Page 1 of 14 

Department of Defense Comments on the 

Development of a Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PA

Comments submitted by: Office of the Secretary of Defense Chemical and Material Risk Management Directorate 

 Organization: Department of Defense Date Submitted: 28 October 

*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E); or Other (O). Also please inoutcome, conclusions or implementation of the assessment. 

Comment 

No. Section 

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Comment Suggested Action, R

and References (if ne

1 Global By requiring that the experiments be performed at 

the same time in the same laboratory, EPA is excluding the highest quality data (absent data from human exposure), i.e., the whole animal cancer bioassays by the standard routes of exposure, i.e.,ingestion or inhalation. A logical extension of this 

approach would be to conclude that it is not appropriate to compare the cancer potencies estimated from any of the NTP or other sets of bioassays, as most of them were not conducted concurrently. If such data were not appropriate tocompare and combine, the procedures generally used by Federal regulatory agencies to compare cancer risks and estimate risks from exposure to more than one carcinogen would also not be appropriate. Moreover, as the document is trying to establish the relative cancer potency of the PAHs, it does not seem logical to exclude the cancer potency data for the individual chemicals when theyare available. Finally, the relative potency estimates from the cancer bioassays could be compared to the relative potency estimates from other data, as a good indicator of whether the other data are producing reasonable estimates.

Exclusion of the whole animadata might encourage stakehoindustrial groups that have alrdata quality challenges to do Thus, it is recommended that selection criteria should be mrelative potency factors (RPFsAlternatively, as this documenthe RPFs for carcinogenicity, could recommend that cancer based on bioassay data by throute of exposure be used whspecific data are available, anbe used in their absence. Ththe advantage of making the devergreen, as well as being oan expert review panel that direlated topic of TEFs for dioxi(teleconference of 10/22/09 cVersar on behalf of EPA’s RisForum). Please also note, the cancer bwere used to estimate the RPsuch as intraperitoneal and imare known to differ in their estpotency than those estimated data from oral or inhalation ro
Page 2 of 14 

Department of Defense Comments on the 

Development of a Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PA

Comments submitted by: Office of the Secretary of Defense Chemical and Material Risk Management Directorate 

 Organization: Department of Defense Date Submitted: 28 October 

*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E); or Other (O). Also please inoutcome, conclusions or implementation of the assessment. 

Comment 

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and References (if ne

2 Global The advisory report of EPA’s Science Advisory 

Board (SAB, 2004; Review of EPA's Draft Supplemental Guidance for Assessing Cancer Susceptibility from Early-Life Exposure to Carcinogens - A Report by the Supplemental Guidance for Assessing Cancer Susceptibility Review Panel of the EPA SAB. At: http://yosemite.epa.gov/sab/sabproduct.nsf/WebReportsbyYearBOARD!OpenView&Start=1&Count=800&Expand=6#6 ) criticized the use of simple cancer potency ratios, i.e., as estimated by q1*, for relative potency estimates. In response, EPA developed a model for determining the relative potency of cancer data for its 2005 supplemental guidance to the cancer guidelines. This model is available on EPA’s web site and was programmed in R, freeware also available on the internet. Use of this model wouldallow stakeholders to perform analyses that use different data, e.g., to see if use of the whole animals bioassays excluded from EPA’s current analyses would change the RPFs.

Given the amount of analyses this document, it would seem use the more accurate relative estimate model already develhttp://epa.gov/cancerguidelineanalyses.htm ). To quote from report: “Even assuming a full by Halmes et al. (2000) is not computation of the relative slofor juveniles and adults could on the log-scale rather than t

scale. Since most models for incidence for tumor onset assform that includes an exponenfunction, changes in the pointa fixed risk would better be recomparison of log-transformeis as follows: P(dose)=1-[1-P(0)]exp(-slopeHence {log[1-P(0)]-log[1-P(dose)]}/do ... For small P(dose) and smformula is approximately equamedium range P(dose) as we equations are not the same. T
Page 3 of 14 

Department of Defense Comments on the 

Development of a Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PA

Comments submitted by: Office of the Secretary of Defense Chemical and Material Risk Management Directorate 

 Organization: Department of Defense Date Submitted: 28 October 

*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E); or Other (O). Also please inoutcome, conclusions or implementation of the assessment. 

