Defective reproductive organ morphology and function in domestic rooster embryonically exposed to o,p'-DDT or ethynylestradiol.

Environmental pollutants with estrogenic activity have a potential to disrupt estrogen-dependent developmental processes. The objective of this study was to investigate if embryonic exposure to the environmental estrogens o,p'-DDT (1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2,2-trichloroethane; 37, 75, 150 or 300 microg/g egg) and EE2 (17alpha-ethynyl estradiol; 60 ng/g egg) affects the reproductive system in domestic roosters. Following egg injection on Embryonic Day 4, the newly hatched chicks were sexed by cloacal inspection. A skewed phenotypic sex ratio with overrepresentation of chicks deemed as females was observed in the groups exposed to the three highest doses of o,p'-DDT but not in the EE2-exposed group. Normal sex ratios were observed in all groups at adulthood. However, a cloacal deformation seemed to remain in the adult roosters, causing an abnormal semen flow upon semen collection. Semen yield was significantly reduced in both o,p'-DDT-exposed and EE2- exposed birds, whereas semen quality was unaffected. When killed, deformations of the left testis were found in all treatment groups. Image analysis revealed a reduced seminiferous tubular area in the roosters exposed to the two highest doses of o,p'-DDT. Embryonic exposure to o,p'-DDT caused decreased comb weight and right-spur diameter, while EE2 only affected right-spur diameter. In conclusion, this study shows that embryonic exposure to estrogenic compounds can induce permanent effects in male birds. The effects of the two studied compounds were partly similar but o,p'-DDT also induced alterations not seen in the EE2-treated birds.

Embryonic exposure to oestrogen causes eggshell thinning and altered shell gland carbonic anhydrase expression in the domestic hen.

Eggshell thinning among wild birds has been an environmental concern for almost half a century. Although the mechanisms for contaminant-induced eggshell thinning are not fully understood, it is generally conceived to originate from exposure of the laying adult female. Here we show that eggshell thinning in the domestic hen is induced by embryonic exposure to the synthetic oestrogen ethynyloestradiol. Previously we reported that exposure of quail embryos to ethynyloestradiol caused histological changes and disrupted localization of carbonic anhydrase in the shell gland in the adult birds, implying a functional disturbance in the shell gland. The objective of this study was to examine whether in ovo exposure to ethynyloestradiol can affect eggshell formation and quality in the domestic hen. When examined at 32 weeks of age, hens exposed to ethynyloestradiol in ovo (20 ng/g egg) produced eggs with thinner eggshells and reduced strength (measured as resistance to deformation) compared with the controls. These changes remained 14 weeks later, confirming a persistent lesion. Ethynyloestradiol also caused a decrease in the number of shell gland capillaries and in the frequency of shell gland capillaries with carbonic anhydrase activity. These data suggested that a disrupted carbonic anhydrase expression was involved in the mechanism for the oestrogen-induced eggshell thinning found in this study. The results support our hypothesis that eggshell thinning in avian wildlife can result from a structural and functional malformation in the shell gland, induced by xeno-oestrogen exposure during embryonic development.

Reproductive toxicity in mink (Mustela vison) chronically exposed to environmentally relevant polychlorinated biphenyl concentrations.

Female mink were exposed to a technical polychlorinated biphenyl (PCB) preparation (Clophen A50 [A50]; 0.1 or 0.3 mg/animal/d), one fraction of A50 containing the non- and mono-ortho-chlorinated congeners (0-1-ortho-chlorobiphenyls [CBs]), another fraction of A50 containing the congeners with two to four ortho-chlorines (2-4-ortho-CBs), or an organic extract from Baltic gray seal blubber. The animals were exposed for 18 months, including two reproduction seasons. Among the animals given the highest dose of A50, the whelping frequency was reduced in the second reproductive season, and all kits died within 24 h of birth. Reproduction was also impaired by the lower dose of A50. Daily exposure to the 0-1-ortho-CBs separated from 0.3 mg A50 severely reduced kit survival. Reproduction was not significantly impaired by daily exposure to the 2-4-ortho-CBs separated from 0.3 mg A50 or by exposure to the blubber extract. We conclude that the reproductive toxicity in chronically PCB-exposed mink is caused by the aryl hydrocarbon (Ah) receptor agonists. The lowest-observed-effect level for reproductive impairment was 2.4 ng 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents (TEQs) per kilogram body weight and day (22 pg TEQs/g feed). Ethoxyresorufin-O-dealkylase (EROD) was strongly induced by the 0-1-ortho-CBs and pentoxyresorufin-O-dealkylase by the 2-4-ortho-CBs. High EROD activity was correlated with low kit production, and consequently EROD may serve as a marker for reproductive toxicity by Ah receptor agonists in mink.

