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Regarding the humane use of animals in scientific research, invertebrates are often recommended in toxicological studies. "Freshwater planarians" refers to numerous free-living freshwater members of the Class "Turbellaria" of the phylum Platyhelminthes. This group of invertebrates has received extensive attention from biologists for many years because of their unique biological characteristics, such as the primitive form of the central nervous system and notable capability to regenerate tissues. Using freshwater planarians as test animals in chemical toxicity studies has grown in popularity since the 1960s. Results from various toxicological experiments have collectively suggested that freshwater planarians can serve as not only alternative models for chemical toxicity screenings in laboratories but also as potential bioindicators for the quality of freshwater environments. However, thus far, no standardized battery of tests for conducting toxicological studies that includes freshwater planarians has been proposed. This paper comprehensively reviews the toxicological information obtained from chemically exposed planarians and proposes practical factors for consideration in toxicity experiments with freshwater planarians as test organisms.

Regeneration is a vital physiological process for survival of adult organisms. Bisphenol A (BPA), diethystilbestrol (DES), 17α-ethinylestradiol (EE2), and 17β-estradiol (E2) were examined for their effects on head formation in decapitated freshwater planarians (Dugesia japonica). The median lethal concentration of the test chemicals and the median inhibitory concentration for decapitated planarians and different regenerative endpoints, were determined for 3–7 d of exposure. For planarian head regeneration, the no-observed-effect level of BPA and DES was 0.05 mg L−1 and 1 mg L−1 for EE2 and E2. The effects of BPA, DES, and EE2 on asexual planarian regeneration did not correspond with the order of their estrogenic potencies, suggesting that the effects, at least partially, were due to general toxicity rather than their estrogenicity. In view of the published data on concentrations of xenoestrogens in water bodies versus the nominal levels tested here, this study suggests that the current environmental level...

Pharmaceutically active compounds are produced worldwide and consumed in large quantities, so these chemicals are frequently detected in limnic environments posing potential ecological risks. Thirty pharmaceutically active compounds were selected for examination of their acute toxicity for freshwater planarians (Dugesia japonica). Among the 30 compounds tested, diclofenac, mefenamic acid, naproxen, propranolol HCl, and diphenhydramine HCl had a 48-h nominal LC50 below10 mg L−1, and for 18 chemicals, it exceeded 100 mg L−1. The 96-h nominal LC50 was below 10 mg L−1 for diclofenac, mefenamic acid, naproxen, propranolol HCl, diltiazem HCl, diphenhydramine HCl, hydroxyzine HCl, and triprolidine HCl, and for 15 chemicals, it exceeded 100 mg L−1. Among different therapeutic groups, analgesics were most toxic to planarians, and antibiotics were least toxic. Antihistamines and beta blockers varied in their acute toxicity to planarians. At the current environmental levels, none of the tested pharmaceutically activ...

Many chemicals commonly occurring in surface water are found to be hormonally active. Fourteen compounds including four sex hormones, three synthetic hormones, one non-steroidal anti-androgen, and six industrial endocrine-disrupting chemicals were selected to examine their acute toxicities on the freshwater planarian, Dugesia japonica. Among all test chemicals, diethylstilbestrol had the highest toxicity. Relatively, the toxicities of the synthetic hormones were higher than the natural ones. Among the six industrial endocrine-disrupting chemicals tested, bisphenol A was the most toxic, with a 48-h LC50 of 8.3 mg L−1. Overall, the natural or synthetic hormones, other than estrone and estriol, were more acutely toxic to planarians than the industrial endocrine disruptors tested. The acute toxicities of the test chemicals to Dugesia japonica were in the same order of magnitude as those to Daphnia magna based on available published data. Despite this study used non-environmentally relevant levels, such kinds ...

