Variability in PAH-DNA Adduct Measurements in Peripheral Mononuclear Cells: Implications for Quantitative Cancer Risk Assessment

Biomarkers such as DNA adducts have significant potential to improve quantitative risk assessment by characterizing individual differences in metabolism of genotoxins and DNA repair and accounting for some of the factors that could affect interindividual variation in cancer risk. Inherent uncertainty in laboratory measurements and within-person variability of DNA adduct levels over time are putatively unrelated to cancer risk and should be subtracted from observed variation to better estimate interindividual variability of response to carcinogen exposure. A total of 41 volunteers, both smokers and nonsmokers, were asked to provide a peripheral blood sample every 3 weeks for several months in order to specifically assess intraindividual variability of polycyclic aromatic hydrocarbon (PAH)-DNA adduct levels. The intraindividual variance in PAH-DNA adduct levels, together with measurement uncertainty (laboratory variability and unaccounted for differences in exposure), constituted roughly 30% of the overall variance. An estimated 70% of the total variance was contributed by interindividual variability and is probably representative of the true biologic variability of response to carcinogenic exposure in lymphocytes. The estimated interindividual variability in DNA damage after subtracting intraindividual variability and measurement uncertainty was 24-fold. Inter-individual variance was higher (52-fold) in persons who constitutively lack the Glutathione S-Transferase M1 (GSTM1) gene which is important in the detoxification pathway of PAH. Risk assessment models that do not consider the variability of susceptibility to DNA damage following carcinogen exposure may underestimate risks to the general population, especially for those people who are most vulnerable.     

Risk Assessment for Aflatoxin: III. Modeling the Relative Risk of Hepatocellular Carcinoma

Estimates have been made of the cancer potency of aflatoxin exposure among the U.S. population. Risk modeling is used to assess the dose-response relationship between aflatoxin exposure and primary liver cancer, controlling for hepatitis B virus (HBV), based on data provided by the Yeh et al. study in China. A relative risk model is proposed as a more appropriate alternative to the additive ("absolute" risk) model for transportation of risk coefficients between populations with different baseline rates. Several general relative risk models were examined; the exponential model provided the best fit. The Poisson regression method was used to fit the relative risk model to the grouped data. The effects of exposure to aflatoxin (AFB1) and hepatitis B infection were both found to be statistically significant. The risk of death from liver cancer for those exposed to AFB1 relative to the unexposed population, increases by 0.05% per ng/kg/day exposure of AFB1 (p less than 0.001). The results also indicated a 25-fold increase in the risk of death from liver cancer among those infected with hepatitis B virus, relative to noncarriers (p less than 0.0001). With a hepatitis prevalence rate of 1%, the aflatoxin intake level associated with liver cancer lifetime excess risk of 1 x 10(-5) for the U.S. population was estimated as 253 ng/day, based on a liver cancer baseline rate of 3.4/100,000/yr.     

An Interagency Comparison of Screening-Level Risk Assessment Approaches

Approaches to risk assessment have been shown to vary among regulatory agencies and across jurisdictional boundaries according to the different assumptions and justifications used. Approaches to screening-level risk assessment from six international agencies were applied to an urban case study focusing on benzo[a]pyrene (B[a]P) exposure and compared in order to provide insight into the differences between agency methods, assumptions, and justifications. Exposure estimates ranged four-fold, with most of the dose stemming from exposure to animal products (8-73%) and plant products (24-88%). Total cancer risk across agencies varied by two orders of magnitude, with exposure to air and plant and animal products contributing most to total cancer risk, while the air contribution showed the greatest variability (1-99%). Variability in cancer risk of 100-fold was attributed to choices of toxicological reference values (TRVs), either based on a combination of epidemiological and animal data, or on animal data. The contribution and importance of the urban exposure pathway for cancer risk varied according to the TRV and, ultimately, according to differences in risk assessment assumptions and guidance. While all agency risk assessment methods are predicated on science, the study results suggest that the largest impact on the differential assessment of risk by international agencies comes from policy and judgment, rather than science.     

Does Medical Risk Perception and Risk Taking Change with Age?

