g. induction of CYP1 A; early life stage edema/mortality
syndrome) and typically these endpoints have been unresponsive to the non-dioxin-like
congeners. So, while these studies can be used to establish no effects levels for dioxin-
like endpoints and in establishing effects endpoints that may be used to distinguish
among dioxin-like and non-dioxin-like congeners, they do not provide for characterizing
non-dioxin-like effects. Available data indicate that non-dioxin-like PCBs and/or their
hydroxylated metabolites have the potential to cause toxicity via disruption of
neuroendocrine pathways, but further studies are needed to demonstrate that the effects
endpoints described to date result in whole organism responses that are ecologically
relevant (i.e., adverse effects on survival, growth or reproduction) and to evaluate the
potential for significant ecological outcomes (e.g. population effects) due to such effects.
4.2.4 Invertebrates
It has been demonstrated that a wide variety of invertebrates including amphipods,
cladocerans, midges, mosquito larvae, sandworms, oligochaete worms, snails, clams and
grass shrimp are insensitive to dioxin and PCB-induced toxicity (West et al., 1997;
Barber et al., 1998; Fisher et al., 1999; see U.S. EPA, 1993 and 2002 for summaries and
references prior to 1998). Reported effects of PCBs in invertebrates include arrested
development and decreased growth, depressed reproduction and decreased survival. In
those cases where toxicity was observed in these studies, it occurred at high
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concentrations and was attributed to narcosis (West et al., 1997; Fisher et al., 1999).
Clear evidence that PCBs can cause endocrine disruption, neurotoxicity or
immunotoxicity in invertebrates at sub-narcotic concentrations is generally lacking.
Acute effects occur at low mg/kg tissue concentrations and chronic effects generally
occur at concentrations about an order of magnitude lower than those that cause acute
toxicity (these effects concentrations are also consistent with narcosis as the mode of
action) . For aquatic organisms, these tissue-residue concentrations are associated with
l-ig/L water concentrations (Jarvinen and Ankley, 1999). While toxicity has been
evaluated for a few individual PCBs congeners (Dillon et al., 1990; Dillon and Burton,
1991; Fisher et al., 1999), the majority of studies have been conducted with PCB
mixtures (e.g., Aroclors; see Jarvinen and Ankley, 1999) which does not allow
determination of the toxicity contributed by non-dioxin-like congeners.
5. Consideration of Non-Dioxin-Like PCBs in Ecological Risk Assessment
5.1 Non-Dioxin-Like Effects Endpoints
Collectively, data currently available from field studies and PCB mixture exposures
provide evidence to indicate that wildlife species are susceptible to effects from non-
dioxin-like PCBs. However, the existing data are inadequate for use in quantitative
ecological risk assessments for several reasons. First, many of the non-dioxin-like PCB
effects so far described are specific to particular cells/tissues and/or species (e.g.,
biochemical changes; neurotoxic effects) or could also be induced by dioxin-like PCBs
(e.g., thyroid effects; immunotoxic effects). Furthermore, lack of well-defined dose-
response relationships for most of the non-dioxin-like effects does not allow for
assessment of the sensitivity of non-dioxin-like effects relative to dioxin-like effects.
Finally, even for endpoints for which there may be well defined dose-response
relationships (e.g. certain biochemical, cellular and tissue level effects), clear linkages
between such effects and typical assessment endpoints in ecological risk assessments
(e.g., growth, survival and reproduction) have not been demonstrated.
5.2 Relative Contribution of Dioxin-Like and Non-Dioxin-Like PCBs
5.2.1. Exposure
Environmental PCB congener profiles: 1) often deviate considerably from original
commercial PCB mixtures; 2) always include both non-dioxin-like PCBs and dioxin-like
PCBs; 3) are often predominately non-dioxin-like congeners on a mass basis.