Although toxic responses of freshwater planarians after exposure to environmental toxicants can be observed through external toxicological end points, physiological responses inside the bodies of treated planarians have rarely been investigated. The present study was designed, using cadmium (Cd) as a reference toxicant, to determine its bioaccumulation and toxicodynamics in the freshwater planarian, Dugesia japonica, after acute toxicity was obtained. Accumulated Cd concentrations, metallothionein levels, and the oxidative status in planarians were determined after exposure to Cd. Furthermore, we hypothesized that the acute death of Cd-treated planarians was associated with increased oxidative stress. After Cd-treated planarians were coexposed to antioxidant, N-acetylcysteine (NAC), we found that NAC protected planarians from Cd lethality by maintaining the oxidative status and decreasing the bioaccumulation of Cd. The results of the present study support planarians being used as a practical model for toxicological studies of environmental contaminants in the future.

Fourteen benzophenone-type UV filters and four paraben preservatives were selected to examine their acute toxicities on Dugesia japonica. The 48-h LC50 values for planarians exposed to benzophenone-type UV filters can be ranked as oxybenzone > mexenone > 5-chloro-2-hydroxybenzophenone > 2,4-dihydroxybenzophenone > 2-hydroxybenzophenone > dioxybenzone > benzophenone > 2,2′,4,4′-tetrahydroxybenzophenone > 4-hydroxybenzophenone > 3-hydroxybenzophenone > 4,4′-dihydroxybenzophenone > 2,2′-dihydroxy-4,4′-dimethoxybenzophenone > 2,3,4-trihydroxybenzophenone > sulisobenzone with a range from 0.9 to 145 mg L−1 with a similar sequence for the 96 h LC50 values, ranging from 0.5 to 77 mg L−1. The 48 and 96 LC50 values for planarians exposed to paraben preservatives can be ranked as butylparaben > propylparaben > ethylparaben > methylparaben. Among all the tested chemicals, oxybenzone was the most toxic and sulisobenzone the least toxic chemical to planarian at each exposure period. Most benzophenone-type UV filters a...

One closed uncontrolled landfill, the Neihu garbage dump, and one active controlled landfill, the Sanzhuku sanitary landfill, were selected for investigation of their leachate characteristics and effects on adjacent river water quality before and after rainfall in northern Taiwan. A total of seven samplings were made during February and June 2007, with four samplings done after individual rainfall events on study sites. Water quality of runoff samples collected from the Sanzhuku sanitary landfill showed less pollution than the water quality of leachates collected from the Neihu garbage dump; however, some water quality levels of leachate samples collected from the Neihu garbage dump were relatively high, such as ammonia nitrogen (NH3-N), orthophosphate (PO43-) and biochemical oxygen demand (BOD5). At the uncontrolled dump, rainfall lead to dilution effects on river water NH3-N and PO43- concentrations, but not other water quality parameters. In contrast, the concentrations of bisphenol A (BPA) and nonylphenol were increased in both types of landfills after rainfall in the present study. Dilution effects of rainfall on most water quality parameters and toxicity tests were observed in the Neihu garbage dump leachates after rainfall, but not for the Sanzhuku Landfill runoff. The highest concentration of BPA measured in this study was 25.8 μg L-1 in the Sanzhuku sanitary landfill runoff after the heaviest rainfall event, during which 236 mm of rainfall accumulated over four days. The results of this study suggest that both uncontrolled and controlled landfill leachates can be an important potential pollution source of BPA to adjacent water bodies.

Compared to the estrogenic effects of 4-nonylphenol (NP), there is little data available on other potential toxic effects of NP in aquatic animals. The effects of NP on cholinesterase (ChE) and carboxylesterase (CbE) activities of male guppies exposed to 10, 60, 150, or 300 μg L−1 NP were examined after 1, 2, 4, and 7 days of treatment. A significant muscle ChE inhibition, that used acetylthiocholine iodide as a substrate, was noted in male guppies in all NP treatment groups after a 4-day exposure, and 60 and 150 μg L−1 of NP treatment groups after a 7-day exposure. All guppies exposed to 300 μg L−1 NP died during the 7-day treatment. However, there was no significant inhibition of muscle ChE that used butyrylthiocholine iodide as a substrate in male guppies for any NP treatments in different exposure times. There were no CbE activity differences in livers of male guppies among NP treatment groups after different exposure times. This is the first report showing the ChE activity inhibition by NP in fish. Further mechanistic studies are needed to define how NP directly or indirectly alters ChE activities at molecular level. The implication of ChE inhibition of NP on potential impacts of aquatic animals also warrants further research.

