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Contents lists available at SciVerse ScienceDirect

Toxicology
journal homepage: www.elsevier.com/locate/toxicol

Application of data fusion in human health risk assessment for hydrocarbon


mixtures on contaminated sites
Roberta Dyck a, , M. Shaqul Islam a , Amin Zargar a , Asish Mohapatra b,1 , Rehan Sadiq a
a
b

School of Engineering, Okanagan Campus, The University of British Columbia, 3333 University Way, Kelowna, BC V1V 1V7, Canada
Contaminated Sites, Environmental Health Program Regions and Programs Branch Health Canada, Suite # 674, 220-4 Avenue SE, Calgary, AB T2G 4X3, Canada

a r t i c l e

i n f o

Article history:
Received 23 April 2012
Received in revised form 9 November 2012
Accepted 24 November 2012
Available online xxx
Keywords:
Data fusion
Human health risk assessment
Contaminated sites
DempsterShafer theory
Petroleum hydrocarbons

a b s t r a c t
The exposure and toxicological data used in human health risk assessment are obtained from diverse and
heterogeneous sources. Complex mixtures found on contaminated sites can pose a signicant challenge to
effectively assess the toxicity potential of the combined chemical exposure and to manage the associated
risks. A data fusion framework has been proposed to integrate data from disparate sources to estimate
potential risk for various public health issues. To demonstrate the effectiveness of the proposed data
fusion framework, an illustrative example for a hydrocarbon mixture is presented.
The Joint Directors of Laboratories Data Fusion architecture was selected as the data fusion architecture and DempsterShafer Theory (DST) was chosen as the technique for data fusion. For neurotoxicity
response analysis, neurotoxic metabolites toxicological data were fused with predictive toxicological
data and then probability-boxes (p-boxes) were developed to represent the toxicity of each compound.
The neurotoxic response was given a rating of low, medium or high. These responses were then
weighted by the percent composition in the illustrative F1 hydrocarbon mixture. The resulting p-boxes
were fused according to DSTs mixture rule of combination. The fused p-boxes were fused again with
toxicity data for n-hexane.
The case study for F1 hydrocarbons illustrates how data fusion can help in the assessment of the health
effects for complex mixtures with limited available data.
2012 Elsevier Ireland Ltd. All rights reserved.

1. Introduction
Human health risk assessment (HHRA) is an important component of the management of risk related to contaminated sites;
however, the exposure and toxicological data used in HHRA are
obtained from diverse and often heterogeneous sources. Uncertainty arises from incomplete, vague or ambiguous data, while
variability is found in the inherent differences between individuals
in a population. Toxicity data may be obtained for different species,
different exposure routes, different organization levels (gene, cell,
organ, system, individual, and population) and different toxicological end points. Exposure data are variable by nature, but uncertainty
is also inevitable it is impossible to completely characterize a site

Disclaimer: This paper uses material from a report that was prepared under contract to Health Canada (Prairies Region), Contaminated Sites, Environmental Health
Program. However, the views and opinions, if any, expressed in this paper and the
report does not necessarily reect the opinion of Health Canada nor is it Health
Canada guidance.
Corresponding author. Tel.: +1 250 486 2936.
E-mail addresses: radyck@interchange.ubc.ca (R. Dyck), shaqul.islam@ubc.ca
(M.S. Islam), amin.zargar@ubc.ca (A. Zargar), asish.mohapatra@hc-sc.gc.ca
(A. Mohapatra), rehan.sadiq@ubc.ca (R. Sadiq).
1
Tel.: +1 403 221 3284.

for all chemical and physical parameters given limited and incomplete data. Complex mixtures found on contaminated sites can pose
a signicant challenge to effectively assess the toxicity potential
of the combined chemical exposure and to manage the associated
risks. Because of the variable nature of complex mixtures, there
are not always sufcient or consistent data about the environmental fate, persistence, bioavailability and toxicity across the range of
constituents in the mixture.
The toxicity of chemical mixtures is generally assessed with
respect to the mixture as a whole, or by somehow combining the
toxicities of the individual components of the mixture. Often, there
is incomplete information for mixtures or their components, or
conicting information about the toxicity of the components. When
considering exposure to chemical mixtures, there are a number of
complicating factors to be considered
variability in the number of constituents and percent weight of
each constituent compound in the mixture,
variability in contaminant transport due to different chemical
properties (e.g., solubility and volatility),
variability in the ability of a receptor to take up the compounds
(kinetic parameters including absorption, metabolism, distribution, and excretion),

0300-483X/$ see front matter 2012 Elsevier Ireland Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tox.2012.11.010

Please cite this article in press as: Dyck, R., et al., Application of data fusion in human health risk assessment for hydrocarbon mixtures on
contaminated sites. Toxicology (2012), http://dx.doi.org/10.1016/j.tox.2012.11.010

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Fig. 1. Proposed data fusion based human health risk assessment framework (Sadiq et al., 2011). The 11 steps within the framework are grouped as problem formulation,
low level fusion, feature level fusion, and decision level fusion.

variability in the toxic response to the compounds (including target organ or tissues, mode of action, temporal variation in effects,
and toxicodynamic properties),
interactions which cause effects either higher or lower than those
achieved by either dose or response additivity. The term additivity is used when the effect of the combination of chemicals
can be estimated directly from the sum of the scaled exposure
levels (dose addition) or the responses (response addition) of the
individual chemicals (US EPA, 2000).
In order to integrate datasets from numerous sources, specialized data fusion techniques (Fig. 1) can be incorporated into the
HHRA framework earlier suggested by National Academy of Sciences (NAS, 2009).
Data fusion is a process used to generate a combined estimate
from data originating from multiple sources. The resultant estimate should be more accurate and informative than the original
source data. Dasarathy (1997) compares multi-sensor systems to
the human brain. Data coming in from our ve senses give us different information about our environment. Each of these sensors
offer signals in a different format, but when combined they lead
to an enhanced understanding of our environment that allows us
to make decisions. This same analogy can be extended to other
systems which have information coming from different sources
which at times do not fully agree. In the case of HHRA, this would

specically include the consideration of data from in vitro, animal,


and whole body studies. Accuracy is improved by data fusion by
allowing us to include more information about the system. In a
deterministic approach, we may ignore information about some
study results in favour of one particular study and in doing so we
may also neglect to propagate any uncertainty in the study results.
Results of data fusion can be more informative because we can
incorporate weighting of each dataset which allows us to give more
weight in our nal result to studies that we consider more credible,
more reliable, or more relevant.
A data fusion framework has been proposed to integrate data
from disparate sources to estimate potential risk for various public
health issues (Sadiq et al., 2011). The proposed framework attempts
to integrate various toxicological datasets from different biological
organizational criteria (gene, cellular, tissue, and organ level) and
integrates data from multiple sources. To demonstrate the effectiveness of the proposed data fusion framework, an illustrative
example for a hydrocarbon mixture is presented.
2. Data fusion
Data fusion has been used in a number of settings to resolve
conict (disagreement) between datasets. Military applications
include threat assessment and surveillance. More recently, data
fusions application has been expanded in commercial applications

