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R L Cooper

Publications and source records attributed to R L Cooper.

At least 37 records · Page 2Linked to original sources
PubMed2001

Neonatal low- and high-dose exposure to estradiol benzoate in the male rat: II. Effects on male puberty and the reproductive tract.

Environmental contaminants with estrogenic properties have been cause for heightened concern about their possible role in inducing adverse health effects. Brief exposure of rodents to high doses of natural estrogens early in life results in permanent alterations of the male reproductive tissues, but the question of whether environmentally relevant doses can cause the same effects remains controversial. The current project was designed to determine the dose-response relationship between neonatal estradiol exposure and the development of the male reproductive tract in the rat. Neonatal male Sprague-Dawley (SD) and Fisher 344 (F344) rats were exposed to beta-estradiol-3-benzoate (EB) at concentrations ranging from 0.015 microg/kg body weight (BW) to 15.0 mg/kg BW and 0.15 microg/kg BW to 1.5 mg/kg BW, respectively. Results showed an inverted U-shaped dose-response profile for testis and epididymis weights in 35-day-old SD rats, with increased organ sizes at the low-dose end of the treatment. This effect was transient and was not sustained into adulthood. Increased hepatic testosterone hydroxylase activities in low-dose animals suggest an advancement of puberty as the cause for increased reproductive organ weights. On postnatal day (PND) 90, a stimulatory low-dose response to EB was present in SD rat testicular and epididymal weights, however at one order of magnitude lower dose than that seen on PND 35, suggesting a separate effect. All SD male reproductive tract organs and serum hormones showed a permanent inhibitory response to high doses of neonatal EB. F344 rats exhibited greater estrogen sensitivity on PND 90. Despite this heightened responsiveness, F344 rats did not exhibit a low-dose effect for any endpoint. These low-dose responses to estradiol are organ and strain specific.

Aging↗
PubMed2001

Alterations in development, behavior, and physiology in Drosophila larva that have reduced ecdysone production.

We investigated behavior, physiology, sensitivity to exogenous application of ecdysone, and nerve terminal structure for differences between the reduced ecdysone genotype, ecd(1)/ecd(1), and wild-type control ecd(1)/TM6B animals during the early and late third instars when raised at 25 degrees C. The ecd(1) mutants were able to survive through larval development and form pupae. However, the results demonstrate that the time to pupation is lengthened by about 50 h for the ecd(1)/ecd(1) as compared with the wild-type control siblings. In addition to the lengthened larval cycle in the mutant, ecd(1)/ecd(1) animals, they also display behavioral differences as compared with controls. The rate of body wall contraction and mouth hook movements are reduced in the early third instar of ecd(1)/ecd(1) as compared with controls. The physiological measure of excitatory junction potential amplitude for the combined Is and Ib terminals did not reveal any differences among the two genotypes during the early third instar but the synaptic strength is reduced in the late third instars for controls. Application of exogenous ecdysone is still effective during the late third instar for the ecd(1)/ecd(1) but not the controls. This suggests that endogenous production of ecdysone have already taken place in the wild-type but not the ecd(1)/ecd(1) larvae, thus the rapid nongenomic responses could still be observed in the late third ecd(1)/ecd(1) larvae. Structurally the number of varicosities and the terminal length showed significant differences between ecd(1)/ecd(1) and the wild-type ecd(1)/TM6B genotype in the late third instars.

Animals↗
PubMed2001

Field resistance of two soybean germplasm lines, HC95-15MB and HC95-24MB, against bean leaf beetle (Coleoptera: Chrysomelidae), western corn rootworm (Coleoptera: Chrysomelidae), and Japanese beetles (Coleoptera: Scarabaidae).

Two recently released, Mexican bean beetle, Epilachna varivestis, Mulsant, resistant soybean, Glycine max (L.) Merrill, germplasm lines, HC95-15MB and HC95-24MB, were examined for foliar and pod feeding resistance to adult bean leaf beetles, Cerotoma trifurcata (Forster), western corn rootworms, Diabrotica virgifera virgifera LeConte, and Japanese beetles, Popillia japonica Newman. Both lines were planted along with a susceptible control cultivar in 18 by 30-m plots and separate 0.8-ha size fields. Insects were sampled on a weekly basis with a sweep net. In late summer, defoliation ratings were recorded along with data on percentage pod feeding. Although a few significant differences in insect densities were obtained among the soybean lines on some sampling dates, no specific trends were observed in the ability of the resistant germplasm to reduce insect numbers. Insect population densities were similarly on all lines. However, both resistant lines were able to reduce defoliation during the growing season. Conversely, percentage pod feeding was similar among all the soybean lines, with no differences observed. The resistant germplasm lines appear able to lower levels of defoliation, and thus, offer a potential management tactic where leaf feeding, i.e., defoliation, is of concern. However, their ability to greatly reduce beetle population densities, and for the bean leaf beetle, to reduce pod feeding, appears limited.

