Studies on transitory laxative effects of sorbitol and maltitol: III: Alterations in serum contents due to laxative effects

Maltitol or sorbitol was administered in doses of 0.8 g/kg to 20 physically healthy subjects (10 males and 10 females) and 6 diabetic patients (3 males and 3 females). Maltitol and sorbitol caused diarrhea in 75% and 95% of the subjects, respectively. Stool was watery in most of the subjects. The serum concentration of each sweetening agent was as low as approximately 0.3 mg/dl 2 hours after administration. The serum concentrations of Na, K, Cl, BUN, glucose and insulin did not change 2 hours after administration.     

Studies on transitory laxative effects of sorbitol and maltitol: II: Differences in laxative effects among various foods containing the sweetening agents

We studied the laxative effect of sweetening agents, hydrogenated glucose syrup (HGS) containing 88–92% maltitol, and sorbitol contained in various foods. The subjects were 89 volunteers (64 males and 25 females). Foods used in the study were tablets, bevarages, chewing gum, jelly, adzuki-bean jelly, chocolate and candies which contained one of the two sweetening agents.The doses of the sweetening agents were 0.4 g/kg for sweets in tablet form and 20 g for the other foods. Approximately 10% of the subjects exhibited diarrhea after taking tablets as a control; approximately 20% did so after taking HGS except for adzuki-bean jelly; and approximately 30% did so after taking sorbitol. There was no significant difference between HGS and the control substance. The incidence of diarrhea tended to be higher with the two sweetening agents only when contained in adzuki-bean jelly. The length of time between the ingestion of test substances and the first onset of diarrheal stool varied widely from less than one hour to 23 hours among individuals. However, adzuki-bean jelly diarrhea was induced within 5 hours in all subjects. Soft stool accounted for 60 – 90% of the macroscopic findings of diarrheal stool. Chief complaints of abdominal symptoms were gurgling, flatus and lower abdominal pain.     

Effects of binary mixtures of six xenobiotics on hormone concentrations and morphometric endpoints of northern bobwhite quail (Colinus virginianus)

This study investigated the effects of six endocrine disrupters in five different doses (0.1, 0.3, 1, 3, 10 mg/kg or microg/kg) in ethanol administered by oral gavage to bobwhite quail eggs. Six eggs each were in each dose group of coumestrol, ethynyl estradiol, indole-3-carbinol, o,p'-DDE, p,p'-DDE, or TCDD. Eggs were also dosed in two sets. One set was ethynyl estradiol (0, 0.03, 0.1, 0.3, 1.0, 3.0, 10.0 microg/kg) and TCDD (0, 0.003, 0.01, 0.03, 0.1, 0.3 microg/kg). This set was dosed below the air cell with corn oil as vehicle. Also, northern bobwhite quail eggs were injected in ovo with nine binary mixtures of six xenobiotics prior to incubation (coumestrol (0.3 mg/kg), ethynyl estradiol (3.0 microg/kg), indole-3-carbinol (3.0 mg/kg), o,p'-DDE (1.0 mg/kg), p,p'-DDE (1.0 mg/kg), TCDD (0.1 microg/kg)). The mixtures injected were p,p'-DDE+indole-3-carbinol, coumestrol+indole-3-carbinol, TCDD+indole-3-carbinol, p,p'-DDE+o,p'-DDE, p,p'-DDE+ethynyl estradiol, coumestrol+ethynyl estradiol, coumestrol+TCDD, o,p'-DDE+ethynyl estradiol, TCDD+ethynyl estradiol. Eggs were dosed once prior to initiating incubation. Quail were allowed to hatch and were sacrificed at 21 days of age. Blood, measurements, and tissues were collected. Survival was significantly affected by increasing concentrations of TCDD in ethanol as revealed by trend analysis. Survival was also affected significantly by o,p'-DDE in ethanol but not by trend. Survival results of mixtures indicate significant differences among mixture, mixture components, and controls for coumestrol+TCDD, ethynyl estradiol+TCDD, and indole-3-carbinol+TCDD. Some trends from doses of single compounds that are supported by results in the literature were observed for hatchling weight of ethynyl estradiol dosed females, weight gain of indole-3-carbinol dosed males, weight gain and liver somatic index of o,p'-DDE dosed males, spleen somatic index of TCDD dosed males, and weight gain, gonad somatic index and egg gland somatic index of TCDD dosed females. In conclusion, the dose response treatments appeared to have effects beyond effects on survival of in ovo dosed quail. For mixtures, plasma estradiol concentrations were significantly different among coumestrol+ethynyl estradiol, ethynyl estradiol, coumestrol, and vehicle treatments. Liver somatic index among the same treatments was also significantly different. Kidney somatic index among ethynyl estradiol+p,p'-DDE, ethynyl estradiol, p,p'-DDE, and vehicle treatments was significantly different. Plasma estradiol and plasma testosterone ratios were very different among o,p'-DDE+p,p'-DDE, o,p'-DDE, p,p'-DDE, and vehicle treatments. Coumestrol and ethynyl estradiol appear antagonistic for plasma estradiol concentrations and liver somatic index when both chemicals are present together. Ethynyl estradiol and p,p'-DDE appear to act additively on kidney somatic index when combined together. Mixtures of compounds, used in this study indicate effects very different from either or both mixture components, indicating the lack of predictability of chemicals when combined in mixtures.     

