The role of retinoic acid receptors and their cognate ligands in reproduction in a context of triorganotin based endocrine disrupting chemicals.

Retinoic acid (RA), an active form of vitamin A, regulates the embryonic development, male and female reproduction and induces important effects on the cell development, proliferation, and differentiation. These effects are mediated by the retinoid (RAR) and rexinoid nuclear receptors (RXR), which are considered to be a ligand-activated, DNA-binding, trans-acting, and transcription-modulating proteins, involved in a general molecular mechanism responsible for the transcriptional responses in target genes. Organotin compounds are typical environmental contaminants and suspected endocrine disrupting substances. They may affect processes of reproductive system in mammals, predominantly via nuclear receptor signaling pathways. Triorganotins, such as tributyltin chloride (TBTCl) and triphenyltin chloride (TPTCl), are capable to bind to RXR molecules, and thus represent potent agonists of RXR subtypes of nuclear receptors not sharing any structural characteristics with endogenous ligands of nuclear receptors. Th is article summarizes selected effects of biologically active retinoids and rexinoids on both male and female reproduction and also deals with the effects of organotin compounds evoking endocrine disrupting actions in reproduction.

Imposex and organotin compounds in ports of the Mediterranean and the Atlantic: Is the story over?

Organotin compounds are toxic substances released into the marine environment from antifouling paints. Sixty-two years following their first application and 9years after the complete ban on their use as biocides in 2003 (EC No. 782/2003), their negative impact on mollusks was still evident, as illustrated by imposex (i.e. the masculinization of female gastropods). This phenomenon is widely used to investigate tributyltin (TBT) pollution, with Hexaplex trunculus and Nassarius nitidus being considered as sensitive bioindicators. H. trunculus specimens and sediment samples collected from the ports of Cagliari (Sardinia), El Kantaoui (Tunisia) and Olhão (Portugal), along with N. nitidus individuals from the port of Faro (Portugal), were used for the assessment of imposex intensity and organotin pollution in these areas. High imposex frequency and organotin concentrations (TBT, triphenyltin (TPhT) and their degradation products) were observed, especially in Sardinia, implying that these chemicals remain a significant pollution issue in the specific Mediterranean ports. Moreover, the highly significant relationship established between penis length of imposex-affected females H. trunculus and TBT/TPhT concentrations offers a rapid and nonsacrificial proxy model for assessing the impact of organotins in coastal environments. Finally, the complementary use of more than one TBT bioindicator is advised in order to obtain more accurate results in detailed monitoring studies of TBT pollution.

Imposex and butyltin contamination still evident in Chile after TBT global ban.

Imposex in gastropods (Acanthina monodon, Oliva peruviana and Xanthochorus cassidiformis), butyltin levels in surface sediments (Coquimbo and Concepcion) and tissues (Valparaiso and Concepcion) were assessed in three areas under the influence of maritime activities along the central Chilean coast. The highest TBT concentrations were observed in São Vicente Bay (Concepcion), reaching 122.3ngSng(-1) in surface sediments and 59.7ngSng(-1) in gastropods tissue, while in Valparaiso ranged from 7.4 to 15.8ngSng(-1) in biota. The lowest TBT concentrations were detected in sediments from Coquimbo (<2ngSng(-1)), which can be attributed to a much lower ship/boat traffic (probably using TBT free products) in association to local oceanographic conditions. Despite DBT and MBT were the predominant analytes, recent inputs of TBT were evident in some areas. In fact, fishing boats may be a relevant source since they were the predominant maritime activity in the most contaminated sites. In addition, the absence of significant differences within BTs levels between both genders of A. monodon suggests that tissues from distinct sexes can be indistinctly used for future contamination studies. Imposex incidence was detected in 11 out of 15 sampled sites, indicating that environmental levels of TBT have been sufficient to induce deleterious effects on the exposed organisms. Thus, the impacts caused by TBT in Chilean coastal areas were detectable and consistent with other studies performed in South America. This present environmental contamination is probably due to the lack of regulations forbidding the use of TBT-based antifouling paints in Chile.

[The role of oxidative inflammatory cascade on pancreatic fibrosis progression in mice induced by DBTC plus ethanol].

