Limited Evidence Of Carcinogenicity Research Articles

Effects of radiofrequency electromagnetic fields (RF EMF) on cancer in laboratory animal studies.

The carcinogenicity of radiofrequency electromagnetic fields (RF EMF) has been evaluated by the International Agency for Research on Cancer (IARC) in 2011. Based on limited evidence of carcinogenicity in humans and in animals, RF EMF were classified as possibly carcinogenic to humans (Group 2B). In 2018, based on a survey amongst RF experts, WHO prioritized six major topics of potential RF EMF related human health effects for systematic reviews. In the current manuscript, we present the protocol for the systematic review of experimental laboratory animal studies (cancer bioassays) on exposure to RF fields on the outcome of cancer in laboratory animals. In the framework of WHO's Radiation Program, the aim of this work is to systematically evaluate effects of RF EMF exposure on cancer in laboratory animals. WHO's Handbook (2014) for guideline development will be followed with appropriate adaptation. The selection of eligible studies will be based on Population, Exposures, Comparators, and Outcomes (PECO) criteria. We will include peer-reviewed articles and publicly available reports from government agencies reporting original data about animal cancer bioassays on exposure to RF EMF. The studies are identified by searching the following databases: MEDLINE (PubMed), Science Citation Index Expanded and Emerging Sources Citation Indes (Web of Science), Scopus, and the EMF Portal. No language or year-of-publication restrictions are applied. The methods and results of eligible studies will be presented in accordance with the PRISMA 2020 guidelines. Study evaluation of individual studies will be assessed using a risk of bias (RoB) tool developed by the Office of Health Assessment and Translation (OHAT) with appropriate considerations including sensitivity for evaluating RF EMF exposure in animal cancer bioassays. The final evaluation on the certainty of the evidence on a carcinogenic risk of RF EMF exposure in experimental animals will be performed using the OHAT Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach with appropriate considerations. The protocol has been registered in an open-source repository (PROSPERO). The study is partly financially supported by the World Health Organization. No additional funding was provided outside author salaries through their places of employment.

Health Effects of Naphthalene Exposure: A Systematic Evidence Map and Analysis of Potential Considerations for Dose-Response Evaluation.

Background:Naphthalene is a polycyclic aromatic hydrocarbon that has been associated with health effects, including cancer. As the state of the science on naphthalene toxicity continues to evolve, updated toxicity reference value(s) may be required to support human health risk assessment.Objectives:We present a systematic evidence map of studies that could be used to derive toxicity reference value(s) for naphthalene.Methods:Human and animal health effect studies and physiologically based pharmacokinetic (PBPK) models were identified from a literature search based on populations, exposures, comparators, and outcomes (PECO) criteria. Human and animal studies meeting PECO criteria were refined to a smaller subset considered most informative for deriving chronic reference value(s), which are preferred for assessing risk to the general public. This subset was evaluated for risk of bias and sensitivity, and the suitability of each study for dose–response analysis was qualitatively assessed. Lowest observed adverse effect levels (LOAELs) were extracted and summarized. Other potentially relevant studies (e.g., mechanistic and toxicokinetic studies) were tracked as supplemental information but not evaluated further. Existing reference values for naphthalene are also summarized.Results:We identified 26 epidemiology studies and 16 animal studies that were considered most informative for further analysis. Eleven PBPK models were identified. The available epidemiology studies generally had significant risk of bias and/or sensitivity concerns and were mostly found to have low suitability for dose–response analysis due to the nature of the exposure measurements. The animal studies had fewer risk of bias and sensitivity concerns and were mostly found to be suitable for dose–response analysis.Conclusion:Although both epidemiological and animal studies of naphthalene provide weight of evidence for hazard identification, the available animal studies appear more suitable for reference value derivation. PBPK models and mechanistic and toxicokinetic data can be applied to extrapolate these animal data to humans, considering mode of action and interspecies metabolic differences. https://doi.org/10.1289/EHP7381

Etoposide. Documentation of proposed values of occupational exposure limits (OELs)

Etoposide. Documentation of proposed values of occupational exposure limits (OELs)

Extremely low-frequency magnetic fields and risk of childhood leukemia: A risk assessment by the ARIMMORA consortium.