Decabrominated diphenyl ether (PBDE 209) is the second most used brominated flame retardant (BFRs). Many studies have shown that some of the BFRs act as endocrine disruptors via alterations in thyroid hormone homeostasis and affect development. Little is known about the effect of prenatal exposure to PBDE 209 on the development in male offspring. Using a CD-1 mouse model, we attempt to estimate the possible effect of in utero exposure to PBDE 209 on thyroid hormone and hepatic enzymes activities in male offspring. Pregnant mice were administered different doses of PBDE 209 (10, 500, and 1500 mg/kg/day) or corn oil for controls per gavage from gestational days 0-17. In adult male offspring whose mothers had been treated with 1500 mg/kg of PBD 209, hepatic enzyme activity of S9 7-ethoxyresorufin O-deethylase (EROD) was weak but significantly increased (54%). However, no significant changes were observed in S9 4-nitrophenol uridinediphosphate-glucuronosyltransferase (UDPGT) in any of the treatment groups. Serum triiodothyronine (T3) was found to have decreased significantly (ca. 21% both 10 mg/kg and 1500 mg/kg) in offspring, but not thyroxine (T4). Histopathological examination revealed that prenatal exposure of PBDE 209 might be related with cell swelling of hepatocytes in male offspring and there were mild changes in the thyroid glands in 1500 mg/kg group. These data demonstrate that PBDE 209 is likely an endocrine disrupter in male mice following exposure during development. Further studies using environmentally relevant doses are needed for hazard identification.

The development of a high-throughput tool is required for screening of environmental pollutants and assessing their impacts on aquatic animals. Freshwater planarians can be used in rapid and sensitive toxicity bioassays. Planarians are known for their remarkable regeneration ability but much less known for their metabolic and xenobiotic biotransformation abilities. In this study, the activities of different phase I and II enzymes were determined in vivo by directly measuring fluorescent enzyme substrate disappearance or fluorescent enzyme metabolite production in planarian culture media. For phase I enzyme activity, O-deethylation activities with alkoxyresorufin could not be detected in planarian culture media. By contrast, O-deethylation activities with alkoxycoumarin were detected in planarian culture media. Increases in 7-ethoxycoumarin O-deethylase (ECOD) activities was only observed in planarians exposed to 1μM, but not 10μM, β-naphthoflavone for 24h. ECOD activity was inhibited in planarians exposed to 10 and 100μM rifampicin or carbamazepine for 24h. For phase II enzyme activity, DT-diaphorase, arylsulfatases, uridine 5'-diphospho (UDP)-glucuronosyltransferase or catechol-O-methyltransferase activity was determined in culture media containing planarians. The results of this study indicate that freshwater planarians are a promising model organism to monitor exposure to environmental pollutants or assess their impacts through the in vivo measurement of phase I and II enzyme activities.

Polychlorinated biphenyls (PCBs) are considered potential endocrine disruptors due to their ability to act as estrogens, antiestrogens and goitrogens. The aim of this study is to ascertain whether acute postnatal treatment with 3,3 ′ ,4,4 ′ -tetrachlorobiphenyl (CB 77) affects sperm function and hormone levels in adult rats. Male Sprague–Dawley rats received CB 77 by ip injection of 2 or 20 mg/kg at day 21 and sacrificed at day 112. At day 112, right and left testis weights were significantly increased, whereas sperm count, motility, total motile sperm count, curvilinear velocity, average path velocity, straight-line velocity, and beat-cross frequency for motile sperm were significantly decreased in rats treated with 20 mg/kg CB 77. Sperm–oocyte penetration rate was significantly reduced in rats treated with either 2 or 20 mg/kg CB 77. There was high sperm acrosome reaction rate (ARR) in the 20 mg/kg CB 77-treated rats. There was a significant increase in thyroid-stimulating hormone level in the 20 mg/kg CB 77 group. However, no changes were seen in serum testosterone, thyroid hormones, or prolactin concentrations at day 112. In summary, this study showed that postnatal exposure to CB 77 might affect spermatogenesis, motility, ARR, and ability of fertilizing oocytes in mature rats. These results suggest that the sperm functions may be more susceptible or adapt less readily than the thyroid functions to endocrine disruption caused by dioxin-like PCB congeners.

