REGULATORY

TOXICOLOGY

AND

PHARMACOLOGY

16,290-3t)o (1992)

Toxic Equivalency Factors (TEFs) for Polycyclic Aromatic Hydrocarbons (PAHs)

IAN C. T. NISBET

AND PETER K. LAGOY’

I.C. T. Nisbet & Company, 72 Codman Road, Lincoln, Massachusetts 01773-3701

Received July 21, I992

The polycyclic aromatic hydrocarbons (PAHs; also referred to as the polynuclear aromatic hydrocarbons or PNAs) are commonly encountered at hazardous waste sites and are often the focus of site remediation activities. However, toxicity criteria are not available for all the PAHs. In the past, EPA has assessedrisks posed by mixtures of PAHs by assuming that all carcinogenic PAHs are as potent as benzo[a]pyrene (B[a]P), one of the most potent PAHs. The available information on the toxicity of the PAHs suggests that most are considerably less potent than B[a]P and therefore, the EPA approach is likely to overestimate risks. Several approaches have been developed to allow the relative potency of the different PAHs to be considered in a sitespecific risk assessment. This paper evaluates these approaches and presents a modified version that we feel more accurately reflects the state of knowledge on the relative potency of these COUIpOUUdS.

0 1992 Academic Press, Inc.

INTRODUCTION

The polycyclic aromatic hydrocarbons (PAHs; also referred to as the polynuclear aromatic hydrocarbons or PNAs) are a complex group of chemicals containing two or more aromatic rings. The PAHs are products of incomplete combustion, are present in petroleum products, and as such are commonly encountered as contaminants at hazardous waste sites. PAHs occur in the environment as complex mixtures of many components with widely varying toxic potencies (Santodonato et al., 1981). Only one of the PAHs, benzo[a]pyrene or B[a]P, has been well characterized toxicologically but some information is available for many other PAHs. The approach adopted by EPA (1980, 1984) as the basis for risk assessment is to separate the PAHs into two subclasses consisting of the carcinogenic and the noncarcinogenic PAHs and to apply a cancer slope factor derived from assays on benzo[a]pyrene to the subclass of carcinogenic PAHs. This approach is a crude version of the toxic equivalency factor (TEF) approach that is used for polychlorinated dibenzo’ To whom correspondence should be addressed at OHM Corporation, 2950 Buskirk Avenue, Suite 3 15, Walnut Creek, CA 94596. 290 0213-23oof92 $5.00 Copyright @ 1992 by Academic Press, Inc. All rights of reproduction in any form reselved.

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p-dioxins and polychlorinated dibenzofurans (PCDDs/PCDFs; NATO, 1988). B[a]P is used as the surrogate compound, a TEF of 1.O is applied to all carcinogenic PAHs, and a TEF of zero is applied to all noncarcinogenic PAHs. Some additional information has been developed on the relative potencies of particular PAHs by Chu and Chen (1984) and Clement Associates Inc. (1988; also presented in an earlier version as Thorslund et al., 1986). Information provided by these authors allows more accurate estimates of the potential risks posed by different PAH mixtures. However, the two approaches have limitations in that they only address a small number of the PAHs that are commonly detected at hazardous waste sites, and the TEFs are unreasonably precise. These approaches have not been widely used, and risk assessments for hazardous waste sites have been based on a variety of approaches. In this paper, we modify the TEF approaches presented by Chu and Chen (1984) and Clement (1988) to yield a set of TEFs that we feel more accurately reflects the state of knowledge on the relative potencies of the different PAHs. Our modified TEF approach also has the advantage of being more amenable to developing TEFs for other compounds and we present TEFs for all 17 PAHs commonly tested for at hazardous waste sites. Although little new scientific information has become available since 1988, an updated review is appropriate and may help to promote a more rational and uniform approach to risk assessment for PAH mixtures. BASIS FOR THE TEF APPROACH The TEF approach requires several assumptions: 1. A reasonably well-characterized compound can be selected to serve as a surrogate or reference compound for all members of the class. 2. The toxic effects of all members of the class are qualitatively similar to those of the surrogate compound and may be characterized quantitatively by means of a relative potency or TEF. 3. TEFs for different toxic end points are similar, so that limited information on relative toxic potencies in one or a few assay systems can be used to assign TEFs to single compounds or subclasses for other end points. 4. The toxic effects of different compounds of the mixtures are additive. For the family of PAHs, assumption 1 is satisifed by the selection of B[a]P as the reference compound. B[a]P is one of the most potent carcinogens in the group and has been tested for carcinogenicity and related effects in several different assay systems, and its mechanisms of action have been investigated in detail. Moreover, carcinogenic slope factors for B[a]P have been derived for both oral ingestion and inhalation exposure, although limitations of the studies make both factors somewhat uncertain (Poirier, 1992). Assumption 2 is simplified for PAHs because the primary concern for risk assessment is carcinogenicity. Many of the PAHs have been tested for carcinogenicity or for related toxic effects in the same assay systems (e.g., mouse skin, bacterial mutagenicity assays, or DNA-binding assays), and at least the more potent compounds are known to have similar effects (IARC, 1983; Santodonato et al., 198 1; EPA 1980). Many PAHs have been classified for carcinogenicity by IARC (1983), and this classification has been used as the basis for a crude TEF approach by EPA (1980, 1984).