Comment 

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transformation is nonlinear ratios will be different [emph

3 Global While the points of departure (PODs) for many of 

the analyses are the ED10, as noted in the comments on Appendix E, some of the PODs from point estimates appear to use much higher response levels, i.e., above the ED50. If this is an 

accurate interpretation of the analysis, a linear extrapolation to low dose levels can not be used, as this is a response level below which a “low level linear” dose-response function can not be expected.

If this interpretation of the anathe document should be editeinterpretation. If the interpretathe analyses should be changRPFs reestimated. 

4 Executive 

Summary 

Pg. iv Para. 1 See also comments for section 2.8 

The actual requirements of using EPA’s dose-additive model (as described in the 1986 guidelines; Guidelines for Carcinogen Risk Assessment. U.S. Environmental Protection Agency, Risk Assessment Forum, Washington, DC, 1986, at: 

http://epa.gov/cancerguidelines/guidelines-carcinogenrisk-assessment-1986.htm) are that the chemicals have the same mechanism of action; that they act as lower concentrations of the index chemical; that they do not interact toxicologically; and that (for the mathematical derivation to work as presented) the log(dose)-response curves must be parallel. [The latter requirement also requires that the chemicalshave the same efficacy, e.g., the same maximal response.] The guidelines allow for approximations, 

The document should be corrstate that these are approximoften used in lieu of the stringmathematical requirements of 
Page 4 of 14 

Department of Defense Comments on the 

Development of a Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PA

Comments submitted by: Office of the Secretary of Defense Chemical and Material Risk Management Directorate 

 Organization: Department of Defense Date Submitted: 28 October 

*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E); or Other (O). Also please inoutcome, conclusions or implementation of the assessment. 

Comment 

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such as those stated in this document, but the actual requirements are more stringent. Please note: the assumption about dose-response curves is consistent with EPA’s SAB’s recommendation to perform the analysis using an exponentiated dose function. 

5 Executive 

Summary 

Pg. iv Para. 1 

These assumptions are not equivalent to additivity.When these conditions are present, additivity of various types may be used, but so may other models,

including dose-additivity within the dose-response function to generate a dose-response surface (as mentioned in one reference in the text, but which is also recommended by a number of experts in the riskassessment of mixtures of chemicals). 

The documents should be corthese approximations allow thdose additivity and the RPF m

6 Executive 

Summary 

Pg. iv Para. 1 See also comments for section 2.8 

The assumption of lack of interaction at low levels is often made, but ignores the possibility of one of the chemicals being a strong antagonist. While this may be a reasonable regulatory assumption, its limitations have been demonstrated experimentally with mixturesof chemicals that are similar. 

Change to state that it is a rearegulatory assumption to be 

7 Executive 

Summary 

Pg. v Para. 2 See also comments for section 2.8 

Studies of defined PAH mixtures should not be excluded, as these will demonstrate the limitations of the method. In particular, such studies of similarchemicals often demonstrate that the dose-response curve of the mixture differs significantly from that of the index chemical, e.g., does not have the same slope and/or is not equally efficacious.

Available data on mixtures of composition should be added estimate uncertainty, quantita
Page 5 of 14 

Department of Defense Comments on the 

Development of a Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PA

Comments submitted by: Office of the Secretary of Defense Chemical and Material Risk Management Directorate 

 Organization: Department of Defense Date Submitted: 28 October 

*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E); or Other (O). Also please inoutcome, conclusions or implementation of the assessment. 

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8 Executive 

Summary 

Pg. vi Para. 1stbullet See also comments on Appendix G 

While simultaneous testing of BaP and other PAHs ispreferable, excluding other assays, especially in vivo

studies, seems excessively restrictive. 

If no other data are available for that endpoint, it would seereasonable to use the data winotation that the estimate is liaccurate. If the less reliable dwhen all data are considered can be discarded later. 