Exposure to extremely low-frequency magnetic fields (ELF-MF) was evaluated in an International Agency for Research on Cancer (IARC) Monographs as "possibly carcinogenic to humans" in 2001, based on increased childhood leukemia risk observed in epidemiological studies. We conducted a hazard assessment using available scientific evidence published before March 2015, with inclusion of new research findings from the Advanced Research on Interaction Mechanisms of electroMagnetic exposures with Organisms for Risk Assessment (ARIMMORA) project. The IARC Monograph evaluation scheme was applied to hazard identification. In ARIMMORA for the first time, a transgenic mouse model was used to mimic the most common childhood leukemia: new pathogenic mechanisms were indicated, but more data are needed to draw definitive conclusions. Although experiments in different animal strains showed exposure-related decreases of CD8+ T-cells, a role in carcinogenesis must be further established. No direct damage of DNA by exposure was observed. Overall in the literature, there is limited evidence of carcinogenicity in humans and inadequate evidence of carcinogenicity in experimental animals, with only weak supporting evidence from mechanistic studies. New exposure data from ARIMMORA confirmed that if the association is nevertheless causal, up to 2% of childhood leukemias in Europe, as previously estimated, may be attributable to ELF-MF. In summary, ARIMMORA concludes that the relationship between ELF-MF and childhood leukemia remains consistent with possible carcinogenicity in humans. While this scientific uncertainty is dissatisfactory for science and public health, new mechanistic insight from ARIMMORA experiments points to future research that could provide a step-change in future assessments. Bioelectromagnetics. 37:183-189, 2016. © 2016 Wiley Periodicals, Inc.

In Vitro Photochemical Induction of Kojic Acid-DNA Adducts

Objective: Kojic Acid (KA) is a natural substance which inhibits skin melanin production and, when used alone or in combination with other compounds, is effective in reducing pigmentation in melasma patients. KA was classified by IARC as presenting limited evidence of carcinogenicity based largely on a single study showing thyroid neoplasms. More recently KA has been shown to be carcinogenic in rat liver, but not mouse skin. KA has produced positive and negative results in both in vivo and in vitro genotoxicity tests and was considered to be genotoxic in vitro by IARC. KA is photochemically unstable causing in vitro breakage of DNA. Consistent with this, photochemically KA is weakly mutagenicity in bacteria and induced chromosome aberrations in Chinese hamster lung cells, although it was negative on mouse epidermis in a photo-micronucleus assay. To assess the potential of KA to photochemically induce formation of DNA adducts, we investigated effects of irradiating KA and DNA with 320 nm light and analyzing for DNA adducts by the nucleotide 32P-postlabeling (NPL) method. Methods: The ability of KA irradiated at 320 nm to induce formation of DNA adducts was compared to direct chemical reaction of chloro-KA with DNA. To ascertain the reliability of this approach, we also studied adduct formation by the photoactivated 8-mehtoxy-(8-MOP) and 4.5`, 8-trimethyl-(TMP) psoralens. Results: All compounds in the presence of UV irradiation produced DNA adducts assessed by one or more of the NPL enhancement methods used. The pattern of major adducts formed photochemically with KA and directly with chloro-KA were similar, but could represent residual KA in chloro-KA samples. Psoralens produced different pattern of adducts. Conclusions: Thus, KA may have the potential to be photoactivated to DNA-damaging products in skin.

