Publications by authors named "Mayumi Ishizuka"

204 Publications

Analysis of lead distribution in avian organs by LA-ICP-MS: Study of experimentally lead-exposed ducks and kites.

Environ Pollut 2021 Apr 5;283:117086. Epub 2021 Apr 5.

Laboratory of Toxicology, Faculty of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo, Hokkaido, 060-0818, Japan.

Lead poisoning of wild birds by ingestion of lead ammunition occurs worldwide. Histopathological changes in organs of lead-intoxicated birds are widely known, and lead concentration of each organ is measurable using mass spectrometry. However, detailed lead localization at the suborgan level has remained elusive in lead-exposed birds. Here we investigated the detailed lead localization in organs of experimentally lead-exposed ducks and kites by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). In both the ducks and kites, lead accumulated diffusely in the liver, renal cortex, and brain. Lead accumulation was restricted to the red pulp in the spleen. With regard to species differences in lead distribution patterns, it is noteworthy that intensive lead accumulation was observed in the arterial walls only in the kites. In addition, the distribution of copper in the brain was altered in the lead-exposed ducks. Thus, the present study shows suborgan lead distribution in lead-exposed birds and its differences between avian species for the first time. These findings will provide fundamental information to understand the cellular processes of lead poisoning and the mechanisms of species differences in susceptibility to lead exposure.
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http://dx.doi.org/10.1016/j.envpol.2021.117086DOI Listing
April 2021

Human Exposures to Neonicotinoids in Kumasi, Ghana.

Environ Toxicol Chem 2021 Apr 6. Epub 2021 Apr 6.

Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.

Neonicotinoid insecticides (NNIs) are now popular in many agricultural systems across Africa; however, the extent of human exposures to NNIs in African countries are scarcely reported. The present study sought to evaluate neonicotinoid exposures in the consumer population of Kumasi, a cosmopolitan city in Ghana. A total of 75 human urine samples were collected from healthy volunteers (non-farmers; age 13-80 years old); and analyzed with LC-ESI/MS/MS system. Seven NNIs and three NNI metabolites were detected in the following pattern (frequency, median concentration, maximum concentration): N-dm-acetamiprid (94.7%, 0.41 µg/L, 8.79 µg/L) > imidacloprid (70.7%, 0.15 µg/L, 211.62 µg/L) > CPMF (62.2%, 0.43 µg/L, 53.85 µg/L) > CPMA (56.8%, 0.10 µg/L, 3.53 µg/L) > clothianidin (40%, >LOQ, 0.45 µg/L) > nitenpyram (18.7%, >LOQ, 0.14 µg/L) ≈ thiamethoxam (18.7%, >LOQ, 0.21 µg/L) > dinotefuran (12.0%, >LOQ, 1.01 µg/L) > acetamiprid (2.7%, >LOQ, 0.08 µg/L) ≈ thiacloprid (2.7%, >LOQ, 0.14 µg/L). About 92% of the subjects were found to be exposed to multiple neonicotinoids simultaneously. The mean, median and maximum IMIeq (imidacloprid equivalence of the relative potency factor of NNIs) were found to be 1.6, 0.5, 22.52 respectively. The median estimated daily intakes of acetamiprid, imidacloprid and nitenpyram were 0.47, 1.27 and 0.02 µg/kg/day for females: and 0.91, 0.66 and 0.08 µg/kg/day for males, respectively. The maximum daily intakes (DI) of all the NNIs were below 1% of their chronic reference doses (cRfDs), except for imidacloprid and thiacloprid which recorded a maximum DIs corresponding to 17.97% and 8.28% of cRfDs respectively. To the best of our knowledge, the present study is the first biomonitoring report on neonicotinoid insecticides in Africa. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/etc.5065DOI Listing
April 2021

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

Pestic Biochem Physiol 2021 Mar 9;173:104774. Epub 2021 Jan 9.

Laboratory of Toxicology, Department of Environmental Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita-18 Nishi-9, Kita-ku, Sapporo 060-0818, Japan. Electronic address:

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 IC 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 (V/K). 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.
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http://dx.doi.org/10.1016/j.pestbp.2021.104774DOI Listing
March 2021

Assessment of LeadCare® II analysis for testing of a wide range of blood lead levels in comparison with ICP-MS analysis.