Disrupted carbonic anhydrase distribution in the avian shell gland following in ovo exposure to estrogen.

Eggshell thinning among wild birds has been an environmental concern for almost half a century and the underlying mechanisms are still not fully understood. Previously we showed that exposure of quail embryos to ethynylestradiol (EE2) caused disorganization of the tubular glands in the shell gland of adult birds. In this study, we have examined the effect of in ovo exposure to EE2 on carbonic anhydrase (CA) localization, especially in the shell gland, because CA is required for shell formation. In the control birds, CA was localized in the cell membranes of the tubular gland cells of the shell gland, whereas the surface epithelium was always devoid of CA. In ovo treatment with 20ng EE2/g egg resulted in a loss of CA activity in the tubular glands while the surface epithelium showed strong induction of both membrane bound and cytoplasmic CA activity in 49+/-1% of the cells. The dose 2ng EE2/g egg resulted in partial loss of tubular gland CA and strong induction of CA activity in 2.5+/-0.5% of the surface epithelial cells and weaker induction in 22+/-2% of the epithelial cells. In conclusion, this study shows that embryonic exposure to a xenoestrogen disrupts CA distribution in the adult shell gland. We propose that eggshell thinning in avian wildlife could reflect a functional malformation in the shell gland, already induced by xenoestrogen during embryonic development rather than being caused solely by exposure of the adult bird.

Anatomical and histological changes in the oviducts of Japanese quail, Coturnix japonica, after embryonic exposure to ethynyloestradiol.

Oestrogen is needed for normal oviductal development in female birds, but excessive early exposure to oestrogen can cause oviductal abnormalities and impair egg-laying ability. In this study, the anatomical and histological effects of in ovo exposure to the synthetic oestrogen ethynyloestradiol on the oviducts of immature and adult female Japanese quail, Coturnix japonica, were investigated. A series of abnormalities was observed after injection of ethynyloestradiol (2 or 20 ng g(-1) egg) into the yolk on day 3 of incubation. Ethynyloestradiol induced precocious differentiation of the luminal epithelium and tubular glands in immature chicks. Right-side oviduct retention occurred at all the ages studied, whereas certain other effects were not evident until sexual maturity. The left oviduct was reduced in size and tubular gland density in the uterus (shell gland) was reduced in sexually mature birds that had been treated with ethynyloestradiol. The utero-vaginal junction was longer than in control birds and had a higher tubular gland density. The epithelial cells in the magnum were taller in birds treated with ethynyloestradiol. Embryonic exposure to the environmental contaminant ethynyloestradiol may cause persisting structural malformations in oviducts of quails, which can impair fertility. As oviductal malformations are indicative of embryonic exposure to exogenous oestrogen, they are potentially useful as biomarkers of xenooestrogen exposure in wild bird populations.

Distribution of bisphenol A and tetrabromobisphenol A in quail eggs, embryos and laying birds and studies on reproduction variables in adults following in ovo exposure.

In a previous study, we showed that bisphenol A (BPA) had oestrogen-like effects in bird embryos, causing malformations of the oviducts in Japanese quail (Coturnix japonica) and feminisation of the left testis in chicken (Gallus domesticus). In this study, uptake and distribution of BPA and tetrabromobisphenol A (TBBPA) in embryos and laying quail were examined as well as variables related to reproduction in adult quail following administration of the compounds into the yolk of embryonated eggs. The uptake of radiolabelled BPA, TBBPA and the reference compound diethylstilboestrol (DES) was studied in the embryos using beta-spectrometry. Autoradiography was employed to examine distribution in egg and embryo after yolk sac injection of BPA or TBBPA and in laying birds, following intravenous and oral administration. Following embryonic exposure to BPA or TBBPA, sexually mature male birds were examined for reproductive behaviour and testis morphology, and females were examined for egg laying and oviduct morphology. Neither BPA (200 microg/g egg) nor TBBPA (15 microg/g egg) caused any significant oestrogen-like effects on the variables studied, although effects on the female oviducts after BPA exposure were indicated. Embryonic exposure to DES is known to cause profound effects on male sexual behaviour and female oviduct morphology at doses 3-5 orders of magnitude lower than the BPA and TBBPA doses used in the present study. The proportions of BPA and TBBPA taken up by the embryos after yolk sac injection were similar to the proportion of DES taken up. Differences in bioavailability, therefore do not account for any major part of the potency differences between DES and the two bisphenol A compounds. The concentration of radioactivity in the embryo, as revealed by autoradiography, was low compared with that in the yolk at all stages studied (days 6, 10 and 15). Pronounced labelling of the bile and the allantoic fluid was observed, however, indicating that both compounds were readily metabolised and excreted. Radiolabelled BPA and TBBPA administered to laying quail were largely excreted via the bile and 9 days after oral dosing, only small amounts of the labelled compound remained within the body. Maternal transfer of labelled BPA and TBBPA to the egg was low.