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The basis for assumption 3 has not been discussed extensively, but the material reviewed has shown reasonably close concordance between relative potencies for different end points (Santodonato et al., 198 1; Clement, 1988). More discussion on this topic is provided below. The basis for assumption 4 on the additivity of effects has not been investigated systematically, but two experimental studies provide limited evidence on this issue. Schmahl et al. (1977) applied B[a]P alone or in combination with mixtures of other PAHs to the shaved skin of mice. Two mixtures were tested: a mixture of three carcinogenic PAHs (mixture B) and a mixture of seven “noncarcinogenic” PAHs (mixture C). The compositions of the mixtures and the results of the experiment are summarized in Table 1. Pfeiffer (1977) injected mice subcutaneously with B[a]P, dibenzo(ah)anthracene, a mixture of noncarcinogenic PAHs, and two combinations of these agents. The composition of the mixtures and the results of the experiment are summarized in Table 2. The results of the Pfeiffer (1977) study show that the mixture of B[a]P and DBA induced more tumors than did either when administered alone. Bearing in mind the nonlinearity of the dose-response curves for each compound, the data are consistent with additivity (see further analysis in Table 6). The mixture of noncarcinogenic PAHs used by Schmahl et al. (1977) showed some carcinogenic activity at a very high dose (group C4 in Table 1). Likewise, the mixture of noncarcinogenic PAHs used by Pfeiffer TABLE 1 DOSE LEVELSAND RESULTSFROMTHE SCHMAHL etal. (1977)s~~~~ Compounds administered Group A Benzo[a]pyrene Group B Benzo[a]pyrene (25%) Dibenzo[a,h]anthracene (18%) Benzo[a]anthracene (35%) Benzo[b]fluoranthene (22%) Group C Phenanthrene (42%) Anthracene ( 13%) Fluoranthene ( 17%) Pyrene (2 1%) Chrysene (2%) Benzo[e]pyrene ( 1%) Benzo[g,h,i]perylene (5%) Group D (B + C)

Dose groups

Dose levels” (fig/treatment)

Cancer incidence

Al A2 A3

1.0 1.7 3.0

13% (10/81) 28% (25/88) 53% (43/8 1)

Bib B2 B3

4.0 6.8 12.0

31% (25/81) 60% (53/88) 70% (63/90)

Cl c2 c3 c4

65 195 585 1755

1% (l/85) 0% (O/84) 1% (l/88) 17% (15/86)

Dl = Bl t Cl D2 = B2 t C2 D3 = B3 + C3

69 202 597

49% (44/89) 58% (54/93) 69% (64193)

a Mixtures were administered to the shaved skin of mice twice a week until the natural death of the animals or until the animals developed a tumor. At the start of the study, each dose group consisted of 100 animals but autolysis limited the total number of animals examined in each group. b B 1, B2, B3 included benzo[a]pyrene at the same dose levels as A 1, A2. A3, respectively.