Acknowledging the fact that commercial PCB mixtures (e.g., Aroclors) do not represent
environmental exposures, experts at a recent WHO consultation concluded that additional
toxicological studies using such mixtures should not be considered relevant from an
environmental risk assessment perspective (WHO, 2001). The consultation
recommended that future studies aimed at determining exposure levels at which non-
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dioxin-like effects occur be conducted using reconstituted mixtures resembling
environmental exposures (WHO, 2001). Any evaluation of exposures to the non-dioxin-
like PCBs must also include consideration of factors which may vary among the dioxin-
like and non-dioxin-like congeners, such as: 1) appropriate dose metric, e.g. lighter
chlorinated, relatively volatile, less persistent congeners may be more appropriately
measured in air and water than sediments or soils; 2) temporal relationship between
exposure and effects, e.g., exposures to some neurotoxic non-dioxin-like congeners
during development appear to cause permanent effects; 3) sensitive organisms and/or life
stages, e.g., disruption of thyroid system during developmental stages may affect
neurological development. However, the modes of action and dose-response
relationships by which non-dioxin-like effects are elicited must be better defined before
many of these exposure considerations can be accommodated in risk assessments.
5.2.2. Effects
As documented in Section 4, the available data provide evidence that PCB mixtures are
likely active via several potential modes of action in mammalian, avian and piscine
wildlife. Due to exposure regimens (e.g. Aroclors) and/or effect endpoints, it is rarely
possible, however, to attribute any effects specifically to non-dioxin-like PCB congeners.
Several previous analyses have indicated that reproductive and/or developmental effects
of Aroclors on fish, birds and mammals can be attributed to the TEC (TCDD equivalence
concentration) concentration of the mixture, suggesting that the dioxin-like congeners
were primarily responsible for the Aroclor toxicity. However, as documented in Section
4, to date non-dioxin-like effects have rarely been looked for (especially in non-
mammalian species) and dose-response relationships that are necessary to evaluate
relative thresholds among effects are non-existent. The WHO consultation (2001)
acknowledged these data gaps and recommended that studies should be conducted with
the goal of determining if adverse effects caused by non-dioxin-like PCBs occur at
exposure levels less than those caused by dioxin-like PCBs. In summary, the data
currently available are not sufficient to assess the relative contributions of dioxin-like and
non-dioxin-like congeners to PCB mixture toxicity with any degree of certainty.
5.2.3. Risk
Although current evidence indicates that the greatest potential for effects on endpoints of
most concern for ecological receptors (e.g., growth, survival, reproduction) from
exposure to PCB mixtures is from the dioxin-like congeners (Giesy and Kannan, 1998;
Rice et al., 2002), risk estimates based solely on the 12 dioxin-like PCBs may
underestimate the total PCB risk. Given that non-dioxin-like PCBs always occur as
mixtures with dioxin-like PCBs and the dioxin-like effects occur at extremely low
concentrations, some have assumed that assessment based on the dioxin-like congeners
will be protective against potential effects from the non-dioxin-like congeners (Giesy and
Kannan, 1998). Others recommend a dual track assessment of both the dioxin-like PCBs
and total PCBs (Rice et al., 2002), because so little is currently known regarding the
potential effects of the non-dioxin-like congeners. A dual analysis of risks based on total
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PCBs and on toxicity equivalence concentrations for dioxin-like PCBs is an approach that
may be taken to assess PCB mixtures (Beltman et al., 1997; Brunstrom and Halldin,
2000; Finley et al., 1997; Giesy and Kannan, 1998; note, however, that these examples
do not incorporate the 1998 taxa-specific WHO TEFs). EPA currently recommends this
combined approach for assessing PCB cancer risks to humans (U.S. EPA, 1996). As
more information becomes available about the toxicity mechanisms and relative potency
of specific non-dioxin-like PCB congeners, alternative methods for assessing their risk
will likely emerge.
Currently, the lack of data regarding the toxicity endpoints and dose-response
relationships for non-dioxin-like PCBs precludes performing quantitative ecological risk
assessments for these congeners, either individually or cumulatively. This problem is not
unique to ecological risk assessment. A 2001 WHO consultation was convened to
evaluate the toxicological properties of non-dioxin-like PCBs in the context of human
health risk assessment (WHO, 2001). Experts at this workshop considered and evaluated
the available exposure, toxicity and epidemiological data for non-dioxin-like PCBs. It
was concluded that an in-depth evaluation of all scientific data on PCBs needs to be
conducted before a decision can be made as to the necessity or possibility of conducting
separate risk assessments for non-dioxin-like PCBs.