Please cite this article in press as: Dyck, R., et al., Application of data fusion in human health risk assessment for hydrocarbon mixtures on
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Table 1
Recent examples of data fusion techniques in HHRA and public health (Zargar et al., 2012).
Data fusion technique

Application areas

Sources

Statistical
GIS overlay (heuristic approach)
Bayesian inference

Genomic data fusion


Assessment of UneXploded Ordnance (UXO) contamination
Multi-study and multi-endpoint BMD
UXO detection
Assessment of UXO contamination
Syndrome surveillance
Disease surveillance
Risk assessment of water treatment
Drinking water quality
Microbial water quality in distribution network
Assessment of UXO contamination
Air pollution level monitoring
Risk assessment of ambient air quality
Public health biosurveillance
Gene prioritization

Lanckriet et al. (2004)


Johnson et al. (2009)
Schmitt (2006)
Zhang et al. (2003)
Johnson et al. (2009)
Banks et al. (2012)
Burkom et al. (2011)
Dmotier et al. (2006)
Sadiq and Rodriguez (2005)
Sadiq et al. (2006)
Johnson et al. (2009)
Barron-Adame et al. (2009)
Ping et al. (2010)
Khan et al. (2010)
Aerts et al. (2006)

DempsterShafer theory

Articial neural networks


Fuzzy sets
Not specied

such as robotics, manufacturing, sensor technology, medical


diagnosis, GIS and remote sensing. Data fusion is also becoming
a valuable tool for handling the data involved in HHRA. Table 1
provides some examples of data fusion techniques used in HHRA
and public health applications (Zargar et al., 2012). The main goals
of data fusion include (Bostrm et al., 2007; Zargar et al., 2012)
rening data and improving data quality,
creating additional inferences and increasing benet from data,
and
improving understanding and decision.
The different formulae available for dealing with conicting data
sets depend on the method that was used to model the data, e.g., in
a possibilistic (fuzzy sets theory) or in a probabilistic (e.g., Bayesian
inferencing) setting. The framework or technique chosen for resolving the conict depends on the nature of the problem, including
the presence of additional types of uncertainty in the data (e.g.,
incompleteness).
2.1. Data fusion architecture
According to Esteban et al. (2005), before undertaking a data
fusion task, a strategy needs to be established to facilitate the solution of the problem in a robust and organized manner. A data fusion
architecture is a platform that connects databases with data fusion
algorithms and techniques. The techniques are the mathematical
models used to combine several sources of datasets. The architecture provides a strategy to gather the data from different sources
and integrate data at various levels. Due to the numerous possible scenarios and the variability between them, it would not be
possible to use a specic architecture for all situations (Esteban
et al., 2005). The architecture is only the framework in which specic methods can be used. The levels of fusion are interpreted
differently in different architectures. For some applications, such
as threat assessment from surveillance, the levels could be pixels,
features and images. In a similar analogy for HHRA applications, the
levels can correspond to different organization levels such as gene,
cell, tissue, organ and individual.
The Joint Directors of Laboratories (JDL) Data Fusion (DF) framework (Llinas et al., 2004; Steinberg et al., 1999; Steinberg and
Bowman, 2004) is a popular model that was originally developed
for military applications. It includes four main levels (Esteban et al.,
2005):
Level 1: Object Renement locates and identies objects using
attributes of the object from multiple sources.

Level 2: Situation Assessment uses incomplete information


from level one to create a picture related to observed events.
Level 3: Threat assessment uses results from level 2 to analyze
the advantages and disadvantages to taking a course of action
from several possible opportunities.
Level 4: Process renement provides a feedback loop to monitor
the performance of the rst three levels and optimize allocation
of sensors.
The exibility of this architecture is one of its key strengths.
Satpathy and Mohapatra (2009) modied the JDL DF architecture for use in cyber security applications. The modication reduced
the number of levels to three as shown in Fig. 2:
Low level fusion includes data cleaning, data transformation
and data reduction to improve the quality and reduce the quantity
of data,
High level fusion uses classication and clustering to extract
useful patterns in the data for the interpretation of activities and
context.
Decision level fusion pertinent patterns are identied and
potential actions are evaluated to draw inferences about future
outcomes.
2.2. Data fusion models (techniques)
Zargar et al. (2012) denes data fusion models (or techniques) as
mathematical models that combine multiple data for a feature into
single data. While data fusion architectures are designed to provide
a frame of reference for discussing fusion, recognizing applicable
problems and categorizing solutions, the data fusion models are
the actual solutions used (Llinas et al., 2004). In most data fusion
architectures, it is possible to incorporate data fusion models at
several levels. Some of the popular models include

Statistical data fusion (classical inference)


Bayesian inference
DempsterShafer Theory (DST)
Articial Neural Networks
Fuzzy fusion.

DempsterShafer Theory (DST) was used in this case study.


One advantage of DST is its ability to express both variability and
uncertainty simultaneously. Variability, also known as aleatory
uncertainty, refers to natural variations present in sampled populations. In HHRA this type of uncertainty can be present in the
spatio-temporal distribution of concentration of contaminants
present in environmental samples as well as exposure factors (e.g.,

Please cite this article in press as: Dyck, R., et al., Application of data fusion in human health risk assessment for hydrocarbon mixtures on
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Fig. 2. Modied Joint Directors of Laboratories modelling framework (adapted from Satpathy and Mohapatra, 2009). Data fusion is completed in three levels: low level, high
level and decision level fusion.

exposure duration, exposure frequency, receptor weight, inhalation rates and ingestion rates). Natural variation can also exist in
toxico-kinetics and toxico-dynamics. Epistemic uncertainty refers
to uncertainty arising from an imperfect understanding of the system (Sentz and Ferson, 2002). This type of uncertainty can occur in
models which attempt to describe processes that are unknown or
unclear. In DST, variability and uncertainty can simultaneously be
represented as a p-box (Ferson et al., 2003).
When data are expressed as a probability density function (PDF),
a series of cumulative distribution functions (CDF) can be constructed to form a p-box. The CDFs represent an upper and lower
bound on the true CDF which lies at an unknown location between
the upper and lower bounds. Therefore, the horizontal variation
(distance) represents the variability in the data, while the vertical distance represents the uncertainty. When multiple sources of
data are available which are likely to be conicting, there are a
number of different rules that can be used for data fusion (combination) under DST (Ferson et al., 2003), depending on the situation.
Some commonly used rules are Dempsters rule (Dempster, 1967),
Yagers rule (Yager, 1987), and mixture rule (Ferson et al., 2003).
A more detailed explanation of the construction of p-boxes and
their use with mixture rule in DST is provided in Supplementary
Information.