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TABLE 2 DOSE LEVELS AND TUMOR INCIDENCERATES FROM THE PFEIFFER( 1977) STUDY Compounds administered

Dose group

Group A Benzo[a]pyrene

Al A2

3.12 6.25 12.5 25 50

A3

A4 A5 A6 Group B Dibenzo[a,h]anthracene

Group C Benzo[e]pyrene (0.8%) Benzo[a]anthracene ( 1.1%) Phenanthrene (46%) Anthracene ( 11%) Pyrene (24%) Fluoranthene (10%) Chrysene ( 1.1%) Perylene (0.1 W) Benzo[g,h,i]perylene (5%) Coronene ( 1.1%) Group D

Group E

100

Bl B2 B3 B4 B5 B6

2.35 4.7 9.3 18.7 37.5 75

Cl

270 550

c2 c3 c4 C5 C6

Dl D2 D3 D4 D5 D6 El E2 E3 E4 E5 E6

= Al = A2 = A3 = A4 = A5 = A6 = Cl = C2 = C3 = C4 = C5 = C6

Dose levels ’ &g/treatment)

9% 35% 51% 57% 77% 83% 37% 39% 44% 56% 65% 69%

2200 4400 8800

6% 8% 6% 4% 13% 5%

5.5 11 22 44 88 175 280 560 1120 2240 4500 9000

48% 44% 61% 68% 69% 79% 41% 55% 61% 72% 68% 82%

1100

+ Bl + B2 + B3 + B4 + B5 + B6 + Dl + D2 + D3 + D4 + D5 + D6

Tumor incidence*

Note. Some of the values have been rounded. ’ Doses were applied in a single subcutaneous injection between the shoulder blades. b All animals were palpated weekly for tumors. A tumor was considered to exist when a knot of approximately 1 cm in size was noticed and this knot grew over the next week. All tumors were confirmed by histopathological examination. A total of 100 animals were started in each group and were assumed to be at risk of developing tumors.

(1977) included small proportions of two compounds, benzo[a]anthracene and chrysene, which are often classified as carcinogenic (IARC, 1983) but with low potency (see Table 3). These noncarcinogenic mixtures did not significantly augment the activity of the carcinogenic mixtures when coadministered with them in either study (see

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results of Group D in Table 1 and Group E in Table 2). Thus, in both studies, the carcinogenic activity was attributable to the carcinogenic PAHs contained in the mixture. Although neither of these studies constitutes a critical test for additivity, the results of both are consistent with the assumption of additivity and the results of Pfeiffer (1977) provide substantial support for it. ASSIGNMENT

OF TEFS

In order to assign TEFs to the individual PAH compounds of concern in this study, we reviewed the papers prepared by Chu and Chen (1984) and Clement (1988). We also reviewed 11 papers in which one or more of the PAHs were tested side by side with B[a]P in the same assay system. These papers are the same as those used by Clement (1988) to estimate TEFs. The end points of these studies included the following: l Carcinomas in lungs of rats exposed via intrapulmonary administration (DeutschWenzel et al., 1983); l Complete carcinogenesis in mouse skin (Habs et al., 1980; Bingham and Falk, 1969; Hoffmann and Wynder, 1966; Wynder and Hoffmann, 1959); l Papillomas and/or carcinomas on mouse skin in initiation-promotion studies (LaVoie et al., 1982; Van Duuren et al., 1966; Hoffmann and Wynder, 1966); l Sarcomas at the site of injection following subcutaneous administration to mice (Pfeiffer, 1977; Bryan and Shimkin, 1943); l PAH-DNA adducts in in vitro studies (Grover and Sims, 1968; Phillips et al., 1979).

Relative potency factors (estimates of TEFs) were calculated by Clement (1988) using the data from each study by applying the same mathematical model of the doseresponse relationship to the data for each compound and comparing the results to those obtained for B[a]P. The specific mathematical model used was a two-stage lowdose-linear case of the multistage model developed by Thorslund et al. (1986) but in most cases the estimates of relative potency factors would not have been sensitive to the specific choice of model. If several estimates of relative potency factor were available for the same compound, they generally showed reasonable concordance. For example, estimates of relative potency factors for DBA, the only PAH with comparably high potency to that of B[a]P, were as follows: 1.1, based on complete carcinogenesis on mouse skin (Wynder and Hoffmann, 1959); 5.3 at low doses and 1.2 at higher doses, based on local tumors induced by subcutaneous injection into mice (Pfeiffer, 1977); and 5-6 at low doses and 1.3 at higher doses, based on local tumors induced by subcutaneous injection into mice (Bryan and Shimkin, 1943). Chu and Chen (1984) determined a relative potency factor of 0.69 for DBA. In general, relative potency estimates for DBA were around five at low doses and close to one at higher doses. For other PAHs, estimates of relative potency derived from different assay systems varied over a similarly narrow range; in no case did the lowest and highest estimates differ by more than a factor of 10 (Clement, 1988). Bearing in mind uncertainties introduced by experimental limitations and model fitting, this provides strong evidence for assumption 3, that TEFs