OBJECTIVE: To explore the role and mechanism of oxidative inflammatory cascade in pancreatic fibrosis progression of chronic pancreatitis (CP) in mice induced by dibutyltin dichloride (DBTC) plus ethanol. METHODS: Thirty-six KM mice were randomly divided into 2 groups (n = 18): control group and model group (DBTC combined with ethanol). The mice in model group were intravenously injected with DBTC (8 mg/kg) in tail vein and drink 10% ethanol. After modeling 2 weeks, 4 weeks and 8 weeks, the mice were anesthetized and sacrificed, the pathological changes and the degree of fibrosis in the pancreas were observed by HE and Masson staining, the F4/80 expression level were detected by immunohistochemistry, the content of superoxide dismutase (SOD), malondialdehyde(MDA) and myeloperoxidase (MPO) were measured in the pancreatic homogenates. RESULTS: The fibroblasts and macrophages (f4/80 positive staining) could be seen obviously in pancreas of model group at 2 weeks. At 4 weeks and 8 weeks, macrophages infiltration increased and pancreatic tissue was substituted by the proliferation of fibrosis significantly. At every time-point, in pancreatic homogenates SOD was decreased, MDA and MPO markedly increased. There was significant differences between two groups (P < 0.05). CONCLUSION: DBTC injection joint ethanol drinking can successfully establish the model of chronic pancreatitis and pancreatic fibrosis in mice. Oxidative inflammatory cascade plays an important role in the progression of pancreatic fibrosis.

Obesity and asthma: the role of environmental pollutants.

Air pollution is a well-known risk for lung diseases, including asthma. Growing evidences suggesting air pollution as a novel risk factor for the development of obesity. Several Epidemiological studies have ascertained an association between various ambient and indoor air pollutants and obesity by medium of endocrine disruptive chemicals that can disrupt the normal development and homeostatic controls over adipogenesis and energy balance and induce obesity. Several obesity-induced mechanisms have been proposed that increases this vulnerability of obese individuals to harmful effects of air pollution rendering them more susceptible to developing air-pollution driven incident asthma or worsening of already existing asthma.

Gene expression profiling and endothelin in acute experimental pancreatitis.

AIM: To analyze gene expression profiles in an experimental pancreatitis and provide functional reversal of hypersensitivity with candidate gene endothelin-1 antagonists. METHODS: Dibutyltin dichloride (DBTC) is a chemical used as a polyvinyl carbonate stabilizer/catalyzer, biocide in agriculture, antifouling agent in paint and fabric. DBTC induces an acute pancreatitis flare through generation of reactive oxygen species. Lewis-inbred rats received a single i.v. injection with either DBTC or vehicle. Spinal cord and dorsal root ganglia (DRG) were taken at the peak of inflammation and processed for transcriptional profiling with a cDNA microarray biased for rat brain-specific genes. In a second study, groups of animals with DBTC-induced pancreatitis were treated with endothelin (ET) receptor antagonists [ET-A (BQ123) and ET-B BQ788)]. Spontaneous pain related mechanical and thermal hypersensitivity were measured. Immunohistochemical analysis was performed using anti-ET-A and ET-B antibodies on sections from pancreatic tissues and DRG of the T10-12 spinal segments. RESULTS: Animals developed acute pancreatic inflammation persisting 7-10 d as confirmed by pathological studies (edema in parenchyma, loss of pancreatic architecture and islets, infiltration of inflammatory cells, neutrophil and mononuclear cells, degeneration, vacuolization and necrosis of acinar cells) and the pain-related behaviors (cutaneous secondary mechanical and thermal hypersensitivity). Gene expression profile was different in the spinal cord from animals with pancreatitis compared to the vehicle control group. Over 260 up-regulated and 60 down-regulated unique genes could be classified into 8 functional gene families: circulatory/acute phase/immunomodulatory; extracellular matrix; structural; channel/receptor/transporter; signaling transduction; transcription/translation-related; antioxidants/chaperones/heat shock; pancreatic and other enzymes. ET-1 was among the 52 candidate genes up-regulated greater than 2-fold in animals with pancreatic inflammation and visceral pain-related behavior. Treatments with the ET-A (BQ123) and ET-B (BQ-788) antagonists revealed significant protection against inflammatory pain related mechanical and thermal hypersensitivity behaviors in animals with pancreatitis (P < 0.05). Open field spontaneous behavioral activity (at baseline, day 6 and 30 min after drug treatments (BQ123, BQ788) showed overall stable activity levels indicating that the drugs produced no undesirable effects on normal exploratory behaviors, except for a trend toward reduction of the active time and increase in resting time at the highest dose (300 µmol/L). Immunocytochemical localization revealed that expression of ET-A and ET-B receptors increased in DRG from animals with pancreatitis. Endothelin receptor localization was combined in dual staining with neuronal marker NeuN, and glia marker, glial fibrillary acidic protein. ET-A was expressed in the cell bodies and occasional nuclei of DRG neurons in naïve animals. However, phenotypic expression of ET-A receptor was greatly increased in neurons of all sizes in animals with pancreatitis. Similarly, ET-B receptor was localized in neurons and in the satellite glia, as well as in the Schwann cell glial myelin sheaths surrounding the axons passing through the DRG. CONCLUSION: Endothelin-receptor antagonists protect against inflammatory pain responses without interfering with normal exploratory behaviors. Candidate genes can serve as future biomarkers for diagnosis and/or targeted gene therapy.

