Suitability of carboxylated porphyrin profiles as a biochemical indicator in whitefish (Coregonus clupeaformis) exposed to bleached kraft pulp mill effluent

The hepatic carboxylated porphyrin profile was studied in whitefish exposed to bleached kraft pulp mill effluent (BKME). The distribution of the porphyrins was different between the samples from the BKME and the reference site, and fish exposed to BKME contained higher amounts of highly carboxylated porphyrins (HOP). The ratios of HCP to protoporphyrin, and coproporphyrin to protoporphyrin, were also significantly different between the two groups. In addition, the cytochrome P-450 activity, liversomatic index, and gonadosomatic index were measured and compared with the prophyrin profile. The results suggest that BKME could inhibit porphyrinogen decarboxylases, and the porphyrin profile is useful as a biochemical indicator for identification of BKME exposure. © 1994 by John Wiley & Sons, Inc..     

Alkylphenol metabolites in fish bile as biomarkers of exposure to offshore oil industry produced water in feral fish

The measurement of low-concentration alkylphenol (AP) exposure in fish is relevant in connection with monitoring and risk assessment of offshore oil industry produced water (PW) discharges. Detection of AP markers in fish bile offers significantly greater sensitivity than detection of AP in tissues such as liver. Recent studies revealed that gas chromatography-mass spectrometry in electron ionization mode (GC-EI-MS) enabled a selective and sensitive analytical detection of PW AP in mixtures with unknown composition. A procedure consisting of enzymatic deconjugation of metabolites in fish bile followed by derivatization with bis(trimethylsilyl)trifluoroacetamide and then separation and quantification of derivatized AP using GC-EI-MS is presented. The use of this procedure as a possible recommended approach for assessment and biomonitoring of AP contamination in fish populations living down-current from offshore oil production fields is presented.     

Structural and functional impairment of the hypothalamo- pituitary-interrenal axis in fish exposed to bleached kraft mill effluent in the St Maurice River,Quebec

The effects of bleached kraft mill effluent (BKME) on blood cortisol levels and the morphology of the pituitary-interrenal axis were investigated in two species of teleost fish, the northern pike, Esox lucius, and the yellow perch, Perca flavescens, sampled upstream and downstream from a pulp and paper mill on the St Maurice River, Quebec. Fish were acutely stressed by a standardized capture and sampling protocol at both sites, and their ability to elevate blood cortisol levels in response to the capture stress was compared. Blood cortisol levels in fish from the upstream site (>100 ng/ml plasma) were higher than the levels in fish from the BKME site, and the pituitary corticotropes and the interrenal steroidogenic cells of the upstream fish were larger and had larger nuclei compared with cells from the downstream fish. The low blood cortisol levels in fish exposed to BKME were correlated to cellular atrophy within the hypothalamo-pituitary-interrenal (HPI) axis. The reduced ability to elevate blood cortisol in response to an acute stress may be an endocrine dysfunction occuring in fish chronically exposed to chemical stressors in their environment     

Are metal mining effluent regulations adequate: identification of a novel bleached fish syndrome in association with iron-ore mining effluents in Labrador, Newfoundland

Water quality guidelines for industrial effluents are in place in many countries but they have generally evolved within a limited ecotoxicological framework. Effluents from iron-ore mines have traditionally been viewed by regulatory bodies as posing little or no risk to the aquatic environment. However, it was recently reported that lake trout taken from a large iron-ore contaminated Lake in Labrador (Wabush Lake) had elevated levels of DNA oxidative damage and were markedly depleted in levels of vitamin A (Payne et al., 1998) in comparison with fish from a Lake (Shabogamo Lake) receiving lesser levels of effluents. Through further observations, it has now been established that the lake trout in Wabush Lake are commonly affected with a marked skin bleaching syndrome in comparison with fish in Shabogamo Lake and a nearby Lake (Ashuanipi) which does not receive effluents. To the authors' knowledge such a syndrome which is characterized by marked reduction in skin pigmentation and overall increase in skin whitening has not been reported before in any fish population in association with contamination. Preliminary information for liver histopathological and blood cell differences have also been obtained in fish in Wabush Lake in comparison with Ashuanipi Lake. It has also been observed through studies on phosphatidyl liposomes that iron-ore leachate contains redox-active material (iron but possibly other transition metals) that has considerable potential for causing oxidative damage to cellular constituents. Using the weight of evidence approach it is indicated that iron-ore effluents may pose more of a risk to the aquatic environment than traditionally considered by regulatory agencies.     