3. Methods
The existing HHRA protocol consists of four stages illustrated in Fig. 3. The
problem formulation (hazard identication) is followed by dose response (toxicity) assessment, exposure assessment and risk characterization (Sadiq et al., 2011).
Based on recommendations and guidelines by National Academy of Sciences (NAS,
2009), Science and Decisions: Advancing Risk Assessment, a general risk assessment
and management framework has been proposed (Fig. 1; Sadiq et al., 2011). The proposed framework incorporates data fusion techniques to process data from multiple
sources to represent more relevant information. The basic framework includes 11
steps that are grouped as problem formulation, low level fusion, feature level fusion,
and decision level fusion. Each of the steps is described in this section to provide an
overview of the method. The detailed analysis done in each step is presented later
in Section 4.

3.1. Problem formulation


The NAS (2009) report places emphasis on the planning, scoping and problem
formulation steps of the risk assessment process. Stakeholders are involved with
risk assessors in a dynamic discussion about the extent of the problem and the
issues of concern, while risk assessors establish the breadth, depth and focus of the
assessment (NAS, 2009).
Step 1: Planning and scoping
Planning and scoping for HHRA has been expanded by NAS (2009) to include
more input from stakeholders early in the process. This step outlines the depth
and breadth of the study.
Step 2: Problem formulation
The more technical aspects of the problem are evaluated at this stage including sources, stressors, receptors, exposure pathways and potential adverse human
health effects. As the problems are introduced, options for remediation or mitigation can be proposed so that the HHRA answers the right questions.
Step 3: Suitability of risk-based assessment
The complexity of the problem and availability of the data will govern whether or
not a detailed risk assessment should be done. At this stage, a type of screening or
preliminary assessment can rule out further detailed analysis if the problem does
not warrant further study.
3.2. Low level fusion
Step 4: Data collection
Data are collected from a variety of sources in this step. Spatial and temporal
variability is taken into consideration for collection of data on site. The data required
for the exposure assessment may include detailed analysis of samples, modelling
of contaminant transport, and human exposure factors.
Step 5: Data estimation
Data that are collected requires further preparation through data reduction, data
transformation and data clean-up. This allows data from diverse sources to be
expressed in similar ways for further fusion at a later step in the process. This
also allows the combination of large quantities of data.
Step 6: Assessment method selection
At this stage the data are further evaluated to determine the suitability of quantitative risk assessment. Complex mixtures should be evaluated at this stage to
determine which method of handling data regarding mixtures is most appropriate.
3.3. Feature level fusion
Steps 7 and 8 are not necessarily conducted sequentially; rather they may be
done simultaneously.

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contaminated sites. Toxicology (2012), http://dx.doi.org/10.1016/j.tox.2012.11.010

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Fig. 3. Existing human health risk assessment protocol (Sadiq et al., 2011).

Step 7: Doseresponse assessment


Dose response data collected Step 4 are fused here to include different end points,
different organization levels and/or different compounds (in the case of complex
mixtures).
Step 8: Exposure assessment
Exposure assessment is conducted to estimate the dose delivered to the target organs to produce a deleterious effect. Data fusion can be used to integrate
data regarding different sources, stressors, exposure pathways, exposure routes,
absorption by the body, and receptor sensitivities.
3.4. Decision level fusion
Step 9: Risk characterization
During risk characterization, the probability of harm in receptors or populations
is evaluated.
Step 10: Relative cost benet analysis and selection of management options
The cost-benet analysis can include monetary costs, as well as social and cultural
costs. Risk management options can be evaluated for their utility.
Step 11: Reporting, guidelines and implementation
Reporting of the assessment is summarized to implement the management decisions as well as identifying the requirements for further research. One important
aspect of reporting is careful explanation of assumptions, uncertainty in the methods and variability in the population and data.
These steps are examined and explained further in the following case study of
F1 hydrocarbon contamination.
3.5. Current and proposed approaches for development of reference concentration
(RfC)
In the doseresponse step of HHRA, the current weight of evidence approach
can be used to calculate an RfC for a given chemical or mixture of chemicals (Schmitt,
2006).2 The RfC is calculated using either the no observed adverse effects level
(NOAEL) or the Benchmark Dose (BMD) approaches. The NOAEL method uses the
highest concentration in animal or human studies for which no adverse effect was
observed. The NOAEL is divided by uncertainty factors for
interspecies differences (when only animal studies are available, typically 10fold),
intraspecies differences (consideration of sensitive individuals within the population, typically 10-fold),
deciencies in the toxicological dataset (lack of chronic studies, lack of reproductive studies, lack of NOAEL, etc., typically 3- to 10-fold), and
considering the nature and severity of the potential effects (3- to 10-fold; Health
Canada, 2010a).
The BMD method uses the dose associated with a given response rate (Benchmark Response, BMR) in a given toxicology data set (usually 110%). Mathematical
models are used to model the response rate for a particular toxic effect. The BMD
method also incorporates uncertainty factors for interspecies and intraspecies differences, consideration of the nature and severity of the effects, and also some
deciencies in the dataset (e.g., lack of chronic studies). No uncertainty factor is
used in the case that no NOAEL is found because uncertainty related to low-dose
extrapolation is already considered within the BMD method (Health Canada, 2010a).

2
Health Canada uses the terminology toxicological reference value (TRV)
instead of reference dose or reference concentration.

For deriving the RfC, either the NOAEL or BMD can be used for situations involving data on one study, species or health endpoint. When there are multiple studies
and one study is identied as being superior to others, then one study can be used
as the basis for the RfC (Schmitt, 2006). [An illustration of the use of NOAEL and one
superior study is given in Supplementary Information.] The one study is chosen, the
NOAEL is determined for that study and the RfC is calculated by dividing the NOAEL
by uncertainty factors.
The current weight of evidence approach can also be used in cases where there
are multiple health endpoints, relevant animal studies or where results from different studies conict (Schmitt, 2006). [An illustration of the use of BMD for multiple
studies is given in Supplementary Information.] A BMD is calculated for each relevant study. The toxicologist uses their judgement to choose the most sensitive
endpoint, study or species based on the lowest BMD. The benchmark dose lower
limit (BMDL) is calculated from the 95th percentile lower limit and divided by the
applicable uncertainty factors to obtain an RfC.
While expert judgement is built into the NOAEL and BMD methods of deriving
an RfC through the selection of studies to be included, some information is lost
by this selection (Schmitt, 2006). The data fusion framework proposed here allows
the incorporation of multiple studies, species or endpoints, however one study or
one BMDL is not chosen from the multiple alternatives (as done in the NOAEL and
BMD methods). Information about each study is included in the RfC and therefore
provides a more robust RfC (Schmitt, 2006). Additionally, uncertainty information
is carried through the data fusion so that we can better represent the uncertainty in
the RfC.