Disruptores endocrinos y obesidad: obesógenos / Endocrine disruptors and obesity: obesogens

La incidencia y prevalencia de sobrepeso y obesidad ha experimentado un gran incremento en las últimas tres décadas y afecta a casi todos los países del orbe. Este fenómeno no se explica fácilmente por los cambios del estilo de vida en las distintas poblaciones con hábitos de partida muy distintos. Por lo que además del cambio del estilo de vida, otros factores empiezan a tenerse en cuenta, los llamados disruptores endocrinos y más concretamente los obesógenos. Revisamos la evidencia que existe sobre sustancias químicas que polucionan el ambiente que potencialmente puedan ser obesógenos en humanos: el dietilestilbestrol (DES), la ginesteína, el bisfenol-A, los derivados orgánicos de estaño y los ftalatos. Los tres primeros actúan principalmente sobre los receptores estrogénicos y los derivados orgánicos del estaño y los ftalatos activando los PPARγ. En conclusión, existen evidencias del efecto obesógeno de estas sustancias en estudios en animales de experimentación, tanto in vitro como in vivo, pero muy pocas en humanos. (AU)

ncidence and prevalence of owerweight and obesity have greatly increased over the past three decades in almost all countries around the world. This phenomenon is not easily explained by lifestyle changes in populations with very different initial habits. This has led to consider the influence of other factors, the so-called endocrine disruptors, and more specifically obesogens. This study reviewed the available evidence about polluting chemical substances which may potentially be obesogens in humans: DES, genistein, bisphenol A, organotins (TBT, TPT), and phthalates. The first three groups of substances mainly act upon estrogen receptors, while organotins and phthalates activate PPARγ. It was concluded that evidence exists of the obesogenic effect of these chemical substances in tissues and experimental animals, but few data are available in humans (AU)

Imposex reduction and residual butyltin contamination in southern Brazilian harbors.

The imposex incidence was appraised in South American gastropods, considering the scenario before and after the global ban of tributyltin (TBT). A statistically significant reduction in imposex indexes was observed in Stramonita haemastoma collected in 2006 and 2010 from areas under the influence of four coastal harbors from southern Brazil. This reduction may be because of the effectiveness of the global ban issued by the International Maritime Organization, although the restrictions on TBT-based antifouling paints in Brazil might also have helped. Even so, a residual organotin contamination was still detected in female tissues (levels ranged from 7.6 to 164.9 ng Sn/g for TBT; from <2 to 214.5 ng Sn/g for dibutyltin; from <3.5 to 178.8 ng Sn/g for monobutyltin; and from <1.5 to 53 ng Sn/g for triphenyltin). Thus, although a reduction in imposex and environmental levels of organotins is expected in every ocean worldwide soon after the implementation of national and international restriction regulations, this will depend on the effectiveness of the global TBT ban; the effectiveness of local restrictions on producing, selling, and using TBT-based antifouling paints; and specific characteristics of local sediments, because metabolization rates and sorption/desorption of TBT previously deposited might affect its environmental bioavailability. Therefore, the reduction trend detected in the present study cannot be extrapolated to other Brazilian or South American coastal areas.

Analgesic effects of gabapentin on mechanical hypersensitivity in a rat model of chronic pancreatitis.