9 Executive 

Summary 

Pg. vi Para. 5thbullet and 3rd

Paragraph See also comments on Appendix G 

Even when tumor incidence is 90% or greater, it is not clear that multiplicity of tumors is informative. Though tempting to use such data (as dose-response assessment for such data is of questionable relevance), an increase in tumors with dose in a target organ is generally only used to increase the qualitative weight of evidence for carcinogenicity. These data should not be used quantitatively without further justification. 

Use of multiplicity of tumors fodose-response estimates is npractice and should be justifiethese data should not be used 

10 2.4 Pg. 34 

Fig 2-3 

It is not clear whether this figure is proposing one 

mode of action that requires all of the key events in the figure, or several potential modes of action that may require one or more of the branches. If this is all one 

mode of action, does EPA anticipate that all pathways are active at all doses, or might different pathways be 

active at different dose levels (cf. discussion on pg 42 line 17 and following text)? 

Please clarify these issues. Passumed to have a mutagenic was so named in EPA’s suppguidance (U.S. EPA. Supplemfor Assessing Susceptibility frExposure to Carcinogens. U.SProtection Agency, WashingtoEPA/630/R-03/003F, 2005) ancarcinogenic PAHs by EPA’s memos (Communication II: PeAssessments that include CaDescribed in the Supplementahaving a Mutagenic Mode of A
Page 6 of 14 

Department of Defense Comments on the 

Development of a Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PA

Comments submitted by: Office of the Secretary of Defense Chemical and Material Risk Management Directorate 

 Organization: Department of Defense Date Submitted: 28 October 

*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E); or Other (O). Also please inoutcome, conclusions or implementation of the assessment. 

Comment 

No. Section 

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and References (if ne

http://www.epa.gov/osa/spc/punication_ii.pdf). In this casekey events posited in Figure 2assumed and should be proveframework in EPA’s cancer gu

11 2.4 Pg. 39 Okey et al. (1994) is not in the reference list. Add to reference list. 12 2.4 Pg. 40 

Line 29 

Please define “linear,” as many mathematically accurate definitions exist, e.g., straight line, linearly proportional to, and each variable existing only once for each power in the reduced form of the equation (i.e., the Hill equation is inherently nonlinear by this last definition). 

Please define “linear” here andifferently elsewhere, at all poused. Alternatively, only use linear in the document and use.g., a straight line, for other c

13 2.4 Pg. 42 

Line 25 

This paragraph asserts that there may be many MOAs for PAHs. While not questioning that conclusion, none of the MOAs are discussed using the framework in EPA’s 2005 cancer guidelines (U.S. EPA. Guidelines for Carcinogen Risk Assessment (2005). U.S. Environmental Protection Agency, Washington, DC, EPA/630/P-03/001F, 2005) – or any other framework.

As such, the MOAs can not be considered to have been determined or established, as recognized by the 

normal procedures. Simply asserting an MOA does not make it so. This is surprising, as the data are likely 

to exist to do so. 

Use EPA’s 2005 cancer guidedetermining a mode of action carcinogenesis, and present twith their MOA framework. 

14 2.4 Pg. 42 No logic or data are provided for selecting the 

“primary mode of carcinogenic action.” Given the 

Selection of a primary mode oor some exposure conditions 
Page 7 of 14 

Department of Defense Comments on the 

Development of a Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PA

Comments submitted by: Office of the Secretary of Defense Chemical and Material Risk Management Directorate 

 Organization: Department of Defense Date Submitted: 28 October 

*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E); or Other (O). Also please inoutcome, conclusions or implementation of the assessment. 

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Line 26 previous paragraph, it is also likely that the MOA 

may change with dose. If this is the primary MOA, it 

is not clear whether it is for the rodent bioassay, the human exposures, all exposure levels and routes, or

some other exposure(s). Determining an MOA is the primary step in choosing a linear or nonlinear extrapolation for lower doses. Moreover, if different MOAs primarily act at different levels of exposure,

the logic for extrapolating from a high-dose MOA toa low-dose MOA should be presented, as the doseresponse functions are likely to vary substantially. 

than a simple assertion in one Please provide the data and lassertion, the conditions of exit is deemed appropriate shouprovided. The data and logic other potential MOAs are not primary should be discussed 

15 2.4 Pg. 53 

 Line 4 

The citation of USEPA 2009 is not in the reference list. The entry for BaP states that the last revision was 12/10/1998; for benz[a]anthracene, 04/01/1997. 