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44
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APPENDIX 1: Nomenclature & Log Kows
PCB NOMENCLATURE: HOMOLOGS
IUPAC # IUPAC Name
Monochlorobiphenyl
Dichlorobiphenyl
Trichlorobiphenyl
Tetrachlorobiphenyl
PentachlorobiDhenvl
CASRN IUPAC #
27323-18-8
25512-42-9
25323-68-6
26914-33-0
25429-29-2
IUPAC Name
Hexachloro bip henyl
Heptachlorobiphenyl
Octachlorobiphenyl
Nonachlorobiphenyl
CASRN
26601-64-9
28655-71-2
55722-26-4
53742-07-7
PCB NOMENCLATURE: MIXTURES
IUPAC # IUPAC Name
Aroclor 1016
Aroclor 1210
Aroclor 1216
Aroclor 1221
Aroclor 1231
Aroclor 1232
Aroclor 1240
Aroclor 1242
CASRN IUPAC #
12674-11-2
147601-87-4
151820-27-8
11104-28-2
37234-40-5
11141-16-5
71328-89-7
53469-21-9
IUPAC Name
Aroclor 1248
Aroclor 1250
Aroclor 1252
Aroclor 1254
Aroclor 1260
Aroclor 1262
Aroclor 1268
Aroclor (unspecified)
CASRN
12672-29-6
165245-51-2
89577-78-6
11097-69-1
11096-82-5
37324-23-5
11100-14-4
12767-79-2
PCB NOMENCLATURE: DIOXIN-LIKE PCBs
IUPAC # IUPAC Name
77 3,3',4,4'-Tetrachlorobiphenyl
81 3,4,4' ,5-Tetrachlorobiphenyl
126 3,3 ',4 ,4' ,5-Pentachlorobiphenyl
169 3,3',4,4',5,5'-Hexachlorobiphenyl
105 2,3,3',4,4'-Pentachlorobiphenyl
114 2,3,4,4',5-Pentachlorobiphenyl
CASRN IUPAC #
32598-13-3 118
70362-50-4 123
57465-28-8 156
32774-16-6 157
32598-14-4 167
74472-37-0 189
IUPAC Name
2,3 ',4,4',5-Pentachlorobiphenyl
2,3',4,4',5'-Pentachlorobiphenyl
2,3,3',4,4',5-Hexachlorobiphenyl
2,3,3',4,4',5'-Hexachlorobiphenyl
2,3 ',4 ,4' ,5, 5'-Hexachloro bip henyl
2,3 ,3' ,4, 4', 5,5 '-Heptachlorobiphenyl
CASRN
31508-00-6
65510-44-3
38380-08-4
68782-90-7
52663-72-6
39635-31-9
45
-------
IUPAC# lUPACName
PCB NOMENCLATURE & log
CASRN log KpW
K,,ws: CONGENERS
IUPAC# lUPACName
CASRN log KpW
Monochlorobiphenyls
1
2
3
2-Chlorobiphenyl
3-Chlorobiphenyl
4-Chlorobiphenyl
2051-60-7
2051-61-8
2051-62-9
4.46
4.69
4.69
Dichlorobiphenyls
4
5
6
7
8
9
10
11
12
13
14
15
2,2 '-Dichlorobiphenyl
2,3 -Dichlorobiphenyl
2,3 '-Dichlorobiphenyl
2,4 -Dichlorobiphenyl
2,4 '-Dichlorobiphenyl
2,5 -Dichlorobiphenyl
2,6 -Dichlorobiphenyl
3,3 '-Dichlorobiphenyl
3,4 -Dichlorobiphenyl
3,4 '-Dichlorobiphenyl
3,5 -Dichlorobiphenyl
4,4 '-Dichlorobiphenyl
13029-08-8
16605-91-7
25569-80-6
33284-50-3
34883-43-7
34883-39-1
33146-45-1
2050-67-1
2974-92-7
2974-90-5
34883-41-5
2050-68-2
4.65
4.97
5.06
5.07
5.07
5.06
4.84
5.28
5.22
5.29
5.28
5.30
Trichlorobiphenyls
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
71
72
2,2 ',3 -Trichlorobiphenyl
2,2 ',4 -Trichlorobiphenyl
