For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from...

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Hormones and endocrine-disrupting chemicals: Low-dose effects and nonmonotonic dose responses

1. Clarification: The 2013 Guidelines make a distinction between euthanasia, humane killing, and slaughter, and state that neither slaughter nor humane killing is covered in the document P.68, S6.1.1. Not included among the definitions of these terms are ending the lives of healthy animals or scientific collection of animals. For clarification, whatever the term used, classification of the method, or reason given for killing animals: euthanasia, humane killing, slaughter, harvest, depopulation, scientific collection, or research-related, the Council on Accreditation’s foremost concern, in all situations, is with humane technique. The goal of humane technique is to minimize pain, distress, and the negative effect to the animal. The technique employed should result in rapid loss of consciousness followed by cardiac or respiratory arrest and, ultimately, a loss of brain function. Although complete absence of pain and distress is preferred, it is understood that it cannot always be achieved P7.13.2.

https://works.bepress.com/cheryl_greenacre/14/download/

AVMA Guidelines for the Euthanasia of Animals: 2013 Edition

https://apps.who.int/iris/bitstream/10665/78102/1/WHO_HSE_PHE_IHE_2013.1_eng.pdf

State of the Science of Endocrine Disrupting Chemicals - 2012

BackgroundIncreasing concern over bisphenol A (BPA) as an endocrine-disrupting chemical and its possible effects on human health have prompted the removal of BPA from consumer products, often label...

Bisphenol S and F: A Systematic Review and Comparison of the Hormonal Activity of Bisphenol A Substitutes.

The use of captive breeding in species recovery has grown enormously in recent years, but without a concurrent growth in appreciation of its limitations. Problems with (1) establishing self-sufficient captive populations, (2) poor success in reintroductions, (3) high costs, (4) domestication, (5) preemption of other re- covery techniques, (6) disease outbreaks, and (7) maintaining administrative continuity have all been signif- icant. The technique has often been invoked prematurely and should not normally be employed before a care- ful field evaluation of costs and benefits of all conservation alternatives has been accomplished and a determination made that captive breeding is essential for species survival. Merely demonstrating that a spe- cies" population is declining or has fallen below what may be a minimum viable size does not constitute enough analysis to justify captive breeding as a recovery measure. Captive breeding should be viewed as a last resort in species recovery and not a prophylactic or long-term solution because of the inexorable genetic and phenotypic changes that occur in captive environments. Captive breeding can play a crucial role in re- covery of some species for which effective alternatives are unavailable in the short term. However, it should not displace habitat and ecosystem protection nor should it be invoked in the absence of comprehensive ef- forts to maintain or restore populations in wild habitats. Zoological institutions with captive breeding pro- grams should operate under carefully defined conditions of disease prevention and genetic~behavioral man- agement. More important, these institutions should help preserve biodiversity through their capacities for public education, professional training, research, and support of in situ conservation efforts.

/pdf/limitations-of-captive-breeding-in-endangered-species-254je76vhz.pdf

Limitations of Captive Breeding in Endangered Species Recovery

The importance of mate behavioural compatibility in parenting and reproductive success by cockatiels, Nymphicus hollandicus

Foraging opportunity and increased physical complexity both prevent and reduce psychogenic feather picking by young Amazon parrots