Across adulthood, people face increasingly more risky medical problems and decisions. However, little is known about changes in medical risk taking across adulthood. Therefore, the current cross‐sectional study investigated age‐related differences in medical risk taking with N = 317 adults aged 20–77 years using newly developed scenarios to assess medical risk taking, and additional measures designed to evaluate risk‐taking behavior in the medical domain. Greater expected benefits on the Domain‐Specific Risk‐Taking Scale—Medical (DOSPERT‐M) predicted more active risk taking, whereas higher perceived risk predicted less active risk taking. Next, we examined differences in active and passive risk taking, where passive risk taking refers to risk taking that is associated with inaction. Age was associated with less passive risk taking, but not with active risk taking, risk perception, or expected benefits on the DOSPERT‐M. Participants were overall more likely to opt for taking medical action than not, even more so for a scenario about a vaccine for a deadly flu than for a scenario about a chemotherapy treatment for cancer. Overall, participants were more likely to accept medication (vaccine or chemotherapy) for their child than for themselves. Increasing age was associated with a lower likelihood of accepting the treatment or vaccine for oneself. Taken together, our study provides important insights about changes in medical risk taking across adulthood when people face an increasing number of complex and risky medical decisions.     

Agreement Between Scales in the Measurement of Breast Cancer Risk Perceptions

The objective of this article is to compare the accuracy and numeric responses of breast cancer risk perception as measured by a frequency scale and percentage scale. A cross-sectional survey was conducted. Perceptions of five-year and lifetime breast cancer risk were measured using a frequency and a percentage scale. Estimation error was calculated as the absolute difference between actual breast cancer risk as determined by the Gail model and perceived risk. Agreement between scales was determined by calculating the mean and standard deviation of the difference between numeric responses. The study was conducted among women enrolled in two primary care clinics associated with an academic medical center. Two-hundred-fifty-four participants were recruited from one of the two participating internal medicine clinics. Inclusion criteria included female gender and age 40-84 years. Exclusion criteria included a history of breast cancer, dementia, or a life expectancy of less than two years. The frequency scale was more accurate than the percentage scale in estimating lifetime risk (p= 0.05), but less accurate in estimating five-year risk (p < 0.02). Only 79 participants (31%) were considered consistent scale users, providing identical responses when using the frequency and percentage scale for a given risk estimate. Although the mean difference (percentage-frequency scale) for estimates of breast cancer lifetime risk was only 2.4, the empirically determined 90% limits of agreement between the frequency and percentage scale for lifetime risk were wide, from -30 to 40. Higher numeracy was associated with consistent use of scales (OR 1.61, 95% CI; 1.09-2.37). We report disagreement in breast cancer risk perceptions when measured by a frequency and a percentage scale. The accuracy and direction of bias associated with each scale varies according to the time frame of risk being assessed.     

A dose-response analysis of skin cancer from inorganic arsenic in drinking water

A study of the prevalence of skin cancer among 40,421 persons consuming arsenic-contaminated drinking water in Taiwan was used for a cancer dose-response assessment of ingested arsenic. The numbers of persons at risk over three dose intervals and four exposure durations were estimated from the data in order to apply the method of maximum likelihood to a multistage-Weibull time/dose-response model. A constant exposure level since birth for each of the exposure categories was assumed. It was found that the cumulative hazard increases as a power of three in age, and is linear or quadratic (with a linear coefficient) in dose. Observations from a smaller epidemiologic survey in Mexico were similar to what would be predicted from the model of the Taiwan data. Assuming that the skin cancer risk from ingested arsenic in the American population would also be similar to the Taiwan population, an American male would have a lifetime risk of developing skin cancer of 1.3 x 10(-3) (3.0 x 10(-3] if exposed to 1 microgram/kg/day for a 76-year lifespan (median lifespan in the U.S.).     

An Improved Approximation to the Exact Solution of the Two-Stage Clonal Growth Model of Cancer

Multistage clonal growth models are of interest for cancer risk assessment because they can explicitly incorporate data on cell replication. Both approximate and exact formulations of the two stage growth model have been described. The exact solution considers the conditional probability of tumors arising in previously tumor-free animals; the approximate solution estimates total probability of tumor formation. The exact solution is much more computationally intensive when time-dependent cell growth parameters are included. The approximate solution deviates from the exact solution at high incidences and probabilities of tumor. This report describes a computationally tractable,'improved approximation'to the exact solution. Our improved approximation includes a correction term to adjust the unconditional expectation of intermediate cells based on the time history of formation of intermediate cells by mutation of normal cells (recruitment) or by cell division in the intermediate cell population (expansion). The improved approximation provided a much better match to the exact solution than the approximate solution for a wide range of parameter values. The correction term also appears to provide insight into the biological factors that contribute to the variance of the expectation for the number of intermediate cells over time.     