Health effects of subchronic exposure to environmental levels of hardwood smoke

Hardwood smoke is a contributor to both ambient and indoor air pollution. As part of a general health assessment of multiple anthropogenic source emissions conducted by the National Environmental Respiratory Center, a series of health assays was conducted on rodents exposed to environmentally relevant levels of hardwood smoke. This article summarizes the study design and exposures, and reports findings on general indicators of toxicity, bacterial clearance, cardiac function, and carcinogenic potential. Hardwood smoke was generated from an uncertified wood stove, burning wood of mixed oak species. Animals were exposed to clean air (control) or dilutions of whole emissions based on particulate (30, 100, 300, and 1000 micromg/m3). F344 rats, SHR rats, strain A/J mice, and C57BL/6 mice were exposed by whole-body inhalation 6 h/day, 7 days/wk, for either 1 wk or 6 mo. Effects of exposure on general indicators of toxicity, bacterial clearance, cardiac function, and carcinogenic potential were mild. Exposure-related effects included increases in platelets and decreases in blood urea nitrogen and serum alanine aminotransferase. Several other responses met screening criteria for significant exposure effects but were not consistent between genders or exposure times and were not corroborated by related parameters. Pulmonary histopathology revealed very little accumulation of hardwood smoke particulate matter. Parallel studies demonstrated mild exposure effects on bronchoalveolar lavage parameters and in a mouse model of asthma. In summary, the results reported here show few and only modest health hazards from short-term to subchronic exposures to realistic concentrations of hardwood smoke.     

Exposure to bleached kraft pulp mill effluent disrupts the pituitary-gonadal axis of white sucker at multiple sites.

Our recent studies have demonstrated reproductive problems in white sucker (Catostomus commersoni) exposed to bleached kraft pulp mill effluent (BKME) at Jackfish Bay on Lake Superior. These fish exhibit delayed sexual maturity, reduced gonadal size, reduced secondary sexual characteristics, and circulating steroid levels depressed relative to those of reference populations. The present studies were designed to evaluate sites in the pituitary-gonadal axis of prespawning white sucker affected by BKME exposure. At the time of entry to the spawning stream, plasma levels of immunoreactive gonadotropin (GtH)-II (LH-type GtH) in male and female white sucker were 30- and 50-fold lower, respectively, than the levels in fish from a reference site. A single intraperitoneal injection of D-Arg6, Pro9N-Et sGnRH (sGnRH-A, 0.1 mg/kg) increased plasma GtH levels in male and female fish at both sites, although the magnitude of the response was greatly reduced in BKME-exposed fish. Fish at the BKME site did not ovulate in response to sGnRH-A, while 10 of 10 fish from the reference site ovulated within 6 hr. Plasma 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P) levels were depressed in BKME-exposed fish and unlike fish at the reference site, failed to increase in response to sGnRH-A. Testosterone levels in both sexes and 11-ketostestosterone levels in males were elevated in fish from the reference site but were not further increased by GnRH treatment. In contrast, BKME-exposed fish exhibit a transitory increase in testosterone levels in response to the GnRH analog. In vitro incubations of ovarian follicles obtained from fish at the BKME site revealed depressed basal secretion of testosterone and 17,20 beta-P and reduced responsiveness to the GtH analog human chorionic gonadotropin and to forskolin, a direct activator of adenylate cyclase. By comparison, ovarian follicles from fish collected at BKME and reference sites produced similar levels of prostaglandin E basally and in response to a phorbol ester and calcium ionophore A23187, suggesting that BKME effects on ovarian function are selective and do not reflect a general impairment of ovarian function. BKME-exposed fish had plasma levels of testosterone glucuronide proportionately lower than those of reference fish, suggesting that there are site differences in the peripheral metabolism of steroids. These studies demonstrate that BKME exposure affects reproduction by acting at multiple sites in the pituitary-gonadal axis.     

