Interactions between chemical and climate stressors: a role for mechanistic toxicology in assessing climate change risks

Abstract

Incorporation of global climate change (GCC) effects into assessments of chemical risk and injury requires integrated examinations of chemical and nonchemical stressors. Environmental variables altered by GCC (temperature, precipitation, salinity, pH) can influence the toxicokinetics of chemical absorption, distribution, metabolism, and excretion as well as toxicodynamic interactions between chemicals and target molecules. In addition, GCC challenges processes critical for coping with the external environment (water balance, thermoregulation, nutrition, and the immune, endocrine, and neurological systems), leaving organisms sensitive to even slight perturbations by chemicals when pushed to the limits of their physiological tolerance range. In simplest terms, GCC can make organisms more sensitive to chemical stressors, while alternatively, exposure to chemicals can make organisms more sensitive to GCC stressors. One challenge is to identify potential interactions between nonchemical and chemical stressors affecting key physiological processes in an organism. We employed adverse outcome pathways, constructs depicting linkages between mechanism-based molecular initiating events and impacts on individuals or populations, to assess how chemical- and climate-specific variables interact to lead to adverse outcomes. Case examples are presented for prospective scenarios, hypothesizing potential chemical-GCC interactions, and retrospective scenarios, proposing mechanisms for demonstrated chemical-climate interactions in natural populations. Understanding GCC interactions along adverse outcome pathways facilitates extrapolation between species or other levels of organization, development of hypotheses and focal areas for further research, and improved inputs for risk and resource injury assessments.

Fig. 1

Adverse outcome and climate acclimation pathways suggested for mechanistic assessments of contaminants and global climate change interactions. Modified from Ankley et al. . [Color figure can be seen in the online version of this article, available at http://wileyonlinelibrary.com.]

Fig. 2

Adverse outcome pathway of the interaction of ultraviolet radiation with polycyclic aromatic hydrocarbons. With permission from Ankley et al. . [Color figure can be seen in the online version of this article, available at http://wileyonlinelibrary.com.]

Fig. 3

Illustrative adverse outcome pathways (AOP) of toxicant-induced climate sensitivities among amphibians reflecting potential dual interactions between global climate change (GCC) and thyroid-disrupting chemicals (TDCs). Five mechanisms of action are depicted with unique molecular initiating events that have been shown to intersect with reduced thyroid hormone levels and impaired metamorphosis among amphibians. These TDC AOPs share a common outcome that could impair accelerated metamorphosis under GCC. See Figure 2 for key to interactions. BPA = bisphenol A; PBDE = polybrominated diphenyl ether; PCB = polychlorinated biphenyl; PTU = propylthiouracil; TBBPA = tetrabromobisphenol A; TCBPA = tetrachlorobisphenol A; TMBPA = tetramethylbisphenol A; TH = thyroid hormone; T3 = triiodothyronine; T4 = thyroxine; TR = thyroid receptor; CRF = corticotropin-releasing factor; TSH = thyroid stimulating hormone. [Color figure can be seen in the online version of this article, available at http://wileyonlinelibrary.com.]

Fig. 4

Adverse outcome pathways (AOPs) for investigating demonstrated combined effects of extreme heat events and mercury toxicity in tree swallow nestlings. Retrospective pathways for potential climate-induced toxicant sensitivity (CITS) and toxicant-induced climate sensitivity (TICS) mechanisms are indicated. See Figure 2 for key to interactions. DIO = iodothyronine deiodinase; GPx = glutathione peroxidase; GSH = reduced glutathione; H₂O₂ = hydrogen peroxide; MT = metallothionein; NMDA-R = N-methyl-d-aspartic acid receptor; NO = nitric oxide; OH = hydroxyl; RSH = protein thiol; RSeH = protein selenol; T3 = triiodothyronine; TrxR = thioredoxine reductase. [Color figure can be seen in the online version of this article, available at http://wileyonlinelibrary.com.]