Quantification of the tissue distribution and accumulation of the neonicotinoid pesticide clothianidin and its metabolites in maternal and fetal mice.

Neonicotinoids (NNs) are commonly used pesticides that have a selective agonistic action on insect nicotinic acetylcholine receptors. Recent evidence has shown that NNs have adverse effects in the next generation of mammals, but it remains unclear how NNs transferred from dams to fetuses are distributed and accumulated in fetal tissues. Here, we aimed to clarify the tissue distribution and accumulation properties of the NN clothianidin (CLO) and its 6 metabolites in 7 tissues and blood in both dams and fetuses of mice administered CLO for a single day or for 9 consecutive days. The results showed that the total concentrations of CLO-related compounds in the brain and kidney were higher in fetuses than in dams, whereas in the liver, heart, and blood they were lower in fetuses. The multi-day administration increased the total levels in heart and blood only in the fetuses of the single administration group. In addition, dimethyl metabolites of CLO showed fetus/dam ratios >1 in some tissues, suggesting that fetuses have higher accumulation property and are thus at higher risks of exposure to CLO-related compounds than dams. These findings revealed differences in the tissue-specific distribution patterns of CLO and its metabolites between dams and fetuses, providing new insights into the assessment of the developmental toxicity of NNs.

Sensitivity assessment of diphacinone by pharmacokinetic analysis in invasive black rats in the Bonin (Ogasawara) Archipelago, Japan.

The Bonin Archipelago is a United Nations Educational, Scientific and Cultural Organization's World Natural Heritage Site in Japan with a unique ecosystem; however, the invasive rodents preying on endemic species have been a significant concern. The anticoagulant rodenticide, diphacinone, sprayed by the Ministry of the Environment, has succeeded; however, its repeated use leads to rodenticide resistance. This study evaluated the sensitivity by in vivo pharmacokinetics/pharmacodynamics (PK/PD) analysis and physiologically-based pharmacokinetic modeling to diphacinone in black rats (Rattus rattus) captured on the Bonin Archipelago in February 2022. The Bonin rats exhibited prolonged coagulation time after diphacinone administration. They recovered earlier than susceptible black rats, indicating that Bonin rats were less susceptible, though there were no genetic mutations in Vkorc1, the target enzyme of diphacinone. After the administration of diphacinone, hepatic expression levels of Fsp1, identified as the vitamin K reductase, was decreased, however, the Bonin rats exhibited the most minor suppression. The PK analysis showed that the excretion capacity of the Bonin rats was lower than that of the resistant black rats. In the PBPK modeling, the resistant black rats showed higher clearance than the Bonin and susceptible black rats due to high hepatic metabolic capacity. The Bonin rats demonstrated slow absorption and relatively low clearance. This study highlighted the reduced rodenticide-sensitive tendency of wild black rats in the Bonin Archipelago at an in vivo phenotype level. At the same time, they do not have known rodenticide resistance mechanisms, such as hepatic metabolic enhancement or Vkorc1 mutations. It is crucial to monitor the biological levels to evaluate rodenticide sensitivity accurately.

FOUR-WEEK ORAL ADMINISTRATION OF BALOXAVIR MARBOXIL AS AN ANTI-INFLUENZA VIRUS DRUG SHOWS NO TOXICITY IN CHICKENS.

High pathogenicity avian influenza is an acute zoonotic disease with high mortality in birds caused by a high pathogenicity avian influenza virus (HPAIV). Recently, HPAIV has rapidly spread worldwide and has killed many wild birds, including endangered species. Baloxavir marboxil (BXM), an anti-influenza agent used for humans, was reported to reduce mortality and virus secretion from HPAIV-infected chickens (Gallus domesticus, order Galliformes) at a dosage of ≥2.5 mg/kg when administered simultaneously with viral challenge. Application of this treatment to endangered birds requires further information on potential avian-specific toxicity caused by repeated exposure to BXM over the long term. To obtain information of potential avian-specific toxicity, a 4-wk oral repeated-dose study of BXM was conducted in chickens (n = 6 or 7 per group), which are commonly used as laboratory avian species. The study was conducted in reference to the human pharmaceutical guidelines for nonclinical repeated-dose drug toxicity studies to evaluate systemic toxicity and exposure. No adverse changes were observed in any organs examined, and dose proportional increases in systemic exposure to active pharmaceutical ingredients were noted from 12.5 to 62.5 mg/kg per day. BXM showed no toxicity to chickens at doses of up to 62.5 mg/kg per day, at which systemic exposure was approximately 71 times higher than systemic exposure at 2.5 mg/kg, the reported efficacious dosage amount, in HPAIV-infected chickens. These results also suggest that BXM could be considered safe for treating HPAIV-infected endangered birds due to its high safety margin compared with the efficacy dose. The data in this study could contribute to the preservation of endangered birds by using BXM as a means of protecting biodiversity.