Gabapentin, an anticonvulsant, is widely accepted as an alternative therapeutic agent for neuropathic pain and has proved to produce analgesic effects in a mouse model of visceral pain. However, it is unknown whether gabapentin is also analgesically effective in chronic pancreatitis. The aim of the present study was to investigate the role and underlying mechanisms of gabapentin in a rat model of chronic pancreatitis. Chronic pancreatitis induced by dibutyltin dichloride (DBTC) produced a marked increase in mechanical sensitivity of the abdomen after the establishment of the model. During the first day to the sixth day in the fourth week, Gabapentin was administered intraperitoneally daily at a dose of 100mg/kg. The behavioral test began 1h after drug administration. The analgesic effect of gabapentin was not evident with a single injection, but gabapentin significantly reduced the responsive frequencies to mechanical stimulation in rats with chronic pancreatitis from the third day to the end of the experiment. To explore the underlying mechanisms, the expression of alpha(2)delta-1 calcium channel subunit was examined in the thoracic spinal cord (T8-11). There was no significant change in alpha(2)delta-1 level of T8-11 following the first injection. But after the sixth injection, the alpha(2)delta-1 level of T8-11 in rats with chronic pancreatitis was declined. Taken together, the present study suggested that repeated administration of gabapentin daily could reduce mechanical hypersensitivity in the upper abdomen and produce an analgesic effect in a rat model of chronic pancreatitis. The down-regulation of alpha(2)delta-1 calcium channel subunit might be one of the mechanisms underlying the analgesic effect of gabapentin.

Organometallic compounds in oncology: implications of novel organotins as antitumor agents.

Since the introduction of cisplatin in cancer therapy, metal complexes and organometallic compounds have been gaining growing importance in oncology. The impressive clinical effectiveness of cisplatin is limited by significant side effects and the emergence of drug resistance. Thus, novel classic and unconventional Pt(II) and Pt(IV) complexes have been introduced in therapy or are presently in advanced clinical trials. Moreover, innovative non-platinum metal-based antitumor agents, whose activity does not rely on direct DNA damage and may involve proteins and enzymes, have been developed. Gold and tin derivatives are enjoying an increasing interest and appear very promising as potential drug candidates.

In vitro cytotoxic activity of tri-n-butyltin(IV)lupinylsulfide hydrogen fumarate (IST-FS 35) and preliminary antitumor activity in vivo.

The cytotoxicity in vitro and antitumor activity in vivo of the organotin compound tri-n-butyltin(IV)lupinylsulfide hydrogen fumarate (IST-FS 35) have been investigated. The IC50 values obtained in a panel of tumor cell lines were compared to those of the parental compound IST-FS 29 in the same cells. IST-FS 35 resulted significantly more active than IST-FS 29 with IC50 values in the range 0.16-1.8 microM. Toxicity studies in vivo, after intravenous administration of escalating concentrations of IST-FS 35, provided the identification of the maximal tolerated dose (3.5 mg/kg) which was employed as therapeutic dose in the antitumor activity experiments. Preliminary results, in transplanted murine tumor models, revealed that both the P388 myelomonocytic leukaemia and the B16-F10 melanoma, implanted subcutaneously in BDF1 mice, were inhibited about 96% in their tumor volume at day 11, following a single intravenous injection of the compound. Additional studies are mandatory to unravel the mechanism of action for the development of IST-FS 35 as potential antitumor drug.

Monitoring the organotin contamination in the Taihu Lake of China by bivalve mussel Anodonta woodiana.

As a part of the pilot study on "Freshwater Mussel Watch", butyltin (monobutyltin, MBT; dibutyltin, DB; tributyltin, TBT), and phenyltins (monophenyltin, MPT; diphenyltin DPT; triphenyltin TPT) were analyzed in soft tissues of 15 bivalve mussels Anodonta woodiana sampled from five separate sites (Huzhou, Xueyan, Dapu, Sansandao, and Wulihu) around the Taihu Lake of China in 2004. The residue of total butyltins and total phenyltins in the all mussels ranged 142-1693 and 3.0-90 ng Sn g(-1) dry weight, respectively. Except for the mussels from Xueyan, DBT and MBT accounted more than 60% of total butyltins in those from other four sites. In contrast, TPT were usually almost 100% of the mussels studied. The present study provides most recent information about the organotin contamination in the Taihu Lake, and suggests Anodonta woodiana can be used as a suitable bioindicator.

Disruption of glucocorticoid action by environmental chemicals: potential mechanisms and relevance.