Chemosphere 2021 May 2;271:129832. Epub 2021 Feb 2.

Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo, 060-0818, Japan. Electronic address:

The LeadCare® testing system, which utilizes anodic stripping voltammetry (ASV) methodology, has been widely used worldwide for cost-effective blood lead level (BLL) screening. However, some concerns have recently been issued regarding inaccurate results obtained using LeadCare®. Hence, we aimed to evaluate the accuracy of BLL measured by LeadCare® II (BLL) by comparison with ICP-MS (BLL) by the Passing-Bablok regression, Deming regression, and Bland-Altman analyses by using 994 venous blood samples. BLL ranged from 3.3 to 162.3 μg/dL, while BLL ranged from 0.8 to 154.8 μg/dL. Although BLL and BLL exhibited a strong and positive correlation, BLL values were generally greater than BLL values, indicative of the overestimation of the LeadCare® analysis. A large positive bias of 19.15 ± 8.26 μg/dL and 29.25 ± 14.04 μg/dL for BLL compared with BLL were recorded in the BLL range of 45.0-64.9 μg/dL and for ≥65.0 μg/dL, respectively. In contrast, a bias of ≤0.3 μg/dL was observed at a BLL of less than 10.0 μg/dL. Blood copper, cadmium, and iron levels did not exhibit an effect on the bias of BLL, indicative of the minimal potential interferences of the metals; these interferences are a cause for concern with the ASV method. In conclusion, LeadCare® analysis is thought to be a good tool for screening purposes at a lower BLL around the reference level of 5 μg/dL in the initial stage; however, conversion or retesting using a laboratory analyzer is recommended at a higher BLL for appropriate clinical evaluation and research.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129832DOI Listing
May 2021

Urinary free metanephrines measurement in dogs with adrenal gland diseases using a new simple liquid chromatography tandem mass spectrometry method.

J Vet Med Sci 2021 Apr 5;83(4):648-655. Epub 2021 Mar 5.

Laboratory of Veterinary Internal Medicine, Department of Clinical Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18-jo Nishi 9-chome, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.

Measurement of urinary metanephrines in spot samples is used for the diagnosis of canine pheochromocytoma (PC). We describe a simple analytical method based on liquid chromatography tandem mass spectrometry (LC-MS/MS) for measuring free metanephrine (MN) and normetanephrine (NMN) in spot urine samples. Using the developed method, we evaluated the stability of urinary free-MN and free-NMN at various storing conditions. In addition, we assessed the feasibility of urinary free-MN and -NMN measurement for diagnosing PC. Urine samples were mixed with stable isotope internal standards and thereafter purified by ultrafiltration. The purified samples were analyzed by LC-MS/MS in the multiple reaction monitoring mode after separation on a multimode octa decyl silyl column. The coefficient of variation of free-MN and -NMN measurement was 7.6% and 5.5%, respectively. The linearity range was 0.5-10 µg/l for both analytes. Degradation was less than 10% for both analytes under any of the storage conditions. The median free-NMN ratio to creatinine of 9 PC dogs (595, range 144-47,961) was significantly higher (P<0.05) than that of 13 dogs with hypercortisolism (125, range 52-224) or 15 healthy dogs (85, range 50-117). The developed method is simple and may not require acidification of spot urine. The results of this preliminary retrospective study suggest that the measurement of urinary free metanephrines is a promising tool for diagnosing canine PC.
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http://dx.doi.org/10.1292/jvms.20-0508DOI Listing
April 2021

Sensitivity of turtles to anticoagulant rodenticides: Risk assessment for green sea turtles (Chelonia mydas) in the Ogasawara Islands and comparison of warfarin sensitivity among turtle species.

Aquat Toxicol 2021 Apr 25;233:105792. Epub 2021 Feb 25.

Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo, 060-0818, Japan. Electronic address:

Although anticoagulant rodenticides (ARs) are effectively used for the control of invasive rodents, nontarget species are also frequently exposed to ARs and secondary poisonings occur widely. However, little data is available on the effects of ARs, especially on marine organisms. To evaluate the effects of ARs on marine wildlife, we chose green sea turtles (Chelonia mydas), which are one of the most common marine organisms around the Ogasawara islands, as our primary study species. The sensitivity of these turtles to ARs was assessed using both in vivo and in vitro approaches. We administered 4 mg/kg of warfarin sodium either orally or intravenously to juvenile green sea turtles. The turtles exhibited slow pharmacokinetics, and prolongation of prothrombin time (PT) was observed only with intravenous warfarin administration. We also conducted an in vitro investigation using liver microsomes from green sea turtles, and two other turtle species (softshell turtle and red-eared slider) and rats. The cytochrome P450 metabolic activity in the liver of green sea turtles was lower than in rats. Additionally, vitamin K epoxide reductase (VKOR), which is the target enzyme of ARs, was inhibited by warfarin in the turtles at lower concentration levels than in rats. These data indicate that turtles may be more sensitive to ARs than rats. We expect that these findings will be helpful for sea turtle conservation following accidental AR-broadcast incidents.
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http://dx.doi.org/10.1016/j.aquatox.2021.105792DOI Listing
April 2021

Aging-related changes in the sensitivity of behavioral effects of the neonicotinoid pesticide clothianidin in male mice.

Toxicol Lett 2021 May 17;342:95-103. Epub 2021 Feb 17.

Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo, 657-8501, Japan.

Neonicotinoids, which act as agonists of the nicotinic acetylcholine receptors of insects, are widely used pesticides worldwide. Although epidemiological studies revealed that the detection amounts of neonicotinoids in urine are higher in the elderly population than other age-groups, there is no available information regarding the risks of neonicotinoids to older mammals. This study was aimed to investigate aging-related differences in the behavioral effects of the neonicotinoid pesticide clothianidin (CLO). We acutely administered a sub-NOAEL level (5 mg/kg) of CLO to adult (12-week-old) and aging (90-week-old) mice and conducted four behavioral tests focusing on the emotional behavior. In addition, we measured the concentrations of CLO and its metabolites in blood, brain and urine. There were age-related changes in most parameters in all behavioral tests, and CLO significantly decreased the locomotor activity in the open field test and elevated plus-maze test in the aging group, but not in the adult group. The concentrations of most CLO and its metabolites were significantly higher in the blood and brain and were slightly lower in the urine in the aging group compared to the adult group. These findings should contribute to our understanding of age-related differences in the adverse effects of neonicotinoids in mammals.
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http://dx.doi.org/10.1016/j.toxlet.2021.02.010DOI Listing
May 2021

Chronic low-dose exposure to imidacloprid potentiates high fat diet-mediated liver steatosis in C57BL/6J male mice.

J Vet Med Sci 2021 Apr 25;83(3):487-500. Epub 2021 Jan 25.

Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.

Hepatic steatosis is known to precede a continuum of events that lead to hepatic metabolic dysfunction, inflammation and carcinogenesis. Recently, studies have linked xenobiotic exposures to hepatic steatogenesis and its associated metabolic disorders; however, the underlying mechanisms remain elusive. This study aimed to elucidate the mechanistic role of imidacloprid in the prevalence of high fat diet (HFD)-induced liver steatosis, using a C57BL/6J mice model. Mice (3 weeks old) were fed with HFD and treated with 0.6 mg/kg bw/day (one-tenth of the NOAEL) of imidacloprid through water or diet, for 24 weeks. In a controlled group, mice were fed with only HFD. At the end of the study, imidacloprid treatment significantly potentiated HFD-induced body weight gain in mice. Also, imidacloprid increased the liver weights of mice, with complimentary reductions in mesenteric and gonadal white adipose tissue weights. Histopathological analysis of liver revealed a drastic steatosis in imidacloprid treated mice. Following a real-time qPCR analysis, imidacloprid upregulated transcriptions of hepatic fatty acid biosynthesis-related transcription factors and genes. Imidacloprid also induced hepatic expression of the gene encoding pregnane X receptor; but had no significant effect on hepatic expressions of liver X receptor and aryl hydrocarbon receptor. The imidacloprid treatment further enhanced serum alanine aminotransferase levels but downregulated hepatic antioxidant mRNA expressions. Ultimately, this study suggested an imidacloprid-potentiation effects on prevalence of HFD-induced liver steatosis via transcriptional modulations of the hepatic FA biosynthesis pathway.
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http://dx.doi.org/10.1292/jvms.20-0479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025430PMC
April 2021

An Investigation of the Wild Rat Crown Incisor as an Indicator of Lead (Pb) Exposure Using Inductively Couple Plasma Mass Spectrometry (ICP-MS) and Laser Ablation ICP-MS.