4. A case study for F1 hydrocarbon contaminated site


4.1. Background
The presence of various potentially toxic chemicals on contaminated sites can lead to environmental, human health and nancial
liabilities (Health Canada, 2010b). One common cause of contamination is spilling and leakage during the storage, transfer and use
of hydrocarbons on industrial, commercial and government sites.
A collection of sites, which reect many of the features common
on hydrocarbon contaminated sites, has been used to demonstrate
the framework. A risk assessment has been carried out for a collection of similar commercial sites which have been contaminated by
long term spilling of gasoline on the ground surface and leakage of
gasoline from underground storage tanks in the subsurface. During
the description of the case study, details of each step have been
described.
4.1.1. Problem formulation
Step 1: Planning and scoping
The site-specic concentration data used for this case study
were presented by Sevigny et al. (2003). The study data were
collected from 5 sites in western Canada that had underground
gasoline storage tanks with similar tank size and fuel types. The
tanks at each of the sites were in active use for a period of
2530 years, followed by decommissioning (which included tank
removal as well as removal of some of the hydrocarbon contaminated soils). In the study, soil vapours were collected and

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contaminated sites. Toxicology (2012), http://dx.doi.org/10.1016/j.tox.2012.11.010

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Table 2
Summary of carbon fractions recommended by CCME (2008) and Edwards et al. (1997).
Fraction

EC #

Corresponding
TPHCWG subfractions

F1

C6 C10

Aromatics
Aliphatics

F2

C>10 C16

Aromatics
Aliphatics

F3

C>16 C34

Aromatics
Aliphatics

F4

C>34 C50

Aromatics
Aliphatics

TDI (mg/kg d)

RfC (mg/m3 )

Critical effect used by TPHCWG


to derive criteria

C>7 C8
C>8 C10
C6 C8
C>8 C10

a
0.04
5.0
0.1

a
0.2
18.4
1.0

a
Hepatotoxicity, neurotoxicity
Neurotoxicity
Hepatic and haematological changes

C>10 C12
C>12 C16
C>10 C12
C>12 C16

0.04
0.04
0.1
0.1

0.2
0.2
1.0
1.0

Decreased body weight


Decreased body weight
Hepatic and haematological changes
Hepatic and haematological changes

C>16 C21
C>21 C34
C>16 C21
C>21 C34

0.03
0.03
0.1
2.0

NAb
NAb
1.0
NAb

Nephrotoxicity
Nephrotoxicity
Hepatic granuloma
Hepatic granuloma

0.03
20.0

NAb
NAb

Nephrotoxicity
Hepatic granuloma

C>34
C>34

EC equivalent carbon.
a
Aromatics C>6 C8 are not considered, as benzene and toluene are the only components and they are considered separately.
b
Subfraction not considered volatile, therefore RfC not determined.

analyzed from monitoring wells on site. The indoor vapour concentrations of hydrocarbon components were estimated using the
JohnsonEttinger model (Johnson and Ettinger, 1991), which is a
commonly used vapour intrusion pathway model.
At the sites presented by Sevigny et al. (2003), the leakage
and spilling of gasoline resulted in contamination of the soil
and groundwater underlying the site. The gasoline components
detected in the subsurface included benzene, toluene, ethylbenzene, xylenes (BTEX) and volatile hydrocarbons. The presence of
BTEX and volatile hydrocarbons in the environment may constitute
an immediate and long term health risk to people living in the surrounding area with respect to both cancer and non-cancer effects.
A risk assessment will be performed to evaluate potential short and
long-term human health impacts due to inhalation, ingestion and
dermal exposures.
Depending on the results of the risk assessment, there are a
number of options available for reducing the impact of the exposure
on the receptors (Hers, 2010)
further removal of the contaminated soil and groundwater,
vapour extraction fan system, with or without groundwater treatment,
passive barriers for the receptor buildings to reduce vapour intrusion,
additional ventilation in the receptor buildings, and
positive pressure ventilation within the buildings.
Step 2: Problem formulation
(a) Contaminants of concern
Gasoline contains a number of hazardous compounds,
including BTEX and a complex mixture of other hydrocarbons. A gasoline contaminated site may have different types
of hydrocarbons: C6 C10 aliphatic and aromatic hydrocarbons,
C1 C5 aliphatic hydrocarbons, hydrocarbons with equivalent
carbon numbers greater than C10 , and polycyclic aromatic
hydrocarbons. The gasoline in the subsurface weathers over
time; the components and concentrations of hydrocarbons
change as they migrate across and off the site, react with other
chemicals in the groundwater and soil, and are metabolized by
microorganisms naturally occurring in the soil and groundwater. For the purposes of this case study, we are only concerned
with the volatile hydrocarbons that we will refer to as Fraction 1 (F1) aliphatic hydrocarbons (as dened by the Canadian
Council of Ministers of the Environment (CCME, 2008), based

upon work by Edwards et al. (1997) for the Total Petroleum


Hydrocarbons Criteria Working Group (TPHCWG) which elute
in the C6 to C10 range during laboratory analysis. The carbon
fractions are summarized in Table 2 along with the tolerable
daily intake (TDI) and RfC for each subfraction. Other strategies
for separating hydrocarbon mixtures into fractions have been
proposed (Park and Park, 2010); however, the consideration of
the impacts of changes in the fractions is outside the scope of
this study.
(b) Receptor pathways
In order to assess the risk to the receptors, it is necessary
to estimate the concentrations of hydrocarbons present in
the groundwater, soil gas, indoor air, outdoor air, dust or airborne particulate, surface water, sediments, and food in order
to assess exposure through ingestion, inhalation and dermal
contact routes.
For the purposes of this case study, it has been assumed that
the release of gasoline has been predominantly from the underground storage tanks; therefore, the release would occur in soil
and groundwater. The F1 hydrocarbons are both soluble and
volatile and can be present in the groundwater, as well as in
the unsaturated zone of soil above the groundwater. For the
purposes of this case study, we are not considering groundwater use as we are assuming that the site is located in the
city and the use of groundwater for drinking within the city
would be unlikely. Because the contamination originated from
underground storage tanks and remains in the subsurface, it
is assumed that dermal contact with impacted soil is limited.
Therefore, the most important pathway is intrusion of vapours
into the building and the most important route of exposure is
inhalation of vapours.
(c) Receptor characteristics
The receptors for the hydrocarbons in the case study site are
the occupants of commercial and residential properties adjacent to the site. The people on commercial sites are expected
to be mostly adults with exposure durations of 10 h per day,
5 days a week, and 48 weeks per year. The residences are
assumed to house people of all ages, who may be home 24 h a
day 7 days a week.
Impacts of exposure to F1 hydrocarbons may vary in different sub groups of population. Acute exposures may result in
respiratory and neurological health effects. Longer term effects
can include hepatic and haematological changes, decreased
body weight and respiratory irritation and inammation

Please cite this article in press as: Dyck, R., et al., Application of data fusion in human health risk assessment for hydrocarbon mixtures on
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(Massachusetts Department of Environmental Protection