Potential Exposure and Cancer Risk from Formaldehyde Emissions from Installed Chinese Manufactured Laminate Flooring

Lumber Liquidators (LL) Chinese‐manufactured laminate flooring (CLF) has been installed in >400,000 U.S. homes over the last decade. To characterize potential associated formaldehyde exposures and cancer risks, chamber emissions data were collected from 399 new LL CLF, and from LL CLF installed in 899 homes in which measured aggregate indoor formaldehyde concentrations exceeded 100 μg/m³ from a total of 17,867 homes screened. Data from both sources were combined to characterize LL CLF flooring‐associated formaldehyde emissions from new boards and installed boards. New flooring had an average (±SD ) emission rate of 61.3 ± 52.1 μg/m²‐hour; >one‐year installed boards had ∼threefold lower emission rates. Estimated emission rates for the 899 homes and corresponding data from questionnaires were used as inputs to a single‐compartment, steady‐state mass‐balance model to estimate corresponding residence‐specific TWA formaldehyde concentrations and potential resident exposures. Only ∼0.7% of those homes had estimated acute formaldehyde concentrations >100 μg/m³ immediately after LL CLF installation. The TWA daily formaldehyde inhalation exposure within the 899 homes was estimated to be 17 μg/day using California Proposition 65 default methods to extrapolate cancer risk (below the regulation “no significant risk level” of 40 μg/day). Using a U.S. Environmental Protection Agency linear cancer risk model, 50th and 95th percentile values of expected lifetime cancer risk for residents of these homes were estimated to be 0.33 and 1.2 per 100,000 exposed, respectively. Based on more recent data and verified nonlinear cancer risk assessment models, LL CLF formaldehyde emissions pose virtually no cancer risk to affected consumers.     

Risk assessment of banknotes as a fomite of SARS-CoV-2 in cash payment transactions

The COVID 19 pandemic has triggered concerns and assumptions globally about transmission of the SARS-CoV-2 virus via cash transactions. This paper assesses the risk of contracting COVID-19 through exposure to SARS-CoV-2 via cash acting as a fomite in payment transactions. A quantitative microbial risk assessment was conducted for a scenario assuming an infectious person at the onset of symptoms, when virion concentrations in coughed droplets are at their highest. This person then contaminates a banknote by coughing on it and immediately hands it over to another person, who might then be infected by transferring the virions with a finger from the contaminated banknote to a facial mucous membrane. The scenario considered transfer efficiency of virions on the banknote to fingertips when droplets were still wet and after having dried up and subsequently being touched by finger printing or rubbing the object. Accounting for the likelihood of the scenario to occur by considering (1) a local prevalence of 100 COVID-19 cases/100,000 persons, (2) a maximum of about one-fifth of infected persons transmit high virus loads, and (3) the numbers of cash transactions/person/day, the risk of contracting COVID-19 via person-to-person cash transactions was estimated to be much lower than once per 39,000 days (107 years) for a single person. In the general populace, there will be a maximum of 2.6 expected cases/100,000 persons/day. The risk for a cashier at an average point of sale was estimated to be much less than once per 430 working days (21 months). The depicted scenario is a rare event, therefore, for a single person, the risk of contracting COVID-19 via person-to-person cash transactions is very low. At a point of sale, the risk to the cashier proportionally increases but it is still low.     

Could Removing Arsenic from Tobacco Smoke Significantly Reduce Smoker Risks of Lung Cancer?

If a specific biological mechanism could be determined by which a carcinogen increases lung cancer risk, how might this knowledge be used to improve risk assessment? To explore this issue, we assume (perhaps incorrectly) that arsenic in cigarette smoke increases lung cancer risk by hypermethylating the promoter region of gene p16INK4a, leading to a more rapid entry of altered (initiated) cells into a clonal expansion phase. The potential impact on lung cancer of removing arsenic is then quantified using a three‐stage version of a multistage clonal expansion (MSCE) model. This refines the usual two‐stage clonal expansion (TSCE) model of carcinogenesis by resolving its intermediate or “initiated” cell compartment into two subcompartments, representing experimentally observed “patch” and “field” cells. This refinement allows p16 methylation effects to be represented as speeding transitions of cells from the patch state to the clonally expanding field state. Given these assumptions, removing arsenic might greatly reduce the number of nonsmall cell lung cancer cells (NSCLCs) produced in smokers, by up to two‐thirds, depending on the fraction (between 0 and 1) of the smoking‐induced increase in the patch‐to‐field transition rate prevented if arsenic were removed. At present, this fraction is unknown (and could be as low as zero), but the possibility that it could be high (close to 1) cannot be ruled out without further data.     