Int J Environ Res Public Health 2021 01 18;18(2). Epub 2021 Jan 18.

Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo 060-0818, Japan.

Lead (Pb) is a metal toxicant of great public health concern. The present study investigated the applicability of the rat incisor in Pb exposure screening. The levels of lead in teeth (Pb-T) in the crown and root of incisors in laboratory Pb-exposed Sprague Dawley rats were quantified using inductively coupled plasma mass spectrometry (ICP-MS). The crown accumulated much Pb-T than the root of the Sprague Dawley rat incisor. The levels of lead in blood (Pb-B) were positively correlated with the Pb-T in the crown and root incisors of the Sprague Dawley rats. As an application of the Pb-T crown results in experimental rats, we subsequently analyzed the Pb-T in the crown incisors of Pb-exposed wild rats () sampled from residential sites within varying distances from an abandoned lead-zinc mine. The Pb-T accumulation in the crown of incisors of rats decreased with increased distance away from the Pb-Zn mine. Furthermore, the Pb-T was strongly correlated ( = 0.85) with the Pb levels in the blood. Laser ablation ICP-MS Pb-T mappings revealed a homogenous distribution of Pb in the incisor with an increased intensity of Pb-T localized in the tip of the incisor crown bearing an enamel surface in both Sprague Dawley and rats. These findings suggest that Pb-T in the crown incisor may be reflective of the rat's environmental habitat, thus a possible indicator of Pb exposure.
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http://dx.doi.org/10.3390/ijerph18020767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830958PMC
January 2021

Lead, Zinc and Cadmium Accumulation, and Associated Health Risks, in Maize Grown near the Kabwe Mine in Zambia in Response to Organic and Inorganic Soil Amendments.

Int J Environ Res Public Health 2020 12 4;17(23). Epub 2020 Dec 4.

Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-Ku, Sapporo 060-0809, Japan.

Health risks due to heavy metal (HM) contamination is of global concern. Despite concerns of high levels of HMs in soils near Kabwe mine in Zambia, edible crop production is common, posing potential health risks. This study assessed the potential of chicken manure (CM), triple superphosphate (TSP) and a blended fertilizer (BF; consisting of Nitrogen, Phosphorous and Potassium (NPK) fertilizer and composted chicken manure) to reduce lead (Pb), zinc (Zn) and cadmium (Cd) in soils and their accumulation in maize grown near the Kabwe mine. Maize was grown to maturity and its HM concentrations and associated health risk indices were calculated. All soil amendments decreased bioavailable soil Pb concentrations by 29-36%, but only CM decreased Zn, while the amendments increased or had no effect on Cd concentrations compared to the control. The amendments reduced Pb (>25%) and Zn concentrations (>18%) in the maize stover and grain. However, Cd concentrations in maize grain increased in the BF and TSP treatments. Bioaccumulation factors showed that Cd had the highest mobility from the soil into maize stover and grain, indicating the need for greater attention on Cd in Kabwe despite its apparently lower soil concentration compared to Pb and Zn. The hazard quotients for Pb and Cd were much greater than one, indicating a high risk of possible exposure to toxic levels by people consuming maize grain grown in this area. This study demonstrated the significant potential of manure and phosphate-based amendments to reduce Pb and Zn, and to some extent Cd, uptake in maize grain and consequently reduce associated health risks.
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http://dx.doi.org/10.3390/ijerph17239038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730587PMC
December 2020

Biosorption of Pb (II) and Zn (II) from aqueous solution by Oceanobacillus profundus isolated from an abandoned mine.

Sci Rep 2020 12 3;10(1):21189. Epub 2020 Dec 3.

Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-Ku, Sapporo, 060-0818, Japan.