Effects of bisphenol A and tetrabromobisphenol A on sex organ development in quail and chicken embryos.

The plastic monomere bisphenol A (BPA) and the flame retardant tetrabromobisphenol A (TBBPA) were examined for estrogen-like developmental effects on the reproductive organs in avian embryos. The synthetic estrogen diethylstilbestrol (DES) was used as a positive control. The test compounds were injected into the yolk of quail and chicken eggs early during incubation and the embryos were examined 2 d before anticipated hatching. At 200 microgram/g egg, BPA induced Müllerian duct (embryonic oviduct) malformation in female quail embryos and feminization of the left testis (ovotestis) in male chicken embryos. The estrogenic potency of BPA compared with DES was species and endpoint specific. Müllerian duct malformation was the most sensitive endpoint in quail embryos, whereas ovotestis formation was the most sensitive response in chicken embryos. Tetrabromobisphenol A caused high embryo mortality at 45 microgram/g egg in both species, but no estrogen-like effects were observed. Bisphenol A caused mortality only in chicken embryos at 67 and 200 microgram/g egg. To our knowledge, this is the first report on estrogen-like or embryolethal effects of BPA and TBBPA in birds.

CYP1A-dependent activation of xenobiotics in endothelial linings of the chorioallantoic membrane (CAM) in birds.

Metabolic activation of the heterocyclic amine 3-amino -1,4-dimethyl-5 H-pyrido[4,3-b]indole (Trp-P-1) and 7-ethoxyresorufin O-deethylase (EROD) activity were examined in the chorioallantoic membrane (CAM) of 15-day-old chicken and 18-day-old eider duck embryos. The embryos were pretreated with an Ah receptor agonist, i.e. beta-naphthoflavone (BNF) or 3,3',4,4',5-pentachlorobiphenyl (PCB 126), or vehicle in ovo. BNF and PCB 126 induced EROD activity and covalent binding of [3H]Trp-P-1 seven- to tenfold in the CAM of chicken embryos. In the CAM of eider duck embryos, which are known to be nonresponsive to coplanar PCBs, PCB 126 treatment had no effect on EROD activity or covalent binding of [3H]Trp-P-1 whereas BNF treatment increased these activities five- and threefold, respectively. Light microscopic autoradiography was used to identify the cellular localization of covalent binding of [3H]Trp-P-1 in the CAM. Preferential binding was observed in endothelial cells in intraepithelial capillaries in the chorionic epithelium and in blood vessels in the mesenchymal layer. The addition of the CYP1A inhibitor ellipticine abolished the covalent binding of [3H]Trp-P-1 in the CAM of BNF- and PCB 126-treated chicken and eider duck embryos. The results suggest that CYP1A-dependent metabolic activity can be induced in blood vessel endothelia in the CAM of bird embryos following exposure to Ah receptor agonists and that the CAM may be a target tissue for CYP1A-activated environmental pollutants. Furthermore, the highly vascularized CAM could be used as a model for studies of Ah receptor-mediated alterations in the vasculature.

Ecotoxicological risk assessment of environmental pollutants in the Arctic.

Concentrations of such persistent organic pollutants (POPs) as polychlorinated biphenyls (PCBs) are high in certain Arctic animal species. The polar bear, Arctic fox, and glaucous gull may be exposed to PCB levels above lowest-observed-adverse-effect-level (LOAEL) values for adverse effects on reproduction in mammals and birds. However, the dioxin-like congeners seem to be major contributors to the reproductive effects of PCBs and the relative concentrations of these congeners are low in polar bears. Temporal trends for POPs in Arctic wildlife and the sensitivities of Arctic species to these compounds determine the risk for future adverse health effects.