Use of Meta-analyses by IARC Working Groups

Use of Meta-analyses by IARC Working Groups

FDA Risk Assessment of Seafood Contamination after the BP Oil Spill

FDA Risk Assessment of Seafood Contamination after the BP Oil Spill

Cell Phones, Cancer, and Children

JNCI | Editorials 1211 We live in a high-tech world of electronics, constantly strolling through invisible fields of radio waves, television waves, microwaves, radar, and Wi-Fi networks. In the 1980s in the Nordic countries and in the 1990s in the United States, a new source of radio frequency waves came into widespread use: The cell phone, which emits nonionizing radio waves through an antenna commonly held close to the head. By 2009, the cell phone had become an integral part of everyday life, with more than 285 million subscribers to cell phone service in the United States (91% of the population) and more than 5 billion worldwide. This ubiquitous exposure to an emerging technology prompted the initiation of large-scale health studies (some started over 20 years ago) in the United States (1,2) and throughout the world (3,4). The results of these epidemiological investigations have been largely consistent and reassuring, with the World Health Organization (WHO) and the US National Cancer Institute concluding that there is no conclusive or consistent evidence that nonionizing radiation emitted by cell phones is associated with cancer risk (5,6). Amid this encouraging evidence from human observational studies, coupled with the negative findings from virtually all exper imental animal and in vitro studies and the absence of any known biological mechanism by which weak nonionizing radio waves emitted from cell phones could damage DNA and lead to cancer (7–9), it may therefore seem surprising that a monograph committee of the International Agency for Research on Cancer (IARC), an agency of the WHO, recently announced that cell phones may be “possibly carcinogenic to humans” (10). The change from “no conclusive evidence” to “possibly carcinogenic” was not new research (11), and it has understandably led to widespread public as well as media concern and confusion (12). The footnote accompanying the IARC press release (10) is often missed—that a “possibly carcinogenic to humans” (2B) classification by IARC is based on “limited evidence of carcinogenicity” and that “chance, bias, or confounding could not be ruled out with reasonable confidence” for the few positive associations reported in the literature. A published summary of the IARC Working Group conclusions (13) noted that some members found the epidemiologic evidence to be inadequate to support the 2B classification. Viewed in

WHO Classification Sparks Debate Over Cell Phone Safety

F ar from settling the question of whether cell phones cause cancer, the latest pronouncement by the World Health Organization that cell phones could “possibly” be carcinogenic has left a wake of confusion and consternation. In July ’ s The Lancet Oncology , the WHO ’ s International Agency for Research on Cancer (IARC) announced that it had classifi ed radiofrequency (RF) electromagnetic fi elds — such as those that wireless phones emit — as “possibly carcinogenic to humans” based on an increased risk of glioma and acoustic neuroma. The move came barely a year after the huge Interphone study found no increased risk of cancer from more than 10 years of cell phone use. But the Interphone results, published here in the Journal ( see J. Natl. Cancer Inst. 2010; 102:13), suggested there might be some risk for people with the heaviest use. The National Cancer Institute, the American Cancer Society, and other organizations were at pains to update their online information and reassure worried consumers that the WHO action was not based on any clinically meaningful new evidence but merely on an evaluation of the existing literature. Experts repeated the familiar mantra “more research is needed,” even as newspaper headlines warned of the potential risk. Some observers missed the small print. The IARC ’ s 2B classifi cation — “possibly carcinogenic to humans” — was based only on “limited evidence of carcinogenicity.” According to IARC, that means: “A positive association has been observed between exposure to the agent and cancer for which a causal interpretation is considered . . . to be credible, but chance, bias, or confounding could not be ruled out with reasonable confi dence.” As Jonathan Samet, M.D. , overall chair of the IARC working group and chair of preventive medicine at the University of Southern California, told a press conference in Lyon, France, on May 31, the classifi cation means “there could be some risk, and therefore we need to keep a close watch for a link between cell phones and cancer risk.”