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FOR PAHs

for different toxic endpoints are similar. However, the observed variation among the estimates shows that estimates of TEFs are subject to uncertainty ranging up to a factor of at least 3. Based on criteria that included similarity of route of exposure to those of concern for risk assessment, adequate conduct and reporting of experiments, comparability of degree of response to B[a]P and other PAHs, and statistical power, five studies were selected by Clement (1988) as the most appropriate bases for the assignment of TEFs (Wynder and Hoffmann, 1959; Habs et al., 1980; Bingham and Falk, 1969; DeutschWenzel et al., 1983; Wislocki et al., 1986). Relative potency factors derived by Clement ( 1988) from these studies for 10 PAH compounds commonly present at hazardous waste sites are listed in Table 3. This table also presents TEFs developed by Chu and Chen (1984) for seven PAHs, as well as those specified by EPA (1980, 1984). The Clement (1988) and the Chu and Chen (1984) TEFs have been used at a number of Superfund sites. However, as noted above, these TEFs are unreasonably precise. Table 4 presents a set of TEFs rounded to order of magnitude, which appropriately reflects the actual state of knowledge on the relative potencies. The TEFs in Table 4 indicate the carcinogenic potency of each compound relative to B[a]P. Multiplying the measured concentration of the individual PAH by the TEF indicates the concentration of chemical in terms of B[a]P equivalents. For example, multiplying a benzo[a]anthracene concentration of 170 mg/kg by the TEF (0.1) gives a B[a]P equivalent concentration of 17 mg/kg. The TEFs in Tabie 4 are based primarily on the Clement (1988) values but also include a consideration of the Chu and Chen (1984) values and the primary literature. The values in Table 4 differ substantially from the Clement values for DBA, anthracene, pyrene, and noncarcinogenic compounds. For DBA, a TEF of 1 appears to be appropriate for high doses but evaluation of available data indicates that a TEF of 5 is more TABLE 3 TOXICI~

EQUIVALENCY

FACTORS

(TEFS)

PROWSED

PREVIOUSLY

FOR INDIVIDUAL

Compound

Clement (1986)

Chu and Chen (1984)

Benzo[a]pyrene Dibenzo[a,h]anthracene Benzo[a]anthracene Benzo[b]fluoranthene Benzo[k]fluoranthene Indeno(l23-c,d)pyrene Acenaphthene Acenaphthylene Anthracene Benzo[g,h,i]perylene Chrysene Fluoranthene Fluorene 2-Methylnaphthalene Naphthalene Phenanthrene Pyrene

1.1 0.145 0.140 0.066 0.232 ND ND 0.32 0.022 0.0044 ND ND ND ND ND 0.08 1

1 0.69 0.013 0.08 0.004 0.017 ND ND ND ND 0.00 I ND ND ND ND ND ND

PAHS

EPA (1984)

296

NISBET AND LAGOY TABLE 4 PROFQSEDTOXICITY EQUIVALENCY FACTORS (TEFS) FOR INDIVIDUAL PAHS Compound

TEF

Dibenzo[a,h]anthracene Benzo[a]pyrene Benzo[a]anthracene Benzo[b]fluoranthene Benzo[k]fluoranthene Indeno[l23-c,d]pyrene Anthracene Benzo[g,h,i]peryIene Chrysene Acenaphthene Acenaphthylene Fhroranthene Fluorene 2-Methylnaphthalene Naphthalene Phenanthrene Pyrene

5” 1 0.1 0.1 0.1 0.1 0.01 0.01 0.01 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001

a A TEF of 1 appears to be appropriate for high doses of DBA but the TEF of 5 is considered more likely to be applicable to environmental exposures (chemical-related tumor incidence rate of lessthan about 25%).