Toxicological assessment of chlorinated diphenyl ethers in the rat

Chlorinated diphenyl ethers are environmental contaminants that have been found in Great Lakes fish and birds. Because of their presence in the food chain, and potential for human exposure, the present short-term study was conducted to assess their toxicity. Groups of 10 male and 10 female rats were each given by gavage 2,2',4,4'6-pentachlorodiphenyl ether (CDE1), 2,2',4,4',5,6-hexachlorodiphenyl ether (CDE2) or 2,2',3,3',4,6'-hexachlorodiphenyl ether (CDE3) at dose levels of 0.04, 0.4, 4.0 or 40 mg/kg b.w./day for a period of 28 days. The control group received an equivalent volume of corn oil only (0.5 ml/100 g b.w.). Treatment with the three CDE congeners did not result in suppression of growth rate or food consumption. Increased liver weights were seen in the animals of both sexes fed 40 mg/kg CDE2, in males treated with 40 mg/kg CDE1, and in females with 40 mg/kg CDE3. Hepatic microsomal aminopyrine demethylase activity was significantly higher in the male rats administered 40 mg/kg CDE2, and aniline hydroxylase activity was elevated in the females following the same treatment. Serum glucose, calcium, protein and urea nitrogen of CDE1-treated males were higher than the control. Levels of uric acid, potassium and LDH of CDE3-treated females were also elevated. No hematological changes were observed. Histological examination revealed that the liver and thyroid were the target organs affected by CDE treatment but the morphological changes were mild even at the highest dose level. Changes in the liver consisted of nuclear vesiculation and increased cytoplasmic volume. Alterations in the thyroid were characterized by increased epithelial height and follicular collapse. Based on the data presented above, the 3 CDE congeners can only be considered moderately toxic in the rat.     

Toxicological assessment of chlorinated diphenyl ethers in the rat

Abstract

Chlorinated diphenyl ethers are environmental contaminants that have been found in Great Lakes fish and birds. Because of their presence in the food chain, and potential for human exposure, the present short‐term study was conducted to assess their toxicity. Groups of 10 male and 10 female rats were each given by gavage 2,2’,4,4'6‐pentachlorodiphenyl ether (CDE1), 2,2’,4,4’,5,6‐hexachlorodiphenyl ether (CDE2) or 2,2’,3,3’,4,6'‐hexachlorodiphenyl ether (CDE3) at dose levels of 0.04, 0.4, 4.0 or 40 mg/kg b.w./day for a period of 28 days. The control group received an equivalent volume of corn oil only (0.5 ml/100 g b.w.). Treatment with the three CDE congeners did not result in suppression of growth rate or food consumption. Increased liver weights were seen in the animals of both sexes fed 40 mg/kg CDE2, in males treated with 40 mg/kg CDE1, and in females with 40 mg/kg CDE3. Hepatic microsomal aminopyrine demethylase activity was significantly higher in the male rats administered 40 mg/kg CDE2, and aniline hydroxylase activity was elevated in the females following the same treatment. Serum glucose, calcium, protein and urea nitrogen of CDE1‐treated males were higher than the control. Levels of uric acid, potassium and LDH of CDE3‐treated females were also elevated. No hematological changes were observed. Histological examination revealed that the liver and thyroid were the target organs affected by CDE treatment but the morphological changes were mild even at the highest dose level. Changes in the liver consisted of nuclear vesiculation and increased cytoplasmic volume. Alterations in the thyroid were characterized by increased epithelial height and follicular collapse. Based on the data presented above, the 3 CDE congeners can only be considered moderately toxic in the rat.     