2,2 ',5 -Trichlorobiphenyl
2,2 ',6 -Trichlorobiphenyl
2,3 ,3' -Trichlorobiphenyl
2,3 ,4-Trichlorobiphenyl
2,3 ,4' -Trichlorobiphenyl
2,3 ,5-Trichlorobiphenyl
2,3 ,6-Trichlorobiphenyl
2,3 ',4 -Trichlorobiphenyl
2,3 ',5 -Trichlorobiphenyl
2,3 ',6 -Trichlorobiphenyl
2,4 ,4' -Trichlorobiphenyl
2,4 ,5-Trichlorobiphenyl
2,4 ,6-Trichlorobiphenyl
2,4 ',5 ,-Trichlorobiphenyl
2,4 ',6 -Trichlorobiphenyl
2,3 ',4 '-Trichlorobiphenyl
2,3 ',5 '-Trichlorobiphenyl
2,3 ',4 ',6 -Tetrachlorobiphenyl
2.3 '.5 .5' -Tetrachlorobiphenvl
38444-78-9
37680-66-3
37680-65-2
38444-73-4
38444-84-7
55702-46-0
38444-85-8
55720-44-0
55702-45-9
55712-37-3
38444-81-4
38444-76-7
7012-37-5
15862-07-4
35693-92-6
16606-02-3
38444-77-8
38444-86-9
37680-68-5
41464-46-4
41464-42-0
5.16
5.25
5.24
5.02
5.57
5.51
5.58
5.57
5.35
5.67
5.66
5.44
5.67
5.60
5.44
5.67
5.44
5.60
5.66
5.98
6.26
35
36
37
38
39
3,3 ',4 -Trichlorobiphenyl
3,3 ',5-Trichlorobiphenyl
3,4,4'-Trichlorobiphenyl
3,4 ,5-Trichlorobiphenyl
3,4 ',5 -Trichlorobiphenyl
37680-69-6
38444-87-0
38444-90-5
53555-66-1
38444-88-1
5.82
5.88
5.83
5.76
5.89
Tetrachlorobiphenyls
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
107
108
2,2 ',3 ,3' -Tetrachlorobiphenyl
2,2 ',3 ,4- Tetrachlorobiphenyl
2,2 ',3 ,4' -Tetrachlorobiphenyl
2,2',3,5-Tetrachlorobiphenyl
2,2 ',3 ,5' -Tetrachlorobiphenyl
2,2 ',3 ,6- Tetrachlorobiphenyl
2,2 ',3 ,6' -Tetrachlorobiphenyl
2,2 ',4 ,4' -Tetrachlorobiphenyl
2,2 ',4 ,5- Tetrachlorobiphenyl
2,2 ',4 ,5' -Tetrachlorobiphenyl
2,2 ',4 ,6- Tetrachlorobiphenyl
2,2 ',4 ,6' -Tetrachlorobiphenyl
2,2 ',5 ,5' -Tetrachlorobiphenyl
2,2 ',5 ,6' -Tetrachlorobiphenyl
2,2 ',6 ,6' -Tetrachlorobiphenyl
2,3,3',4-Tetrachlorobiphenyl
2,3 ,3' ,4' -Tetrachlorobiphenyl
2,3,3',5-Tetrachlorobiphenyl
2,3 ,3' ,5' -Tetrachlorobiphenyl
2,3,3',6-Tetrachlorobiphenyl
2,3 ,4, 4'-Tetrachlorobiphenyl
2,3 ,4, 5-Tetrachlorobiphenyl
2,3 ,4, 6-Tetrachlorobiphenyl
2,3, 4', 5-Tetrachlorobiphenyl
2,3, 4', 6-Tetrachlorobiphenyl
2,3 ,5, 6-Tetrachlorobiphenyl
2,3 ',4 ,4' -Tetrachlorobiphenyl
2,3 ',4, 5-Tetrachlorobiphenyl
2,3 ',4 ,5' -Tetrachlorobiphenyl
2,3 ',4, 6-Tetrachlorobiphenyl
2,3 ',4 ',5 -Tetrachlorobiphenyl
2,3 ,3' ,4' ,5-Pentachlorobiphenyl
2.3 .3' .4. 5'-Pentachlorobiphenvl
38444-93-8
52663-59-9
36559-22-5
70362-46-8
41464-39-5
70362-45-7
41464-47-5
2437-79-8
70362-47-9
41464-40-8
62796-65-0
68194-04-7
35693-99-3
41464-41-9
15968-05-5
74338-24-2
41464-43-1
70424-67-8
41464-49-7
74472-33-6
33025-41-1
33284-53-6
54230-22-7
74472-34-7
52663-58-8
33284-54-7