appropriate for environmental exposures (chemical-related tumor incidence rate of less than 25%). The TEF presented by Clement (1988) for anthracene is based on a single study and other studies suggest that anthracene has only limited carcinogenic potency. We consequently assigned a TEF of 0.0 1 for this compound. For pyrene, the Clement (1988) TEF is based on an elevated tumor incidence in a mid-dose group. No trend toward increasing incidence with increasing dose was observed and other studies suggest that pyrene has little if any cancer potency (Wynder and Hoffman, 1959). Consequently, we assigned a TEF of 0.001 to this compound. Because even PAHs determined to be not carcinogenic by IARC ( 1983), such as phenanthrene, have been shown to have some, albeit limited, carcinogenic activity in some studies (EPA, 199 l), we assign a TEF of 0.001 even to these noncarcinogenic PAHs. DISCUSSION In order to evaluate the adequacy of the TEFs, we compared the expected results using our TEFs with the empirical results of the Schmahl et al. (1977) and Pfeiffer (1977) studies. Tables 5 and 6 present the results of these comparisons. Based on the results of these comparisons, it appears that our TEFs will provide reasonable estimates for mixtures of carcinogenic PAHs but are likely to overestimate cancer potency for groups of noncarcinogenic PAHs. However, both data sets are somewhat limited in that the two most potent PAHs, namely B[a]P and DBA, are responsible for much of the observed response. Table 7 indicates the B[a]P equivalent concentrations determined using the EPA approach (TEF = 1 for all carcinogenic PAHs and TEF = 0 for all noncarcinogenic

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FOR PAHs

TABLE 5 COMPARISONOF DATA FROM THE STUDY BY SCHMAHL et al. (1977) WITH PREDICTIONSBASED ON THE TEF SCHEME PROPOSEDIN THIS PAPER Total dose Group A 1.0 1.7 3.0 Group B 4.0 6.8 12 Group C 65 195 585 1755 Group D 69 117.3 207

Observed incidence @I

Expected incidence * @)

1.7 3

13 28 53

13 28 53

1.9’ 3.3 5.8

31 60 70

32 58 80

0.08 0.24 0.72 2.1

1 0 1 17

2 8 34

2.0 3.5 5.1

49 58 69

34 60 75

B(ahssuiv.’ dose I

0 Calculated using the TEFs in Table 4. * “Expected” incidence is derived from a dose-response curve hand-fitted to the observed data for B[a]P (Group A). A mathematical curve-fitting approach is not appropriate given the low precision of the data set. The expected incidence is given to two significant figures although somewhat lower precision is probably warranted. ‘A TEF of 1 was used for DBA in this evaluation based on the results of studies (Pfeiffer, 1977; Bryan and Shimkin, 1943) that suggest that at incidence rates above approximately 25% for B[a]P, a TEF of 1 more accurately reflects the relative potency of DBA.

PAHs) and our method on some data from a creosote sample collected in southern Mississippi. For this data set our TEFs estimate that risks are about 0.3 times those estimated using the EPA approach. In the EPA calculation, more than half the total activity is attributed to the benzofluoranthenes, which is unreasonable in view of their relatively low potencies in actual bioassays (Table 3). CONCLUSIONS We feel that our TEFs represent an advance over previous approaches for two primary reasons. First, they provide a more accurate representation of the precision (or lack of precision) in the TEFs. Second, because we use only order of magnitude estimates in most cases, it is easier to determine TEFs for other PAHs that may be detected at a particular waste site. For example, we propose TEFs of 0.001 for naphthalene and 2-methylnaphthalene, two of the 17 PAHs commonly detected at hazardous waste sites, based on the limited data available for these compounds and a comparison with data for B[a]P. We feel that the TEFs presented in Table 4 are the most defensible values for PAH relative potency that are currently available and that their use would substantially

298

NISBET AND LAGOY TABLE 6 RESULTS OF THE PFEWFER(1977) STUDY AND EXPECTED INCIDENCEBASED ON TEFs

Total dose Group A Al 3.12 A2 6.25 A3 12.5 A4 25 A5 50 A6 100 Group B Bl 2.35 B2 4.7 B3 9.3 B4 18.7 B5 37.5 B6 75 Group D (A + B) Dl 5.5 D2 11 D3 22 D4 44 D5 88 D6 175 Group C Cl 270 c2 550 c3 1100 c4 2200 c5 4400 C6 8800 Group E (C + D) El 280 E2 560 E3 1120 E4 2240 E5 4500 E6 9000

B(a)P,,,.” dose

Observed incidence (%I

Expected incidenceb 6)