Urban air pollution is a serious problem in both developing and developed countries, and antioxidant enzyme activities in plants have been suggested as a useful bioindicator of air pollution. In this study, the seasonal and spatial variability of peroxidase and superoxide dismutase activities were measured in leaves of Ficus microcarpa at eight sampling sites in the Taipei metropolitan area and one background site in rural area at each month for a year. The spatial pattern of peroxidase activity in figs collected from the Taipei metropolitan area was similar to the spatial pattern of O3 concentration in the Taipei metropolitan area. The peroxidase activities of Ficus microcarpa were significantly higher at sampling sites from the outer zone of the metropolitan area than those from the inner zone of the metropolitan area in spring and summer. On the other hand, the spatial pattern of superoxide dismutase activity in fig leaves did not show significant differences between the inner and outer zones of the Taipei metropolitan area. In addition, peroxidase activities, but not superoxide dismutase activities, of Ficus microcarpa were significantly higher in sites with high traffic density than those in low traffic density sites. Even though peroxidase activities in Ficus microcarpa tended to be higher in high traffic density sites or some sites with high ozone concentration, site-specific changes of peroxidase activity in Ficus microcarpa due to O3 pollution were not clearly observed in this study. Based on these results, neither peroxidase nor superoxide dismutase in Ficus microcarpa is a sensitive bioindicator for O3 pollution, although peroxidase shows some potential to be used as a general bioindicator of air quality.

Polychlorinated biphenyls (PCBs) with the liable 2,3,6-substitution are important components of certain commercial mixtures and frequently detected in biota, but little is known about their enzyme induction abilities and possible endocrine-disrupting effects. CB 132 (2,2',3,3',4,6'-hexachlorophenyl) and CB 149 (2,2'3,4',5',6-hexachlorophenyl) were investigated in weanling female rats dosed intraperitoneally on days 21 and 22 and killed on day 24 of age. Uterotropic response, serum thyroid hormone, and hepatic enzyme induction were examined in prepubertal female rats treated with these two environmentally relevant 2,3,6-substituted chlorobiphenyl (CB) congeners from 8 mg/kg to 96 mg/kg. The readily metabolized CB 132 did not cause any significant increase in all endpoints measured in the present study. On the other hand, CB 149 was a weak PROD and BROD inducer and a modest depleter of serum thyroxine in prepubertal female rats. The finding of thyroid hormone disruption by CB 149 may lead to biologically significant neurobehavioral and neurochemical changes in developing animals via milk lactation.

Polychlorinated biphenyls (PCBs) with the labile 2,3,6-substitution are important components of atmospheric and certain food chain exposures, but little is known about their biological activities. Chlorobiphenyl 110 (2,3,3',4',6-pentaCB) was investigated in weanling female rats dosed ip on days 21 and 22 and killed on day 23 of age. The initial preparation of CB 110 markedly induced 7-ethoxyresorufin O-dealkylase (EROD) activity and was found to be contaminated with coplanar 3,3',4,4',5-pentaCB (CB 126). The contaminated preparation (CB 110C) was purified with activated charcoal (CB 110P). The CB 110P induced pentoxyresorufin O-dealkylase (PROD), was weakly uterotropic and a modest depleter of serum thyroxine (T4). CB 110C caused increased liver weight, induced EROD, PROD, and UDP glucuronyl transferase activities and caused a greater depletion of serum T4; on the other hand, it suppressed the PROD induction and the uterotropic effect of CB 110P. Hepatic residues of CB 110 were a constant 2-3% of the dose while those of CB 126 (from CB 110C) increased with increasing dose to as much as 50% of the dose.