Effects of hardwood smoke exposure on allergic airway inflammation in mice

Hardwood smoke (HWS) from wood burning stoves and fireplaces can be a significant contributor to the composition of ambient air pollution. We hypothesize that the inhalation of HWS by ovalbumin (OVA)-sensitized mice with preexisting lung inflammation leads to the exacerbation of allergic airway responses. Two different models were employed to characterize the effects of inhaled wood smoke on allergic airway inflammation. In both models, male BALB/c mice were sensitized by injection with OVA and alum. In one model, mice were challenged by inhalation with OVA 1 day prior to exposure to HWS (30, 100, 300, or 1000 microg particulate matter [PM]/m(3)) for 6 h/day on 3 consecutive days. In the other model, mice were exposed by inhalation to OVA, rested for 11 days, were exposed to HWS for 3 consecutive days, and then were exposed to OVA immediately after the final HWS exposure. Bronchoalveolar lavage (BAL), and blood collection were performed approximately 18 h after the last HWS or OVA exposure. HWS exposure after the final allergen challenge (first model) led to a significant increase in BAL eosinophils only at the 300 microg/m(3) level. In contrast, changes in BAL cells did not reach statistical significance in the second model. There were no HWS-induced changes in BAL interleukin (IL)-2, IL-4, IL-13, and interferon (IFN)gamma levels in either model following OVA challenge. These results suggest that acute HWS exposure can minimally exacerbate some indices of allergic airway inflammation when a final OVA challenge precedes HWS exposure, but does not alter Th1/Th2 cytokine levels.     

Contribution of PCB exposure from fish consumption to total dioxin-like dietary exposure

Polychlorinated biphenyls (PCB) are the second greatest cause of fish advisories, and are often the greatest contributors to dioxin-like toxic equivalency (TEQ) in fish and seafood. Because fish consumption is associated with both contaminant risks and health benefits, incremental health risks from PCBs in fish should be considered within the context of overall TEQ associated dietary risk to enable consumers to make informed decisions about choosing to eat fish or alternate foodstuffs. In this paper, potential TEQ exposure from PCBs in fish for adults with a variety of consumption patterns and consuming fish from a variety of sources are calculated using recent consumption and fish contaminant data from the literature and compared to total TEQ exposure from all sources. For high-level consumers and individuals eating fish from relatively contaminated sites, PCB TEQ exposure from fish consumption alone may exceed the 1 pg TEQ/kg/day average adult daily intake estimated by EPA, which itself carries an upper bound cancer risk of 1 in 1000. PCB TEQ risk for average consumers of commercial fish is expected to be far less, but is highly uncertain, since there is a dearth of congener specific PCB data for commercial fish and seafood.     

Comparative responses of molluscs and fish to environmental estrogens and an estrogenic effluent