3.1 6.3 12.5 25 50 100

9 35 51 57 77 81

9 35 51 57 77 81

9’ 9’ 9 19 38 75

37 39 44 56 65 79

39 37 37 55 69 79

12 15 22 44 88 175

48 44 61 68 69 79

49 50 58 71 80 85

6 8 6 4 13 5

2 4 9 16 30 49

41 55 61 72 68 82

49 51 60 72 81 85

0.42 0.84 1.7 3.4 6.8 14 13 16 24 47 95 190

’ Calculated using the TEFs in Table 4. b “Expected” incidence is derived from a dose-response curve hand-fitted to the observed data for B[a]P (Group A). A mathematical curve-fitting approach is not appropriate given the low precision of the data set. The expected incidence is given to two significant figures although somewhat lower precision is probably warranted. ’ TEFs of 4 and 2 are used for DBA in the first two entries in this table based on considerations cited in footnote c to Table 5.

reduce the uncertainty in risk assessments involving the PAHs. A certain amount of uncertainty will likely always be associated with evaluation of the toxicity of PAHs because of the infinite number of possible PAH mixtures. The different types or amounts of PAHs in a given mixture can have a profound effect on potency by influencing such factors as bioavailability, competition for binding sites, cocarcinogenic

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FACTORS

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FOR PAHs

TABLE 1 A COMPARISONOF B[u]P-EQUIVALENT CONCENTRATIONSFOR A CREOSOTESAMPLE Measured concentration

Compound Anthracene Benzo[a]anthracene Benzo[b]fluoranthene Benzo[k]fluoranthene Benzo[g,h,i]perylene Benzo[a]pyrene Chrysene Dibenzo[a,h]anthracene Fluoranthene Indeno[l2.%c,d]pyrene Naphthalene Phenanthrene Pyrene B[a]P-equivalents Note.

EPA (1984)

This paper

WlP,ti~

69 28 104 21 10 39 31 5 61 30 10 30 66

515

WP,..

0 28 104 21 0 39 31 5 0 30 0 0 0

0.1 2.8 10.4 2.1 0.1 39 0.4 25 0.1 3 0 0 0.1

210

84

All concentrations in mg/kg.

action, or metabolism. Based on review of two such mixtures (Pfeiffer, 1977; Schmahl et al., 1977) our TEFs are unlikely to underestimate risks but may overestimate risks, particularly for mixtures containing high levels of noncarcinogenic PAHs. Additional toxicological information is available or being developed on individual PAHs and on PAH-containing mixtures and this information should be used to refine the TEF approach for PAHs in the same manner that the TEFs for PCDDs/PCDFs have been refined. REFERENCES BINGHAM, D., AND FALK, H. L. (1969). The modifying effect of carcinogens on the threshold response. Arch. Environ.

Health

19, 119-183.

BRYAN, W. R., AND SHIMKIN, M. B. (1943). Quantitative analysis of dose-response data obtained from three carcinogenic hydrocarbons in strain C3H male mice. J. Nat/. Cancer Inst. 9,984-990. CHU, M. M. L., AND CHEN, C. W. (1984). Evaluation and Estimation of Potential Carcinogenic Risks of Polynuclear Aromatic Hydrocarbons. Paper presented at the Symposium on Polycyclic Aromatic Hydrocarbons in the Workplace, Pacific Rim Risk Conference, Honolulu, HI. Clement Associates, Inc. (Clement) (1988). Comparative Potency Approach for Estimating the Cancer Risk Associated with Exposure to Mixtures of Polycyclic Aromatic Hydrocarbons (Znterim Final Report). Prepared for EPA under Contract 68-02-4403. ICF-Clement Associates, Fairfax, VA, April 1988. DEUTCH-WENZEL, R. P., BRUNE, H., GRIMMER, O., DE~BARN, G., AND MIS~ELD, J. (1983). Experimental studies in rat lungs on the carcinogenicity and dose-response relationships of eight frequently occurring environmental polycyclic aromatic hydrocarbons. J. Natl. Cancer Inst. 71, 539-544. Environmental Protection Agency (EPA) (1980). Ambient Water Quality Criteria for Polynuclear Aromatic Hydrocarbons. EPA 440/5-80-069. Ofice of Water Regulations and Standards, Criteria and Standards Division, Washington, DC, October 1980. Environmental Protection Agency (EPA) (1984). Health Eficts Assessment for Polycyclic Aromatic Hydrocarbons (PAH). EPA 540/l-86-013. Environmental Criteria and Assessment Office, Cincinnati, OH. Environmental Protection Agency (EPA) (199 1). Integrated Risk Information System (ZRZS). ChemicalSpecific

Reference

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Potency

Factors

and EPA

Toxiciology

Background

Documents.

