Comments on the opinions published by Bergman et al. (2015) on Critical Comments on the WHO-UNEP State of the Science of Endocrine Disrupting Chemicals (Lamb et al., 2014).

Recently Bergman et al. (2015) took issue with our comments (Lamb et al., 2014) on the WHO-UNEP(1) report entitled the "State of the Science of Endocrine Disrupting Chemicals - 2012" (WHO 2013a). We find several key differences between their view and ours regarding the selection of studies and presentation of data related to endocrine disrupting chemicals (EDCs) under the WHO-IPCS(2) definition (2002). In this response we address the factors that we think are most important: 1. the difference between hazard and risk; 2. the different approaches for hazard identification (weight of the evidence [WOE] vs. emphasizing positive findings over null results); and 3. the lack of a justification for conceptual or practical differences between EDCs and other groups of agents.

Critical comments on the WHO-UNEP State of the Science of Endocrine Disrupting Chemicals - 2012.

Early in 2013, the World Health Organization (WHO) released a 2012 update to the 2002 State of the Science of Endocrine Disrupting Chemicals. Several significant concerns have been identified that raise questions about conclusions reached in this report regarding endocrine disruption. First, the report is not a state-of-the-science review and does not follow the 2002 WHO recommended weight-of-evidence approach. Second, endocrine disruption is often presumed to occur based on exposure or a potential mechanism despite a lack of evidence to show that chemicals are causally established as endocrine disruptors. Additionally, causation is often inferred by the presentation of a series of unrelated facts, which collectively do not demonstrate causation. Third, trends in disease incidence or prevalence are discussed without regard to known causes or risk factors; endocrine disruption is implicated as the reason for such trends in the absence of evidence. Fourth, dose and potency are ignored for most chemicals discussed. Finally, controversial topics (i.e., low dose effects, non-monotonic dose response) are presented in a one-sided manner and these topics are important to understanding endocrine disruption. Overall, the 2012 report does not provide a balanced perspective, nor does it accurately reflect the state of the science on endocrine disruption.

Toxicological review of male reproductive effects and trichloroethylene exposure: assessing the relevance to human male reproductive health.

Effects of trichloroethylene (TCE) on male reproduction and fertility have been studied in mice and rats, and assessed in workers exposed to TCE. Only limited evidence exists for any male reproductive effects in rats or humans. The human studies of TCE male reproductive effects failed to provide much useful information for risk assessment. First, the TCE-specific studies are limited in group size, scope, and typically provide no data on dose, so dose-response assessment is impossible. In other studies, TCE is only one of many solvents identified in the workplace, such that the confounding exposures or lack of evidence of specific exposures make the exposure assessment useless. For TCE risk assessment, one currently must rely upon animal studies as more reliable and useful. The rat studies were generally negative, showing systemic toxicity but little or no male reproductive toxicity. The mouse studies showed various organ effects in the male reproductive system and were typically associated with increased liver weight and kidney toxicity. Enzyme induction and oxidative metabolism appear to be important in the systemic toxicity and may likewise play a role in the reproductive toxicity of TCE. Oxidative metabolites of TCE are formed in the mouse epididymis resulting in epididymal damage, and at systemically toxic high doses, TCE may adversely affect the maturation of sperm and decreasing sperm motility. Protection against systemic toxicity should also protect against adverse effects including male reproductive toxicity.