Glucocorticoids play an essential role in the regulation of key physiological processes, including immunomodulation, brain function, energy metabolism, electrolyte balance and blood pressure. Exposure to naturally occurring compounds or industrial chemicals that impair glucocorticoid action may contribute to the increasing incidence of cognitive deficits, immune disorders and metabolic diseases. Potentially, "glucocorticoid disruptors" can interfere with various steps of hormone action, e.g. hormone synthesis, binding to plasma proteins, delivery to target cells, pre-receptor regulation of the ratio of active versus inactive hormones, glucocorticoid receptor (GR) function, or export and degradation of glucocorticoids. Several recent studies indicate that such chemicals exist and that some of them can cause multiple toxic effects by interfering with different steps of hormone action. For example, increasing evidence suggests that organotins disturb glucocorticoid action by altering the function of factors that regulate the expression of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) pre-receptor enzymes, by direct inhibition of 11beta-HSD2-dependent inactivation of glucocorticoids, and by blocking GR activation. These observations emphasize on the complexity of the toxic effects caused by such compounds and on the need of suitable test systems to assess their effects on each relevant step.

Citotoxic effects of stannous salts and the action of Mytenus ilicifolia, Bacchris genistelloides and Cymbopogon citratus aqueous extracts

In nuclear medicine, stannous, as stannous chloride (SnCl2) and stannous fluoride (SnF2), are used as reducing agents to obtain radiopharmaceuticals labeled with technetium-99m. In the literature, the SnCl2 action was studied and it seems to be mediated through free radicals (FR) production in a Fenton-like reaction. In this work it was evaluated: (i) the in vitro SnF2 effects in different concentrations using pBCKS plasmid deoxyribonucleid acid (DNA); (ii) the SnF, effects in different Escherichia coli (E.coli) cultures, proficient or deficient in DNA repair genes, treated simultaneously with FR scavengers; and (iii) the biological effects of Maytenus ilicifolia, Baccharis genistelloides and Cymbopogon citratus aqueous extracts on the SnCL2 action in E.coli culture. The SnF2 treatment induced plasmidd DNA damages (single and double DNA strand breaks), in a dose-dependent manner. Citotoxicity mediated by SNf2 was observed and the simultaneous tratment with FR scavengers has increased the cell survival, suggesting the participation of FR on the SnF2-deleterious effects. The vegetal extrracts prottected the E.coli cells agains the SnCl2 effects. The components of the extracts could be interacting with SnCl2 blocking its participation in the FR formation.

Triphenyltin as a potential human endocrine disruptor.

Organotin compounds have been implicated as reproductive toxicants and endocrine disruptors primarily through studies in aquatic organisms, with little information available in mammals. Among the organotins, aryltins have been less studied than alkyltins. Extensive data is available on mammalian developmental and reproductive toxicity of one aryltin compound, triphenyltin (TPT), from toxicity studies conducted in connection with the registration of triphenyltin hydroxide (TPTH) as a pesticide and supporting publications from the open literature. Indications of adverse functional and morphological effects on the reproductive tract of rats were reported in a dose range of 1.4-20 mg/kg/d. Gonadal histopathology (both ovaries and testes) and infertility were affected at the higher doses, while reproductive-tract cancer, smaller litter sizes, and reproductive organ weights were affected at the lower end of the dose range. In vitro studies indicate that TPT can directly activate androgen receptor-mediated transcription and inhibit enzymes that are involved in steroid hormone metabolism. These data suggest that the aryltin TPT can be active as a reproductive toxicant in mammals and may be a human endocrine disruptor.

[Butyltin and its degradation products in the aspect of food toxicology]. / Butylocyna i produkty jej degradacji w aspekcie toksykologii zywnosci.

The paper briefly reviews and up-dates available data on some aspects of toxicity of organotins and especially of butyltins, their applications, legal aspects as well as aquatic environment, seafood and food contamination. Special attention is paid on assessed rates of daily intake of butyltins with fish diet by some local groups of inhabitants with high consumption rates of fish originating from the region of the Gulf of Gdanski.

Specific detection of organotin compounds with a recombinant luminescent bacteria.