It is now well established that there is a diverse array of chemical discharged into the environment that can mimic or antagonise the action of hormones. These endocrine-disrupting chemicals (EDCs) can thus interact with physiological systems and cause alterations in development, growth and reproduction in wildlife that are exposed to them. As yet, however, there is little information on the relative sensitivities of different wild life groups to these chemicals and/or mixtures of them (e.g. estrogenic effluents) and hence, there are fundamental shortfalls in our knowledge of the ecological chemicals (17alpha-ethinylestradiol; EE2, bisphenol-A, and 4-tert octylphenol) and a mixture containing these chemicals (treated sewage effluent) on embryo production in the prosobranch mollusc, Potamopyrgus antipodarum, were studied and compared with the effects of EE2 and the same estrogenic effluent on vitellogenin induction and/or egg production in various species of freshwater fish (fathead minnow; Pimaphales promelas, rainbow trout (Oncorhynchus mykiss); Cyprinus carpio, carp; Cyprinus carpio). The lab-based studies demonstrated that all of the tested chemicals (known to be estrogenic and to cause reproductive effects in fish) also affected embryo production in P. antipodarum. Furthermore, exposure to EE2 induced similar reproductive responses in the snails as in the fathead minnow (Pimephales promelas), stimulating egg/embryo production at low doses (up to 1 ng/l in the minnow and 25 ng/l in the snail) and causing inhibitory effects at higher doses. A similar pattern of embryo production occurred in P. antipodarum when it was exposed to a graded concentration of treated sewage effluent containing mixtures of estrogenic EDCs and hence, the total number of new embryos produced by the snails increased steadily over the 9 week exposure period in treated snails. Plasma vitellogenin concentrations in two species of male fish (the rainbow trout and the carp) also increased over the same time period. These data indicate that both the nature of the response and the relative sensitivities to environmental estrogens in P. antipodarum and three different fish species fish are comparable. P. andtipodarum is thus, potentially a sensitive test organism for assessing estrogenicity of chemicals with a relevance to their activity in vertebrates.     

Comparative responses of molluscs and fish to environmental estrogens and an estrogenic effluent

It is now well established that there is a diverse array of chemicals discharged into the environment that can mimic or antagonise the action of hormones. These endocrine-disrupting chemicals (EDCs) can thus interact with physiological systems and cause alterations in development, growth and reproduction in wildlife that are exposed to them. As yet, however, there is little information on the relative sensitivities of different wildlife groups to these chemicals and/or mixtures of them (e.g. estrogenic effluents) and hence, there are fundamental shortfalls in our knowledge of the ecological importance of endocrine disruption in wildlife. In this study, the effects of exposure to individual estrogenic chemicals (17alpha-ethinylestradiol; EE2, bisphenol-A, and 4-tert octylphenol) and a mixture containing these chemicals (treated sewage effluent) on embryo production in the prosobranch mollusc, Potamopyrgus antipodarum, were studied and compared with the effects of EE2 and the same estrogenic effluent on vitellogenin induction and/or egg production in various species of freshwater fish (fathead minnow; Pimaphales promelas, rainbow trout (Oncorhynchus mykiss); Cyprinus carpio, carp; Cyprinus carpio). The lab-based studies demonstrated that all of the tested chemicals (known to be estrogenic and to cause reproductive effects in fish) also affected embryo production in P. antipodarum. Furthermore, exposure to EE2 induced similar reproductive responses in the snails as in the fathead minnow (Pimephales promelas), stimulating egg/embryo production at low doses (up to 1 ng/l in the minnow and 25 ng/l in the snail) and causing inhibitory effects at higher doses. A similar pattern of embryo production occurred in P. antipodarum when it was exposed to a graded concentration of treated sewage effluent containing mixtures of estrogenic EDCs and hence, the total number of new embryos produced by the snails increased steadily over the 9 weeks exposure period in treated snails. Plasma vitellogenin concentrations in two species of male fish (the rainbow trout and the carp) also increased over the same time period. These data indicate that both the nature of the response and the relative sensitivities to environmental estrogens in P. antipodarum and three different fish species fish are comparable. P. antipodarum is thus, potentially a sensitive test organism for assessing estrogenicity of chemicals with a relevance to their activity in vertebrates.     