A Compendium of Challenges: Assessing the State of the Science on Occupational Carcinogens

Uncertainties abound about the adverse health effects of exposure to carcinogens found in today’s workplaces. Even with substantial toxicologic evidence of carcinogenicity, cancer risks for humans often remain inconclusive, thus delaying regulatory action and the search for safer alternatives. A new systematic review by the International Agency for Research on Cancer (IARC) identifies research gaps and needs for 20 agents prioritized for review on the basis of evidence of widespread human exposures and potential carcinogenicity in animals or humans [EHP 118(10):1355–1362; Ward et al.]. Drawing from an international collaboration by 25 health and research agencies and institutions, the report summarizes recommendations and broaches key topics pertaining to several chemicals, metals, dusts, and physical agents for which there is widespread human exposure, predominantly in occupational settings. The authors emphasize that carcinogenic agents can act through multiple pathways and mechanisms, including oxidative stress, epigenetic mechanisms, and immuno- and hormonal modulation. They then discuss overarching issues pertinent to the study of these mechanisms. For example, regarding the validation of oxidative stress biomarker assays, they write, “Research is needed to examine the relationship between exposure to toxic agents and oxidative stress biomarkers, and between these biomarkers and risk of cancer, while controlling for the many individual factors that contribute to oxidative stress.” Concerning genetic susceptibility to carcinogenic exposures, the authors caution that stable and reproducible associations are few. Examining genetic polymorphisms related to carcinogen metabolism and/or DNA repair may aid the identification of higher cancer risks in susceptible subgroups and clarify the role of specific agents in mixed exposures. Nonetheless, the magnitude of such associations may be modest and could entail multiple genes or metabolic pathways—thus making them hard to detect. The report deals with only a fraction of the potentially carcinogenic agents found in today’s workplaces, most of which have sufficient evidence of carcinogenicity in animals but limited evidence for carcinogenicity in humans. Because of a paucity of well-designed animal bioassays and human studies, insufficient evidence exists to evaluate animal or human carcinogenicity for most other agents. The report ends on a somber note, noting that substantial challenges for the study of environmental carcinogens remain, including a recent decline in funding for occupational cancer research, and that fewer scientists are entering the fields of epidemiology, toxicology, and exposure assessment.

Electric and magnetic fields at power frequencies

Exposures to electric and magnetic fields are among the most ubiquitous exposures that the Canadian population experiences. Sources of electric and magnetic field exposures may be occupational or residential and include proximity to certain types of electrical equipment, transmission and distribution power lines as well as appliance use. The early studies of children tended toward a consistent association between risks for leukemia and brain cancer and residential proximity to power lines having high wire configuration. More recent studies-and studies which have attempted to improve upon the measurement of exposure by using calculated fields, point-in-time or personal monitoring-have been inconsistent, with some suggesting increased risk and others not. Occupational exposures have suggested an increase in risk for leukemia, and to a lesser extent brain cancer and Non-Hodgkin lymphoma. However, studies of residential exposures and cancer in adults generally have suggested no effect. Laboratory work has been unable to demonstrate a biological mechanism which might explain the epidemiological findings. In spite of extensive efforts over the past 20 years and many expert reviews, it has been difficult to reach consensus regarding the carcinogenic effects of electric and magnetic fields. Exposure assessment has proven to be complex, and agreement on the relevant exposure metric has not yet been obtained. There is justification to question whether point-in-time measures in homes are appropriate indices of the relevant etiological exposure, as they fail to account for changes over time, peak exposures or time-varying fields. Nevertheless, it is probably desirable to err on the side of caution in not placing too much weight on the inconsistencies. The IARC has classified EMF as a "possible carcinogen" which refers to the circumstances where there is limited evidence of carcinogenicity in humans and inadequate evidence in experimental animals. The IARC review indicated limited evidence for the carcinogenicity of extremely low-frequency magnetic fields in relation to childhood leukemia at high level exposure in the residential environment (average residential magnetic field strength >0.4 μT). Even higher levels of exposure in the occupational environment may increase the risk of leukemia in adults.