(MADEP), 2003). In the case of inhalation exposures, the most
exposed receptors are considered to have a reasonable maximum of 70 years continuous exposure at the identied site,
unless actual exposure averaging times are known (i.e., years
spent at a location where receptors have potential for intake
of the contaminants).
Step 3: Suitability of risk-based assessment
The impacts of gasoline constituent compounds can be acute or
chronic. There are numerous studies addressing exposure and toxicity for hydrocarbon exposure in animals and in humans (Agency
for Toxic Substances and Disease Registry (ATSDR), 1995). The pathways and routes of exposure are generally well understood and
explained. Based on the availability of data, the severity of the
effects and the nature of the compounds, a risk-based assessment
is possible and suitable.
There are several levels of HHRA that are recommended in
Canada (Health Canada, 2010a). A screening assessment may be
qualitative or semi-quantitative (e.g., comparison of environmental concentrations to established criteria), but does not generally
include site-specic risk assessment. Preliminary Quantitative Risk
Assessment and Detailed Quantitative Risk Assessment are more
complex. Where there are data available and the risks warrant,
detailed quantitative risk assessment should be done. In this case,
there is sufcient evidence and potential for harm to allow a
detailed risk assessment.
(a) Mixtures
Many contaminated sites involve chemical mixtures. Gasoline is a complex mixture of hydrocarbons which contains over
150 individual compounds present in a range of quantities. For
such complex mixtures, it can be prohibitive to consider the toxicity of each compound individually if sufcient toxicity data are
not available for each compound.
(b) Whole mixture toxicity
Where sufcient data are available related to the whole mixture or a sufciently similar mixture, one BMDL or RfC can be
derived for the entire mixture. Alternatively, when there are
data regarding a group of similar mixtures, we must evaluate
the toxicity of our mixture of interest against the toxicity of the
known mixture for which more data are available.
(c) Components toxicity
If there are insufcient data to consider the entire mixture as
a whole, there are a number of ways that the toxicity information for the individual components of the mixture can be used to
evaluate the toxicity of the mixture. For constituents of the mixture which are toxicologically similar to each other and to the
properties of the mixture as a whole, dose addition methods are
commonly used. These include relative potency factor, toxicity
equivalence factor and hazard index methods. If there are insufcient toxicity data for numerous components of the mixture,
quantitative structure activity relationships (QSAR) could also
be helpful in determining the potential toxicity of a compound.
Additionally, interactions between chemicals in the mixture
could lead to effects that are greater or less than additive.
The use of surrogate chemical toxicity represents a method
that is commonly used for chemical mixtures. In the case of
hydrocarbons in the C6 C10 range, the toxicity of commercial
hexane has been used to represent the toxicity of the C6 C8
range of the hydrocarbon fraction (Edwards et al., 1997). It was
concluded that consideration of hexanes toxicity will be protective
of other hydrocarbons in that range. This method may neglect the
relative prevalence of the compounds in the F1 fraction, and also

overlook interactions leading to effects that are either greater or


less than additive. This consideration is also based mainly on neurotoxic properties of hexane, while newer reports are questioning
whether or not that would be protective of irritancy, especially
in cases where the hexane concentration is low (Wilson Scientic
Consulting Inc. and Meridian Environmental Inc., 2007).
The ultimate choice of method for risk assessment of chemical mixtures can only be made following collection and analysis of
toxicology data for the mixture as a whole, as well as the components of the mixture. For F1 hydrocarbons in this case study, there
is insufcient evidence for the consideration of the mixture as a
whole, therefore individual components will be considered based
on their toxicity.
4.1.2. Low level data fusion
Step 4: Data collection
In this step, data were collected for all identied possible sources, stressors, transport pathways, exposure routes,
chemical combinations, end points receptors, and population
vulnerabilities. As discussed above in problem formulation, the
most likely exposure pathway is inhalation following vapour
migration to the indoor environment. Exposure models for
vapour intrusion are available from Health Canada (2008) and
Johnson and Ettinger (1991). Background and typical vapour
concentrations are available from literature (Sevigny et al.,
2003), as well as the American Petroleum Institute website
(http://www.api.org/ehs/groundwater/bioattenuation.cfm).
The CCME Canada-Wide Standards (CWS) for Petroleum Hydrocarbons (PHC) were derived using the TPHCWG analysis by
Edwards et al. (1997). Recent studies (Park and Park, 2010) suggest the use of other hydrocarbon fractionation systems, and
Equilibrium Environmental Inc. (2005) suggested that the use of nhexane as a surrogate is over-conservative. The percent of n-hexane
in weathered gasoline and in the weathered F1 fraction is relatively
small, and may be insignicant in comparison to the concentrations
of other compounds in the fraction (e.g., octane or heptane). It is also
possible that while not evidently toxic individually, mixtures could
result in effects that are greater than additive which may elicit similar toxic effects as n-hexane (MADEP, 2003). Due to these factors,
it may be advisable to consider the toxicity of each component and
then fuse them to form a single toxicity for the entire F1 fraction.
The relative amounts of the components of the F1 hydrocarbon
fraction present on a contaminated site will vary based on the original source of contamination, the subsurface contaminant transport,
weathering, and the degradation of the hydrocarbons over time.
Typical mass fractions and percent by weight for components of
gasoline were provided by ATSDR (1999). The relative percent of
each compound in the F1 mixture will be used to provide weighting
to the toxicity of each compound in the mixture for determination
of the total toxicity for the mixture, as explained in Step 5.
Toxicology data for F1 hydrocarbons have been summarized
by Edwards et al. (1997), by the ATSDR Toxicological Proles for
Total Petroleum Hydrocarbons (1999) and Gasoline (ATSDR, 1995),
by MADEP (2003) as well as the CCME Canada-Wide Standard
for Petroleum Hydrocarbons (PHC) in Soil: Scientic Rationale
Supporting Technical Document (2008), and the CCME Toxicity
Reference Value (TRV) Advisory Sub Group 2005 Review of CanadaWide Standards for Petroleum Hydrocarbons in Soil. Data regarding
the human health endpoints can also be obtained from literature.
Available toxicological data were reviewed for each component of F1. The compounds and summaries of the relevant studies
are presented in tables in Supplementary Information (API, 1982,
1983; Bahima et al., 1984; Biodynamics Inc., 1978; Bus et al., 1979;
Carpenter et al., 1978; Cavender et al., 1984; Criteria Group for
Occupational Standards, 1983; Dunnick et al., 1989; Egan et al.,

Please cite this article in press as: Dyck, R., et al., Application of data fusion in human health risk assessment for hydrocarbon mixtures on
contaminated sites. Toxicology (2012), http://dx.doi.org/10.1016/j.tox.2012.11.010

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1980; Equilibrium, 2005; Frontali et al., 1981; Galvin and Bond,