Modifications of the sex pheromonal communication of trichogramma brassicae by a sublethal dose of deltamethrin

Pyrethroid insecticides, by their intensive use and their persistence that can exceed 3 months, largely contribute to the environmental pollution. In this work, we determined the effects of a very low dose of deltamethrin on the sex pheromonal communication of Trichogramma brassicae. The dose used was a dose that would theoretically kill one insect over 1000 (an LD 0.1). We found that this dose slightly but very significantly increased the arrestment behavior of treated males responding to the female pheromone. On the other hand when females were exposed to the same dose of insecticide, the response of males to their pheromone was very significantly decreased. In Trichogramma, like in other insects, sex pheromonal communication probably involves nervous transmissions both for the reception and the emission of the pheromone. Then, the sublethal effects of deltamethrin, observed in this work, are certainly due to multiple actions of this insecticide on nervous transmissions. Trichogramma is a beneficial insect that contributes to the control of pest populations of moths. Actions of this insecticide at a dose that can correspond to environmental pollution could be a real threat to the equilibrium of these populations.     

Reproduction and growth of progeny of female mice mated after treatment with crufomate

Effects on reproduction and litter growth were studied for two successive reproductive periods (RP)--interval between caging females with males and whelping--in female mice treated dermally with crufomate at 100 or 50 mg/kg on days 35 and 21 before caging with untreated males. Each treatment with crufomate caused about 50% reversible inhibition of cholinesterase activity without inducing any signs of toxicity. The higher dose reduced the conception rate and the number of litters and young born and weaned during the two RPs. It also reduced the lactation index, weaning weight of males and females, and mature weight of males in the first litter. The lower dose prolonged the gestation period and reduced the lactation index and the number of litters and young weaned in the first RP and conception rate and number of litters and young born and weaned in the second RP. The lower dose reduced the weaning and mature weights of the first litter and mature weight of males in the second litter. The higher dose reduced the body weight and the lower dose increased the adrenal weight of the treated females.     

Dioxin-like and non-dioxin-like PCBs in human serum of Slovak population

In the present study, non-ortho, mono-ortho and other ortho-substituted PCB congeners were analysed in individual blood serum samples taken from healthy adults (196 males and 119 females) in the polluted area of the Michalovce district and in the background area of the Stropkov/Svidnik districts in Eastern Slovakia by high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS). The samples from general population living in villages and towns of two regions were taken between August 2001 and February 2002 within the project of the EC's 5th Framework Programme (PCBRISK, ). The medians of dioxin-like PCBs (dl-PCBs)--expressed as TEQs on lipid basis--of all males (24.7 pg g(-1) lipid) and females (21.4 pg g(-1) lipid) were comparable, but there was a significant difference between both of the areas studied. In the district of Michalovce, the medians of males (47.3 pg g(-1) lipid) and females (41.1 pg g(-1) lipid) were 2.3 times higher than in the area of the Stropkov/Svidnik districts. The medians of total non-dioxin-like PCB concentration were 1,835 and 1,033 ng g(-1) lipid in males and females, respectively. The data show a trend toward higher concentrations of both dl- and non-dioxin-like PCBs in the older age groups. The substantial increase was observed for the 60+ age group. PCB-126 was the most abundant non-ortho congener. PCBs-118 and 156 were the predominant mono-ortho congeners. They were quantitated in all samples analysed. Congeners 153, 138(+163), 180 and 170(+190) were the main contributors to total non-dioxin-like PCB concentrations. Mean mutual ratio HexaCBs:HeptaCBs:OctaCBs in the non-dioxin-like group was 37:50:1. The results of this study represent the overall information about the congener distribution of dioxin-like and non-dioxin-like PCBs in human serum blood of adult Slovaks.     