Cytochrome P450-dependent binding of 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (B[a]P) in murine heart, lung, and liver endothelial cells.

Autoradiography was used to investigate the cellular sites of irreversible binding of 3H-labelled 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (B[a]P) in mice. Autoradiograms obtained from solvent-extracted tape-sections revealed an even distribution of DMBA- and B[a]P-derived radioactivity in control mice lacking sites of selective binding in the tissues. In mice pretreated with a cytochrome P4501A (CYP1A) inducer, beta-naphthoflavone (BNF) or 3,3',4,4', 5-pentachlorobiphenyl (PCB 126), a noticeable accumulation of bound radioactivity was observed in the pulmonary alveolar region. Increased labelling was also observed in heart tissue of induced mice. As demonstrated by microautoradiography of tissues from CYP1A-induced mice treated with 3H-DMBA or 3H-B[a]P in vivo, irreversible binding in lung tissue was present in endothelial cells of arteries and veins, in the alveolar septal walls, and in type 2 pneumocytes. In heart tissue, binding was confined to endothelial cells of arteries, capillaries and veins. In liver, binding was found in the hepatocytes as well as in endothelial cells of the portal veins, whereas no binding was seen in endothelial cells of the sinusoids, central veins, or arteries. These findings were confirmed in vitro using 3H-DMBA-exposed precision-cut slices, indicating that reactive intermediates of DMBA and B(a)P were formed in situ. The addition of the CYP1A inhibitor ellipticine abolished binding in the target endothelial cells. Increased endothelial binding in the lungs and liver of CYP1A-induced mice was concomitant with increased 7-ethoxyresorufin O-deethylase (EROD) and DMBA hydroxylase activity. In heart, endothelial binding was positively correlated with EROD, but not with DMBA hydroxylase. The results suggest that endothelial cells may be targets for CYP-dependent activation of such toxicants as polycyclic aromatic hydrocarbons. Consequently, the possibility that chemically induced endothelial dysfunction is a risk factor in the aetiology of cardiovascular disease demands consideration.

Sexual behavior in Japanese quail as a test end point for endocrine disruption: effects of in ovo exposure to ethinylestradiol and diethylstilbestrol.

Chemicals having a capacity to disturb the endocrine system have attracted considerable interest during recent years. There is a shortage of well-characterized in vivo tests with which to study such disturbances in different classes of vertebrates. In the present study, test end points related to reproduction in the Japanese quail were used to examine the estrogenic activity of chemicals. The synthetic estrogens ethinylestradiol (EE(2)) and diethylstilbestrol (DES), used as model compounds, were injected into the yolk of embryonated eggs. After the birds had been raised to sexual maturity, we examined sexual behavior, plasma testosterone concentrations, and testis morphology in adult males. The lowest doses resulting in a significantly depressed male sexual behavior were 6 ng/g egg for EE(2) and 19 ng/g egg for DES. Testis weight asymmetry was increased at 6 ng EE(2)/g egg, but DES had no effect at any treatment level. The area of the androgen-dependent cloacal gland was significantly reduced at 57 ng DES/g egg. No effects on plasma testosterone concentration or body weight following exposure to EE(2) or DES were observed at any dose level. Depressed male sexual behavior was the most sensitive of the end points studied, and we suggest that this ecologically relevant end point be included in avian in vivo testing for neuroendocrine disruptors.

The avian egg as a test system for endocrine disrupters: effects of diethylstilbestrol and ethynylestradiol on sex organ development.

Many environmental contaminants are known or suspected to interfere with hormonal function in animals. In vivo test methods to detect and characterize chemicals that disrupt the endocrine system are therefore urgently needed. In this study, we assessed the usefulness of abnormalities of the reproductive organs as test endpoints for estrogenic activity of xenobiotics in Japanese quail embryos. Two synthetic estrogens, diethylstilbestrol (DES) and ethynylestradiol (EE2), were injected into the yolks of embryonated eggs. At a dose as low as 2 ng EE2/g egg, all male embryos became feminized, containing ovary-like tissue in the left testis. The extent of feminization of the testes was determined by measuring the relative area of the ovary-like component. Persistent Müllerian ducts (oviducts) in male embryos, and malformations of the Müllerian ducts in females occurred at 2 ng EE2/g egg and higher doses. DES was approximately one-third to one-tenth as potent as EE2. The morphological changes studied were dose-dependent, indicating that they are useful as test endpoints for estrogenic activity. Feminization of the left testis in males proved to be the most sensitive endpoint. We propose the quail egg as a simple in vivo test system for estrogenic compounds.