32598-10-0
73575-53-8
73575-52-7
60233-24-1
32598-11-1
70424-68-9
70362-41-3
5.66
5.69
5.76
5.75
5.75
5.53
5.53
5.85
5.78
5.85
5.63
5.63
5.84
5.62
5.21
6.11
6.11
6.17
6.17
5.95
6.11
6.04
5.89
6.17
5.95
5.86
6.20
6.20
6.26
6.04
6.20
6.71
6.71
46
-------
IUPAC# lUPACName
PCB NOMENCLATURE &
CASRN logKo
log K,,ws: CONGENERS
„ IUPAC# lUPACName
CASRN log KpW
73 2,3',5',6-Tetrachlorobiphenyl 74338-23-1 6.04
74 2,4,4',5-Tetrachlorobiphenyl 32690-93-0 6.20
75 2,4,4',6-Tetrachlorobiphenyl 32598-12-2 6.05
76 2,3',4',5'-Tetrachlorobiphenyl 70362-48-0 6.13
77 3,3',4,4'-Tetrachlorobiphenyl 32598-13-3 6.36
78 3,3',4,5-Tetrachlorobiphenyl 70362-49-1 6.35
79 3,3',4,5'-Tetrachlorobiphenyl 41464-48-6 6.42
80 3,3',5,5'-Tetrachlorobiphenyl 33284-52-5 6.48
81 3,4,4',5-Tetrachlorobiphenyl 70362-50-4 6.36
Pentachlorobiphenyls
82 2,2',3,3',4-Pentachlorobiphenyl 52663-62-4 6.20
83 2,2',3,3',5-Pentachlorobiphenyl 60145-20-2 6.26
84 2,2',3,3',6-Pentachlorobiphenyl 52663-60-2 6.04
85 2,2',3,4,4'-Pentachlorobiphenyl 65510-45-4 6.30
86 2,2',3,4,5-Pentachlorobiphenyl 55312-69-1 6.23
87 2,2',3,4,5'-Pentachlorobiphenyl 38380-02- 6.29
88 2,2',3,4,6-Pentachlorobiphenyl 55215-17-3 6.07
89 2,2',3,4,6'-Pentachlorobiphenyl 73575-57-2 6.07
90 2,2',3,4',5-Pentachlorobiphenyl 68194-07-0 6.36
91 2,2',3,4',6-Pentachlorobiphenyl 68194-05-8 6.13
92 2,2',3,5,5'-Pentachlorobiphenyl 52663-61-3 6.35
93 2,2',3,5,6-Pentachlorobiphenyl 73575-56-1 6.04
94 2,2',3,5,6'-Pentachlorobiphenyl 73575-55-0 6.13
95 2,2',3,5',6-Pentachlorobiphenyl 38379-99-6 6.13
96 2,2',3,6,6'-Pentachlorobiphenyl 73575-54-9 5.71
97 2,2',3,4',5'-Pentachlorobiphenyl 41464-51-1 6.29
98 2,2',3,4',6'-Pentachlorobiphenyl 60233-25-2 6.13
99 2,2',4,4',5-Pentachlorobiphenyl 38380-01-7 6.39
100 2,2',4,4',6-Pentachlorobiphenyl 39485-83-1 6.23
101 2,2',4,5,5'-Pentachlorobiphenyl 37680-73-2 6.38
102 2,2',4,5,6'-Pentachlorobiphenyl 68194-06-9 6.16
103 2,2',4,5',6-Pentachlorobiphenyl 60145-21-3 6.22
104 2,2',4,6,6'-Pentachlorobiphenyl 56558-16-8 5.81
105 2,3,3',4,4'-Pentachlorobiphenyl 32598-14-4 6.65
106 2,3,3',4,5-Pentachlorobiphenyl 70424-69-0 6.64
143 2,2',3,4,5,6'-Hexachlorobiphenyl 68194-15-0 6.60
144 2,2',3,4,5', 6-Hexachlorobiphenyl 68194-14-9 6.67
145 2.2 '.3.4.6.6'-Hexachlorobiphenyl 74472-40-5 6.25
109 2,3,3',4,6-Pentachlorobiphenyl 74472-35-8 6.48
110 2,3,3',4',6-Pentachlorobiphenyl 38380-03-9 6.48
111 2,3,3',5,5'-Pentachlorobiphenyl 39635-32-0 6.76
112 2,3,3',5,6-Pentachlorobiphenyl 74472-36-9 6.45
113 2,3,3',5',6-Pentachlorobiphenyl 68194-10-5 6.54