The effect of EDTA and citric acid on phytoremediation of Cd, Cr, and Ni from soil using Helianthus annuus

The possibility to clean heavy metal contaminated soils with hyperaccumulator plants has shown great potential. One of the most recently studied species used in phytoremediation applications are sunflowers. In this study, two cultivars of Helianthus annuus were used in conjunction with ethylene diamine tetracetic acid (EDTA) and citric acid (CA) as chelators. Two different concentrations of the chelators were studied for enhancing the uptake and translocation of Cd, Cr, and Ni from a silty-clay loam soil. When 1.0 g/kg CA was used, the highest total metal uptake was only 0.65 mg. Increasing the CA concentration posed a severe phytotoxicity to both cultivars as evidenced by stunted growth and diminished uptake rates. Decreasing the CA concentration to 0.1 and 0.3 g/kg yielded results that were not statistically different from the control. EDTA at a concentration of 0.1 g/kg yielded the best results for both cultivars achieving a total metal uptake of approximately 0.73 mg compared to approximately 0.40 mg when EDTA was present at 0.3 g/kg.     

Thyroid ultrasound volume, structure and function after long-term high exposure of large population to polychlorinated biphenyls, pesticides and dioxin

We examined 2,046 adults (834 males and 1,212 females aged 20-75 years) from polluted district in East Slovakia (POLL) and two neighboring upstream and upwind located districts of background pollution (BCGR). By ultrasound we estimated the thyroid volume (ThV), hypoechogenicity (HYE), nodules and cysts. Serum levels of thyrotropin (TSH), thyroperoxidase antibodies (TPOab) and thyroglobulin were estimated by electrochemiluminiscent assay and these of 15 PCB congeners, p,p'-DDE, p,p'-DDT, hexachlorobenzene (HCB) and hexachlorocyclohexane by high-resolution gas chromatography. In 320 subjects also selected hydroxylated and methylsulfonated PCB metabolites, polychlorinated dibenzo-dioxins (PCDDs), -furans (PCDFs), five dioxin-like coplanar and eight mono-ortho PCB congeners were estimated. Urinary iodine was measured by automatic microplate method. Reciprocal positive association was found between three major POPs (PCBs, DDE and HCB), the levels of these and also PCDDs plus PCDFs in polluted area being considerably higher than in background pollution area. ThV in groups of males and females from POLL with high PCBs level was significantly higher (p<0.001 by t-test) then in age and sex matched groups from BCGR with low PCBs level. In 1,048 males and females aged <60 years with serum PCBs level >1,000 ng g(-1) lipid (median=1,756 ng g(-1)) a significant effect of age on ThV was found (p<0.01 by ANOVA), while in 921 respective subjects with PCBs level <1,000 ng g(-1) (median=661 ng g(-1)) it was not. These findings supported the view on the additional effect of PCBs on ThV other than that of age. Since the urinary iodine in both districts showed optimal range, any interfering effect of unsatisfactory iodine intake on ThV may be excluded. The frequency of autoimmune thyroiditis signs such as HYE, increased serum level of TPOab and TSH resulting in subclinical or overt thyroid hypofunction was positively associated with sex, age and organochlorine levels. The increase of such frequency in males with POPs levels was much more abrupt than that in females. No considerable differences in the frequency of thyroid nodules as related to PCBs level were found.     

The subchronic toxicity of acridine in the rat

Abstract

The subchronic toxicity of acridine was investigated in rats following dietary exposure at 0, 1, 10, 100 and 500 ppm for 13 weeks. The growth rate and food consumption were not affected by treatment and no clinical signs of toxicity were observed. There was a slight but significant decrease in spleen weight, both in absolute terms and as a percent of body weight, in the 500 ppm males and a slight increase in absolute thymus weight in the females of the same dose group. Both hepatic ethoxyresorufin O‐deethylase (EROD) and pentoxyresorufin O‐dealkylase (PROD) activities were slightly, but significantly, elevated in females in the 500 ppm dose group. No haematological or other biochemical changes were observed. Females also displayed dose‐related increases in inorganic phosphate and uric acid levels. Treatment‐related histopathological changes were seen in the thyroid, liver and kidney and included hepatic anisokaryosis and vesiculation of nuclei and glomerular adhesions, reticulin sclerosis and nuclear pyknosis in the kidney. Residue data showed a dose‐dependent accumulation of acridine in liver, kidney and adipose with the highest concentration being found in the fat of the 500 ppm dose group. Based on these data, the no observable adverse effect level of acridine was judged to be 100 ppm or 12 mg/kg bw/day.     