Levels of dioxin-like compounds in sewage sludge determined with a bioassay based on EROD induction in chicken embryo liver cultures.

A bioassay for the detection of dioxin-like compounds was used to estimate levels in sewage sludge from Swedish sewage treatment plants (STPs). The sludge extracts were HPLC-separated into three fractions containing a) monoaromatic/aliphatic, b) diaromatic (e.g. polychlorinated biphenyls [PCBs], polychlorinated dibenzodioxins and polychlorinated dibenzofurans [PCDDs/Fs]), and c) polyaromatic compounds (e.g. polycyclic aromatic hydrocarbons [PAHs]). The bioassay, which is based on EROD (7-ethoxyresorufin O-deethylase) induction in cultured chicken embryo livers detected dioxin-like activity in all unfractionated extracts and in the di- and polyaromatic fractions of all sludge extracts, but not in the monoaromatic/aliphatic fractions. The levels ranged between 6 and 109 pg bio-TEQ/g sludge (d.w.). In sediment samples from rural lakes in Sweden, levels of about 5 pg bio-TEQ/g (d.w.) have been found. The polyaromatic fractions of the sludge samples were potent in the bioassay, probably due to various PAHs and other polyaromatics in the sludge. The levels of six PAHs that are screened for in the sludge at Swedish STPs accounted for only 3-10% of the observed EROD-induction by the polyaromatic fractions. Consequently, many other polyaromatic EROD-inducing compounds were present in the sludge. Inclusion of a biological test like the chicken embryo liver bioassay in the screening of sludge would improve the ability to detect the presence of bioactive dioxin-like compounds. A theoretical estimation of bio-TEQ concentrations in farm-soil following long-term application of sludge with bio-TEQ concentrations similar to those observed in this investigation indicated that the bio-TEQ levels in soil would increase very slowly over time. The chicken embryo liver bioassay proved useful in assessing levels of dioxin-like compounds in sewage sludge and it gives valuable complementary information to chemical analysis data.

Basal and induced EROD activity in the chorioallantoic membrane during chicken embryo development.

The chorioallantoic membrane (CAM) is a highly vascularized tissue that takes part in the respiratory exchange of gases through the eggshell. Although the CAM may be exposed to environmental contaminants, its response to pollutants has not been studied. We examined the cytochrome P4501A (CYP1A)-catalyzed deethylation of 7-ethoxyresorufin (EROD) in the CAM during chicken embryo development. EROD was constitutively present and was inducible by the aryl hydrocarbon (Ah) receptor agonist 3,3',4,4',5-pentachlorobiphenyl (PCB 126). Our results suggest the CAM as a first line of defence of the avian embryo against toxic compounds, but also as a target for CYP1A-activated chemicals.

Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife.

An expert meeting was organized by the World Health Organization (WHO) and held in Stockholm on 15-18 June 1997. The objective of this meeting was to derive consensus toxic equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and dioxinlike polychlorinated biphenyls (PCBs) for both human, fish, and wildlife risk assessment. Based on existing literature data, TEFs were (re)evaluated and either revised (mammals) or established (fish and birds). A few mammalian WHO-TEFs were revised, including 1,2,3,7,8-pentachlorinated DD, octachlorinated DD, octachlorinated DF, and PCB 77. These mammalian TEFs are also considered applicable for humans and wild mammalian species. Furthermore, it was concluded that there was insufficient in vivo evidence to continue the use of TEFs for some di-ortho PCBs, as suggested earlier by Ahlborg et al. [Chemosphere 28:1049-1067 (1994)]. In addition, TEFs for fish and birds were determined. The WHO working group attempted to harmonize TEFs across different taxa to the extent possible. However, total synchronization of TEFs was not feasible, as there were orders of a magnitude difference in TEFs between taxa for some compounds. In this respect, the absent or very low response of fish to mono-ortho PCBs is most noticeable compared to mammals and birds. Uncertainties that could compromise the TEF concept were also reviewed, including nonadditive interactions, differences in shape of the dose-response curve, and species responsiveness. In spite of these uncertainties, it was concluded that the TEF concept is still the most plausible and feasible approach for risk assessment of halogenated aromatic hydrocarbons with dioxinlike properties.