Animals↗
PubMed2001

Comparative evaluation of vessel elements in S alix spp. (Salicaceae) endemic to the Athabasca sand dunes of northern Saskatchewan, Canada.

Vessel element (VE) characters, including density, lumen diameter, length, and clustering, were evaluated using light and scanning electron microscopy in four endemic Salix taxa from the Lake Athabasca sand dunes in northern Saskatchewan, Canada. These data were compared with the widespread putative sister species for each endemic. Endemic taxa exhibited similar VE densities as compared to their associated sister species. Salix brachycarpa var. brachycarpa and its derived endemic, var. psammophila, had the highest VE density values of all endemic-progenitor pairs in this study. Values for VE lumen diameter and VE length were significantly different in some of the species pairs. Lumen diameter of the endemic S. planifolia ssp. tyrrelli was significantly less than that of its widespread sister species, ssp. planifolia. Salix turnorii had significantly greater values for both VE lumen diameter and length than its progenitor, S. lutea. Vessel element clustering did not differ significantly between endemic and progenitor taxa with the exception of S. silicicola and its arctic progenitor, S. alaxensis. Structural differences for these endemic willows appear related to their open sand habitat, and taxonomic implications for endemic-progenitor pairs are discussed.

Journal Article↗
PubMed2000

Statistical methods for assessing the dimensions of synaptic vesicles in nerve terminals.

Chemical transmission between neurons occurs by the release of neurotransmitter packaged within vesicles of the presynaptic neuron onto a postsynaptic target. The amount of transmitter contained within a vesicle is in part regulated by the size of the vesicle. Thus, it is of general interest to quantify the dimension of vesicles in understanding the basic principles of chemical synaptic transmission. These vesicles can only be measured by electron microscopic techniques. Obtaining the true dimensions of synaptic structures is therefore complicated by stereological considerations. In this study, we suggest improved methods for determining the distributions (and mean sizes) for populations of vesicle diameters by mathematical processes involving (1) an implicit inversion of the empirical data distribution, (2) an explicit inversion approach, and (3) an approach based on substituting the empirical distribution into the inversion formula and then isotonizing using an iterated convex minorant algorithm. These procedures provide distributions that better represent the true population distributions (and means) for comparisons with other data sets of vesicle diameter measures.

Animals↗
PubMed2000

Characterization of muscles associated with the articular membrane in the dorsal surface of the crayfish abdomen.

The anatomy, physiology, and biochemistry of the dorsal membrane muscle (DMA) and the superficial extensor muscle accessory head (SEAcc) in the abdomen of the crayfish, Procambarus clarkii and lobster, Homarus americanus, are reported. These muscles have not been previously characterized physiologically or biochemically. The anatomy was originally described by Pilgrim and Wiersma (1963. J Morph 113:453-587). The arrangement of these muscles varies depending on the abdominal segment. The function of the dorsal membrane muscle is to retract the thin articulating membrane joining the cuticular segments so that the dorsal membrane does not evert during extension of the abdomen. Consequently, the articular membrane does not protrude, and thus potential damage to the membrane is minimized. Examination of nerve terminal morphology revealed strings of varicosities, usually only associated with tonic terminals. The electrophysiological data indicate that there are at least four tonic excitatory and one inhibitory motor neuron innervating these muscles. Facilitation indices and fatigue-resistance indicate physiologically the tonic nature of innervation. Anti-GABA antibodies demonstrate the anatomical presence of an inhibitor motor neuron. The SDS electrophoretic analysis of myofibrillar proteins and Western blots of key protein isoforms for these muscles in crayfish and lobsters also indicate that the DMA and SEAcc muscles are tonic phenotype. J. Exp. Zool. 287:353-377, 2000.

