Assessing effects of environmental chemicals on neuroendocrine systems: potential mechanisms and functional outcomes.

Environmental pollutants encompass a vast array of compounds. Most studies in birds have focused on toxicological effects, with little attention to non-lethal effects. Consequently, it has proven difficult to assess potential risk associated with exposure to endocrine disrupting chemicals (EDCs). Assessing potential adverse effects due to exposure is further complicated by the great variation that occurs across avian species. These include variations in reproductive strategies, life span, sexual differentiation, and migration. Differences in reproductive strategies, particularly in the developmental patterns and mechanisms for precocial and altricial chicks, predispose birds to wide variations in response to steroids and steroid-like EDCs. We have investigated the effects of EDCs in precocial birds including Japanese quail (Coturnix japonica) and mallard ducks (Anas platyrhynchos) as well as in wild altricial songbirds. Studies in Japanese quail characterized endogenous steroid hormone changes during development and have demonstrated that the developing embryo uses the yolk as a 'steroid hormone depot'. It appears that actual embryonic exposure is quantitatively lower than indicated by the treatment in egg injections and that the true amount of compound necessary for bioactivity may be quite low relative to the actual dosage delivered. Additionally, embryonic exposure to specific EDCs adversely affected sexual differentiation in quail, especially impacting male sexual behavior as well as neural systems, immune response, and thyroid hormones. Many of these studies considered single compounds; however, wild birds are exposed to complex mixtures and multiple compounds. We tested complex mixtures of polychlorinated biphenyls (PCBs) at concentrations that bracketed those found in eggs in contaminated regions. Results indicated that the predictive value of the toxic equivalency (TEQ), based on comparative activation of the aryl hydrocarbon receptor (AhR) relative to dioxin was not as accurate as expected. We discuss the potential of developing an endocrine disruption index (EDI) to bridge the inconsistencies observed between responses predicted by the TEQ and those observed in vivo following exposure to EDCs. Further, we will discuss how an EDI would complement the adverse outcome pathways analyses to consider the range of effects of endocrine disruptors in birds.

Comparative Lethality of In ovo Exposure to PCB 126, PCB 77, and 2 Environmentally Relevant PCB Mixtures in Japanese Quail (Coturnix japonica).

The Japanese quail (Coturnix japonica) egg bioassay was used to directly compare the toxicity of 3,3',4,4',5-pentachlorobiphenyl (PCB 126), 3,3',4,4'-tetrachlorobiphenyl (PCB 77), and 2 environmentally relevant polychlorinated biphenyl (PCB) mixtures over specified dose ranges relative to vehicle and uninjected controls. Measures included lethality and deformities. Results showed clear dose-response relationships for PCB 126 and the 2 PCB mixtures by logistic analysis of covariance using a varying threshold model because there was a low but significant slope for mortality of vehicle controls over incubation. No dose-dependent increase in mortality was observed with PCB 77 treatment. Mortality increased above baseline for PCB 126 and the 2 mixtures after embryonic day 7 (ED07) to a stable slope from ED10. Median lethal doses and thresholds for response differed for PCB 126 and the 2 PCB mixtures, with the mixtures having lower initial toxicity and all showing progressively greater toxicity over the course of development. Further, the lethality of the PCB mixtures appeared to involve both aryl hydrocarbon receptor (AhR) and non-AhR mechanisms. Incidence of deformities was unrelated to treatments. In summary, complex mixtures of PCBs were lethal in a dose-related manner, with sublethal effects from exposure to PCB 77. Environ Toxicol Chem 2019;38:2637-2650. © 2019 SETAC.

Uptake of radiolabeled 3,3',4,4'-tetrachlorobiphenyl into Japanese quail egg compartments and embryo following air cell and albumen injection.

The avian embryo is an excellent model for testing adverse developmental effects of environmental chemicals as well as uptake and movement of xenobiotics within the egg compartments. Before incubation at embryonic day 0, 14 C 3,3',4,4'-tetrachlorobiphenyl (14 C PCB 77) was injected into Japanese quail eggs either onto the air cell or into the albumen. All egg components were collected on embryonic day 1, 5, or 10, and concentrations of 14 C PCB 77 were measured in various egg components (shell, membrane, yolk, albumen, and embryo). The results showed measurable 14 C PCB 77 in all egg components, with changing concentrations in each egg component over the course of embryonic development. Specifically, concentrations in the shell content decreased between embryonic days 1 and 10, increased in albumen from embryonic days 1 to 5 and then decreased at embryonic day 10, and increased in both yolk and embryo from embryonic days 1 to 10. Vehicle and injection site both influenced 14 C PCB 77 allantoic fluid concentrations, with little effect on other egg components except for the inner shell membrane. The fatty acid vehicle injected into the albumen yielded the highest 14 C PCB 77 recovery. These findings demonstrate dynamic movement of toxicants throughout the egg components during avian embryonic development and a steady increase of relatively low levels of 14 C PCB 77 in the embryo compared with the yolk, albumen, and shell, suggesting that embryonic uptake (i.e., exposure) mirrors utilization of egg components for nutrition and growth during development. Environ Toxicol Chem 2018;37:126-135. © 2017 SETAC.