Although freshwater planarians are evolutionarily primitive, they are some of the simplest bilateral animals possessing integrated neural networks similar to those in vertebrates. We attempted to develop planarian Dugesia japonica as a model for investigating the neurotoxicity of environmental pollutants such as cadmium (Cd). This study was therefore designed to study the effects of Cd on the locomotor activity, neurobehavior, and neurological enzymes of D. japonica. After planarians were exposed to Cd at high concentrations, altered neurobehavior was observed that exhibited concentration-dependent patterns. Morphological alterations in Cd-treated planarians included irregular shape, body elongation, screw-like hyperkinesia, and bridge-like position. To study the direct effects of Cd on neurological enzymes, tissue homogenates of planarians were incubated in vitro with Cd before their activity was measured. Results showed that acetylcholinesterase (AChE), adenosine triphosphatase (ATPase), and monoamine oxidase A (MAO-A) activities were inhibited in a concentration-dependent manner. MAO-B activity was significantly induced by Cd at low concentrations and inhibited at high concentrations. Changes in the in vivo activity of AChE and ATPase were also found after planarians were treated with Cd at a sublethal concentration (5.56 μM). These observations indicate that neurotransmission systems in planarians are disturbed after Cd exposure.

Cigarette smoke is a risk factor for human health, and many studies were conducted to investigate its adverse effects on humans and other mammals. However, since large amounts of cigarette products are produced and consumed, it is possible that tobacco chemicals can end up in aquatic environments through several routes, thus influencing aquatic organisms. In this study, the presence of tobacco-specific nitrosamine (TSNA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), in aquatic environment was demonstrated. Since toxic effects on and distribution patterns of tobacco chemicals in aquatic organisms were rarely studied, after results of an acute toxicity pretest were obtained, experiment was conducted to investigate the bioaccumulation pattern of NNK and distribution patterns of its metabolites, mainly 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), in NNK-treated freshwater planarians, Dugesia japonica. Results from in vivo and in vitro studies showed that NNK was readily converted to NNAL through the carbonyl reduction in bodies of NNK-treated planarians. Tissue concentrations of both chemicals increased in time- and dose-dependent manners. Furthermore, we examined the end products of NNK/NNAL α-hydroxylation in NNK-treated planarians, but only 1-(3-pyridyl)-1,4-butanediol was detected, suggesting that NNK metabolism in planarians partially differs from that in mammalian systems. This is the first report on NNK metabolism in an aquatic organism and can be used as a foundation for developing freshwater planarians as a new in vivo model for the study of NNK toxicology in the future.

Eight widely used surfactants (cetyltrimethylammonium bromide; CTAB, benzethonium chloride; Hyamine 1622, 4-nonylphenol; NP, octylphenol ethoxylate; Triton X-100, dodecylbenzene sulfonate; LAS, lauryl sulfate; SDS, pentadecafluorooctanoic acid; PFOA, and perfluorooctane sulfonate; PFOS) were selected to examine their acute toxicities and effects on oxidative stress and cholinesterase (ChE) activities in Dugesia japonica. The differences in acute toxicity among eight surfactants to planarians were at least in the range of three orders of magnitudes. The toxicity rank of surfactants according to estimated 48-h LC(50) was SDS>NP>LAS>Hyamine 1622>CTAB>Triton X-100>PFOS>PFOA. The toxicity rank of surfactants according to 96-h LC(50) was as follows: SDS>CTAB>NP>LAS>Hyamine 1622>Triton X-100>PFOS>PFOA. There were significant increases in catalase activities in planarians exposed to LAS at nominal concentrations of 0.5 or 1 mgl(-1) and to PFOS at nominal concentrations of 5 or 10 mgl(-1) after 48-h exposure. Inhibitions of ChE activities were found in planarians exposed to Hyamine 1622 at all concentrations tested, to PFOS at nominal concentration of 10 mgl(-1), to PFOA at nominal concentrations of 50 or 100 mgl(-1) and to NP at nominal concentration of 0.5 mgl(-1). A significant increase in ChE activities was also observed in planarian exposed to Triton X-100 at nominal concentration of 5 mgl(-1). The implication of ChE inhibition by NP, PFOS and PFOA on neurological and behavioral effects in aquatic animals requires further investigation.

