Linear low-dose extrapolation for noncancer health effects is the exception, not the rule

The nature of the exposure-response relationship has a profound influence on risk analyses. Several arguments have been proffered as to why all exposure-response relationships for both cancer and noncarcinogenic end-points should be assumed to be linear at low doses. We focused on three arguments that have been put forth for noncarcinogens. First, the general “additivity-to-background” argument proposes that if an agent enhances an already existing disease-causing process, then even small exposures increase disease incidence in a linear manner. This only holds if it is related to a specific mode of action that has nonuniversal properties—properties that would not be expected for most noncancer effects. Second, the “heterogeneity in the population” argument states that variations in sensitivity among members ofthe target population tend to “flatten out and linearize” the exposure-response curve, but this actually only tends to broaden, not linearize, the dose-response relationship. Third, it has been argued that a review of epidemiological evidence shows linear or no-threshold effects at low exposures in humans, despite nonlinear exposure-response in the experimental dose range in animal testing for similar endpoints. It is more likely that this is attributable to exposure measurement error rather than a true non-threshold association. Assuming that every chemical is toxic at high exposures and linear at low exposures does not comport to modern-day scientific knowledge of biology. There is no compelling evidence-based justification for a general low-exposure linearity; rather, case-specific mechanistic arguments are needed

Lymphohematopoietic malignancies

In this chapter, we present the 2017 revised WHO classification as the current reference standard for lymphohematopoietic malignancies. According to this, we discuss in detail the subgroups of myeloid and lymphoid malignancies, characterizing their biological and clinical features. Then, based on the current list of putative carcinogens maintained by the International Agency for Research on Cancer (updated to November 2018), we describe the possible occupational risk factors for myeloid and lymphoid malignancies. In particular, we focus on ionizing radiations (including fission products, phosphorus-32, strontium-90, thorium-232, and its decay products), benzene, 1,3-butadiene, formaldehyde, two pesticides (lindane and pentachlorophenol), and a generically identified industrial process (rubber production industry). As reviewed in the chapter, the case definitions adopted in epidemiological studies seldom met the classification criteria established by WHO. Hence, knowledge on putative risk factors for lymphohematopoietic malignancies is limited to major groupings, such as non-Hodgkin lymphoma, chronic lymphoid leukemia. Future researches should be oriented to study specific diseases and based on case definitions derived by systematic classifications of lymphohematopoietic malignancies