1999a,b; Howd et al., 1982; Huang et al., 1989, 1992; Ichihara et al.,
1998; IRDC, 1992; Litton Bionetics, 1979; Lungarella et al., 1984;
MacEwen and Vernot, 1985; Malley et al., 2000; Mast et al., 1987,
1988; NTP, 1991; Olson et al., 1986; Ono et al., 1981, 1982; Parnell
et al., 1988; Perbellini et al., 1986; Pryor et al., 1982; Rabovsky et al.,
1986; Sanz et al., 1995; Sayre et al., 1986; Serve et al., 1991, 1992,
1993, 1994, 1995; Takeuchi et al., 1981; Valentini et al., 1994; Yuasa
et al., 1996).
Step 5: Data estimation
Before performing toxicity assessment, it is essential to dene
what would be considered an adverse effect. The US EPA (2012)
denes an adverse effect as A biochemical change, functional
impairment, or pathologic lesion that affects the performance of
the whole organism, or reduces an organisms ability to respond to
an additional environmental challenge. As such, it is possible to
identify adverse effects of chemical exposures from toxicity studies that demonstrate clinical responses, physiological effects and
histopathological effects.
After collection of data from sources listed above, for different
media and different exposure routes, lower level data fusion was
carried out. The studies included were limited to studies which

were conducted on rats,


considered sub-chronic exposure (less than 6 months),
considered inhalation, and
used neurotoxicity as an endpoint.

As a more generalized approach, studies conducted on other


species for other exposure durations, pathways and endpoints
could also be fused using conversion factors and weighting as
advised by toxicologists.
(a) Construction of p-boxes and data fusion
The rst step in the data fusion was the derivation of p-boxes for
the toxicity of each substance. Each p-box was constructed for the
PDF of a data source. One of the benets of data fusion using DST is
the ability to convert words (qualitative terms) into probabilities.
This is especially useful where we want to capture expert opinion
on our data. Our experts can dene certain signals or responses in
studies as being low, medium or high. These words are converted into p-boxes which represent, not only the categories which
the experts have designated (Fig. 4, x-axis on p-box plots, but also
the probability or condence they have in that assessment (Fig. 4, yaxis on p-box plots). Details regarding the construction of p-boxes
is provided in Supplementary Information. General information is
provided here.
Three types of evidence were summarized including neurotoxic response, formation of neurotoxic metabolites, and
structureactivity relationships. These types of evidence were
summarized from the studies themselves (Tables S-V and S-VI Supplementary Information) or from the summary provided by Galvin
and Bond (1999a) and Equilibrium (2005). Based on comments
made in the studies or in the summaries, the neurotoxic response
was allocated a rating of No when no neurotoxic response was
noted, and Low, Medium or High dependant on the strength
of the response, and how much the response could be attributed
to the compound of interest. For example, for 2-methylpentane in
a study by Ono et al. (1981), the response was described as no
signicant difference in motor nerve conduction velocity, motor
distal latency; mixed nerve conduction velocity (distal); signicant
difference in mixed nerve conduction velocity (proximal) after 8
weeks and was allocated a rating of medium. This allocation would

be highly subjective and depend strongly on the judgement of the


assessor and would therefore be an excellent opportunity for toxicologists to improve the assessment. The production of metabolites
was determined by reporting in the studies (yes or no, depending on
if they were reported as present), as was the structural potential for
neurotoxic metabolites to be formed (which was described in the
summary by Equilibrium (2005) as having a structure favourable
to neurotoxicity of much greater, greater, equal, less than or much
less than that of n-hexane). The denition of the response as high,
medium or low and the structural considerations are areas that
could be further rened by expert opinion of toxicologists.
The input used for data fusion is shown in Table 3. The p-boxes
shown in Fig. 4 were generated as follows:
Three types of evidence are considered, Response, Metabolites
and SAR.
The responses of no, low, medium or high were allocated
toxicity index values in %.
The p-boxes for response (labelled (1) in Fig. 4) represent
no response (0% on the x-axis which represents toxicity),
low response (033% on the x-axis, with probabilities indicated
by the y-axis for each value of x between 0% and 33%),
medium response (3366% on the x-axis, with probabilities
indicated by the y-axis for each value of x between 33% and
66%) and
high response (66100% on the x-axis, with probabilities indicated by the y-axis for each value of x between 66% and 100%).
The p-boxes for metabolite show 0 or 100% on the toxicity index
(x-axis) in Fig. 4.
The p-boxes for SAR represent structure favourable to neurotoxicity compared to n-hexane
much less than (05% on the x-axis),
less than (535% on the x-axis),
equal to (3565% on the x-axis)
greater than (6595% on the x-axis) or
much greater than (95100% on the x-axis).
The values for each evidence type for each of the compounds
considered are listed in Table 3.
The studies for each compound were given a Study number which
corresponds to number (2) in Fig. 4. The p-boxes from the evidence type for each study (labelled (1)) were fused (using DST
mixture rule see Supplementary Information for more detail
on the technique) to form the p-boxes labelled (2) in Fig. 4 which
represent the toxicity indicated by each individual study for the
different compounds considered. The compounds are grouped in
Fig. 4 at (2) because in fusing the different evidence types, there
were only 5 different p-boxes that resulted due to the similarity
in the response in the studies for the different compounds.
The p-boxes labelled (2) represented various studies for each
compound. The studies for each compound were fused to provide
a p-box representing toxicity for each compound shown at number (3).
Each p-box at number (3) representing a compound in the F1
mixture was allocated a weight based on its percent of the mass
composition in the mixture (labelled (4)).
The resultant p-box (labelled (5)) is the fused p-box for all the
compounds shown at (3), weighted according to the percent mass
indicated at (4).
This was done including all of the components of the F1 hydrocarbon mixture for which there were studies indicating the toxicity
relative to the types of evidence used here and where the percent
mass in the mixture was known. This did not include n-hexane.
The p-box for n-hexane is constructed to indicate that n-hexane
is toxic. This is represented by the vertical line at 50%. This toxicity was allocated to n-hexane because it was the compound that

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contaminated sites. Toxicology (2012), http://dx.doi.org/10.1016/j.tox.2012.11.010

Duration

Resp. 1

2-Methylpentane
(summarized by Galvin
and Bond (1999a))

Frontali et al. (1981)

14 wk, 9 h/d, 5 d/wk

No

API (1982, 1983)

22 h/d, 7 d/wk
Up to 6 mo
22 h/d, 7 d/wk
Up to 6 mo
22 h/d, 7 d/wk
Up to 6 mo
14 wk, 9 h/d, 5 d/wk

Low

22 h/d, 7 d/wk
Up to 6 mo
22 h/d, 7 d/wk
Up to 6 mo
22 h/d, 7 d/wk
Up to 6 mo
9 h/d, 5 d/wk 1500 ppm

Low

API (1982, 1983)


Egan et al. (1980)
6

3-Methylpentane
(summarized by Galvin
and Bond (1999b))

Frontali et al. (1981)

API (1982, 1983)


API (1982, 1983)
Egan et al. (1980)
Cyclohexane (from
summary in
Equilibrium (2005))

n-Hexane
Heptane
7
2-Methylhexane

Frontali et al. (1981)