Organotin compounds are widely used as biocides in marine and terrestrial environments. Several currently used techniques allow either the measurement of the chemicals or their effects on living organisms. Our current research focuses on the development of a complementary method based on a bacterial bioluminescence-based bioassay for the specific detection of organotin compounds. The performance of the bioassay was assessed. The Escherichia coli bacterial strain used in this study is specific for TBT and DBT (with Cl, Br or I as the halogen group) with the central tin atom important for light production. The assay is conducted after overnight culture of the bacterial strain, followed by 60 min of contact time with the organotin compound for significant light production. The detection limits were found to be 0.08 microM for TBT (26 microgl(-1)) and 0.0001 microM for DBT (0.03 microgl(-1)) with a linear range of one logarithm. The repeatability of the bioassay is 8% and the reproducibility for TBT and DBT was approximately 14%. Lyophilization of the strains did not significantly modify the detection limit as well as the range of detection. Applications of the bioassay to environmental samples are discussed.

Imposex and organotin concentrations in Buccinum undatum and Neptunea antiqua from the North Sea: relationship to shipping density and hydrographical conditions.

The presence and the development of imposex were investigated in the common whelk (Buccinum undatum) and the red whelk (Neptunea antiqua) from the open North Sea and the Skagerrak. Imposex development was related to levels of organotins in snails and in the fine fractions (< 63 microm) of the sediments they inhabit. The sampling locations were classified according to three levels of traffic densities of ships of > or = 100 gt per day passing within 15 Nautical miles of the sampling station, shipping levels being: high (> 10 ships day(-1)), intermediate (5--10 ships day(-1)), and low (< 5 ships day(-1)). Sampling stations were also classified according to presence or absence of a vertically stratified water column. In the snails the body levels of the butyltin metabolites MBT and DBT and the parent phenyltin compound TPT, were higher than those of TBT and PT metabolites. In the sediment, the parent compounds and the mono-substituted metabolites MBT and MPT were present in the highest concentrations. The highest body levels of all organotin compounds and the highest imposex indices for the common whelk were found at those locations in the Southern Bight and the German Bight that had a high shipping density as well as a homogeneously mixed water column during the whole year. At these locations sediment levels of organotins were also higher than at other sites. In contrast, the body levels of organotins were low and imposex was sometimes even completely absent in snails from stratified deep-water stations in the Skagerrak, despite a very high shipping density in the entrance area of the Baltic. In sediments from stratified locations with low or intermediate shipping densities, organotin compounds were below or close to their respective limits of detection. These stations were located in areas with a stratified water column during the whole year. The results can be explained by postulating a much higher resistance for dissolved organotins to migrate through a pycnocline. Organotins could only transgress through a pycnocline when adsorbed to settling particles that manage to transgress the boundary between layers. N. antiqua could only be obtained in sufficient numbers from deeper water stations, which almost all had a stratified water column. At stations where both snail species were obtained and imposex was present, the imposex index was higher in the red whelk. Hence N. antiqua seems to be the more sensitive species of the two. In the red whelk, imposex development increased with shipping density too, though in the smaller samples the trend was not significant. Average biota-sediment accumulation factors (BSAFs; normalised for lipid content in snails and TOC content in the fraction < 63 microm in sediments) for Buccinum ranged from 0.4 to 1.0 for butyltins and were similar to literature values reported for TBT in other marine species. Higher average BSAF values were found for phenyltins 1.5 (MPT) to 17 (TPT). The high values for TPT match the ranges expected from equilibrium partitioning concepts of persistent hydrophobic compounds. The ratio of live snails to the total number of live snails plus empty shells ranged between 2.5 and 93%. This parameter might be a useful indicator to compare past and present densities of populations of both species in different areas of the North Sea.

Cytochrome P450 differences in normal and imposex-affected female whelk Buccinum undatum from the open North Sea.

Normal and imposex-affected female Buccinum undatum were sampled from the open North Sea at three locations, one with low, and two with high shipping densities. Cytochrome P450 components and P450 aromatase activity were determined in the microsomal fractions isolated from pooled digestive gland/gonads. Cytochrome P450 aromatase activity was significantly higher (P < 0.05) in normal females collected in the low shipping density area (1,325 +/- 295 fmol/h/mg protein) than levels from imposex animals from a high shipping density area (620 +/- 287 fmol/h/mg protein). A negative correlation was found between aromatase activity and organotin body burden (r = -0.99). Levels of CYP450, cytochrome b5 and NADPH cytochrome c reductase activity did not show differences among groups. This is the first field evidence of depressed aromatase activity in imposex affected females, although additional research under laboratory controlled conditions is required to fully understand the mechanisms underlying the development of imposex in this species.