Acute toxicity of 4-nonylphenol (NP) was examined in six freshwater species from three phyla - platyhelminthes, arthropoda and mollusca. Values of the 48-hour LC(50) of NP for six species ranged from 20 to 508 ug/L and values of the 96-hour LC(50) for four species ranged from 120 to 457 ug/L. The most sensitive species tested was a water flea, Ceriodaphnia cornuta, with a 48-hour LC(50) of 20 microg/L. The no observed adverse effect level (NOAEL) and lowest observed adverse effect level (LOAEL) values of NP found were in the range of

Subsurface soil from a National Priorities List landfill containing about 2.5% polychlorinated biphenyls (PCBs) was extracted and the extract cleaned by Florisil slurry and alumina column chromatography. The refined extract contained 48 mg/mL PCB, mainly trichlorobiphenyls and tetrachlorobiphenyls, traces of polychlorinated naphthalenes, 125 micrograms/mL 2,2-bis-p-chlorophenyl-1,1-dichloroethylene (DDE), and low levels of chlorinated dibenzofurans. The refined extract was dissolved in corn oil and administered intraperitoneally to weanling (day 20) female rats on days 20 and 21; rats were terminated on day 22. Limited data indicated possible hematopoietic effects, including neutrophilia. There were no changes in relative uterus, kidney, or adrenal gland weights between total doses of 3 to 96 mg/kg total PCB. Relative liver weights increased significantly at 36 mg/kg and activities of P450s 1A1 (as ethoxyresorufin O-dealkylase) and 2B (as pentoxyresorufin O-dealkylase) increased at 12 mg/kg and plateaued at 36 (P450 1A1) or 48 (P450 2b) mg/kg. Serum total thyroxine (T4) declined significantly at doses of 36 mg/kg and greater; thyroid follicular epithelial cells were significantly larger within the same dose range, but the follicular colloid area decreased to less than 60% control values at 12 mg/kg and remained at this size through 72 mg/kg. Maximum mobilization of T4 apparently occurred at 12 mg/kg and attenuated measured declines in circulating levels. Even though a large proportion of proven and probable estrogenic chlorobiphenyls (CBs) were present, the lower amounts of more potent antiestrogenic aryl hydrocarbon (Ah) receptor agonists and/or decreased responsiveness because of low serum T4 levels may have antagonized the uterotropic response.

Polychlorinated biphenyls (PCBs) are among the ubiquitously persistent chemicals possessing endocrine-disrupting effects. Most of the environmentally abundant CB congeners have one or more ortho chlorines in the biphenyl ring. Because ortho-chlorinated CB congeners do not avidly bind to the aryl hydrocarbon (Ah) receptor, this clearly suggests that the estrogenicity of PCBs is not related to potency as Ah receptor agonists. It is important to investigate the estrogenicity of those ortho-chlorinated CB congeners in order to more accurately predict the hazards from PCB residues in the environment. The hydroxylated metabolites are presumably more reactive with the estrogen receptor, but induction of phase 2 enzymes at the higher doses could sequester the metabolites resulting in the lower serum residues of parent compound and attenuated estrogenic activity observed at higher doses. It was of interest to determine if a di-ortho CB congener which is more readily metabolized and an ineffective PROD inducer exhibited similar nonlinear dose:response relationships for estrogenicity and serum residues as observed for CB 153. CB 18 (2,2{prime}, 5-trichlorobiphenyl) is very rapidly metabolized to more polar products by sheep liver microsomes, rats and house flies. The detection of greater amounts of mono-hydroxylated metabolites from slower metabolized congeners than from CB 18more » reflects further secondary metabolism in these extended (up to 1 hour) microsomal incubations. Such secondary metabolism should be relatively constant up to very high doses in vivo, since CB 18 should be a very poor P450 2B1 inducer. Even though CB 18 commonly occurs in environmental samples, there is little information regarding its biological effects. In this study, we used immature Sprague-Dawley female rats as an animal model to examine the uterotropic response, thyrotoxic effect and enzyme induction potency of CB 18. 17 refs., 3 tab.« less