Nor is there any such action mentioned for 2009 at 

http://www.epa.gov/ncea/iris/recent.htm. EPA’s 

Office of the Science Advisor issued an implementation memo on June 14, 2006 addressing the use of PAHs using the 1993 provisional guidance, which is cited in the document. The reference lists the citation as 2008, but a search of that year in the url above as well as a search of the 75 results for a search of the IRIS site for “Polycyclic Aromatic Hydrocarbons” also did not disclose this reference. 

As such a document would be an analysis of this document, citation, with a more specific uIRIS internet site, should be pMoreover, it would be useful tinformation on the authors anthis PAH document. 

16 2.8 Global Although the Executive Summary states that data 

from complex mixtures will not be used, the main document uses such data, e.g., in this section. References are also made throughout the document 

Throughout the document, the modified to state that mixtures to estimate the RPFs quantitaimportantly, the document sho
Page 8 of 14 

Department of Defense Comments on the 

Development of a Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PA

Comments submitted by: Office of the Secretary of Defense Chemical and Material Risk Management Directorate 

 Organization: Department of Defense Date Submitted: 28 October 

*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E); or Other (O). Also please inoutcome, conclusions or implementation of the assessment. 

Comment 

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and References (if ne

to studies where complex mixtures support their analyses, e.g., section 4.2 that includes epidemiological studies. 

those studies of mixtures of csimilar mechanism of action wdose- nor response-additivity 

17 2.8 Pg. 46 

Line 30 

The sentence regarding dose additivity that begins at the end of this line is illogical. If binary mixtures of PAHs “can exhibit antagonism, synergism, or additivity...” more complex mixtures must also exhibit all of these interactions. Indeed there are 

examples of such in the literature. Dose additivity of PAHs is a reasonable, regulatory assumption as a screening method – but it is not accurate. 

It is recommended that the indthat begins this sentence be msuggestion is, “It is reasonablfor regulatory, screening assePAHs are additive,...” 

18 4.1 Pg. 60-61 

Line 28 and following text 

It is unclear why mutagenicity, and not AhR binding, is considered relevant for estimating RPFs when a previous section (2.6) discussed that the receptor binding correlated better than mutagenicity with the cancer bioassays. If the RPFs are to vary with dose, e.g., by using the dose-response surface model proposed, as mentioned on page 48, line 27, or if the document were to propose different RPFs for different MOAs that occur at different doses, the use of mutagenicity at lower doses might be able tobe justified, after the MOAs were established and the approximate dose ranges for the MOAs estimated. Finally, it would appear that mutationswould be an indicator of dose and should use dose additivity, rather than response additivity. Many of 

the attempts to relate mutagenic potency with carcinogenic potency have demonstrated that this is

not a simple correlation. 

Although mutagenicity is a caendpoint, its selection for comcomparing directly with tumor logical inconsistency that shoThere are several ways that thaccomplished, e.g., by determthat relates mutagenic potenccarcinogenic potency, and it is RPFs would need to be recalcUse of the AhR binding data wrequire use of a nonlinear extstandard receptor-binding datnonlinear (e.g., Simon et al., 2

http://toxsci.oxfordjournals.org2 ). Finally, the logic for using additivity rather than dose addmutagenicity as a precursor to be justified, i.e., in contrast to 
Page 9 of 14 

Department of Defense Comments on the 

Development of a Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PA

Comments submitted by: Office of the Secretary of Defense Chemical and Material Risk Management Directorate 

 Organization: Department of Defense Date Submitted: 28 October 

*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E); or Other (O). Also please inoutcome, conclusions or implementation of the assessment. 