Abdomen↗
PubMed2000

Assessing accurate sizes of synaptic vesicles in nerve terminals.

Chemical synaptic transmission occurs when vesicles within a presynaptic neuron fuse to the membrane and release their neurotransmitter content into the synaptic cleft, eliciting a response in the postsynaptic cell. If concentration of neurotransmitter is the same in all synaptic vesicles, the volume of the vesicle determines how much transmitter is released. Thus, variation in vesicular volume may contribute to observed variance of synaptic quantal unit size. The present study provides an approach to more fully and accurately characterize the dimensions of synaptic vesicles within a population containing varied sizes of vesicles. The methodology can be applied in a wide range of stereological problems. The approach characterizes the distribution of vesicle sizes within a population and provides a means to assess effects of experimental manipulations on vesicle dimensions. The mathematical treatments to obtain the true distribution of vesicle sizes involve extraction of the observed distribution from an enlarged population containing smaller vesicle diameters produced by sectioning of the specimens. A FORTRAN program is provided.

Algorithms↗
PubMed2000

Influence of serotonin on the kinetics of vesicular release.

The mechanisms by which synaptic vesicles are transported and primed to fuse with the presynaptic membrane are important to all chemical synapses. Processes of signal transduction that affect vesicular dynamics, such as the second-messenger cascades induced by neuromodulators, are more readily addressed in assessable synaptic preparations of neuromuscular junctions in the crayfish. We assessed the effects of serotonin (5-HT) through the analysis of the latency jitter and the quantal parameters: n and p in the opener muscle of the walking leg in crayfish. There is an increase in the size of the postsynaptic currents due to more vesicles being released. Quantal analysis reveals a presynaptic mechanism by an increase in the number of vesicles being released. Latency measures show more events occur with a short latency in the presence of 5-HT. No effect on the frequency or size of spontaneous release was detected. Thus, the influence of 5-HT is presynaptic, leading to a release of more vesicles at a faster rate.

Animals↗
PubMed2000

Muscle type-specific myosin isoforms in crustacean muscles.

Differential expression of multiple myosin heavy chain (MyHC) genes largely determines the diversity of critical physiological, histochemical, and enzymatic properties characteristic of skeletal muscle. Hypotheses to explain myofiber diversity range from intrinsic control of expression based on myoblast lineage to extrinsic control by innervation, hormones, and usage. The unique innervation and specialized function of crayfish (Procambarus clarkii) appendicular and abdominal musculature provide a model to test these hypotheses. The leg opener and superficial abdominal extensor muscles are innervated by tonic excitatory motoneurons. High resolution SDS-PAGE revealed that these two muscles express the same MyHC profile. In contrast, the deep abdominal extensor muscles, innervated by phasic motoneurons, express MyHC profiles different from the tonic profiles. The claw closer muscles are dually innervated by tonic and phasic motoneurons and a mixed phenotype was observed, albeit biased toward the phasic profile seen in the closer muscle. These results indicate that multiple MyHC isoforms are present in the crayfish and that differential expression is associated with diversity of muscle type and function.

Animals↗
PubMed2000

The effects of 5-HT on sensory, central and motor neurons driving the abdominal superficial flexor muscles in the crayfish.

Serotonin (5-HT) induces a variety of physiological and behavioral effects in crustaceans. However, the mechanisms employed by 5-HT to effect behavioral changes are not fully understood. Among the mechanisms by which these changes might occur are alterations in synaptic drive and efficacy of sensory, interneurons and motor neurons, as well as direct effects on muscles. We investigated these aspects with the use of a defined sensory-motor system, which is entirely contained within a single abdominal segment and consists of a 'cuticular sensory neurons segmental ganglia abdominal superficial flexor motor neurons-muscles' circuit. Our studies address the role of 5-HT in altering (1) the activity of motor neurons induced by sensory stimulation; (2) the inherent excitability of superficial flexor motor neurons; (3) transmitter release properties of the motor nerve terminal and (4) input resistance of the muscle. Using en passant recordings from the motor nerve, with and without sensory stimulation, and intracellular recordings from the muscle, we show that 5-HT enhances sensory drive and output from the ventral nerve cord resulting in an increase in the firing frequency of the motor neurons. Also, 5-HT increases transmitter release at the neuromuscular junction, and alters input resistance of the muscle fibers.