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Office of Health and Environmental Assessment,Environmental Criteria and Assessment Office,Cincinnati, OH. GROVER, P. L., AND SIMS, P. (1968). Enzyme-catalysed reactions of polycyclic hydrocarbons with deoxyribonucleic acid and protein in vitro. Biochem. J 110, l59- 160. HABS, M., SCHMAHL, D.. AND MISFELD, J. (1980). Local carcinogenicity of some environmentally relevant polycyclic aromatic hydrocarbons after lifelong topical application to mouse skin. Arch Geschwulstforsch. 50,266-214. HOFFMANN, D., AND WYNDER, E. L. (1966). Beitrag zur carcinogen Wirkung von Dibenzopyrenen. 2. Krebsforsch. 68, 131- 149. International Agency for Research on Cancer (IARC) (1983). ZARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Vol. 32, Part I. World Health Organization, Lyon, France. LAVOIE, E. J., AMIN, S., HECHT, S. S., FURUYA, K., AND HOFFMANN, D. (1982). Tumour initiating activity of dihydrodiols of benzo[b]fluoranthene, benzo[j]fluoranthene, and benzo[k]fluoranthene. Curcinogenesis 3, 49-52. North Atlantic Treaty Organization (NATO) (1988). Pilot Study on International Information Exchange on Dioxins and Related Compounds. International Toxicity Equivalency Factor (I-TEF) Method of Risk Assessment for Complex Mixtures of Dioxins and Related Compounds. Committee on the Challenges of Modem Society, Report 176, August 1988. PHILLIPS, D. H., GROVER, P. L., AND SIMS, P. (1979). A quantitative determination of the covalent binding of a series of polycyclic hydrocarbons to DNA in mouse skin. Znt. J. Cancer 23,201-208. PFEIFFER,E. H. (1977). Oncogenic interaction of carcinogenic and non-carcinogenic polycyclic aromatic hydrocarbons. In Air Pollution and Cancer in Man (V. Mohr, D. Schmahl, and L. Tomatis, Eds.), IARC Scientific Publication 16. World Health Organization, Lyon, France. POIRIER, K. A., Director, Superfund Health Risk Technical Center, Chemical Mixtures and Assessment Branch, U.S. EPA Office of Research and Development, Cincinnati, OH. [Letter to S. Levinson. U.S. EPA Region I, January 23, 19921. SANTODONATO, J., HOWARD, P., AND BASU, D. (198 1). Health and ecological assessment of polynuclear aromatic hydrocarbons, J. Environ. Pathol. Toxicol. 5, l-365. SCHMAHL, D., SCHMIDT, K. G., AND HABS, M. (1977). Syncarcinogenic action of polycyclic aromatic hydrocarbons in automobile exhaust gas condensates. In Air PolIution and Cancer in Man. (V. Mohr, D. Schmahl, and L. Tomatis, Eds.), IARC Scientific Publication 16. World Health Organization, Lyon, France. THORSLUND. T. W., CHARNLEY, G., AND ANDERSON, E. L. (1986). Innovative Use of Toxicological Data to Improve Cost-Effectivenessof Waste Cleanup. Presented at Superfund ‘86: Management of Uncontrolled Waste Sites. Washington, DC, December l-3, 1986. VAN DUUREN, B. L., SIVAK, A., SEGAL, A., ORRIS, L., AND LANGSETH, L. (1966). The tumor promoting agents of tobacco leaf and tobacco smoke condensate. JNCZ 37,5 19-526. WISLOCKI, P. G., BAGAN, E. S., Lu, A. Y. H., DOOLEY, K. L., Fu, P. P., HAN-HSU, H., BELAND, F. A., AND KADLUBAR, F. F. (1986). Tumorigenicity of nitrated derivatives of pyrene, benz[a]anthracene, chrysene, and benz[a]pyrene in the newborn mouse assay.Carcinogenesis 7, 13 l7- 1322. WYNDER, E. L., AND HOFFMANN, D. (1959). A study of tobacco carcinogenesis. VII. The role of higher polycyclic hydrocarbons. Cancer 12, 1079- 1086.

Toxic equivalency factors (TEFs) for polycyclic aromatic hydrocarbons (PAHs).

The polycyclic aromatic hydrocarbons (PAHs; also referred to as the polynuclear aromatic hydrocarbons or PNAs) are commonly encountered at hazardous w...
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