Epidemiologic evaluation of pharmaceuticals with limited evidence of carcinogenicity.

Thorough review by the International Agency for Research on Cancer (IARC) has resulted in classifying many substances, including pharmaceuticals, as probably or possibly carcinogenic to humans, based on experiments on animals or limited data on humans. We evaluated 9 such pharmaceuticals for evidence of carcinogenicity in patients receiving them in a large medical care program with automated pharmacy records and a cancer registry. Nested case-control analyses were performed in a cohort of 6.5 million subscribers with up to 12 years of follow-up, focusing on cancer sites suggested by previous evidence and other sites with odds ratio of at least 1.50, p < 0.01 and some evidence of dose-response. Unmeasured confounding was estimated in sensitivity analyses. We found some supportive evidence for carcinogenicity of griseofulvin, metronidazole and phenytoin and for the known carcinogen, cyclophosphamide, which was added for validation of our data and analyses. Findings for chloramphenicol, iron-dextran complex, phenoxybenzamine and phenobarbital were essentially non-contributory. Confounding by cigarette smoking and prior thyroid disease could account, respectively, for associations of oxazepam with lung cancer and propylthiouracil with thyroid cancer. Although not definitive, these findings should be considered in the evaluations of these pharmaceuticals.

ELF MFs: Straif et al. Respond

Mild et al. suggest that we should have included magnetic fields at extremely low frequencies (ELF MFs) in our listing of occupational carcinogens (Siemiatycki et al. 2004). We acknowledge that ELF MFs have been classified as “possibly carcinogenic to humans” (Group 2B) by the Monographs Programme of the International Agency for Research on Cancer (IARC 2002) and that there is significant occupational exposure, thereby meeting our operational criterion for inclusion as a possible occupational carcinogen. However, the nature of the evidence that led to the IARC classification complicates the designation of ELF MFs as an occupational carcinogen. For our article (Siemiatycki et al. 2004), we drew on the evaluations of the IARC Monographs Programme. Each evaluation was based on data that were available at the time of the deliberations of the working group. We supplemented the evaluation by adding information on major occupational exposure circumstances and on the cancer sites affected. For some carcinogens, notably those evaluated recently, such information was explicitly mentioned in the published monograph, but for others it was based on our expert judgment. For ELF MFs, the IARC evaluation of “possibly carcinogenic” was founded on a determination that there was limited evidence of carcinogenicity in humans based on its effects on childhood leukemia and “inadequate evidence” in experimental animals (IARC 2002). In contrast with an earlier evaluation [National Institute of Environmental Health Sciences (NIEHS) 1998], the IARC Working Group considered that studies conducted among adults, at work or elsewhere, did not provide consistent enough and strong enough evidence to support an evaluation of carcinogenicity. There is no clear-cut way to classify an exposure that has only been demonstrated to be carcinogenic (albeit group 2B) in children, but also occurs among workers. Although we decided not to include ELF MFs in our tables of occupational carcinogens (Siemiatycki et al. 2004), we could have done so with a footnote to explain that the evidence supporting that evaluation was based on children. Mild et al. also discuss the evidence on the carcinogenic effects of ELF MFs that has arisen since 2002. Although we agree that some of these studies may substantially contribute to an evaluation of the carcinogenic effects of ELF MFs, it was not in the scope of our work to evaluate new information and update the evaluations on all of the agents reviewed. The World Health Organization (WHO) will be holding a meeting of an Environmental Health Criteria Task Group in October 2005; this task group will evaluate the health effects of ELF MFs (including cancer and noncancer outcomes). We anticipate that they will review the recent evidence in conjunction with the evaluation of the 2002 IARC Monograph. The WHO Environmental Health Criteria document on ELF MFs should be published shortly after this meeting.