Improving the Regulation of Carcinogens by Expediting Cancer Potency Estimation1

The statutory language of the Safe Drinking Water and Toxic Enforcement Act of 1986 (Proposition 65; California Health and Safety Code 25249.5 et seq.) encourages rapid adoption of “no significant risk levels” (NSRLs), intakes associated with estimated cancer risks of no more than 1 in 100,000. Derivation of an NSRL for a carcinogen listed under Proposition 65 requires the development of a cancer potency value. This paper discusses the methodology for the derivation of cancer potencies using an expedited procedure, and provides potency estimates for a number of agents listed as carcinogens under Proposition 65. To derive expedited potency values, default risk assessment methods are applied to data sets selected from an extensive tabulation of animal cancer bioassays according to criteria used by regulatory agencies. A subset of these expedited values is compared to values previously developed by regulatory agencies using conventional quantitative risk assessment and found to be in good agreement. Specific regulatory activities which could be facilitated by adopting similar expedited procedures are identified.     

Aging and Cardiometabolic Risk in European HEMS Pilots: An Assessment of Occupational Old‐Age Limits as a Regulatory Risk Management Strategy

Old‐age limits are imposed in some occupations in an effort to ensure public safety. In aviation, the “Age 60 Rule” limits permissible flight operations conducted by pilots aged 60 and over. Using a retrospective cohort design, we assessed this rule's validity by comparing age‐related change rates of cardiometabolic incapacitation risk markers in European helicopter emergency medical service (HEMS) pilots near age 60 with those in younger pilots. Specifically, individual clinical, laboratory, and electrocardiogram (ECG)‐based risk markers and an overall cardiovascular event risk score were determined from aeromedical examination records of 66 German, Austrian, Polish, and Czech HEMS pilots (average follow‐up 8.52 years). Risk marker change rates were assessed using linear mixed models and generalized additive models. Body mass index increases over time were slower in pilots near age 60 compared to younger pilots, and fasting glucose levels increased only in the latter. Whereas the lipid profile remained unchanged in the latter, it improved in the former. An ECG‐based arrhythmia risk marker increased in younger pilots, which persisted in the older pilots. Six‐month risk of a fatal cardiovascular event (in or out of cockpit) was estimated between 0% and 0.3%. Between 41% and 95% of risk marker variability was due to unexplained time‐stable between‐person differences. To conclude, the cardiometabolic risk marker profile of HEMS pilots appears to improve over time in pilots near age 60, compared to younger pilots. Given large stable interindividual differences, we recommend individualized risk assessment of HEMS pilots near age 60 instead of general grounding.     

Perceived physical work capacity, stress, sleep disturbance and occupational accidents among firefighters working during a strike

Fire-fighting and rescue work are arranged in such a way that various kinds of accidents and catastrophes can be handled. In an understaffed situation, such as a strike, this goal may not be met. The objective of this study was to investigate factors associated with perceived physical work capacity, stress, sleep disturbance, and occupational accidents among firefighters who remained at work during an extended strike. A cross-sectional questionnaire study was carried out among 543 firefighters (83% of the target group) in 71 fire brigades in Finland. After the strike had lasted for 9 to 11 weeks, most of the firefighters perceived their physical work capacity to be rather good or very good. Stress increased along with a decreasing number of personnel in a crew (OR= 2.3, CI= 1.0-5.3, for less than 75% of a normal crew vs. normal crew) and with decreasing number of personnel in a shift (OR= 2.4, CI= 1.1-5.4, for less than 25% of normal shift vs. normal shift). Sleep disturbance was reported to occur as soon as the total working time exceeded 50 h/week. Working more than 70 h/week increased the risk of occupational accidents almost 4-fold compared with working no more than 50 h/week. These results suggest that exceptional situations, such as a strike, are a challenge to human capacity. With time, increased stress and sleep disturbance may lead to serious consequences.     