A stable isotope analysis of the dietary patterns of the aquatic apex predator, the African tigerfish (Hydrocynus vittatus).

Stable isotope analyses, specifically δ13 C and δ15 N, are useful tools increasingly used to understand ecosystem function, food web structures, and consumer diets. Although the iconic tigerfish Hydrocynus vittatus is regarded as an apex predator in southern African freshwater systems, little information is available regarding their feeding behavior and how this may change with growth or differ between ecosystems, with most information stemming from stomach content analyses (SCA). The aim of the present study was to address this lack of information through a baseline study of the diet of large and small tigerfish in various lentic and lotic ecosystems in South Africa using stable isotope methods. Fish and various food web components and food sources were collected from two river and two lake ecosystems in South Africa. The δ13 C and δ15 N values for all samples were determined and multivariate analyses and Bayesian analytical techniques applied to determine the feeding ecology of H. vittatus and how this may differ with size and habitat type. Analyses revealed a substantial difference in the type and abundance of food sources contributing to the diet of H. vittatus between ecosystems, most prominently between the lotic systems, where less dietary specialization was observed, and lentic systems where more specialization was observed. Furthermore, there was a distinct difference in diet between small and large tigerfish, especially in the lotic system, indicating an ontogenetic diet shift as tigerfish grow and further supporting previous SCA studies. This is the first study of its kind on the African continent for H. vittatus and the findings illustrate the value of stable isotope analysis in providing in-depth information into the feeding ecology of consumers and how this may differ between size classes and habitat types.

Cytochrome P450 2J Genes Are Expressed in Dogs, Cats, and Pigs, and Encode Functional Drug-Metabolizing Enzymes.

Cytochrome P450s (P450s) have been identified and analyzed in dogs and pigs, species that are often used in preclinical drug studies. Moreover, P450s are clinically important for drug therapy not only in humans, but also in species under veterinary care, including dogs and cats. In the present study, seven P450s homologous to human CYP2J2, namely, dog CYP2J2; cat CYP2J2; and pig CYP2J33, CYP2J35, CYP2J91, and CYP2J93, were newly identified and characterized, along with pig CYP2J34 previously identified. The cDNAs of these CYP2Js contain open reading frames of 502 amino acids, except for CYP2J35 (498 amino acids), and share high sequence identity (77%-80%) with human CYP2J2. Phylogenetic analysis revealed that dog and cat CYP2J2 were closely related, whereas pig CYP2Js formed a cluster. All seven CYP2J genes contain nine coding exons and are located in corresponding genomic regions, with the pig CYP2J genes forming a gene cluster. These CYP2J2 mRNAs were predominantly expressed in the small intestine with additional expression in the kidney and brain for dog CYP2J2 and pig CYP2J91 mRNAs, respectively. All seven CYP2Js metabolized human CYP2J2 substrates terfenadine, ebastine, and astemizole, indicating that they are functional enzymes. Dog CYP2J2 and pig CYP2J34 and CYP2J35 efficiently catalyzed ebastine primary hydroxylation and secondary carebastine formation at low substrate concentrations, just as human CYP2J2 does. Velocity-versus-substate plots exhibited sigmoidal relationships for dog CYP2J2, cat CYP2J2, and pig CYP2J33, indicating allosteric interactions. These results suggest that dog, cat, and pig CYP2Js have similar functional characteristics to human CYP2J2, with slight differences in ebastine and astemizole oxidations. SIGNIFICANCE STATEMENT: Dog CYP2J2; cat CYP2J2; and pig CYP2J33, CYP2J34, CYP2J35, CYP2J91, and CYP2J93, homologous to human CYP2J2, were identified and characterized by sequence, phylogenetic, and genomic structure analyses. Intestinal expression patterns of CYP2J mRNAs were characteristic in dogs, cats, and pigs. Dog, cat, and pig CYP2Js likely play roles as drug-metabolizing enzymes in the small intestine, similar to human CYP2J2.