Abdominal Muscles↗
PubMed2000

Heart rate measures in blind cave crayfish during environmental disturbances and social interactions.

Most animals continually assess the environment in which they live and alter their behavior according to various stimuli. As an observer, one looks for changes in a behavior indicating that an animal responded to a particular event. When the animal does not make significant behavioral changes as measured by bodily movements, the animal may be characterized as unresponsive to a given stimulus. This study demonstrates that when behavioral body movements can not be observed an internal physiological measure of heart rate (HR) shows dramatic changes following presentation of defined stimuli. This study used the blind cave crayfish and examined their responsiveness to the following stimuli: light (infrared, dim red, and white), water-borne vibrations, removal of water, olfactory cues, and social interaction with partners. This study demonstrates that there is substantial individual variation of HR at basal levels and with the intensity of an social interaction. We find HR is a reasonable measure of the responsiveness of blind cave crayfish to given stimuli even in the absence of observable behavioral changes. This enables the observer to determine if an individual is responsive to and making an assessment of particular cues.

Animals↗
PubMed2000

Sensitivity of transformed (phasic to tonic) motor neurons to the neuromodulator 5-HT.

Long-term adaptation resulting in a 'tonic-like' state can be induced in phasic motor neurons of the crayfish, Procambarus clarkii, by daily low-frequency stimulation [Lnenicka, G.A., Atwood, H.L., 1985b. Long-term facilitation and long-term adaptation at synapses of a crayfish phasic motoneuron. J. Neurobiol. 16, 97-110]. To test the hypothesis that motor neurons undergoing adaptation show increased responses to the neuromodulator serotonin (5-HT), phasic motor neurons innervating the deep abdominal extensor muscles of crayfish were stimulated at 2.5 Hz, 2 h/day, for 7 days. One day after cessation of conditioning, contralateral control and conditioned motor neurons of the same segment were stimulated at 1 Hz and the induced excitatory post-synaptic potentials (EPSPs) were recorded from DEL(1) muscle fibers innervated by each motor neuron type. Recordings were made in saline without and with 100 nM 5-HT. EPSP amplitudes were increased by 5-HT exposure in all cases. Conditioned muscles exposed to 5-HT showed a 2-fold higher percentage of increase in EPSP amplitude than did control muscles. Thus, the conditioned motor neurons behaved like intrinsically tonic motoneurons in their response to 5-HT. While these results show that long-term adaptation (LTA) extends to 5-HT neuromodulation, no phenotype switch could be detected in the postsynaptic muscle. Protein isoform profiles, including the myosin heavy chains, do not change after 1 week of conditioning their innervating motor neurons.

Animals↗
PubMed2000

Heart rate within male crayfish: social interactions and effects of 5-HT.

Behaviors, such as those that establish dominant and subordinate social status, are thought to be driven by various neuromodulators and hormones. In crustaceans, the level of serotonin (5-HT) in the hemolymph is correlated with degree of aggressiveness. The crustacean heart is neurogenic and is modulated by neural secretion of 5-HT in the hemolymph, which bathes the cardiac tissue. We discuss and present the results of measuring heart rate (HR) of crayfish during interactions, as an indication of their state of excitability. HR is the result of multiple influences: a cocktail of hormones and modulators. HR was monitored during the periods in which crayfish established aggressive and submissive social status, during sham injections, and following injections of various doses of 5-HT. Crayfish, during an interaction to establish social status, can increase HR. Both the aggressive and submissive crayfish can dampen their HR within seconds during a pause in the interaction, while still posturing in an aggressive or submissive state. Injections of 5-HT to obtain systemic levels of approximately 100 nM-10 microM increase HR substantially for hours. This suggests that aggressive interactions and the establishment of a dominant posture may not be related to large increases in the free concentrations of 5-HT within the circulating hemolymph, since a sustained HR is not observed in aggressive animals. Instead, the results may demonstrate that inhibitory cardiac regulation is present in the aggressors during interactions and that a regulator is possibly 5-HT.

Animals↗
PubMed2000

Endocrine-disrupting chemicals: prepubertal exposures and effects on sexual maturation and thyroid activity in the female rat. A focus on the EDSTAC recommendations.