Effects of Risk Representation and Scope on Willingness to Pay for Reduced Risks: Evidence from Tokyo Bay, Japan

When applying the contingent valuation method (CVM) in risk reduction studies, some studies report that willingness to pay (WTP) is insensitive to the magnitude of risk reduction while other studies do not. On the other hand, social-psychological research has shown that the affect heuristic biases judgments on probability, relative frequency, and risk. This article examines both magnitude (or scope) effect and affect heuristic (or representation) effect on WTP for risk reduction measures against tsunamis by introducing two experimental (i.e., absolute and relative) systems with four different representations to evaluate public behaviors in two different scenarios of risk reduction. Two common denominators (100 and 10,000) are introduced into absolute risk reduction representation (i.e., "of every 100 persons, from present 2 deaths to 1") to form different formats (i.e., "of every 10,000 persons from 200 to 100," and "of every 100,000 persons from 2,000 deaths to 1,000"). There is little evidence that WTP estimates are sufficiently sensitive to the magnitude of risk reduction, but relative risk reduction representations may be better than the absolute one given in CVM mail surveys when the risk is small. There is a statistically insignificant effect of risk reduction representations on respondent frequency, but mixed effects on the monetary values of WTP at the level of 0.05. The representation effect of absolute risk reduction on the WTP value varies with the common denominator. The larger the common denominator, the less the WTP to reduce the risk of tsunamis, and the significance probability is improved to less than the level of 0.05 when the common denominator becomes large enough. The findings suggest that improved methods are required for estimating the rates of tradeoff between fatality risk and other goods among consumers.     

Quantitative risk assessment of rabies being introduced into mainland France through worldwide noncommercial dog and cat movements

France has been rabies-free among nonflying mammals since 2001. Despite this status, the rabies virus has been introduced several times through noncommercial pet movements, posing a threat of infection by this 100%-lethal zoonosis among local animal and human populations. To quantify the risk of rabies being introduced through worldwide noncommercial dog and cat movements, we performed a quantitative risk assessment using stochastic scenario tree modeling. The mean annual probability of at least one rabies introduction incident was 0.35 (median: 0.24, 90% prediction interval (PI) [0.04; 0.98]) and the mean annual number of rabies-infected pets introduced through pet movements was 0.96 (median: 0.27, 90% PI [0.04; 3.88]). These results highlight a nonnegligible, even high risk due to the associated consequences of such events. In alternative scenario testing, preventive anti-rabies vaccination proved to be an effective measure since removing the vaccination requirement led to a > 15-fold increase in risk. The serological testing requirement had less of an effect (approximately two-fold increase when removed) and the posttest waiting period to ensure that antibodies were not linked to an infection had a negligible effect. Any change in pet owner compliance, especially regarding vaccination, could have a major impact on the risk. This study also shows that reinforced border control staff training could be more effective in reducing risk than more frequent checks. These results provide quantitative data for assessing the probability of the rabies virus entering France, and could help policymakers decrease this risk in rabies-free areas.     

Factors in Exposure Assessment: Ethnic and Socioeconomic Differences in Fishing and Consumption of Fish Caught along the Savannah River

South Carolina has issued fish consumption advisories for the Savannah River based on mercury and radionuclide levels. We examine differences in fishing rates and fish consumption of 258 people interviewed while fishing along the Savannah River, as a function of age, education, ethnicity, employment history, and income, and test the assumption that the average consumption of fish is less than the recreational value of 19 kg/year assumed by risk assessors. Ethnicity and education contributed significantly to explaining variations in number of fish meals per month, serving size, and total quantity of fish consumed per year. Blacks fished more often, ate more fish meals of slightly larger serving sizes, and consumed more fish per year than did Whites. Although education and income were correlated, education contributed most significantly to behavior; people who did not graduate from high school ate fish more often, ate more fish per year, and ate more whole fish than people who graduated from high school. Computing consumption of fish for each person individually indicates that (1) people who eat fish more often also eat larger portions, (2) a substantial number of people consume more than the amount of fish used to compute risk to recreational fishermen, (3) some people consume more than the subsistence level default assumption (50 kg/year) and (4) Blacks consume more fish per year than Whites, putting them at greater risk from contaminants in fish. Overall, ethnicity, age, and education contributed to variations in fishing behavior and consumption.     