Sex-specific behavioral effects of acute exposure to the neonicotinoid clothianidin in mice.

Although neonicotinoids are among the major classes of pesticides that affect mammalian nervous systems, little is known about sex differences in their effects. This study aimed to examine whether the neurobehavioral effects of a neonicotinoid, clothianidin (CLO), differed between sexes. Male and female C57BL/6N mice were orally administered CLO (5 or 50 mg/kg) at or below the chronic no-observed-adverse-effect-level (NOAEL) and subjected to behavioral tests of emotional and learning functions. Changes in neuroactivity in several brain regions and the concentrations of CLO and its metabolites in blood and urine were measured. Acute CLO exposure caused sex-related behavioral effects; decreases in locomotor activities and elevation of anxiety-like behaviors were more apparent in males than in females. In addition, male-specific impairment of short- and long-term learning memory by CLO exposure was observed in both the novel recognition test and the Barnes maze test. Male-dominant increases in the number of c-fos positive cells were observed in the paraventricular thalamic nucleus in the thalamus and in the dentate gyrus in the hippocampus, which are related to the stress response and learning function, respectively. The concentrations of CLO and most metabolites in blood and urine were higher in males. These results support the notion that male mice are more vulnerable than females to the neurobehavioral effects of CLO and provide novel insights into the risk assessment of neonicotinoids in mammalian neuronal function.

Toxicokinetic analysis of the anticoagulant rodenticides warfarin & diphacinone in Egyptian fruit bats (Rousettus aegyptiacus) as a comparative sensitivity assessment for Bonin fruit bats (Pteropus pselaphon).

Anticoagulant rodenticides have been widely used to eliminate wild rodents, which as invasive species on remote islands can disturb ecosystems. Since rodenticides can cause wildlife poisoning, it is necessary to evaluate the sensitivity of local mammals and birds to the poisons to ensure the rodenticides are used effectively. The Bonin Islands are an archipelago located 1000 km southeast of the Japanese mainland and are famous for the unique ecosystems. Here the first-generation anticoagulant rodenticide diphacinone has been used against introduced black rats (Rattus rattus). The only land mammal native to the archipelago is the Bonin fruit bat (Pteropus pselaphon), but little is known regarding its sensitivity to rodenticides. In this study, the Egyptian fruit bats (Rousettus aegyptiacus) was used as a model animal for in vivo pharmacokinetics and pharmacodynamics analysis and in vitro enzyme kinetics using their hepatic microsomal fractions. The structure of vitamin K epoxide reductase (VKORC1), the target protein of the rodenticide in the Bonin fruit bat, was predicted from its genome and its binding affinity to rodenticides was evaluated. The Egyptian fruit bats excreted diphacinone slowly and showed similar sensitivity to rats. In contrast, they excreted warfarin, another first-generation rodenticide, faster than rats and recovered from the toxic effect faster. An in silico binding study also indicated that the VKORC1 of fruit bats is relatively tolerant to warfarin, but binds strongly to diphacinone. These results suggest that even chemicals with the same mode of action display different sensitivities in different species: fruit bat species are relatively resistant to warfarin, but vulnerable to diphacinone.

The VKORC1 ER-luminal loop mutation (Leu76Pro) leads to a significant resistance to warfarin in black rats (Rattus rattus).

Well-known 4-hydroxycoumarin derivatives, such as warfarin, act as inhibitors of the vitamin K epoxide reductase (VKOR) and are used as anticoagulants. Mutations of the VKOR enzyme can lead to resistance to those compounds. This has been a problem in using them as medicine or rodenticide. Most of these mutations lie in the vicinity of potential warfarin-binding sites within the ER-luminal loop structure (Lys30, Phe55) and the transmembrane helix (Tyr138). However, a VKOR mutation found in Tokyo in warfarin-resistant rats does not follow that pattern (Leu76Pro), and its effect on VKOR function and structure remains unclear. We conducted both in vitro kinetic analyses and in silico docking studies to characterize the VKOR mutant. On the one hand, resistant rats (R-rats) showed a 37.5-fold increased IC50 value to warfarin when compared to susceptible rats (S-rats); on the other hand, R-rats showed a 16.5-fold lower basal VKOR activity (Vmax/Km). Docking calculations exhibited that the mutated VKOR of R-rats has a decreased affinity for warfarin. Molecular dynamics simulations further revealed that VKOR-associated warfarin was more exposed to solvents in R-rats and key interactions between Lys30, Phe55, and warfarin were less favored. This study concludes that a single mutation of VKOR at position 76 leads to a significant resistance to warfarin by modifying the types and numbers of intermolecular interactions between the two.