Lactational transfer of mercury and polychlorinated biphenyls in polar bears

We examined concentrations of total mercury (tHg, inorganic and methylated forms) and polychlorinated biphenyls (PCBs) in blood and milk from free-ranging Southern Beaufort-Chukchi Sea polar bears (Ursus maritimus) to assess maternal transfer of contaminants during lactation and the potential health risk to nursing young. Concentrations of contaminants in the blood of dependent and juvenile animals (ages 1-5 years) ranged from 35.9 to 52.2 μg kg(-1) ww for tHg and 13.9 to 52.2 μg kg(-1) ww (3255.81-11067.79 μg kg(-1) lw) for ΣPCB(7)s, similar to those of adult females, but greater than adult males. Contaminant concentrations in milk ranged from 5.7 to 71.8 μg tHg kg(-1)ww and 160 to 690 μg ΣPCB(11)s kg(-1) ww (547-5190 μg kg(-1) lw). The daily intake levels for tHg by milk consumption estimated for dependent young were below the tolerable daily intake level (TDIL) of tHg established for adult humans. Although the daily intake levels of PCBs through milk consumption for cubs of the year exceeded the TDIL thresholds, calculated dioxin equivalents for PCBs in milk were below adverse physiological thresholds for aquatic mammals. Relatively high concentrations of non-dioxin like PCBs in polar bear milk and blood could impact endocrine function of Southern Beaufort-Chukchi Sea polar bears, but this is uncertain. Transfer of contaminants during mid to late lactation likely limits bioaccumulation of dietary contaminants in female polar bears during spring. As polar bears respond to changes in their arctic sea ice habitat, the adverse health impacts associated with nutritional stress may be exacerbated by tHg and PCBs exposure, especially in ecologically and toxicologically sensitive polar bear cohorts such as reproductive females and young.     

Reproduction disturbances of Brachionus calyciflorus (rotifer) for the screening of environmental endocrine disrupters

Rotifers and especially the Brachionus calyciflorus species have already shown advantages (e.g. good sensitivity, simplicity, ecological relevance, short generation time) for the chronic toxicity assessment of water pollutants. In this study, the B. calyciflorus three-day test was evaluated on ethinylestradiol, nonylphenol and testosterone for the determination of endocrine disrupting (reproductive) effects. Reproduction (intrinsic rate of population increase) and sex ratio (males/females and mictic females/amictic females) were explored and discussed as suitable endpoints. B. calyciflorus has shown a fair sensitivity to detect reproductive disrupting effects after exposure to ethinylestradiol, nonylphenol and testosterone. Population growth (intrinsic rate of population increase, r) and the ratio ovigerous females/non-ovigerous females are both suitable endpoints, whereas the occurrence of males was not frequent enough to be used as endpoint.     

Concentrations and accumulation patterns of organochlorine contaminants in the blubber of harbour porpoises, Phocoena phocoena, from the coast of Newfoundland, the Gulf of St Lawrence and the Bay of Fundy/Gulf of Maine

Concentrations of 99 organochlorine compounds were measured in the blubber of 196 harbour porpoises, Phocoena phocoena, killed in commercial gill net fisheries in the western North Atlantic. PCBs and chlorinated bornanes (CHB) were the dominant contaminants in all porpoises. Mean concentrations (with standard deviations) of PCBs and CHBs from the three regions were as follows: Bay of Fundy/Gulf of Maine, PCB males 17.3 +/- 11.2 microg/g, PCB females 11.4 +/- 4.8 microg/g, CHB males 11.5 +/- 6.6 microg/g, CHB females 8.4 +/- 5.3 microg/g; Gulf of St Lawrence, PCB males 10.6 +/- 5.4 microg/g, PCB females 7.2 +/- 3.9 microg/g, CHB males 14.1 +/- 8.8 microg/g, CHB females 9.0 +/- 6.3 microg/g; southeast Newfoundland, PCB males 5.2 +/- 2.5 microg/g, PCB females 5.5 +/- 4.4 microg/g, CHB males 7.0 +/- 2.2 microg/g, CHB females 5.5 +/- 3.0 microg/g. The relative composition of the major contaminant groups found in male and female harbour porpoise blubber from the three locations varied. In order of decreasing concentration, porpoises from Fundy/Maine had PCBs > CHB > DDT > chlordanes (CHL), whereas Gulf of St Lawrence and Newfoundland porpoises had CHB > PCB > DDT > CHL. Significant increases with age were observed for most contaminants in male harbour porpoises, and significant decreases were observed in females. Females lose about 15% of their contaminant burden per birth. PCB and DDT levels in porpoises from the Bay of Fundy are significantly lower than those recorded in the 1970s.     