Demasculinization of male fish by wastewater treatment plant effluent

Adult male fathead minnows (Pimephales promelas) were exposed to effluent from the City of Boulder, Colorado wastewater treatment plant (WWTP) under controlled conditions in the field to determine if the effluent induced reproductive disruption in fish. Gonadal intersex and other evidence of reproductive disruption were previously identified in white suckers (Catostomus commersoni) in Boulder Creek downstream from this WWTP effluent outfall. Fish were exposed within a mobile flow-through exposure laboratory in July 2005 and August 2006 to WWTP effluent (EFF), Boulder Creek water (REF), or mixtures of EFF and REF for up to 28 days. Primary (sperm abundance) and secondary (nuptial tubercles and dorsal fat pads) sex characteristics were demasculinized within 14 days of exposure to 50% and 100% EFF. Vitellogenin was maximally elevated in both 50% and 100% EFF treatments within 7 days and significantly elevated by 25% EFF within 14 days. The steroidal estrogens 17β-estradiol, estrone, estriol, and 17α-ethynylestradiol, as well as estrogenic alkylphenols and bisphenol A were identified within the EFF treatments and not in the REF treatment. These results support the hypothesis that the reproductive disruption observed in this watershed is due to endocrine-active chemicals in the WWTP effluent.     

Ethylenethiourea in urine as an indicator of exposure to mancozeb in vineyard workers

In the present study, the personal exposure to mancozeb and/or ethilenethiourea (ETU) in 13 Italian vineyard workers and in 13 subjects without occupational exposure to pesticides was investigated. With this aim, the level of ETU in urine and the dermal exposure to mancozeb were determined. Baseline urinary ETU results were lower than the analytical limit of detection for all controls (<0.5 microg/g creatinine) and for ten workers (median <0.5, range <0.5-3.4 microg/g creatinine). In workers, urinary ETU was significantly increased at the end of shift (2.5, <0.5-95.2 microg/g creatinine) compared with baseline levels. End-shift urinary ETU was higher in operators using open tractors (n=7) than in those using closed tractors (n=5) (16.2 vs. 2.4 microg/g creatinine), but the difference was not significant (P=0.073). End-shift urinary ETU was positively correlated with dermal exposure to mancozeb determined both over the clothes and on the skin (Spearman's rho=0.770 and 0.702, P=0.009 and 0.024, respectively). Wine consumption positively influenced the excretion of ETU.     

Changes in growth, secondary sex characteristics, and reproduction of fathead minnows exposed for a life cycle to bleached sulfite mill effluent

To assess the potential effects of exposure to bleached sulfite mill effluent, long-term fathead minnow (Pimephales promelas) exposures were carried out on-site at the pulp mill secondary treatment lagoons. Exposure concentrations included 0, 1, 3, 10, 30, 50, or 100% final effluent, with the synthetic estrogen ethinylestradiol (10 ng/L) as a positive control compound. Fertilized minnow eggs were hatched in effluent and monitored through 140 d posthatch. The effluent produced a significant increase in the growth (length, weight, condition factor) of female fish (but not male fish). Exposure to high effluent concentrations resulted in a majority of fish with female secondary sex characteristics. Male fish with female characteristics and female fish with male sex characteristics were present at effluent concentrations of > or = 30%, but not in fish exposed to control water from the Saint John River. Effluent exposures (> or = 30%) also produced a reduction in the number of fish with testes, and most fish had ovaries when examined internally. A sensitive and meaningful endpoint was a decrease in reproduction. Fish exposed to 1 - 3% effluent produced a similar number of eggs to control fish; however, exposure to 10% effluent reduced egg production by over 80%. Fish exposed for an entire life cycle to > or = 30% effluent failed to produce eggs. The research demonstrates the feasibility and potential usefulness of on-site flow-through fish life-cycle exposures for the assessment of pulp mill final effluents.     