The effects of fipronil on emotional and cognitive behaviors in mammals.

Fipronil is a phenylpyrazole insecticide that is widely used as a pesticide and a veterinary drug, although studies suggest that it could be toxic to mammals. The objectives of this study were to examine the pharmacokinetic profile of fipronil in mice, dogs, and cats, and to evaluate its effects on emotional and cognitive behaviors of dogs and cats using the data obtained from mice. The assessment of in vivo kinetics of fipronil was conducted in mice and dogs. We also performed behavioral tests (elevated plus-maze and Y-maze) and measured the levels of neurotransmitters in mice exposed to fipronil. In addition, the in vitro metabolism of fipronil were evaluated using liver microsomes of rats, mice, dogs, and cats. The results revealed that fipronil is distributed throughout the body (blood, brain, adipose tissue, and liver) of mice after dermal application. It was metabolized to fipronil sulfone primarily in the liver. The data on kinetics show that both fipronil and fipronil sulfone have a longer half-life in dogs and cats than in mice. The behavioral tests indicated that fipronil and fipronil sulfone could affect emotional and cognitive behaviors and alter the levels of neurotransmitters (dopamine in the striatum and serotonin in the hippocampus) in mice. Furthermore, we found that dogs and cats have a low ability to metabolize fipronil than mice and rats. However, further comprehensive studies are needed to determine whether fipronil affects the emotional and cognitive behaviors when administered to dogs and cats. To the best of our knowledge, this is the first study to examine the pharmacokinetic data and verify the effects of fipronil on emotional and cognitive behaviors of dogs and cats using the data obtained from mice.

Land Use in Habitats Affects Metal Concentrations in Wild Lizards Around a Former Lead Mining Site.

We investigated the potential effects of different land use and other environmental factors on animals living in a contaminated environment. The study site in Kabwe, Zambia, is currently undergoing urban expansion, while lead contamination from former mining activities is still prevalent. We focused on a habitat generalist lizards (Trachylepis wahlbergii). The livers, lungs, blood, and stomach contents of 224 lizards were analyzed for their lead, zinc, cadmium, copper, nickel, and arsenic concentrations. Habitat types were categorized based on vegetation data obtained from satellite images. Multiple regression analysis revealed that land use categories of habitats and three other factors significantly affected lead concentrations in the lizards. Further investigation suggested that the lead concentrations in lizards living in bare fields were higher than expected based on the distance from the contaminant source, while those in lizards living in green fields were lower than expected. In addition, the lead concentration of lungs was higher than that of the liver in 19% of the lizards, implying direct exposure to lead via dust inhalation besides digestive exposure. Since vegetation reduces the production of dust from surface soil, it is plausible that dust from the mine is one of the contamination sources and that vegetation can reduce exposure to this.

Accumulation patterns and risk assessment of metals and metalloid in muscle and offal of free-range chickens, cattle and goat in Benin City, Nigeria.

The use of free range animals for monitoring environmental health offers opportunities to detect exposure and assess the toxicological effects of pollutants in terrestrial ecosystems. Potential human health risk of dietary intake of metals and metalloid via consumption of offal and muscle of free range chicken, cattle and goats by the urban population in Benin City was evaluated. Muscle, gizzard, liver and kidney samples were analyzed for Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Cd, and Pb concentrations using inductively coupled plasma mass spectrometer (ICP-MS) while Hg was determined using Hg analyzer. Mean concentrations of metals (mg/kg ww) varied significantly depending upon the tissues and animal species. Human health risk estimations for children and adults showed estimated daily intake (EDI) values of tissues below oral reference dose (RfD) threshold for non essential metals Cd, As, Pb and Hg thus strongly indicating no possible health risk via consumption of animal based food. Calculated Hazard quotient (THQ) was less than 1 (< 1) for all the metals analyzed for both adult and children. However, Cd and As had the highest value of THQ suggestive of possible health risk associated with continuous consumption of Cd and As contaminated animal based foods. Hazard Index (HI) for additive effect of metals was higher in chicken liver and gizzard for children and chicken liver for adults. Thus, HI indicated that chicken liver and gizzard may contribute significantly to adult and children dietary exposure to heavy metals. Principal component analysis (PCA) showed a clear species difference in metal accumulation between chickens and the ruminants. This study provides baseline data for future studies and also valuable evidence of anthropogenic impacts necessary to initiate national and international policies for control of heavy metal and metalloid content in food items.