The present study investigated biosorption of Pb (II) and Zn (II) using a heavy metal tolerant bacterium Oceanobacillus profundus KBZ 3-2 isolated from a contaminated site. The effects of process parameters such as effect on bacterial growth, pH and initial lead ion concentration were studied. The results showed that the maximum removal percentage for Pb (II) was 97% at an initial concentration of 50 mg/L whereas maximum removal percentage for Zn (II) was at 54% at an initial concentration of 2 mg/L obtained at pH 6 and 30 °C. The isolated bacteria were found to sequester both Pb (II) and Zn (II) in the extracellular polymeric substance (EPS). The EPS facilitates ion exchange and metal chelation-complexation by virtue of the existence of ionizable functional groups such as carboxyl, sulfate, and phosphate present in the protein and polysaccharides. Therefore, the use of indigenous bacteria in the remediation of contaminated water is an eco-friendly way of solving anthropogenic contamination.
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http://dx.doi.org/10.1038/s41598-020-78187-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713119PMC
December 2020

Clinical biochemical parameters associated with the exposure to multiple environmental metals in residents from Kabwe, Zambia.

Chemosphere 2021 Jan 17;262:127788. Epub 2020 Aug 17.

Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo, 060-0818, Japan. Electronic address:

Lead (Pb) interferes with various bodily functions. Although high blood Pb (Pb-B) levels in residents from Kabwe, Zambia have been reported, the accumulation pattern of other metals remains unknown. The study was designed to determine the Pb-B, blood cadmium (Cd-B), and zinc (Zn-B) values of 504 representative samples from Kabwe, as well as the potential associated adverse health effects. The Pb-B level ranged from 0.79 to 154.75 μg/dL and generally increased in areas near the mine. A significant elevation of Cd-B was observed in two areas (0.37 ± 0.26 and 0.32 ± 0.30 μg/L) where the two highest mean Pb-B levels were recorded. By contrast, the Zn-B values did not differ greatly with respect to area. Some blood biochemical parameters relating to hepatic and renal functions were out of the normal range in approximately 20-50% of studied adult participants. The δ-aminolevulinic acid dehydratase (δ-ALAD) activity was significantly inhibited in the two areas contaminated by Pb and Cd. A significant negative relationship was observed between metal levels and clinical parameters, e.g., between Pb-B and δ-ALAD for all the age categories and between Cd-B and the estimated glomerular filtration rate for all the age categories except 0-4 years. The elevated Cd-B in areas near the mine relative to the other areas suggested the potential adverse health effects of Cd and/or the interaction of Pb and Cd. A significant association of metal levels with clinical parameters also indicated the effects of metal exposure on hematopoietic, hepatic, and renal systems.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127788DOI Listing
January 2021

Levels of DDTs and other organochlorine pesticides in healthy wild Nile crocodiles (Crocodylus niloticus) from a flagship conservation area.

Chemosphere 2021 Feb 18;264(Pt 1):128368. Epub 2020 Sep 18.

Water Research Group, Unit for Environmental Sciences and Management, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa; Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.

Mass Nile crocodile (Crocodylus niloticus) deaths in Africa's premier conservation area, the Kruger National Park (KNP), prompted numerous studies to determine possible causes of the sudden die-offs. The majority highlighted the involvement of the anthropocene to crocodile mass mortalities. One of the potential causative agents was identified as legacy compounds such as organochlorine pesticides (OCPs) present in the various aquatic ecosystems of the KNP. Thus, this study aimed to quantify OCP levels in wild crocodiles from the aquatic systems associated with the KNP. As part of a larger study, muscle tissue samples were collected from tails of 12 wild crocodiles. Results indicated that eight of the 19 OCPs analysed for were quantifiable. These included DDTs (2130-167968 ng/g lw), chlordanes (BD - 7583 ng/g lw) and cyclodeines (BD - 872 ng/g lw). Measured concentrations indicated spatial- and sex-related differences in accumulation patterns. DDT and its metabolites, paricularly p,p'-DDE accumulated to the highest concentrations of the OCP groups. Levels of the different groups of OCPs were the highest recorded in recent history from any crocodilian tissue. The different measured OCP residues were between 2.5 and 120 times higher than levels reported in literature, depending on the compound. These results are of ecotoxicological significance and have several management implications. In view of individuals being sampled from a conservation area it emphasizes the fact that pollutants know no boundaries and that premier conservation areas such as the world renowned KNP may be some of the most contaminated areas of the world.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128368DOI Listing
February 2021

Interspecies differences in cytochrome P450-mediated metabolism of neonicotinoids among cats, dogs, rats, and humans.