Assessment of the impact of a bleached kraft mill effluent on a south‐central USA river

We initiated a multifaceted, integrated investigation of the general health of the aquatic environment near a bleached kraft pulp and paper mill. This southcentral U.S. mill discharges about 125,000 cubic meters of treated effluent per day into an adjacent river. The sampling sites for this study were 1.8 km upstream from the mill's discharge, 0.25 km below the mill's outlet, and 5 km downstream from the discharge area. No toxicity was observed using Ceriodaphnia dubia and Pimephales promelas in aqueous phase tests or with Hyalella azteca and Chironomus tentans in sediment phase tests. Field examinations of two small fish species and sediment macroinvertebrate communities from each sampling site revealed no significant adverse effects. Bluegill sunfish (Lepomis macrochirus) were exposed for 35 days to site sediments and were evaluated for ethoxyresorufin O‐dethylase (EROD) activity, cytochrome P4501A (CYP1A) content, DNA strand breaks, condition index, organ indices, gross pathology, and immune responses. No significant adverse effects were observed in sediments immediately below the mill's effluent outlet, though detoxification enzyme activity was elevated in liver tissue of bluegill sunfish exposed to site 3 sediment. Embryos of mosquitofish (Gambusia affinis) were evaluated for developmental and reproductive abnormalities following a static laboratory exposure of gravid females to sediments from the three study sites for 56 days. The embryos showed no significant effects on a suite of reproductive parameters among the three sites. We concluded that there was no significant evidence of adverse impacts on the receiving river or its biota attributable to treated bleached kraft mill effluent based on a comprehensive suite of bioindicators of exposure and effects. ©2000 John Wiley & Sons, Inc. Environ Toxicol 15: 28–39, 2000     

Risk assessment of dietary exposure to methylmercury in fish in the UK

Risk assessment of chemicals in food is generally based upon the results of toxicological studies in laboratory animals, allowing for uncertainties relating to interspecies differences, human variability, and gaps in the database. Use of quantitative human data is preferable if available, as in the example of methylmercury. Methylmercury is a neurotoxic environmental contaminant, for which fish is the main source of dietary exposure. Human data from poisoning incidents and epidemiological studies have been used by expert committees to derive a guideline intake level for methylmercury, based on the susceptibility of the most sensitive lifestage, the developing fetus. In the UK, an expert group of nutritionists and toxicologists was formed to review the benefits and risks associated with fish consumption. A formal risk-benefit analysis was not possible because the nutritional data were not sufficiently quantitative. The Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT), therefore, modified the risk assessment approach to derive different guideline intake levels for different subgroups of the population. The COT opinion was used to provide targeted advice on how much fish can be consumed without undue risk from the contaminants. Consumption by adults of one weekly portion (140 g) of shark, swordfish or marlin, would lead to an exceedance of the guideline intake for methylmercury of 40-90%, set to protect the developing fetus, without considering intake from the rest of the diet. Pregnant women and women who may become pregnant within 1 year were, therefore, advised to avoid consumption of these species. Intakes in other adults would be within a higher guideline intake, set to protect groups of the population other than the developing fetus. However, consumption by children of one weekly portion of these species could lead to an exceedance of this guideline intake by up to 60%, without considering intake from the rest of the diet. It was, therefore, advised that consumption of these species by children should be avoided.     

Ecotoxicogenomics: linkages between exposure and effects in assessing risks of aquatic contaminants to fish

Understanding the biological effects of exposures to chemicals in the environment relies on classical methods and emerging technologies in the areas of genomics, proteomics, and metabonomics. Linkages between the historical and newer toxicological tools are currently being developed in order to predict and assess risk. Being able to classify chemicals and other stressors based on effects they have at the molecular, tissue, and organismal levels helps define a systems biology approach to development of streamlined, cost-effective, and comprehensive testing approaches for evaluating environmental hazards. The challenges of the individual technologies and the combinations of tools for ecotoxicogenomics are discussed in application to aquatic toxicology with a particular emphasis on fish testing.     

Determination of S-phenylmercapturic acid in urine as an indicator of exposure to benzene.