Investigation of hepatic warfarin metabolism activity in rodenticide-resistant black rats (Rattus rattus) in Tokyo by in situ liver perfusion.

Anti-blood coagulation rodenticides, such as warfarin, have been used all over the world. They inhibit vitamin K epoxide reductase (VKOR), which is necessary for producing several blood clotting factors. This inhibition by rodenticides results in lethal hemorrhage in rodents. However, heavy usage of these agents has led to the appearance of rodenticide-resistant rats. There are two major mechanisms underlying this resistance, i.e., mutation of the target enzyme of warfarin, VKOR, and enhanced metabolism of warfarin. However, there have been few studies regarding the hepatic metabolism of warfarin, which should be related to resistance. To investigate warfarin metabolism in resistant rats, in situ liver perfusion of warfarin was performed with resistant black rats (Rattus rattus) from Tokyo, Japan. Liver perfusion is an in situ methodology that can reveal hepatic function specifically with natural composition of the liver. The results indicated enhanced hepatic warfarin hydroxylation activity compared with sensitive black rats. On the other hand, in an in vitro microsomal warfarin metabolism assay to investigate kinetic parameters of cytochrome P450, which plays a major role in warfarin hydroxylation, the Vmax of resistant rats was slightly but significantly higher compared to the results obtained in the in situ study. These results indicated that another factor like electron donators may also contribute to the enhanced metabolism in addition to high expression of cytochrome P450.

Anthropogenic and Naturally Produced Brominated Phenols in Pet Blood and Pet Food in Japan.

Present study determined concentrations and residue patterns of bromophenols (BPhs) in whole blood samples of pet cats and pet dogs collected from veterinary hospitals in Japan. BPhs concentrations were higher in cat blood than in dog blood, with statistically insignificant differences (p = 0.07). Among the congeners, 2,4,6-tribromophenol (TBPh) constituted the majority of BPhs (>90%) detected in both species. Analysis of commercial pet food to estimate exposure routes showed that the most abundant congener in all pet food samples was 2,4,6-TBPh, accounting for >99% of total BPhs. This profile is quite similar to the blood samples of the pets, suggesting that diet might be an important exposure route for BPhs in pets. After incubation in polybrominated diphenyl ether (PBDE) mixtures (BDE-47, BDE-99 and BDE-209), 2,4,5-TBPh was found in dog liver microsomes but not in cat liver microsomes, implying species-specific metabolic capacities for PBDEs. Formation of 2,4,5-TBPh occurred by hydroxylation at the 1' carbon atom of the ether bond of BDE-99 is similar to human study reported previously. Hydroxylated PBDEs were not detected in cats or dogs; therefore, diphenyl ether bond cleavage of PBDEs can also be an important metabolic pathway for BPhs formation in cats and dogs.

Trace Element Contamination in Tissues of Four Bird Species from the Rift Valley Region, Ethiopia.

Concentrations of ten trace elements (Hg, As, Cd, Pb, Co, Cr, Cu, Ni, Se and Zn) were determined in different tissues (liver, kidney, muscle, heart and brain) of African sacred ibis (Threskiornis aethiopicus), Hamerkop (Scopus umbretta), marabou stork (Leptoptilos crumeniferus) and great white pelican (Pelecanus onocrotalus) inhabiting the Ethiopian Rift Valley region. There were differences in trace element patterns among the bird species. Significantly (p < 0.05) higher concentrations of Cd (5.53 µg/g dw ± 2.94) in kidney and Hg (0.75 µg/g ww ± 0.30) in liver were observed in the great white pelican compared to the other species, and liver concentrations of these two elements showed positive correlations with trophic level. Concentrations of toxic elements (As, Cd, Pb and Hg) in liver were below their respective toxicological thresholds, indicating that the data may provide baseline information for future studies.