Induction of ethoxyresorufin O-deethylase (EROD) and endothelial activation of the heterocyclic amine Trp-P-1 in bird embryo hearts.

The xenobiotic-metabolizing activity of avian heart was investigated in chicken and Eider duck embryos exposed to aryl hydrocarbon (Ah) receptor agonists in ovo. Both beta-naphthoflavone (BNF) and 3,3',4,4',5-pentachlorobiphenyl (PCB 126) induced 7-ethoxyresorufin O-deethylase (EROD) activities in chicken embryo hearts whereas Eider duck embryos only responded to BNF. The differential responses of chicken and Eider duck embryos were used to examine the involvement of Ah receptor-mediated enzyme induction in the activation of the environmental and food mutagen 3-amino- 1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1). As determined by light microscopic autoradiography, there was a highly selective binding of non-extractable 3H-Trp-P-1-derived radioactivity in endothelial cells of large vessels and capillaries in hearts of BNF- and PCB 126-treated chicken embryos. No binding occurred at these sites in vehicle-treated controls. There was also a strong endothelial binding of 3H-Trp-P-1 in hearts of BNF-treated Eider duck embryos whereas no binding occurred in hearts of PCB 126-treated Eider duck embryos. A positive correlation between induction of EROD activity and covalent binding of 3H-Trp-P-1 to protein in heart homogenates from BNF- and PCB 126-treated chicken and Eider duck embryos was also observed. The results suggest a cytochrome P450 1A (CYP1A)-mediated activation of Trp-P-1 in avian heart endothelial cells although involvement of other Ah receptor-regulated enzymes is also possible. We propose that heart endothelial cells may be targets for bioactivation and toxicity of environmental contaminants in birds exposed to Ah receptor agonists.

Methods for studying xenoestrogenic effects in birds.

The embryonated bird egg provides a simple whole organism test system that allows examination of xenoestrogenic effects at different levels of biological organisation. Test compounds are injected into the yolk, the albumen or the air chamber at defined stages of embryonic development. Bioavailability and embryonic exposure may be determined by autoradiography and image analysis. Females represent the heterogametic sex (ZW) and estrogens determine differentiation into the female phenotype in birds. Xenoestrogenic effects can be examined by markers of gene expression and anatomical or histological characterization of the gonads and tubular sex organs. Chicks may be raised to sexual maturity and examination of sexual behaviour and reproductive physiology performed. The Japanese quail is a suitable test organism due to its small size and early sexual maturation.

EROD induction by environmental contaminants in avian embryo livers.

The CYP1A (EROD)-inducing potencies of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4',5-pentachlorobiphenyl (PCB126) and benzo(k)fluoranthene (B(k)F) were studied in avian embryo livers. TCDD and PCB126 proved to be much more potent as inducers in the chicken than in the other species examined. This finding is consistent with a considerably higher sensitivity of the chicken compared with a number of other avian species to the embryotoxic effects of these compounds. Furthermore, the relative potencies of the tested Ah receptor agonists as CYP1A inducers differed substantially between species. B(k)F and PCB126 showed similar induction potencies in domestic duck embryos, whereas PCB126 is much more potent than B(k)F in the chicken. Also, the potency of PCB126, relative to that of TCDD, was much lower in quail embryo liver in vitro than in chicken embryo liver. Thus, there are large interspecific differences in birds in the sensitivity to CYP1A inducers and furthermore, the relative potencies of these compounds may differ substantially between species.

Lethality and EROD-inducing potency of chlorinated chrysene in chick embryos.

Chrysene was non-specifically chlorinated and the toxic potency of the mixture formed was studied. The chlorinated mixture was considerably more potent than the parent compound in terms of embryolethality and EROD and AHH induction in a 2-week test in chick embryos. The chlorinated chrysene caused anomalies, including edema and beak defects, similar to those previously found after treatment of chick embryos with coplanar PCBs. Chlorinated chrysene was also much more potent than chrysene as an inducer of EROD in a 72-hour test in chick embryos in ovo and in chick embryo liver in vitro. It seems that the mechanism of toxicity of chlorinated chrysene in chick embryos is similar to that of the coplanar PCBs and other Ah receptor ligands. The effects of the chlorinated mixture were mainly accounted for by 6- chlorochrysene and 6,12-dichlorochrysene.