114 2,3,4,4',5-Pentachlorobiphenyl 74472-37-0 6.65
115 2,3,4,4',6-Pentachlorobiphenyl 74472-38-1 6.49
116 2,3,4,5,6-Pentachlorobiphenyl 18259-05-7 6.33
117 2,3,4',5,6-Pentachlorobiphenyl 68194-11-6 6.46
118 2,3',4,4',5-Pentachlorobiphenyl 31508-00-6 6.74
119 2,3',4,4',6-Pentachlorobiphenyl 56558-17-9 6.58
120 2,3',4,5,5'-Pentachlorobiphenyl 68194-12-7 6.79
121 2,3',4,5',6-Pentachlorobiphenyl 56558-18-0 6.64
122 2,3,3',4',5'-Pentachlorobiphenyl 76842-07-4 6.64
123 2,3',4,4',5'-Pentachlorobiphenyl 65510-44-3 6.74
124 2,3',4',5,5'-Pentachlorobiphenyl 70424-70-3 6.73
125 2,3',4',5',6-Pentachlorobiphenyl 74472-39-2 6.51
126 3,3',4,4',5-Pentachlorobiphenyl 57465-28-8 6.89
127 3,3',4,5,5'-Pentachlorobiphenyl 39635-33-1 6.95
Hexachlorobiphenyls
128 2,2',3,3',4,4'-Hexachlorobiphenyl 38380-07-3 6.74
129 2,2',3,3',4,5-Hexachlorobiphenyl 55215-18-4 6.73
130 2,2',3,3',4,5'-Hexachlorobiphenyl 52663-66-8 6.80
131 2,2',3,3',4,6-Hexachlorobiphenyl 61798-70-7 6.58
132 2,2',3,3',4,6'-Hexachlorobiphenyl 38380-05-1 6.58
133 2,2',3,3',5,5'-Hexachlorobiphenyl 35694-04-3 6.86
134 2,2',3,3',5,6-Hexachlorobiphenyl 52704-70-8 6.55
135 2,2',3,3',5,6'-Hexachlorobiphenyl 52744-13-5 6.64
136 2,2',3,3',6,6'-Hexachlorobiphenyl 38411-22-2 6.22
137 2,2',3,4,4',5-Hexachlorobiphenyl 35694-06-5 6.83
138 2,2',3,4,4',5'-Hexachlorobiphenyl 35065-28-2 6.83
139 2,2',3,4,4',6-Hexachlorobiphenyl 56030-56-9 6.67
140 2,2',3,4,4',6'-Hexachlorobiphenyl 59291-64-4 6.67
141 2,2',3,4,5,5'-Hexachlorobiphenyl 52712-04-6 6.82
142 2,2',3,4,5,6-Hexachlorobiphenyl 41411-61-4 6.51
179 2,2',3,3',5,6,6'-Heptachlorobiphenyl 52663-64-6 6.73
180 2,2',3,4,4',5,5'-Heptachlorobiphenyl 35065-29-3 7.36
181 2.2'.3.4.4'.5.6-Heptachlorobiphenyl 74472-47-2 7.11
47
-------
IUPAC# lUPACName
PCB NOMENCLATURE & log
CASRN log KpW
K,,ws: CONGENERS
IUPAC# lUPACName
CASRN log KpW
146 2,2',3,4',5,5'-Hexachlorobiphenyl 51908-16-8 6.89
147 2,2',3,4',5,6-Hexachlorobiphenyl 68194-13-8 6.64
148 2,2',3,4',5,6'-Hexachlorobiphenyl 74472-41-6 6.73
149 2,2',3,4',5',6-Hexacblorobiphenyl 38380-04-0 6.67
150 2,2',3,4',6,6'-Hexachlorobiphenyl 68194-08-1 6.32
151 2,2',3,5,5',6-Hexacblorobiphenyl 52663-63-5 6.64
152 2,2',3,5,6,6'-Hexachlorobiphenyl 68194-09-2 6.22
153 2,2',4,4',5,5'-Hexacblorobiphenyl 35065-27-1 6.92
154 2,2',4,4',5,6'-Hexacblorobiphenyl 60145-22-4 6.76
155 2,2',4,4',6,6'-Hexachlorobiphenyl 33979-03-2 6.41
156 2,3,3',4,4',5-Hexacblorobiphenyl 38380-08-4 7.18
157 2,3,3',4,4',5'-Hexacblorobiphenyl 68782-90-7 7.18