The disposition and metabolism of tetrabromobisphenol-A after a single i.p. dose in the rat.

Tetrabromobisphenol-A (TBBP-A) is used as a reactive (primary use) or an additive flame retardant and as an intermediate in the production of other flame retardants. In our study TBBP-A[14C] was administered intraperitoneally (i.p.) in a single dose of 250 or 1000 mg/kg body weight (about 300 kBq per animal). The level of radioactivity in erythrocytes was 10 times higher than in plasma 72 h after the administration. In all examined tissues the peak level of 14C could be observed within the first hour after the administration, and the highest concentrations were detected in the fat tissue, followed by liver, sciatic nerve, muscles and adrenals. Total excretion in faeces 72 h after the administration was about 51-65% of the dose, whereas in urine it was only 0.3%. About 20% was still retained in the rat organism.     

Persistent organochlorines in beluga whales (Delphinapterus leucas) from the St Lawrence River estuary--I. Concentrations and patterns of specific PCBs, chlorinated pesticides and polychlorinated dibenzo-p-dioxins and dibenzofurans

Blubber samples from beluga whales (Delphinapterus leucas) in the St Lawrence River estuary were analysed for PCB congeners (ortho- and non-ortho-substituted) and other persistent organochlorines as well as chlorinated dibenzo-dioxins/furans (PCDD/Fs). Major individual components (mean concentrations > 1 microg g(-1)) were 4,4'-DDE, -DDD and -DDT, T12 (a toxaphene-related compound), trans-nonachlor, oxychlordane, mirex, HCB, tris(p-chlorophenyl) methane and dieldrin. Concentrations of SigmaPCBs (8.3-412 microg g(-1)), SigmaDDT (3.36-389 microg g(-1)) and mirex (0.18-6.8 microg g(-1)) were particularly elevated relative to other odontocetes in Canadian waters. SigmaDDT, PCBs (as Aroclor), mirex and T12 concentrations were positively correlated with age of adult females (> 10 years) but only weakly, or not significantly, correlated with age of adult males. PCDD/Fs were present at low ng kg(-1) levels and consisted mainly of penta- and hexachlorofurans, and hepta- and octachlorodioxin. CB126 (3,3',4,4',5-PCB) was the most prominent non-ortho-substituted PCB congener in beluga blubber. Total TCDD toxic equivalents averaged 330 ng kg(-1) in females and 1400 ng kg(-1) in males and were dominated by CB126, and the mono-ortho-substituted congeners CB105 and CB118. Biomagnification factors (BMFs) for mirex and SigmaPCB from fish to beluga ranged from 11 to 16, and were similar to BMFs in Arctic animals, indicating that elevated levels in St Lawrence animals are a consequence of relatively high levels of recalcitrant organochlorines in prey of the beluga in the St Lawrence river system.     

Effects of a selenium-enriched diet on antioxidant response in adult crayfish (Procambarus clarkii)

Many diets employed in aquaculture are enriched with selenium to improve the diet quality and its conservation. The aim of the study was to investigate the effects of a diet enriched in selenium (1.21 mg kg(-1)) on the antioxidant response of Procambarus clarkii (Girard, 1852). Crayfish fed a diet with lower selenium content (0.30 mg kg(-1)) were the control. Selenium accumulation, enzymatic activities, and total glutathione were evaluated in hepatopancreas of adults of both sexes fed with both diets for 50 days at two experimental times (T(30), T(50) days). Treated females exhibited the highest selenium bioaccumulation during both experimental times, while treated males displayed the highest selenium concentration after 30 days, compared to control crayfish. A sex-related difference was found for the response of the analyzed enzymes in the selenium diet-treated specimens. In fact, superoxide dismutase, glutathione peroxidase and glyoxalase I activities in males were more sensitive compared with females, showing depleted activities in both experimental times. Catalase activity was induced in females (T(50)), while glutathione S-transferase activity was the highest in treated females and the lowest in treated males, compared with own controls. Only glutathione reductase activity and glutathione content showed the same trend in both sexes, which were both lowered in treated specimens, when compared with control crayfish. This result might be due to the effect of selenium toxicity on this freshwater species. Males and females of P. clarkii showed a different susceptibility to the prooxidant effects in a Se-enriched diet.     