Perceived physical work capacity,stress, sleep disturbance and occupational accidents among firefighters working during a strike

Fire-fighting and rescue work are arranged in such a way that various kinds of accidents and catastrophes can be handled. In an understaffed situation, such as a strike, this goal may not be met. The objective of this study was to investigate factors associated with perceived physical work capacity, stress, sleep disturbance, and occupational accidents among firefighters who remained at work during an extended strike. A cross-sectional questionnaire study was carried out among 543 firefighters (83% of the target group) in 71 fire brigades in Finland. After the strike had lasted for 9 to 11 weeks, most of the firefighters perceived their physical work capacity to be rather good or very good. Stress increased along with a decreasing number of personnel in a crew (OR= 2.3, CI= 1.0-5.3, for less than 75% of a normal crew vs. normal crew) and with decreasing number of personnel in a shift (OR= 2.4, CI= 1.1-5.4, for less than 25% of normal shift vs. normal shift). Sleep disturbance was reported to occur as soon as the total working time exceeded 50 h/week. Working more than 70 h/week increased the risk of occupational accidents almost 4-fold compared with working no more than 50 h/week. These results suggest that exceptional situations, such as a strike, are a challenge to human capacity. With time, increased stress and sleep disturbance may lead to serious consequences.     

Risk Perception Among Nuclear Power Plant Personnel: A Survey

This study investigated risk perception, well-being, and organizational commitment among nuclear power plant personnel. The study group, 428 employees from a nuclear power plant, completed a questionnaire which included the same questions as those in previous surveys on risk perception of lay persons and industrial workers. Hazards at work were not seen as a sizable problem by nuclear power plant personnel. The study group estimated the safety of nuclear power plants better and the possibility of a serious nuclear accident as more unlikely than the general public. Compared to employees in other industrial companies, the overall perceived risks at work among plant personnel did not exceed the respective perceptions of the reference groups. Risk-related attitudes did not explain well-being among plant personnel, but the relationship between the perceived probability of a serious nuclear accident at work and organizational commitment yielded to a significant correlation: Those plant workers who estimated the likelihood of an accident higher were less committed to the organization.     

Knowledge and Risk Perception Among Nuclear Power Plant Employees

This is a study of knowledge, risk perception, and attitudes among nuclear power plant employees. A total of 236 persons participated, belonging to 10 different professional groups and working at two Swedish power plants. Job-related radiation risks were judged about average as compared to a number of other risks. On the whole, the participants in the study were satisfied with the measures of safety at work, but there were some exceptions to this rule, especially among those hired for temporary jobs through external contractors. The experience of job-related radiation risks was related to the level of knowledge about radiation and its risks: those who knew less experienced larger risks. General level of anxiety did not correlate with risk perception. The latter was accounted for mainly by perceived radiation risks. Job satisfaction was more strongly related to perceived conventional job risks than to nuclear risks. Risk ratings were related to how subjects defined the concept of risk. Those who stressed consequences as part of their risk definition gave higher risk ratings.     

Cancer risk estimation for mixtures of coal tars and benzo(a)pyrene.

Two-year chronic bioassays were conducted by using B6C3F1 female mice fed several concentrations of two different mixtures of coal tars from manufactured gas waste sites or benzo(a)pyrene (BaP). The purpose of the study was to obtain estimates of cancer potency of coal tar mixtures, by using conventional regulatory methods, for use in manufactured gas waste site remediation. A secondary purpose was to investigate the validity of using the concentration of a single potent carcinogen, in this case benzo(a)pyrene, to estimate the relative risk for a coal tar mixture. The study has shown that BaP dominates the cancer risk when its concentration is greater than 6,300 ppm in the coal tar mixture. In this case the most sensitive tissue site is the forestomach. Using low-dose linear extrapolation, the lifetime cancer risk for humans is estimated to be: Risk < 1.03 x 10(-4) (ppm coal tar in total diet) + 240 x 10(-4) (ppm BaP in total diet), based on forestomach tumors. If the BaP concentration in the coal tar mixture is less than 6,300 ppm, the more likely case, then lung tumors provide the largest estimated upper limit of risk, Risk < 2.55 x 10(-4) (ppm coal tar in total diet), with no contribution of BaP to lung tumors. The upper limit of the cancer potency (slope factor) for lifetime oral exposure to benzo(a)pyrene is 1.2 x 10(-3) per microgram per kg body weight per day from this Good Laboratory Practice (GLP) study compared with the current value of 7.3 x 10(-3) per microgram per kg body weight per day listed in the U.S. EPA Integrated Risk Information System.