S-phenylmercapturic acid (S-PMA) was measured in urine from 145 subjects exposed to low benzene concentrations in the air (C(I), benzene). The 8-h, time-weighted exposure intensity of individual workers was monitored by means of charcoal tubes and subsequent gas-chromatographic analysis after desorption with CS2. S-PMA excretion level in urine was determined by high-performance liquid chromatography with fluorescence detection. The following linear correlation was found between S-PMA concentrations in urine and benzene concentrations in the breathing zone: log(S-PMA, microg/g creatinine) = 0.712 log (C(I)-benzene, ppm) + 1.644 (n = 145, r = 0.74, P < 0.001). The geometric mean (GSD) of S-PMA concentrations in urine from 45 subjects occupationally not exposed to benzene but smoking more than 20 cigarettes/day was 7.8 microg/g creatinine (2.11), the corresponding value among non-smokers being 1.0 microg/g creatinine (2.18). It is concluded that the urinary level of S-PMA can be regarded as a useful indicator of exposure to benzene.     

Vagal tone monitoring: a potential indicator of anti-cholinesterase exposure in Macaca mulatta

A vagal tone monitor (VTM) was used to evaluate cardiac rhythm changes in Rhesus monkeys (Macaca mulatta) after intramuscular (i.m.) administration of an anti-cholinergic (atropine sulfate), two carbamates (pyridostigmine bromide and physostigmine salicylate), and combinations of pyridostigmine and atropine. Twelve monkeys were studied in 4 experiments using Latin Square blind designs. Experiment I tested the VTM responses to atropine sulfate injections of 0, 14, 44 and 140 micrograms/kg. Experiment II tested the responses to 0, 100, 200 and 400 micrograms/kg pyridostigmine injections. Experiment III tested the responses to physostigmine injections of 0, 25, 50 and 100 micrograms/kg. Experiment IV tested the same atropine sulfate treatments as Experiment I 30 min after a pyridostigmine pretreatment of 200 micrograms/kg. The VTM analysis produced an estimate of vagal tone (V) every 30 s, and V was averaged over 15 min. The results indicated that V responded more to physostigmine and atropine than pyridostigmine. There was also an attenuated response to atropine following pyridostigmine pretreatment. The attenuated response had been demonstrated earlier in organophosphate (OP) treated dogs. The results suggest that V may be used as a non-invasive indicator of cholinergic drug effects.     

Elevation of individual serum bile acids on exposure to trichloroethylene or alpha-naphthylisothiocyanate

Rats were treated with trichloroethylene via intraperitoneal (ip) injection or inhalation, or with ip alpha-naphthylisothiocyanate (ANIT). Serum samples were assayed for indices of liver injury including alanine aminotransferase (ALT), sorbitol dehydrogenase (SDH), alkaline phosphatase (AP), and bilirubin. Liver from some rats was examined for histological appearance. These data were compared to levels of individual serum bile acids (SBA) determined by high-performance liquid chromatography. Trichloroethylene and ANIT, each at their highest dose only, caused elevations in ALT, but not SDH or AP. The highest dose of ANIT also caused elevated serum bilirubin and cholangitis in the liver. SBA were also elevated in response to both trichloroethylene and ANIT, but at doses below those at which other parameters of liver function were increased. For both chemicals, taurocholic acid was the most sensitive of the bile acids assayed, being elevated at the lowest doses tested of 10 mumols/kg for trichloroethylene and 5 mumols/kg for ANIT. As the doses were raised more of the individual bile acids showed increases. On exposure to trichloroethylene via inhalation taurocholic acid was one of two SBA to show elevation. Thus, both trichloroethylene and ANIT cause elevation in SBA at doses well below those which cause an increase in standard indicators of liver dysfunction. This suggests that SBA and perhaps taurocholic acid, in particular, may provide a sensitive tool for studying hepatobiliary effects of chemicals.