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin or 2,2',4,4',5,5'-hexachlorobiphenyl on vitamin K-dependent blood coagulation in male and female WAG/Rij-rats

Newborns are susceptible to hemorrhages (hemorrhagic disease of the newborn or HDN) due to vitamin K deficiency. Induction of cytochrome P450 in the fetal liver by maternal anticonvulsant therapy such as phenobarbital or phenytoin is considered to be a major cause. An observed increase in late hemorrhagic disease (LHD) in breast fed neonates gave rise to the hypothesis that PCBs and dioxins, P450-inducing contaminants present in human milk, might effect vitamin K-dependent blood coagulation. This hypothesis was studied in rats. Administration of a single oral dose of 0.003, 0.03, 0.3, 3 or 30 nmol 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) per kg bodyweight or 0.75, 4, 20, 100 or 500 micromol 2,2',4,4',5,5'-hexachlorobiphenyl/kg bw (HxCB) to female and male rats resulted in dose-related reductions of the vitamin K-dependent coagulation factor VII. The highest factor VII reduction in female rats was 44%, observed after TCDD exposure. The Lowest Observed Adverse Effect Level (LOAEL) of TCDD on female factor VII levels was 0.3 nmol/kg bw (96 ng/kg). There was a significant inverse correlation between Factor VII levels and induction of hepatic ethoxyresorufin O-deethylating (EROD) activity, reflecting CYP1A1, and total P450 content. HxCB had no effect on female coagulation factors. In contrast, in male rats only exposure to HxCB, which induces mainly CYP2B1 and 2B2, decreased both coagulation factors dramatically up to 88%. The LOAEL of HxCB on factor VII in male rats was 100 micromol/kg bw (36 mg/kg). In general, effects on coagulation factors in male rats exceeded those in females. In addition, sex-dependent differences of TCDD and HxCB were observed on the hepatic vitamin K cycle enzyme activities in female and male rats. Vitamin K-dependent (gamma-glutamyl carboxylase activity was mainly induced in female rats; 2.3-fold in the highest dose group of TCDD. In male rats only vitamin K 2,3-epoxide reductase (KO-reductase) activity was induced 1.7-fold by the highest dose of HxCB. KO-reductase activity in female rats was also increased by TCDD, however, less pronounced than the carboxylase activity. Concluding, the hepatic vitamin K cycle still functions and is not blocked by TCDD or HxCB, thus explaining the observed reduction in factor VII. Finally, the possible role of P450 in vitamin K deficiency is discussed. Based on these results it is suggested to investigate the possible role of PCBs and dioxin-like compounds in LHD in more detail.     

Reproduction disturbances of Brachionus calyciflorus (rotifer) for the screening of environmental endocrine disrupters

Rotifers and especially the Brachionus calyciflorus species have already shown advantages (e.g. good sensitivity, simplicity, ecological relevance, short generation time) for the chronic toxicity assessment of water pollutants. In this study, the B. calyciflorus three-day test was evaluated on ethinylestradiol, nonylphenol and testosterone for the determination of endocrine disrupting (reproductive) effects. Reproduction (intrinsic rate of population increase) and sex ratio (males/females and mictic females/amictic females) were explored and discussed as suitable endpoints. B. calyciflorus has shown a fair sensitivity to detect reproductive disrupting effects after exposure to ethinylestradiol, nonylphenol and testosterone. Population growth (intrinsic rate of population increase, r) and the ratio ovigerous females/non-ovigerous females are both suitable endpoints, whereas the occurrence of males was not frequent enough to be used as endpoint.     

Effect of dietary protein on the distribution of cadmium,zinc and copper in rats following the oral administration of cadmium

Cadmium, 100 μg/rat/day, was administered orally 100 times (total amount of Cd administered, 10 mg), under conditions of low protein intake. The total amount of Cd in the liver and kidneys was as follows: females fed 20% protein diets > females fed 5% protein diets > males fed 20% protein diets ≒ males fed 5% protein diets. A decreased Zn concentration was found in the liver of males and the pancreas of males and females fed with the 5% protein diet. The Cu concentration in the kidneys was markedly influenced by low protein intake.