Cancer Risk among Workers at Danish Companies using Trichloroethylene: A Cohort Study

Trichloroethylene is an animal carcinogen with limited evidence of carcinogenicity in humans. Cancer incidence between 1968 and 1997 was evaluated in a cohort of 40,049 blue-collar workers in 347 Danish companies with documented trichloroethylene use. Standardized incidence ratios for total cancer were 1.1 (95% confidence interval (CI): 1.04, 1.12) in men and 1.2 (95% CI: 1.14, 1.33) in women. For non-Hodgkin's lymphoma and renal cell carcinoma, the overall standardized incidence ratios were 1.2 (95% CI: 1.0, 1.5) and 1.2 (95% CI: 0.9, 1.5), respectively; standardized incidence ratios increased with duration of employment, and elevated standardized incidence ratios were limited to workers first employed before 1980 for non-Hodgkin's lymphoma and before 1970 for renal cell carcinoma. The standardized incidence ratio for esophageal adenocarcinoma was 1.8 (95% CI: 1.2, 2.7); the standardized incidence ratio was higher in companies with the highest probability of trichloroethylene exposure. In a subcohort of 14,360 presumably highly exposed workers, the standardized incidence ratios for non-Hodgkin's lymphoma, renal cell carcinoma, and esophageal adenocarcinoma were 1.5 (95% CI: 1.2, 2.0), 1.4 (95% CI: 1.0, 1.8), and 1.7 (95% CI: 0.9, 2.9), respectively. The present results and those of previous studies suggest that occupational exposure to trichloroethylene at past higher levels may be associated with elevated risk for non-Hodgkin's lymphoma. Associations between trichloroethylene exposure and other cancers are less consistent.

Exposure to titanium dioxide and risk of lung cancer in a population-based study from Montreal.

This study assessed the lung cancer risk from exposure to titanium dioxide, an important pigment with limited evidence of carcinogenicity in experimental animals but sparse data for humans. The risk of lung cancer among residents in Montreal, Canada, was analyzed, including 857 histologically confirmed cases of lung cancer diagnosed during 1979-1985 among men aged 35-70 years and a group of referents comprising 533 randomly selected, healthy residents and 533 persons with cancer in organs other than the lung. Exposure to titanium dioxide and other titanium compounds was assessed by a team of industrial hygienists on the basis of a detailed occupational questionnaire. Thirty-three cases and 43 referents were classified as exposed to titanium dioxide. The odds ratio was 0.9 [95% confidence interval (95% CI) 0.5-1.5]. No trend was apparent according to the estimated frequency, level, or duration of exposure. The odds ratio was 1.0 (95% CI 0.3-2.7) for medium or high exposure for at least 5 years. Few subjects were classified as exposed to titanium dioxide fumes or to other titanium compounds, but the risk of lung cancer was nonsignificantly increased for exposure to these agents. Although misclassification of exposure and low exposure prevalence might have resulted in false negative results, this study does not suggest that occupational exposure to titanium dioxide increases the risk of lung cancer.

Is the human carcinogen arsenic carcinogenic to laboratory animals?