In 1996, the US Environmental Protection Agency was given a mandate by Congress to develop a screening program that would evaluate whether variously identified compounds could affect human health by mimicking or interfering with normal endocrine regulatory functions. Toward this end, the Agency chartered the Endocrine Disruptor Screening and Testing Advisory Committee in October of that year that would serve to recommend a series of in vitro and in vivo protocols designed to provide a comprehensive assessment of a chemical's potential endocrine-disrupting activity. A number of these protocols have undergone subsequent modification by EPA, and this review focuses specifically on the revised in vivo screening procedure recommended under the title Research Protocol for Assessment of Pubertal Development and Thyroid Function in Juvenile Female Rats. Background literature has been provided that summarizes what is currently known about pubertal development in the female rat and the influence of various forms of pharmaceutical and toxicological insult on this process and on thyroid activity. Finally, a section is included that discusses technical issues that should be considered if the specified pubertal endpoints are to be measured and successfully evaluated.

Animals↗
PubMed2000

Endocrine-disrupting chemicals: prepubertal exposures and effects on sexual maturation and thyroid function in the male rat. A focus on the EDSTAC recommendations. Endocrine Disrupter Screening and Testing Advisory Committee.

Puberty in mammalian species is a period of rapid interactive endocrine and morphological changes. Therefore, it is not surprising that exposure to a variety of pharmaceutical and environmental compounds has been shown to dramatically alter pubertal development. This concern was recognized by the Endocrine Disrupter Screening and Testing Advisory Committee (EDSTAC) that acknowledged the need for the development and standardization of a protocol for the assessment of the impact of endocrine-disrupting compounds (EDC) in the pubertal male and recommended inclusion of an assay of this type as an alternative test in the EDSTAC tier one screen (EPA, 98). The pubertal male protocol was designed to detect alterations of pubertal development, thyroid function, and hypothalamic-pituitary-gonadal (HPG) system peripubertal maturation. In this protocol, intact 23-day-old weanling male rats are exposed to the test substance for 30 days during which pubertal indices are measured. After necropsy, reproductive and thyroid tissues are weighed and evaluated histologically and serum taken for hormone analysis. The purpose of this review was to examine the available literature on pubertal development in the male rat and evaluate the efficacy of the proposed protocol for identifying endocrine-disrupting chemicals. The existing data indicate that this assessment of puberty in the male rat is a simple and effective method to detect the EDC activity of pesticides and toxic substances.

Animals↗
PubMed2000

Atrazine disrupts the hypothalamic control of pituitary-ovarian function.

The chloro-S-triazine herbicides (i.e., atrazine, simazine, cyanazine) constitute the largest group of herbicides sold in the United States. Despite their extensive usage, relatively little is known about the possible human-health effects and mechanism(s) of action of these compounds. Previous studies in our laboratory have shown that the chlorotriazines disrupt the hormonal control of ovarian cycles. Results from these studies led us to hypothesize that these herbicides disrupt endocrine function primarily through their action on the central nervous system. To evaluate this hypothesis, we examined the estrogen-induced surges of luteinizing hormone (LH) and prolactin in ovariectomized Sprague-Dawley (SD) and Long-Evans hooded (LE) rats treated with atrazine (50-300 mg/kg/day, by gavage) for 1, 3, or 21 days. One dose of atrazine (300 mg/kg) suppressed the LH and prolactin surge in ovariectomized LE, but not SD female rats. Atrazine (300 mg/kg) administered to intact LE females on the day of vaginal proestrus was without effect on ovulation but did induce a pseudopregnancy in 7 of 9 females. Three daily doses of atrazine suppressed the estrogen-induced LH and prolactin surges in ovariectomized LE females in a dose-dependent manner, but this same treatment was without effect on serum LH and prolactin in SD females. The estrogen-induced surges of both pituitary hormones were suppressed by atrazine (75-300 mg/kg/day) in a dose-dependent manner in females of both strains evaluated after 21 days of treatment. Three experiments were then performed to determine whether the brain, pituitary, or both organs were the target sites for the chlorotriazines. These included examination of the ability of (1) the pituitary lactotrophs to secrete prolactin, using hypophyosectomized females bearing pituitary autotransplants (ectopic pituitaries); (2) the synthetic gonadotropin-releasing hormone (GnRH) to induce LH secretion in females treated with high concentrations of atrazine for 3 days; and (3) atrazine (administered in vivo or in vitro) to suppress LH and prolactin secretion from pituitaries, using a flow-through perifusion procedure. In conclusion, the results of these studies demonstrate that atrazine alters LH and prolactin serum levels in the LE and SD female rats by altering the hypothalamic control of these hormones. In this regard, the LE female appeared to be more sensitive to the hormone suppressive effects of atrazine, as indicated by the decreases observed on treatment-day 3. These experiments support the hypothesis that the effect of atrazine on LH and prolactin secretion is mediated via a hypothalamic site of action.

