Organization versus activation: the role of endocrine-disrupting contaminants (EDCs) during embryonic development in wildlife.

Guillette, Louis J.; Crain, D. Andrew; Rooney, A A; Pickford, Daniel B.

doi:10.1289/ehp.95103s7157

Cited by 274 publications

(151 citation statements)

References 66 publications

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“…It has been suggested that the abnormalities observed in these alligators are similar to those reported following embryonic exposure to the potent synthetic estrogen diethylstilbestrol (DES) (4). Prenatal exposure to DES in both humans and experimental animals has been associated with an array of reproductive abnormalities (5,6).…”

mentioning

confidence: 88%

Interaction of environmental chemicals with the estrogen and progesterone receptors from the oviduct of the American alligator.

Vonier¹,

Crain²,

McLachlan³

et al. 1996

Environ Health Perspect

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212

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Reports of reproductive abnormalities in the American alligator from Lake Apopka, Florida, have been linked to a spill of DDT and other pesticides suspected of having hormonelike activity. To determine whether environmental chemicals had the potential to function as exogenous hormones in the American alligator, we examined the ability of chemicals to bind the estrogen receptor (aER) and progesterone receptor (aPR) in a protein extract prepared from the oviduct of the alligator. In competition binding assays with [3H]17 beta-estradiol, some DDT metabolites showed inhibition of [3H]17 beta-estradiol binding to aER. A combination of DDTs demonstrated an additive decrease in [3H]17 beta-estradiol binding to aER. Modern-use chemicals such as alachlor, trans-nonachlor, endosulfan, and atrazine also competed with [3H]17 beta-estradiol for binding to the aER. To test the effect of chemicals identified in alligator eggs from Lake Apopka on [3H]17 beta-estradiol binding, we mixed these chemicals at concentrations measured in eggs in the competition binding assay. 2,2-bis(4-chlorophenyl)-N-(methoxymethyl)acetamide (p,p'-DDD) and trans-nonachlor, both found in Lake Apopka, interacted with aER, whereas others such as chlordane and toxaphene did not. Surprisingly, combinations of these chemicals decreased [3H]17 beta-estradiol binding in a greater than additive manner. To assess the ability of chemicals to interact with aPR, we performed commpetition binding assays with the synthetic progestin [3H]R5020. Most of the chemicals tested did not reduce [3H]R5020 binding to aPR, whereas endosulfan, alachlor, and kepone inhibited binding. These results provide the first evidence that environmental chemicals bind the aER and aPR from the American alligator, supporting the hypothesis that the reported reproductive abnormalities may be related to the modulation of endocrine-related responses. The findings that combinations of chemicals demonstrated a greater than additive interaction with the aER and some chemicals bind to the aPR in the competition binding assay are novel. This suggests that interactions of these chemicals with the endocrine system are complex. Images Figure 1. A Figure 1. B Figure 2. Figure 3. Figure 3. Figure 4. A Figure 4. B

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mentioning

confidence: 88%

Interaction of environmental chemicals with the estrogen and progesterone receptors from the oviduct of the American alligator.

Vonier¹,

Crain²,

McLachlan³

et al. 1996

Environ Health Perspect

Self Cite

212

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“…The simulations allow us to assess whether PCBs pose toxicological risks to killer whale populations either during the past or into the future. Adverse effects of PCBs on wildlife, which have been extensively studied, include changes to immune function, neurological development, endocrine endpoints, and/or reproductive health (41)(42)(43)(44)(45)(46). In the absence of thresholds determined specifically for PCB-related health effects in killer whales, we selected the threshold that was established from a long-term captive feeding study designed to measure the effects of POPs (among which the PCBs dominated) on harbor seals (Phoca vitulina).…”

Section: History Of Pcbs In Southern Resident Killer Whalesmentioning

confidence: 99%

Killer Whales (Orcinus orca) Face Protracted Health Risks Associated with Lifetime Exposure to PCBs

Hickie

Ross

Macdonald

et al. 2007

Environ. Sci. Technol.

107

110

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Polychlorinated biphenyl (PCB) concentrations declined rapidly in environmental compartments and most biota following implementation of regulations in the 1970s. However, the metabolic recalcitrance of PCBs may delay responses to such declines in large, long-lived species, such as the endangered and highly PCB-contaminated resident killer whales (Orcinus orca) of the Northeastern Pacific Ocean. To investigate the influence of life history on PCB-related health risks, we developed models to estimate PCB concentrations in killer whales during the period from 1930 forward to 2030, both within a lifetime (∼50 years) and across generations, and then evaluated these in the context of health effects thresholds established for marine mammals. Modeled PCB concentrations in killer whales responded slowly to changes in loadings to the environment as evidenced by slower accumulation and lower magnitude increases in PCB concentrations relative to prey, and a delayed decline that was particularly evident in adult males. Since PCBs attained peak levels well above the effects threshold (17 mg/kg lipid) in ∼1969, estimated concentrations in both the northern and the more contaminated southern resident populations have declined gradually. Projections suggest that the northern resident population could largely fall below the threshold concentration by 2030 while the endangered southern residents may not do so until at least 2063. Long-lived aquatic mammals are therefore not protected from PCBs by current dietary residue guidelines.

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“…Developmental abnormalities due to exposure to endocrine-disrupting drugs (e.g., DES) are also well documented (George and Wilson 1994;Mittendorf 1995;Swan and vom Saal 2001). The importance of small changes in the concentration of endocrine-signaling molecules during critical periods in development has been studied extensively in laboratory animals and wildlife (Colborn et al 1993;Fry 1995;Guillette et al 1995;vom Saal 1989;vom Saal et al 1997).…”

Section: Timing Frequency and Duration Of Exposurementioning

confidence: 99%

Exposure assessment for endocrine disruptors: some considerations in the design of studies.

Rice

Birnbaum

Cogliano

et al. 2003

Environ Health Perspect

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In studies designed to evaluate exposure-response relationships in children's development from conception through puberty, multiple factors that affect the generation of meaningful exposure metrics must be considered. These factors include multiple routes of exposure; the timing, frequency, and duration of exposure; need for qualitative and quantitative data; sample collection and storage protocols; and the selection and documentation of analytic methods. The methods for exposure data collection and analysis must be sufficiently robust to accommodate the a priori hypotheses to be tested, as well as hypotheses generated from the data. A number of issues that must be considered in study design are summarized here.

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Organization versus activation: the role of endocrine-disrupting contaminants (EDCs) during embryonic development in wildlife.

Cited by 274 publications

References 66 publications

Interaction of environmental chemicals with the estrogen and progesterone receptors from the oviduct of the American alligator.

Interaction of environmental chemicals with the estrogen and progesterone receptors from the oviduct of the American alligator.

Killer Whales (Orcinus orca) Face Protracted Health Risks Associated with Lifetime Exposure to PCBs

Exposure assessment for endocrine disruptors: some considerations in the design of studies.

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