Arsenic has long been known to cause cancer in humans (Hutchinson, 1987, 1988), and has been correlated convincingly with cancers of the skin, lung, liver, kidney, and urinary bladder (IARC, 1987; NTP, 2000). Paradoxically, we now know that arsenic has been shown to be “anticarcinogenic” as well, and of potential benefit in the treatment of acute promyelocytic leukemia (Zhu et al., 1999). Whereas this is a major cancer chemotherapeutic advance, we believe use of arsenicals in human medicine must be tempered by toxicological realities (Huang et al., 1998; Huff et al., 1999). Nonetheless, most if not all cancer chemotherapeutic agents are carcinogenic to animals, and cause eventual second primaries in humans. In summarizing the informative and valued proceedings from a recent symposium on arsenic, Goering et al. (1999) stated that “animal carcinogenicity data for arsenic is considered either negative or equivocal.” These authors make a more discerning statement two paragraphs later: “Animal bioassays are considered either flawed or incomplete for establishing carcinogenicity of arsenic in rodents.” They also contend that “the International Agency for Research on Cancer (IARC) has determined that arsenic is the only agent to be a definitive human carcinogen in the face of ‘inadequate’ evidence of carcinogenic potential in animals.” In fact, none of these statements is fully correct; the second quoted sentence above comes close. In 1987 IARC evaluated arsenic and arsenic compounds and concluded “there is limited evidence of carcinogenicity in experimental animals,” meaning there are tumor responses in some studies on arsenic carcinogenicity in animals but due to certain deficiencies (too few animals, low doses, short duration, no controls, arsenic mixtures) the findings were not considered sufficient evidence of carcinogenicity in animals. In these assorted and seemingly numerous studies, various forms of inorganic arsenic were associated with tumors of the lung, respiratory tract, and stomach (IARC, 1980, 1987). Moreover, as we have stated previously (Huff et al., 1998a,b), arsenic trioxide and other inorganic (and until now organic) arsenicals have in reality never been tested adequately for carcinogenesis, and never by the inhalation route. Thus, to state that arsenic has not been shown to cause cancer in laboratory animals is patently premature (Chan and Huff, 1997). Unfortunately, a common and perpetuated incorrect statement is often made that arsenic is carcinogenic to humans and not to experimental animals. Bioassays should be done, in particular with arsenic trioxide, to satisfy this frequently but wrongly opined discrepancy. As history often repeats, this reminds some of us of when benzene was also heralded as being carcinogenic to humans but not to animals, and the “lack” of carcinogenicity in animals for both arsenic and benzene was used to discount the relevancy of bioassay testing results for predicting human cancer risks. It is now clear that, after adequate testing of benzene in animals, the results have been overwhelmingly positive for carcinogenicity (Huff et al., 1989; Maltoni et al., 1989). We believe the same will occur if inorganic arsenic is tested properly in laboratory animals. In addition to arsenic, and contrary to the quoted comment by Goering et al. (1999), other IARC Group-1 human carcinogens have less than sufficient evidence of carcinogenicity in animals, largely because only one study has been reported, and in some cases there is no evidence at all because no bioassays have been done. These substances are listed in Table 1. For some of these there may be more recent experimental data that we are either unaware or have been unable to locate. Despite this collective observation, correlations between bioassays and epidemiology findings are excellent (Huff, 1994, 1998, 1999a; Tomatis et al., 1989; Wilbourn et al., 1986). And of course, in addition to these 10, plus arsenic, one must recognize that there are six mixtures, 13 industries or occupations, as well as 10 biological agents or viruses (Table 2) that are carcinogenic to humans, and that have not, and typically cannot, be studied in animals. Granted, for many of these, bioassays either cannot be done or can only be accomplished with great difficulty, although particular agents within an in1 To whom correspondence should be addressed. Fax: (919) 558-7055. E-mail: huff1@niehs.nih.gov. TOXICOLOGICAL SCIENCES 55, 17–23 (2000) Copyright © 2000 by the Society of Toxicology

Lifetime health risk assessment from exposure of recreational users to polycyclic aromatic hydrocarbons.