Malley et al. (2000)


See studies in Table S-VI
Takeuchi et al. (1981)
Frontali et al. (1981)
Bahima and
Menendez-Gallego (1984)
Perbellini et al. (1986) and
Sayre et al. (1986)

10 h/d, 6 d/wk 2500 ppm


6 h/d, 5 d/wk, 14 w

Resp. 2
0%

033.3%

Metabolite

SAR

SAR

Study

Mass % in
gasoline

05%

C6 -1

8.12

28.14

05%

C6 -2

5.18

18.0

No

0%

05%

C6 -3

No

0%

05%

C6 -4

No

0%

05%

C6 -5

05%

C6 -6

033.3%

No

0%

05%

C6 -7

No

0%

05%

C6 -8

No

0%

05%

C6 -9

05%

C6 -10

Med

33.366.6%

1.75

6.32
12 h/d, 7 d/wk, 16 wk
9 h/d, 5 d/wk, 30 wk
6 h/d, 5 d/wk, 12 wk

No
No
No

0%
0%
0%

1
1
1

<
<
<

535%
535%
535%

C7 -1
C7 -2
C7 -3

2.76

No

0%

05%

C7 -4

3.49

Recalcd %
in F1

6.07

21.9
9.58

R. Dyck et al. / Toxicology xxx (2012) xxxxxx

Author

12.1

2,5-Dimethylhexane
3,4-Dimethylhexane

Serve et al. (1991)


Sanz et al. (1995)

No
No

0%
0%

Not reported
Not reported

<

535%
95100%

C8 -1
C8 -2

Inconclusive

In vitro 3,4-dimethylhexane

n-Nonane

Carpenter et al. (1978)

6 h/d, 5 d/wk, 12 wk

No

0%

<

535%

C9 -1

0.60

2.04

10

n-Decane

Criteria Group for


Occupational Standards
(1983)

18 h/d, 7 d/wk, 123 d

No

0%

<

535%

C10 -1

0.63

2.18

100

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Compound

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Table 3
Data fusion input for F1 in weathered gasoline, inhalation, rats only, sub-chronic, up to 6 months.

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10

R. Dyck et al. / Toxicology xxx (2012) xxxxxx

Fig. 4. Multi-study and multi-compound inference for F1 neuropathic toxicity in rats using DempsterShafer mixture fusion (averaging). p-Boxes were constructed to
represent the toxic response, generation of toxic metabolites and the structure activity relationship for compounds in the F1 range. p-Boxes for six compounds were assigned
weights according to the percent composition in the F1 range.

each other compound was compared to in the summaries of studies, and also because it is used for some derivations of toxicity for
this hydrocarbon fraction. Following this, we apply the toxicity of
the F1 mixtures to the dose response curve for n-hexane.
The resulting p-box in Fig. 4 at number (5) represents the toxicity
of the entire mixture with probabilities for each possible value on
the x-axis. This provides a more complete picture of the toxicity of
the mixture than choosing one reference compound or one study.
Step 6: Assessment method selection
In the case of a petroleum hydrocarbon site, F1 hydrocarbons
are commonly detected in the subsurface, along with BTEX. The
components of the F1 hydrocarbon fraction can be present in

varying concentrations based on the source chemical and the


amount of weathering, therefore it is recommended to consider F1
as a mixture.
4.1.3. Feature level fusion
Step 7: Doseresponse assessment
High level or feature level data fusion can be illustrated using
a case adapted from Schmitt (2006). Schmitt (2006) uses two
sources of data in the derivation of BMDL: ndings from multiple
empirical studies along with data calculated from a mechanistic
model. The proposed framework can be applied to this data. In
the case of F1 hydrocarbons, the toxicity of each compound considered was applied to the PDF of the NOAEL concentrations from
studies on n-hexane, for which there were much more toxicity

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11

Fig. 5. p-Box of neurotoxicity NOAEL for F1 hydrocarbon mixture.

data. The p-boxes for the toxicities were separated into upper and
lower CDFs and multiplied by the distribution for NOAEL by Monte
Carlo simulations using the software @Risk (Palisade Corporation,
2010). The separation of the p-box into upper and lower CDFs
should represent the possible values (upper CDF) and probable
values (Lower CDF) because the true CDF lies somewhere within
these two. The combined p-box for the upper and lower limits
of the NOAEL for F1 mixture is shown in Fig. 5. This p-box was
generated by placing the upper and lower CDFs on one plot.
Step 8: Exposure assessment
In this case only vapour inhalation was considered as an exposure pathway because the sub-surface soil would not be available
for dermal contact or accidental ingestion on a paved site. Also,
groundwater in the city is not usually used for consumption
or irrigation. As a result, the relevant pathways are soil and
groundwater contamination to soil vapours through cracks in the
residential foundation to the residents inside.
Hydrocarbon vapour concentrations have been measured in the
soil. Sevigny et al. (2003) used the Johnson Ettinger vapour intrusion model to estimate indoor air concentrations in the buildings.
Probability distributions for the exposure factors for the receptors are used to estimate exposures. The exposure assessment was
conducted using exposure factors provided by Health Canada for
residential and occupational exposures.
Health Canada (2010a) recommends the following equation for
indoor inhalation of contaminant vapours
Dose

 mg/kg 
d

Cia IRA AFinh ET


RW

where Cia is the concentration of contaminant in indoor air


(mg/m3 ); IRA is the air inhalation rate (m3 /day); AFinh is the relative absorption factor for inhalation (unitless); ET is the exposure
term (unitless); and BW is the body weight (kg).
PDFs for each of the exposure factors were combined with the
site indoor vapour concentrations using Monte Carlo simulations.
In this case, the absorption factor for inhalation is assumed to be
1. Because the receptors are residents that have the potential to be
exposed 24 h a day for a lifetime, it is conservative to assume that
the exposure term is also 1.
4.1.4. Decision level fusion
Step 9: Risk characterization

The NOAEL from the doseresponse assessment applies for rats


in a sub-chronic study. Where NOAEL values were not available, the
lowest observed adverse effect level (LOAEL) values were divided
by an uncertainty factor of 10. Other uncertainty factors that can
be applied include

10 for interspecies differences


10 for intraspecies differences and
3 or deciencies in the data set.

No uncertainty factor is being used for the severity of toxic


effects, as a factor was included in calculating the combined NOAEL
for F1.
The RfC is calculated by dividing the NOAEL by the uncertainty
factors. The NOAEL in this case was presented as a p-box. While
there is software available to multiply p-boxes together, for computational simplicity in this case we used the average of the upper
and lower bound 95th percentiles which is 639 mg/m3 . This results
in an RfC of 2.13 mg/m3 . This value is calculated only for the purposes of illustrating the approach. This should not be interpreted
as a new RfC or TDI.3
In order to compare this to the exposure doses, we used the
inhalation rate and body weight of each age group to generate an
age-specic TDI.