Sediment Metal Contamination in the Kafue River of Zambia and Ecological Risk Assessment.

Zambia's Kafue River receives wastes from various sources, resulting in metal pollution. This study determined the degree of contamination of 13 metals (Al, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Cd, Hg and Pb) in Kafue River sediment and the associated ecological risks at six sites in three different seasons. The level of contamination for most metals showed significant site and seasonal differences. The contamination factor and pollution load index indicated that concentrations of most metals particularly copper (Cu), cobalt (Co), manganese (Mn) and arsenic (As) were very high at sites within the Copperbelt mining area. The geoaccumulation index showed an absence of anthropogenic enrichment with Cd and Hg at all the study sites and extreme anthropogenic enrichment with Cu at sites in the Copperbelt mining area. Potential ecological risk showed that Cu and As were likely to cause adverse biological effects to aquatic organisms in the Copperbelt mining region of the Kafue River.

Organohalogen Compounds in Pet Dog and Cat: Do Pets Biotransform Natural Brominated Products in Food to Harmful Hydroxlated Substances?

There are growing concerns about the increase in hyperthyroidism in pet cats due to exposure to organohalogen contaminants and their hydroxylated metabolites. This study investigated the blood contaminants polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) and their hydroxylated and methoxylated derivatives (OH-PCBs, OH-PBDEs, and MeO-PBDEs), in pet dogs and cats. We also measured the residue levels of these compounds in commercially available pet foods. Chemical analyses of PCBs and OH-PCBs showed that the OH-PCB levels were 1 to 2 orders of magnitude lower in cat and dog food products than in their blood, suggesting that the origin of OH-PCBs in pet dogs and cats is PCBs ingested with their food. The major congeners of OH-/MeO-PBDEs identified in both pet food products and blood were natural products (6OH-/MeO-BDE47 and 2'OH-/MeO-BDE68) from marine organisms. In particular, higher concentrations of 6OH-BDE47 than 2'OH-BDE68 and two MeO-PBDE congeners were observed in the cat blood, although MeO-BDEs were dominant in cat foods, suggesting the efficient biotransformation of 6OH-BDE47 from 6MeO-BDE47 in cats. We performed in vitro demethylation experiments to confirm the biotransformation of MeO-PBDEs to OH-PBDEs using liver microsomes. The results showed that 6MeO-BDE47 and 2'MeO-BDE68 were demethylated to 6OH-BDE47 and 2'OH-BDE68 in both animals, whereas no hydroxylated metabolite from BDE47 was detected. The present study suggests that pet cats are exposed to MeO-PBDEs through cat food products containing fish flavors and that the OH-PBDEs in cat blood are derived from the CYP-dependent demethylation of naturally occurring MeO-PBDE congeners, not from the hydroxylation of PBDEs.

Novel revelation of warfarin resistant mechanism in roof rats (Rattus rattus) using pharmacokinetic/pharmacodynamic analysis.

Roof rats (Rattus rattus) live mainly in human habitats. Heavy use of rodenticides, such as warfarin, has led to the development of drug resistance, making pest control difficult. There have been many reports regarding mutations of vitamin K epoxide reductase (VKOR), the target enzyme of warfarin, in resistant rats. However, it has been suggested there are other mechanisms of warfarin resistance. To confirm these possibilities, closed colonies of warfarin-susceptible roof rats (S) and resistant rats from Tokyo (R) were established, and the pharmacokinetics/pharmacodynamics of warfarin in rats from both colonies was investigated. R rats had low levels of warfarin in serum and high clearance activity. These rats can rapidly metabolize warfarin by hydroxylation. The levels of accumulation in the organs were lower than those of S rats. R rats administered warfarin showed high expression levels of CYP2B, 2C, and 3A, which play roles in warfarin hydroxylation, and may explain the high clearance ability of R rats. The mechanism of warfarin resistance in roof rats from Tokyo involved not only mutation of VKOR but also high clearance ability due to high levels of CYP2B, 2C and 3A expression possibly induced by warfarin.

Accumulation properties of inorganic mercury and organic mercury in the red-crowned crane Grus japonensis in east Hokkaido, Japan.