Comment 

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mutagenicity as an endpoint bparticular, if EPA believes thaspecific mutations required focarcinogenicity, it would seem that a stochastic process is ocone of the assumptions for re

19 4.3 Pg. 89 

Para. 1 

Positive studies that did not follow the criteria for 

excluding negative studies should also be excluded from the quantitative analysis. The same reasoning

used to exclude the negative studies for quantitative 

analysis should exclude the positive studies from use quantitatively. In particular, if the animals wereobserved for less than 6 month and were positive, the 

potency estimate from these studies is likely to vary from the potency estimate that would be estimated from a two-year bioassay, i.e., the tumor incidence

would be expected to increase with increased exposure time. Even if a time-to-tumor analysis were used, the estimated potency from a longer study might produce a different cancer potency factor. Thus, such positive studies also should be only used for a weight 

of evidence determination, as they would be unlikely to 

fulfill the conditions for estimating a slope factor and therefore, the associated RPF. 

Either clarify that these positivnot used quantitatively, or re-eRPFs without them as one meuncertainty analysis. 
Page 10 of 14 

Department of Defense Comments on the 

Development of a Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PA

Comments submitted by: Office of the Secretary of Defense Chemical and Material Risk Management Directorate 

 Organization: Department of Defense Date Submitted: 28 October 

*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E); or Other (O). Also please inoutcome, conclusions or implementation of the assessment. 

Comment 

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20 5.1 Pg. 107 

Line 5 

Although use of number, i.e., multiplicity, of tumors is 

“discussed in Section 4.3,” neither there nor here is the 

rationale for the use of these data (other than that they 

exist) explained or referenced. Indeed, the second

paragraph (line 15) states that, in many cases, incidence and multiplicity were either not correlated or 

inversely correlated. Justification for the use of these data should be supplied. 

Use of multiplicity or tumors foanalysis of potency is a non-sprocedure. As stated in this dhave generally shown multipliunreliable estimate of potencyshould not be used. 

21 8.5 Pg. 209 

2nd paragraph

Chemicals with a similar mode of action should be combined by dose additive methods according to EPA’s mixtures guidelines and guidance. Use of response additivity for chemicals with similar modes of action seems contrary to the assumption in that model that the chemicals act independently. 

The use of response addition with a similar mode of action explanation, especially with reguidelines and guidance on ththe document assumes a linemodel, the results are identicaNevertheless, the appropriate models should be identified a

22 8.5 Pg. 209 

Last paragraph 

No data will ever completely support the assumption of 

additivity, as it is a useful model that is sufficiently 

accurate for some purposes under some sets of conditions. 

This paragraph should be rewthe reality of models rather thunrealistic ideal that may raise that can not be met. 

23 Appendix D General It appears that most of these runs were performed in 

2005. The software has been modified since then. Would this make a difference in the result, especially with regard to whether the lower confidence limit is actually a two-sided, 95% confidence limit? 

If the changes in the software the results, the data should be 
Page 11 of 14 

Department of Defense Comments on the 

Development of a Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PA

Comments submitted by: Office of the Secretary of Defense Chemical and Material Risk Management Directorate 

 Organization: Department of Defense Date Submitted: 28 October 

*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E); or Other (O). Also please inoutcome, conclusions or implementation of the assessment. 

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24 Appendix E Pg. E-2 Relative potency usually is defined as the ratio of the 

doses required to produce the same effect. Given that the analyses were such that a dose to produce an equivalent effect, e.g., a BMR of 0.1, was always estimated, the ratio of those doses can and should be 

used without further calculation. 

Unnecessary conversions obfand in this case, the results ssame. 

25 Appendix E Pg. E-2 Hoffmann and Wynder and other such studies in the 

table should not be used. EPA’s cancer guidelines allow the combination of cancers with papillomas, but 

papillomas alone are not considered a positive response for cancer. 

Recommend deleting these danalysis. Given the wealth of reason to use marginal data, on page E-3 where the type(s“unspecified”. 