Brains of nonmammalian vertebrates typically contain multiple forms of gonadotropin-releasing hormone (GnRH). Until recently, only the mammalian form of GnRH (mGnRH) had been isolated in placental mammals. Biochemical and histological data show that both mGnRH and chicken-II GnRH (cGnRH-II) are present in a primitive placental mammal, the musk shrew (Suncus murinus). Similar to the case in nonmammalian species, in the musk shrew, neurons that express cGnRH-II are located in a discrete cluster in the midbrain. We have used a combination of radioimmunoassay and immunocytochemistry, analyzed at the light level and with electron microscopy, to describe the distribution of cGnRH-II cell bodies and fibers in the musk shrew brain. All cGnRH-II-immunoreactive (ir) neurons reside in the midbrain, and this area contains the greatest concentration of cGnRH-II peptide in the brain. At the light and electron micrographic levels, we have identified synaptic terminals containing dense core vesicles that are immunoreactive for cGnRH-II in the medial habenula. Radioimmunoassay reveals that this region contains the second greatest concentration of cGnRH-II in the brain. Widely scattered cGnRH-II-ir fibers are present throughout the forebrain, particularly in the medial septum, hypothalamus, and midbrain central gray. Scant cGnRH-II fibers are present in the median eminence, arcuate nucleus, and infundibular stem, and only low concentrations of the peptide are detected in these areas. Finally, intravenous administration of mGnRH is ten times more effective than cGnRH-II in promoting ovulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution of chicken-II gonadotropin-releasing hormone in mammalian brain.

The distribution of cells and fibers immunoreactive (ir) for either chicken gonadotropin-releasing hormone I (cGnRH I; [Gln8]GnRH) or II ([His5,Trp7,Tyr8]GnRH) was determined in brains of turkey hens to reveal whether these peptides occur in separate neuronal systems. ir-cGnRH I cells were located: along the medial aspect of the ventriculus lateralis, nucleus accumbens, and bed nucleus of the stria terminalis; ventral to the tractus septomesencephalicus and extending medially to the third ventricle, and caudally into the lateral hypothalamic area; and in a diffuse band extending from the nucleus preopticus medialis to the nucleus dorsomedialis anterior thalami. cGnRH I fibers were evident in these areas in addition to the hippocampus, nucleus subhabenularis medialis, nucleus ventromedialis hypothalami, and median eminence. Two groups of ir-cGnRH II cells were observed: a magnocellular group lying between the substantia grisea centralis and the nucleus ruber; and a parvicellular group lying medial to the nucleus of the basal optic root and extending into the lateral hypothalamic area. ir-cGnRH II fibers were prominent in limbic structures (cortex piriformis, lateral to nucleus taeniae, hippocampus); olfactory areas (tuberculum olfactorium, nucleus subhabenularis lateralis, nucleus septalis lateralis); areas that in other avian species have steroid-concentrating cells or receptors (medial edge of lobus parolfactorius, nucleus septalis medialis, nucleus periventricularis magnocellularis, nucleus dorsomedialis posterior thalami); and areas containing ir-GnRH I cells or fibers but not in median eminence. These results suggest that cGnRH I and II occur in separate neuronal systems and that cGnRH II does not directly promote pituitary gonadotropin secretion.

Immunohistochemical localization of chicken gonadotropin-releasing hormones I and II (cGnRH I and II) in turkey hen brain.

There are major changes in circulating luteinizing hormone (LH), prolactin (PRL), estrogens (E), and progesterone (P) in relation to the onset of reproduction, egg laying, incubation, and care of young. LH levels increase in the prelaying period, followed some days later by increased circulating levels of E, P, and PRL. Levels of these hormones tend to stabilize during egg laying with periodic ovulatory cycle changes. Around the onset of incubation PRL levels increase, while LH, E, and P levels fall. During incubation PRL reaches very high levels, falling sharply when incubation is terminated. Stimulatory effects of hypothalamic neurotransmitters, peptides, and ovarian steroids on PRL secretion have been shown. The prelaying increase is dependent on E and P and the high levels of incubation require a functional serotonergic system. The causal relationships and roles of PRL in incubation of gallinaceous birds are, however, still unclear.

James R. Millam

Papers

The importance of mate behavioural compatibility in parenting and reproductive success by cockatiels, Nymphicus hollandicus

Foraging opportunity and increased physical complexity both prevent and reduce psychogenic feather picking by young Amazon parrots

Distribution of chicken-II gonadotropin-releasing hormone in mammalian brain.

Immunohistochemical localization of chicken gonadotropin-releasing hormones I and II (cGnRH I and II) in turkey hen brain.

Regulation of prolactin and its role in gallinaceous bird reproduction