J Toxicol Environ Health B Crit Rev

Since the inception of the | in the early 1970s, this | has developed 119 | Volumes on more than 1000 agents for which there exists some evidence of cancer risk to humans. Of these, 120 agents were found to meet the criteria for classification as | (Group 1). Volume 100 of the |, compiled in 2008-2009 and published in 2012, provided a review and update of the 107 Group 1 agents identified as of 2009. These agents were divided into six broad categories: (I) pharmaceuticals; (II) biological agents; (III) arsenic, metals, fibers and dusts; (IV) radiation; (V) personal habits and indoor combustions; and (VI) chemical agents and related occupations. The Group I agents reviewed in Volume 100, as well as five additional Group 1 agents defined in subsequent Volumes of the |, were used to assess the degree of concordance between sites where tumors originate in humans and experimental animals including mice, rats, hamsters, dogs, and non-human primates using an anatomically based tumor nomenclature system, representing 39 tumor sites and 14 organ and tissue systems. This evaluation identified 91 Group 1 agents with | (82 agents) or | (9 agents) of carcinogenicity in animals. The most common tumors observed in both humans and animals were those of the respiratory system including larynx, lung, and lower respiratory tract. In humans, respiratory system tumors were noted for 31 of the 111 distinct Group 1 carcinogens identified up to and including Volume 109 of the |, comprising predominantly 14 chemical agents and related occupations in category VI; seven arsenic, metals, fibers, and dusts in category III, and five personal habits and indoor combustions in category V. Subsequent to respiratory system tumors, those in lymphoid and hematopoietic tissues (26 agents), the urothelium (18 agents), and the upper aerodigestive tract (16 agents) were most often seen in humans, while tumors in digestive organs (19 agents), skin (18 agents), and connective tissues (17 agents) were frequently seen in animals. Exposures to radiation, particularly X- and \u3b3-radiation, and tobacco smoke were associated with tumors at multiple sites in humans. Although the | did not emphasize tumor site concordance between animals and humans, substantial concordance was detected for several organ and tissue systems, even under the stringent criteria for | of carcinogenicity used by IARC. Of the 60 agents for which at least one tumor site was identified in both humans and animals, 52 (87%) exhibited tumors in at least one of the same organ and tissue systems in humans and animals. It should be noted that some caution is needed in interpreting concordance at sites where sample size is particularly small. Although perfect (100%) concordance was noted for agents that induce tumors of the mesothelium, only two Group 1 agents that met the criteria for inclusion in the concordance analysis caused tumors at this site. Although the present analysis demonstrates good concordance between animals and humans for many, but not all, tumor sites, limitations of available data may result in underestimation of concordance.P30 ES029067/ES/NIEHS NIH HHS/United StatesR01 ES029911/ES/NIEHS NIH HHS/United States31795923PMC7139235788