In order to assess the lifetime risk of skin cancer for recreational users from dermal exposure to polycyclic aromatic hydrocarbons (PAHs), sediment samples were collected from beach sites along the St. Marys River near Sault Ste. Marie, Ontario, and in Hamilton Harbor and Toronto Harbor, Ontario, and analyzed for PAHs. Dermal exposure and lifetime skin cancer risk were estimated as follows: Concentrations of 11 PAHs with sufficient or limited evidence of carcinogenicity or mutagenicity were converted to benzo(a)pyrene (BaP) equivalents using toxic equivalency factors (TEFs). Lifetime dermal exposure values were derived based on the BaP equivalents in the silt + clay fraction taken as representative of suspended sediment particulates to which recreational users would be exposed. The lifetime health risk of skin cancer associated with such exposures was above the negligible risk level of 1.0 x 10(-6) at offshore Rytac, Lake George Channel, and Bell Point beaches in the St. Marys River; at Pier 4 Park in Hamilton Harbor; and at Humber Bay, Sunnyside Beach, Cherry Beach, and Water Rats Sailing Club in Toronto Harbor. Risk was negligible inshore at the Rytac and Bell Point beaches and at Squirrel Island and Ojibway Trailer Park along St. Marys River, at Lax Beach in Hamilton Harbor; and at Centre Island in Toronto Harbor. Strategies to reduce risk were developed with these communities; a key recommendation was to take a bath or shower within 24 h after a swim because virtually all the PAHs on the skin would be removed.

Potency Equivalency Factors for Some Polycyclic Aromatic Hydrocarbons and Polycyclic Aromatic Hydrocarbon Derivatives

Potency equivalency factors (PEFs) for cancer induction relative to benzo[a]pyrene have been derived for 21 polycyclic aromatic hydrocarbons (PAHs) and PAH derivatives based on a data preference scheme. PEFs have been derived only for PAHs with demonstrated carcinogenicity in bioassays. Cancer potency values and inhalation unit risks are presented for four additional carcinogenic PAHs based on expedited risk assessments conducted for California's Proposition 65. A much larger number of PAHs and PAH derivatives are considered mutagenic or genotoxic and may have limited evidence for carcinogenicity, but these compounds are not considered in this evaluation. New cancer bioassay data and possibly structure-activity analysis may indicate that additional PAHs are carcinogenic. Thus, additional PAHs may be identified as potential human carcinogens when such data become available. However, until that time the PEFs proposed for use in risk assessment were estimated only for PAHs currently classified as carcinogens.

Tetrachloroethylene: Evaluation of risks to health from environmental exposure in Canada

Abstract Tetrachloroethylene is included on the List of Priority Substances to be assessed under the Canadian Environmental Protection Act. Available data on human exposure in Canada and potential health effects resulting from exposure to this substance in the environment were critically evaluated. Based upon available data on the incidence and mechanisms of tumour induction in laboratory animals, tetrachloroethylene may be considered “unlikely to be carcinogenic to humans”. The estimated average daily intakes of tetrachloroethylene by the general population of Canada are approximately 13‐ to 28‐fold less than the tolerable daily intake, derived on the basis of hepatic effects in inhalation studies in laboratory animals, and which takes into account the limited evidence of carcinogenicity.

Polycyclic aromatic hydrocarbons in edible tissue of fish from the Gulf after the 1991 oil spill

Concentrations of 10 PAHs were determined in the edible parts of fish collected during April 1992 on Leg IV of the NOAA-R/V Mt. Mitchell scientific cruise from four locations along the western side of the Gulf. The average total amount of PAHs was 105.3 μg kg −1 dry wt, with a range 2.51–563.6 μg kg −1 dry wt. The average concentrations of PAHs in fish from stations E (north Abu Ali), F (south Abu Ali), G (Rennie Shoals) and I (Qatar) were 165.9, 91.7, 55.8 and 108.6 μg kg −1 respectively. The slightly elevated average concentration of total PAHs in samples from station E shows that north Abu Ali was the most oil impacted area. Pyrene and phenanthrene were detected most frequently (in 75% of the fish) whereas chrysene and benz(a)anthracene had the lowest frequency of detection (in 5% of the fish). Based on qualitative classification of PAH carcinogenicity, detected PAHs classified as having sufficient or limited evidence for carcinogenicity [benz(a)pyrene, benz(a)anthracene and chrysene] were lower in concentration and frequency of detection than those classified as having insufficient or no evidence for carcinogenicity (fluoranthene, anthracene, phenanthracene and pyrene).