26 Appendix E Pg. E-2 LaVoie et al.: The same method should be used to 

calculate the doses for all of the chemicals in one

analysis. In this case, three of the chemicals used a point estimate, and presumably the BMR for the fourth 

(which required dropping the highest dose to get this 

method to work) was also not a very good fit. Changing the method by which the doses are estimated within one study is likely to add unnecessary 

uncertainty. Also, the use of a linear extrapolation at low dose

levels is violated in some of the estimates made in this 

document. These data appear to have been extrapolated from a greater than 80% response level, 

a response level below which a “low level linear” doseresponse function can not be expected.

We suggest changing the calcThe RPF needs to be estimatresponse level. Using a straigextrapolation to the origin can from low BMRs, e.g., 10% or cancer slope factor, i.e., the pincorrectly estimated, as will tpotency. 
Page 12 of 14 

Department of Defense Comments on the 

Development of a Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PA

Comments submitted by: Office of the Secretary of Defense Chemical and Material Risk Management Directorate 

 Organization: Department of Defense Date Submitted: 28 October 

*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E); or Other (O). Also please inoutcome, conclusions or implementation of the assessment. 

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27 Appendix E Pg. E-5 As stated previously, multiplicity of tumors is not a 

standard method for quantifying cancer potency. Even 

if this were a standard method, the process for detecting the number of tumors would need to be vetted. Even for skin tumors, small tumors may be missed, or tumors that have grown together may be incorrectly counted. Again, as most of these tumors 

are only papillomas or unspecified, these data should not be used anyway. Moreover, it appears that someof the data, e.g., Cavalieri et al.,1983, appear to be used for both methods, thus double-counting and overweighting these data. 

It is recommended that Table eliminated, and the data not ucalculating RPFs. 

28 Appendix F Pg. “G-1” The page number incorrect. The page number should be c29 Appendix G Pg. G-1 

Line 28 

By requiring that the experiments be performed at the 

same time in the same laboratory, EPA is excluding the highest quality data, i.e., the whole animal cancer 

bioassays. Moreover, a logical extension of this approach would be to state that it is not appropriate to compare the cancer potencies estimated from any of the NTP or other sets of bioassays as most of them were not conducted concurrently (as discussed in Comment #1). 

This criterion for exclusion of changed, at a minimum for thbioassays. As suggested befmethod should only be used achemical-specific potencies. chemical-specific data are avapreferable to a model that, whmore uncertainties and assumin its use. 
Page 13 of 14 

Department of Defense Comments on the 

Development of a Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PA

Comments submitted by: Office of the Secretary of Defense Chemical and Material Risk Management Directorate 

 Organization: Department of Defense Date Submitted: 28 October 

*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E); or Other (O). Also please inoutcome, conclusions or implementation of the assessment. 

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30 Appendix G Pg. G-3 

Line 3 

Data from newborn animals should not be used in estimating RPFs, as EPA’s 2005 supplemental guidance demonstrates that newborns react to these chemicals differently than the adults. These data might be able to be used to estimate different cancer potency for exposures to younger animals, as stated in EPA’s 2005 cancer guidelines and supplemental guidance. 

It is recommended that such deliminated from the RPF calcuother data are available, the rshould have an accompanyin

31 Appendix G Pg. G-6 

Line 18 and text following 

This statement is puzzling, given that a quick PubMed 

search turned up the following citation for heterocyclic amines (HAs): Bogen KT 1994. Food Chem Toxicol. 32(6):505-15. The abstract states, “Thus, in addition to 

82 tumor-type-specific potencies estimated for these compounds, 24 additional estimates of aggregate potency (to induce one or more tumor types) were made, using different methods to scale estimated bioassay cancer potency to humans. The currently unknown potency of an additional cooked-food HA was estimated using linear regressions of logcarcinogenic on log-mutagenic potency for the other10 HAs, some of which were highly significant (e.g. r = 

0.85, P < 0.004).” Also missing are citations from

several studies that found no or limited correlations between cancer potency and mutagenic potency, including one by the National Academies. 

A more complete data search Negative studies should also 

32 G-2 Pg. G-6 This section could have been significantly reduced 

by consulting a special issue of Mutation Research (March 1992) that addressed it.