M.-H. Li, Y.-D. Zhao, L. G. Hansen Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois, Urbana, Illinois 61801, USA Received: 25 October 1993/Accepted: 1 March 1994 Accurate assessment of polychlofinated biphenyl (PCB) hazards remains a challenge because of multiple effects and multiple components of PCB mixtures (Hansen, 1979; 1987). A given chlorobiphenyl (CB) in an environmental residue may antagonize and/or potentiate the effects of other CBs in the mixture; furthermore, PCBs can induce biou'ansformation enzymes such as ethoxyresorufin O-deethylase (EROD, P450IA1) and pentoxyresorufin O-depentylase (PROD, P450IIB1) which can qualitatively as well as quantitatively alter the action(s) of individual CBs. Dose:response relationships of even single CBs may well be nonlinear due to these changes. Therefore, important effects may not be detected depending on the dose of the CB. There is growing public health concern regarding the potential risk from exposure to environmental estrogens. In a recent epidemiological study a significant positive association was reported between levels of 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) in blood and risk of breast cancer; a positive, but nonsignificant association, was also observed for PCBs (Wolff et al. 1993). Estrogenic activity has been ascribed to some lower-chlorinated Aroclor mixtures (Bitman and Cecil 1970; Ecobichon and Mackenzie 1974; Jansen et al. 1993); however, coplanar CBs (Jansen et al. 1993; Krishnan and Safe 1993) as well as 2,3,7,8-tetrachtorodibenzo- p-dioxin (TCDD) (Astroff and Safe 1988) have been shown to be antiesta'ogenic. The antiestrogenic potency appears to be related to

David Villar, 1'2 Mei-Hui Li, 1 and David J. Schaeffer ~ 1University of Illinois, Department of Veterinary Biosciences, 2001 South Lincoln Avenue, Urbana, Illinois 61801 USA and 2Departamento de Pharmacologia y Toxicologia, Universidad de Cordoba, Avda, Madina Azahara, 9, 14071-Cordoba, Spain

Recently, investigators have reported bioaccumulation of polychlorinated biphenyls (PCBs) in insects collected at hazardous waste sites. Little is known about differences in bioaccumulation of particular PCB congeners in insects. The authors report on the toxicokinetics of a non-coplanar ortho substituted congener, 2,2',4,4'-tetrachlorobiphenyl (PCB-47) and a coplanar non-ortho substituted PCB, 3,3',4,4'-tetrachlorobiphenyl (PCB-77) in topically treated house crickets. Penetration and excretion were more rapid for PCB-47 than for PCB-77. PCB-47 demonstrated a high affinity for abdomen, gut, and gonads, whereas, PCB-77 had a greater affinity for the head and thorax. Sex differences were observed in excretion and distribution. Females had an increased excretion of PCBs and increased accumulation in gut and gonads compared to males. Differences in lipophilicity can explain differences in distribution between sexes and of compounds within sexes. However, to explain the observed difference in penetration, it is necessary to invoke explanations based on stearic factors associated with coplanarity of the molecules. Differences in excretion are likely related to sex differences in mixed-function oxidase activities. These toxicokinetic data suggest that the more toxic coplanar congener, PCB-77, is likely to be more persistent in crickets compared to PCB-47, despite its lower lipophilicity.