Step 10: Relative cost-benet analysis and selection of management options


A cost benet analysis should always be conducted to assess the
potential management options. The cost benet analysis is outside
of the scope of work of this case study.
Step 11: Reporting, guideline and implementation
The Health Canada Guidance on Complex human health detailed
quantitative risk assessment for chemicals (Health Canada, 2010a)
presents a suggested report outline. This outline could be used to
form the basis for reporting for this case study, however, the intent
of this case study is the demonstration of the use of data fusion in
HHRA, not the actual risk assessment for this site.

3
These results do not necessarily reect the opinion of Health Canada nor is it
Health Canada guidance.

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5. Discussion
The case study considered only those compounds for which
sufcient data were available on toxicity as well as percent composition in the gasoline on site. The CCME F1 hydrocarbon mixture was
considered to consist only of aliphatic hydrocarbons with equivalent carbon numbers C6 C10 . The health end point considered was
neurotoxicity for sub-chronic exposure. The case study did not consider
contaminants other than CCME F1 hydrocarbons,
other fraction strategies for classifying hydrocarbon mixtures,
other health effects including respiratory irritation and reproductive effects,
results that are greater or less than additive,
chronic or acute exposure,
toxicity studies on animals other than rats, or
toxicity studies for oral or dermal exposure.
Three types of evidence were included in the data fusion
neurotoxic responses, including clinical, physiological and histological responses
formation of neurotoxic metabolites
chemical structure favouring the formation of neurotoxic
metabolites (structureactivity relationship).
The neurotoxic responses reported in the studies were allocated values of no, low, medium or high. These responses
could be expressed in numerical values where appropriate. In this
case study, the risk assessor assigned a value to the strength of
the neurotoxic response shown in each animal study; however, in
other applications, the input of several experts could be considered. Where these opinions differed, data fusion could be used to
address the conict between the opinions. These opinions could be
weighted according to the perceived reliability or credibility of the
experts.
Toxicity data were more readily available for n-hexane than
for the other components of the mixture, therefore the n-hexane
toxicity data were considered separately from the other components. The results of the data fusion represent a more complete
picture of the toxicity than just consideration of n-hexane, because
they incorporate data from many compounds weighted by their
relative amounts in the mixture. The resulting RfC (presented for
illustrative purposes only) is 2.13 mg/m3 . This is smaller than the
RfC of 18.4 mg/m3 for C6 C8 fraction provided by CCME (2008)
and Edwards et al. (1997), but larger than that given for C8 C10 of
1.0 mg/m3 . This result was expected because the fusion was conducted for the entire range of C6 C10 . The calculated Hazard Indices
were low; however, the actual risk assessment was not the main
objective of this case study, rather the application of the proposed
data fusion framework to HHRA for complex mixtures. Data fusion
is used here in the context of conducting doseresponse evaluations and toxicity assessments in the context of human health risk
assessment; the purpose of this exercise was not to present a new
RfC for petroleum hydrocarbons, but to present the use of data
fusion in the derivation of RfCs.
For the application of this type of data fusion to other sites, accurate characterization of components and relative amounts in the
mixture would be required. Although data fusion was conducted in
this assessment for sub-chronic inhalation studies, data from oral
studies or studies with other durations (chronic or acute) could
be included in the fusion if adequate conversion factors could be
derived for comparing oral to inhalation data and sub chronic to
chronic or acute data.

Data fusion as a tool for toxicologists conducting or evaluating


HHRA does have some limitations. These mathematical constructs
are somewhat unfamiliar in the eld of toxicology. This unfamiliarity might make it difcult for the analyst to choose data fusion
architecture and methods. The results of the data fusion may be
signicantly affected by the choice of fusion method. This is partly
because each of the fusion methods handle conict differently.
Therefore, a solid understand of the fusion methods and the circumstances which make one preferable is important but attainable.
Data fusion methods are somewhat limited by the data that is
available. Analysts require sources of data that are sufciently similar in order to conduct data fusion. In this case study, only one end
point, one exposure route and one species were considered: other
weighting factors would need to be added for extrapolation to those
conditions. The selection and use of the data fusion methods are further complicated by the different types of uncertainty that can be
present. While data fusion allows the selection of different methods for modelling uncertainty (e.g., possibilistic, probabilistic, and
fuzzy), the selection of those methods often depends heavily on the
dataset. Computational complexity can increase when some of the
data are presented in probabilities while others are presented in
possibilities.
Another limitation specic to this application is the uncertainty
in exposure. Generally, a hydrocarbon mixture on a contaminated
site is not uniform. The composition will also change with time.
Differences in spatial and temporal variation were not considered
here. In spite of these limitations, data fusion is a useful tool for
combining data from numerous sources in a way that preserves
information about uncertainty.
6. Summary and conclusions
Uncertainty occurs in HHRA due to data used in the assessment
which can be incomplete, conicting, vague or ambiguous. Complex chemical mixtures can present further uncertainty due to the
differences in toxicity between the components in the mixture.
To address these uncertainties, a data fusion framework for HHRA
was proposed to integrate toxicity information from three evidence
types for components of the F1 hydrocarbon mixture. The Joint
Directors of Laboratories (JDL) Data Fusion (DF) framework was
chosen as the data fusion architecture, in which DST was implemented as the data fusion technique. The use of p-boxes allowed
for consideration of probabilities and uncertainty.
The case study considered was a contaminated site which
historically contained underground gasoline tanks. The CCME
hydrocarbon fraction F1, corresponding to C6 C10 , was considered
as a complex mixture for which risk assessment was required. Data
were reviewed for the toxicity of the components of the mixture.
Three types of evidence were considered for neurotoxicity
1. neurotoxic response,
2. presence of neurotoxic metabolites, and
3. structureactivity relationships.
Toxicity data for the components of the mixture were combined with toxicity data for n-hexane due to the greater amount
of information available for n-hexane. The resulting RfC for the
C6 C10 mixture was lower than RfCs given by other sources (CCME,
2008; Edwards et al., 1997) for C6 C8 , and higher than that given
for C8 C10 .
Future data fusion studies are recommended and should include
consideration of
contaminants other than CCME F1 hydrocarbons, other fraction strategies for classifying hydrocarbon mixtures, other health

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effects including respiratory irritation and reproductive effects,


emerging system biology datasets integration and application of
data fusion
Human Health/Public Health Data Fusion
interactions between mixture components which would cause
effects that are greater or less than additive, chronic or acute
exposure, toxicity studies on animals other than rats, toxicity
studies for oral or dermal exposure, and
other data fusion techniques (such as those listed in Section 2.2).
The inclusion of data fusion as a tool in future HHRA provides
an opportunity to address uncertainties, inconsistencies and lack
of information. Complex mixtures represent one area where such
data fusion would address specically the variable nature of the
components of complex mixtures and allows the risk assessor to
use the available data to the fullest extent.
Conict of interest statement
The authors declare that there are no conicts of interest.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tox.2012.11.010.
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