Animals↗
PubMed2000

Estrogenic activity of octylphenol, nonylphenol, bisphenol A and methoxychlor in rats.

Considerable attention has recently been focused on environmental chemicals that disrupt the reproductive system by altering steroid receptor function. Although numerous in vitro and in vivo methods have been shown to be useful approaches for identifying chemicals that can disrupt reproduction through a direct interaction with the estrogen receptor, it is imperative that the protocols selected be capable of detecting chemicals with a broad range of estrogenic activity. Here we evaluate the reliability of the 3-day uterotrophic assay for detecting chemicals with strong or weak estrogenic activity in both prepubertal and ovariectomized adult Long Evans rats. These data were compared to additional measures of estrogenic activity, which included the age of vaginal opening, the induction of cornified vaginal epithelial cells in ovariectomized adult rats, and estrous cyclicity in intact adult rats. Test chemicals selected for these studies included 17-beta-estradiol, ethynyl estradiol, methoxychlor, 4-tert-octylphenol, 4-nonylphenol and bisphenol A. Data from in vitro receptor binding assays compared the ability of the test chemicals to compete with [3H]-estradiol or [3H]-promegestone for binding to estrogen or progesterone receptors. As expected, the binding affinities for the estrogen receptor ranged from high to low, as reflected by Ki concentrations of 0.4 nM for 17-beta-estradiol and ethynyl estradiol, and 0.05-65 microM for 4-tert-octyphenol, 4-nonylphenol, and methoxychlor. Although none of the test chemicals demonstrated a high affinity for binding to the progesterone receptor, 4-tert-octylphenol and 4-nonylphenol exhibited a weak affinity, with Ki concentrations ranging from 1.2 to 3.8 microM. In vivo studies indicated that the 3-day uterotrophic assay in prepubertal rats was the best method for detecting estrogenic activity when compared with all other end points, based upon the dose-response data for ethynyl estradiol (0.01-0.1 mg/kg), 4-tert-octylphenol (50-200 mg/kg, oral), and 4-nonylphenol (25-100 mg/kg, oral). Although oral doses of ethynyl estradiol (0.01 mg/kg) and 4-nonylphenol (50 mg/kg) induced a significant increase in uterine weight in the prepubertal rats, these doses were ineffective for stimulating a similar response in ovariectomized adult rats. The age of vaginal opening was advanced following oral exposure from postnatal days 21-35 to ethynyl estradiol (0.01 mg/kg), methoxychlor (50 mg/kg), 4-tert-octylphenol (200 mg/kg), and 4-nonylphenol (50 mg/kg). Although bisphenol A (200 mg/kg, oral) induced a significant uterotrophic response within 3 days in prepubertal rats, doses up to 400 mg/kg failed to advance the age of vaginal opening. Monitoring changes in the vaginal epithelium of ovariectomized adult rats was the least effective method for detecting estrogenic activity for 4-tert-octylphenol and bisphenol A. The number of 4-5 day estrous cycles was reduced during a 25-day exposure to ethynyl estradiol (0.01 mg/kg), methoxychlor (50 mg/ kg), 4-tert-octylphenol (200 mg/kg), 4-nonylphenol (100 mg/kg), and bisphenol A (100 mg/kg) by oral gavage. Although long periods of extended diestrus (7-14 days) were generally correlated with exposure to ethynyl estradiol and 4-tert-octylphenol, the cycling patterns following exposure to methoxychlor, 4-nonylphenol and bisphenol A were not as clearly defined, with shorter periods of extended diestrus (4-7 days) and/or estrus (3-5 days) intermittently observed throughout the exposure period. Together these data provide a comparison of the 3-day uterotrophic assay with alternative measures of estrogenic activity for a group of test chemicals with a broad range of affinities for the estrogen receptor. These data can be useful during the assessment and validation of methods for screening environmental chemicals for endocrine disrupting activity.

Animals↗