Chemistry Reference
In-Depth Information
2006). Similarly, a few occupational exposure limits
(OELs) for asphalt fumes (0.5 mg/m
3
), cotton dust (0.2
mg/m
3
), coal dust (0.4 mg/m
3
), and Stoddard solvent
(100 ppm) have been established (
http://www.acgih.org
;
http://www.cdc.gov/niosh/homepage.html
; NIOSH, 2006).
In a manner analogous to the hazard index approach
for noncarcinogens, a hazard index for carcinogens can
be estimated by dividing chemical exposure levels by
doses (DR) associated with a set level of cancer risk
(U.S. EPA, 1986; 2000a):
6.2.2 The Similar Mixture Approach
Chem. Exposure
1
Chem. Exposure
2
Chem. Exposure
3
HI =
+
+
DR
1
DR
2
DR
3
The second approach used is the “similar mixture”
approach and can be applied on a case-by-case basis to
a candidate mixture or groups of mixtures that could
act similarly (Durkin
et al.
, 1995). It is used when ade-
quate information is not available for the mixture of
concern and is often applied to complex mixtures that
have been extensively investigated, such as coke oven
emissions, diesel exhaust, and wood stove emissions.
However, a minimum of information should be avail-
able to consider a mixture suffi ciently similar to the
mixture of concern. For example, if a risk assessment is
needed for gasoline contamination of groundwater and
information is available on the chronic toxic effects of
gasoline, it may be possible to use the available informa-
tion to assess risks from the contaminated groundwater.
However, there are no set criteria to help decide when
a mixture is suffi ciently similar. Hence, the health asses-
sor is left to determine whether the two chemical mix-
tures are suffi ciently similar and whether this similarity
justifi es use of surrogate risk or toxicity data. The fi rst
two approaches, the mixture of concern and the similar
mixture approach, are used for those mixtures that have
been experimentally tested as a whole to some extent.
In terms of estimating risk, the HI values obtained
using the HI approach should be interpreted carefully.
For example, if chemical mixture “X” yields an HI value
of 4, it need not be interpreted as twice as toxic as mixture
“Y” that yields a value of 2. However, it can be said that
mixture “X” is more toxic than mixture “Y”. Thus the
HI approach can be used for priority setting of mixtures.
As the value of the HI increases toward unity, the con-
cern for the potential hazard of a mixture increases. The
potential health effects of a mixture are further analyzed
and investigated if the HI value is equal to or greater
than 1. The HI approach assumes that all components
have similar joint action, that is their uptake, pharma-
cokinetics, and dose-response curves have similar shape
(Teuschler and Hertzberg; 1995; U.S EPA, 2000). For car-
cinogens, the preceding equation assumes that each car-
cinogen has a linear dose-response curve and that each
carcinogen is acting independently (U.S. EPA, 1986).
6.2.4 The Target-Organ Toxicity Dose (TTD)
In terms of estimating risk, it is important that the
estimates be realistic. The use of acceptable exposure
levels (MRLs or RfDs) that are based on a critical effect
to assess secondary effects could lead to overestima-
tion of risk (U.S. EPA, 1989). To circumvent this prob-
lem, target-organ toxicity doses (TTDs) can be used
(Mumtaz
et al.
, 1997). TTDs, in essence, are effect- or
organ-specifi c MRLs and are calculated by use of the
same method and process. Thus, for a given chemical,
there could be an MRL for hepatotoxicity and a series
of TTDs for nephrotoxicity, neurotoxicity, and repro-
ductive toxicity (ATSDR, 2001a). The TTD method is
a simple modifi cation of the HI approach and yields
a series of HIs for various toxic effects. The values of
endpoint-specifi c hazard indices are treated the same
as that of a HI of a mixture (Mumtaz
et al.
, 1997).
The hazard index approach is a simple approach to
implement but somewhat limited in its scope and, as
a result, may either underpredict or overpredict risk
estimates of mixtures of industrial, occupational, and
environmental chemicals if synergistic and antago-
nistic interactions occur (Feron and Groten, 2002;
U.S. E.PA.,1986; 2000a). It is important that the risk
6.2.3 The Hazard Index Approach
The third approach, the hazard index (HI) approach,
is the method most often used. This approach inte-
grates the exposure level and the related toxicity into
a single value by use of potency-weighted dose or
response addition. The goal of the HI approach is to
approximate the toxicity index that would have been
determined had the mixture itself been tested (Mumtaz
et al.
, 2002b). Initially, the potential health hazard from
exposure to each chemical is estimated by calculating its
individual hazard quotient (HQ). The HQ is derived by
dividing a chemical's actual exposure level (E) through
an environmental medium by its acceptable/allowable
exposure level (AE) such as a minimal risk level (MRL)
or a reference dose (RfD). The hazard index (HI) of the
mixture is then calculated by adding together all the
component hazard quotients, as illustrated below for
three chemicals in a mixture:
Chem. Exposure
1
Chem. Exposure
2
Chem. Exposure
3
HI =
+
+
AE
1
AE
2
AE
3