158 2,3,3',4,4',6-Hexacblorobiphenyl 74472-42-7 7.02
159 2,3,3',4,5,5'-Hexachlorobiphenyl 39635-35-3 7.24
160 2,3,3',4,5,6-Hexachlorobiphenyl 41411-62-5 6.93
161 2,3,3',4,5',6-Hexacblorobiphenyl 74472-43-8 7.08
162 2,3,3',4',5,5'-Hexacblorobiphenyl 39635-34-2 7.24
163 2,3,3',4',5,6-Hexacblorobiphenyl 74472-44-9 6.99
164 2,3,3',4',5',6-Hexacblorobiphenyl 74472-45-0 7.02
165 2,3,3',5,5',6-Hexachlorobiphenyl 74472-46-1 7.05
166 2,3,4,4',5,6-Hexachlorobiphenyl 41411-63-6 6.93
167 2,3',4,4',5,5'-Hexacblorobiphenyl 52663-72-6 7.27
168 2,3',4,4',5',6-Hexacblorobiphenyl 59291-65-5 7.11
169 3,3',4,4',5,5'-Hexacblorobiphenyl 32774-16-6 7.42
Heptachlorobiphenyls
170 2,2',3,3',4,4',5-Heptachlorobiphenyl 35065-30-6 7.27
171 2,2',3,3',4,4',6-Heptachlorobiphenyl 52663-71-5 7.11
172 2,2',3,3',4,5,5'-Heptacblorobiphenyl 52663-74-8 7.33
173 2,2',3,3',4,5,6-Heptachlorobiphenyl 68194-16-1 7.02
174 2,2',3,3',4,5,6'-Heptacblorobiphenyl 38411-25-5 7.11
175 2,2',3,3',4,5',6-Heptachlorobiphenyl 40186-70-7 7.17
176 2,2',3,3',4,6,6'-Heptachlorobiphenyl 52663-65-7 6.76
177 2,2',3,3',4,5',6'-Heptachlorobiphenyl 52663-70-4 7.08
178 2,2',3,3',5,5',6-Heptachlorobiphenyl 52663-67-9 7.14
182 2,2',3,4,4',5,6'-Heptachlorobiphenyl 60145-23-5 7.20
183 2,2',3,4,4',5',6-Heptachlorobiphenyl 52663-69-1 7.20
184 2,2',3,4,4',6,6'-Heptachlorobiphenyl 74472-48-3 6.85
185 2,2',3,4,5,5',6-Heptachlorobiphenyl 52712-05-7 7.11
186 2,2',3,4,5,6,6'-Heptachlorobiphenyl 74472-49-4 6.69
187 2,2',3,4',5,5',6-Heptachlorobiphenyl 52663-68-0 7.17
188 2,2',3,4',5,6,6'-Heptachlorobiphenyl 74487-85-7 6.82
189 2,3,3',4,4',5,5'-Heptachlorobiphenyl 39635-31-9 7.71
190 2,3,3',4,4',5,6-Heptachlorobiphenyl 41411-64-7 7.46
191 2,3,3',4,4',5',6-Heptachlorobiphenyl 74472-50-7 7.55
192 2,3,3',4,5,5',6-Heptachlorobiphenyl 74472-51-8 7.52
193 2,3,3',4',5,5',6-Heptachlorobiphenyl 69782-91-8 7.52
Octachlorobiphenyls
194 2,2',3,3',4,4',5,5'-Octachlorobiphenyl 35694-08-7 7.80
195 2,2',3,3',4,4',5,6-Octachlorobiphenyl 52663-78-2 7.56
196 2,2',3,3',4,4',5,6'-Octachlorobiphenyl 42740-50-1 7.65
197 2,2',3,3',4,4',6,6'-Octachlorobiphenyl 33091-17-7 7.30
198 2,2',3,3',4,5,5',6-Octachlorobiphenyl 68194-17-2 7.62
199 2,2',3,3',4,5,5',6'-Octachlorobiphenyl 52663-75-9 7.62
200 2,2',3,3',4,5,6,6'-Octachlorobiphenyl 52663-73-7 7.20
201 2,2',3,3',4,5',6,6'-Octachlorobiphenyl 40186-71-8 7.27
202 2,2',3,3',5,5',6,6'-Octachlorobiphenyl 2136-99-4 7.24
203 2,2',3,4,4',5,5',6-Octachlorobiphenyl 52663-76-0 7.65
204 2,2',3,4,4',5,6,6'-Octachlorobiphenyl 74472-52-9 7.30