The red-crowned (Japanese) crane Grus japonensis is native to east Hokkaido, Japan, in contrast to the East Asia mainland. Previously, we reported that red-crowned cranes in Hokkaido were highly contaminated with mercury in the 1990s and that the contamination rapidly decreased to a moderate level in the 2000s. In the present study, we determined levels of organic mercury (O-Hg) in the liver and kidney of cranes in east Hokkaido in comparison with levels of total mercury (T-Hg). T-Hg levels in the kidneys were higher than those in the livers in adults but not in subadults and juveniles; however, the reverse was the case for O-Hg even for adults. The ratio of O-Hg to T-Hg in both the liver and kidney decreased as T-Hg increased in the three developmental stages. While the ratios of O-Hg to T-Hg in the liver and kidney of adults were significantly lower than those of juveniles, the ratios were similar for adults and juveniles in a lower range of T-Hg. The ratio of selenium (Se) to T-Hg decreased as T-Hg increased in both the liver and kidney, irrespective of stages. Mercury burdens in feathers were about 59% and 67% of the total body burdens for juveniles and adults, respectively. Furthermore, ratios of carbon and nitrogen stable isotopes to T-Hg varied greatly, with no relation to mercury level in the liver. The results suggest slow accumulation of inorganic mercury in the kidney of red-crowned cranes in east Hokkaido, Japan.

Human health risks from metals and metalloid via consumption of food animals near gold mines in Tarkwa, Ghana: estimation of the daily intakes and target hazard quotients (THQs).

Heavy metal and metalloid contamination in food resulting from mining is of major concern due to the potential risk involved. Food consumption is the most likely route of human exposure to metals. This study was therefore to assess metals in different organs and different animal species near gold mines used for human consumption (free-range chicken, goat and sheep) in Tarkwa, Ghana, and to estimate the daily intake and health risk. The concentrations of Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Cd, and Pb were measured with an inductively coupled plasma-mass spectrometer and Hg analysis was done using the mercury analyzer. Principal component analysis of the results showed a clear separation between chicken, grouped on one side, and the ruminants clustered on another side in both offal and muscle. Interestingly, As, Cd, Hg, Mn and Pb made one cluster in the offal of chicken. Chicken muscle also showed similar distribution with As, Hg and Pb clustered together. The daily intake of metals (µg/kg body weight/day) were in the following ranges; As [0.002 (kidneys of goat and sheep)-0.19 (chicken gizzard)], Cd [0.003 (chicken muscle)-0.55 (chicken liver)], Hg [0.002 (goat muscle)-0.29 (chicken liver)], Pb [0.01 (muscles and kidneys of goat and sheep)-0.96 (chicken gizzard)] and Mn [0.13 (goat kidney)-8.92 (sheep liver)]. From the results, daily intakes of As, Cd, Hg, Pb and Mn in these food animals were low compared to the provisional tolerable daily intake guidelines. The THQs although less than one, indicated that contributions of chicken gizzard and liver to toxic metal exposure in adults and especially children could be significant.

Health risk assessment of heavy metals and metalloid in drinking water from communities near gold mines in Tarkwa, Ghana.

Concentrations of heavy metals and metalloid in borehole drinking water from 18 communities in Tarkwa, Ghana, were measured to assess the health risk associated with its consumption. Mean concentrations of heavy metals (µg/L) exceeded recommended values in some communities. If we take into consideration the additive effect of heavy metals and metalloid, then oral hazard index (HI) results raise concerns about the noncarcinogenic adverse health effects of drinking groundwater in Huniso. According to the US Environmental Protection Agency's (USEPA) guidelines, HI values indicating noncarcinogenic health risk for adults and children in Huniso were 0.781 (low risk) and 1.08 (medium risk), respectively. The cancer risk due to cadmium (Cd) exposure in adults and children in the sampled communities was very low. However, the average risk values of arsenic (As) for adults and children through drinking borehole water in the communities indicated medium cancer risk, but high cancer risk in some communities such as Samahu and Mile 7. Based on the USEPA assessment, the average cancer risk values of As for adults (3.65E-05) and children (5.08E-05) indicated three (adults) and five (children) cases of neoplasm in a hundred thousand inhabitants. The results of this study showed that residents in Tarkwa who use and drink water from boreholes could be at serious risk from exposure to these heavy metals and metalloid.