205 2,3,3',4,4',5,5',6-Octachlorobiphenyl 74472-53-0 8.00
Nonachlorobiphenyls
206 2,2',3,3',4,4',5,5',6-Nonachlorobiphenyl
207 2,2',3,3',4,4',5,6,6'-Nonachlorobiphenyl
208 2,2',3,3',4,5,5',6,6'-Nonachlorobiphenyl
DecacWorobiphenyls
209 2,2',3,31,4,41,5,51,6,61-Decachlorobiphenyl 2051-24-3 8.18
Footnotes:
Dioxin-like congeners are indicated by shading.
log Kow values are from Hawker and Connell, 1988.
40186-72-9 8.09
52663-79-3 7.74
52663-77-1 7.71
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APPENDIX!: ERASC Request
ECOLOGICAL RISK ASSESSMENT SUPPORT CENTER REQUEST FORM
Request #0002: What are the non-dioxin-like effects of PCBs and how can they be evaluated in
ecological risk assessments?
Requestor : Bruce Duncan (R10)
Background: EPA is developing a framework (using TEFs) to estimate the dioxin-like effects of PCB
congeners. It is unclear whether the n-d-l effects can also be significant at the same time. The n-d-l effects
will be from a different suite of congeners and via a different mechanism. The ERAF needs to move from
evaluating PCBs as totals or aroclors (or even homologues) to evaluating congeners for the range of
effects these congeners elicit.
Expected Outcome:
1. Describe the mode of action of non-dioxin-like compounds and types of effects in receptors (i.e., those
congeners that "travel" with the listed dioxins, furans, and PCBs but just don't act via the Ah receptor).
2. Discuss n-d-l toxicity relative to congener characteristics (something like a QSAR discussion).
3. Discuss which congeners are of greatest concern (potency) for n-d-l toxicity (dose/response type
information in the narcotic range of effects).
4. Recommend how this scientific information on action, effects, and toxicity should be used in ecological
risk assessment where PCBs are present (preferred use of the data, considerations for site-specific
application, etc.).
5. Discuss whether a general narcosis model can or should be used to evaluate n-d-l effects (as a function
of range of contaminant concentration typically seen at low, medium, and highly contaminated sites) - see
below as well.
6. Provide an interactive video-conference on this topic and the one related to congener analytical
methodology.
Additional Comments :
Summarize and update from the recent review of n-d-l activity. Find an example or two of sites where TEF
and n-d-l approaches were used or recommend how they would be used at an example site (example of
application).
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