Comp Biochem Physiol C Toxicol Pharmacol 2021 Jan 3;239:108898. Epub 2020 Oct 3.

Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan. Electronic address:

Neonicotinoid insecticides are used for agricultural and non-agricultural purposes worldwide. Pets are directly exposed to neonicotinoids in veterinary products and through environmental contamination. Cytochrome P450 (CYP) is among the most significant xenobiotic metabolizing enzymes that oxidizes several chemicals, including neonicotinoids. However, CYP activities and metabolite compositions of neonicotinoid metabolites are unknown in most domesticated pet species. Our objectives were to reveal the differences in metabolites of neonicotinoids (imidacloprid, clothianidin, and acetamiprid) and CYP activities among common pet species (cats and dogs), humans, and rats. The results indicated that the CYP-mediated neonicotinoid metabolism was different depending on species and each neonicotinoid. Among these four species, the kinetics of imidacloprid metabolism indicated that rats have the highest rate of oxidation of imidacloprid to 4OH-imidacloprid, while the greatest enzyme kinetics of imidacloprid metabolism to 5OH-imidacloprid were found in rats and humans. Clothianidin was rapidly metabolized to 1-methyl-3-nitroguanidine and dm-clothianidin in rats, but cats and humans showed the lowest formation of dm-clothianidin. CYP activities in metabolism of acetamiprid to dm-acetamiprid and N-acetyl-acetamiprid were determined to be significantly higher in humans compared to other species. However, further studies should be targeted at identifying the differences in hepatic metabolism of neonicotinoids in these species using recombinant CYP enzymes.
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http://dx.doi.org/10.1016/j.cbpc.2020.108898DOI Listing
January 2021

Assessing the population-wide exposure to lead pollution in Kabwe, Zambia: an econometric estimation based on survey data.

Sci Rep 2020 09 15;10(1):15092. Epub 2020 Sep 15.

Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, 060-0818, Japan.

This study quantitatively assessed the population-wide lead poisoning conditions in Kabwe, Zambia, a town with severe lead pollution. While existing data have reported concerning blood lead levels (BLLs) of residents in pollution hotspots, the data representing the entire population are lacking. Further, selection bias is a concern. Given the lack of compulsory testing schemes, BLLs have been observed from voluntary participants in blood sampling surveys, but such data can represent higher or lower BLLs than the population average because of factors simultaneously affecting participation and BLLs. To illustrate the lead poisoning conditions of the population, we expanded the focus of our surveys and then econometrically estimated the BLLs of individuals representing the population, including those not participating in blood sampling, using background geographic, demographic, and socioeconomic information. The estimated population mean BLL was 11.9 μg/dL (11.6-12.1, 95% CI), lower than existing data because of our wide focus and correction of selection bias. However, the scale of lead poisoning remained immense and 74.9% of residents had BLLs greater than 5 μg/dL, the standard reference level for lead poisoning. Our estimates provide a deeper understanding of the problem and a foundation for policy intervention designs.
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http://dx.doi.org/10.1038/s41598-020-71998-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492281PMC
September 2020

Acute exposure to environmentally relevant lead levels induces oxidative stress and neurobehavioral alterations in larval zebrafish (Danio rerio).

Aquat Toxicol 2020 Oct 19;227:105607. Epub 2020 Aug 19.

Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan. Electronic address:

The ubiquitous contamination of environmental lead (Pb) remains a worldwide threat. Improper Pb mine waste disposal from an abandoned lead-zinc mine has recently unearthed widespread Pb poisoning in children in Kabwe Zambia. Although the adverse effects of Pb on human health have begun to receive attention, the ecotoxicological effects on aquatic vertebrates still need further investigation. In addition, there is paucity in the knowledge on the behavioural and molecular subcellular responses in larval zebrafish exposed to Pb within the range of environmental relevant concentration (average 3 μg/L with maximum of 94 μg/L) on aquatic organisms such as zebrafish. The adverse effects of environmentally relevant levels of Pb on larval zebrafish was evaluated by measuring swimming behaviour under alternating dark and light conditions. Larval zebrafish acutely exposed to environmentally relevant Pb exhibited neuro-behavioural alteration including enhanced hyperactivity under light conditions evidenced by increased distanced covered and speed compared to the control. The alteration of entire behavioral profiles was further associated with the disturbed expression patterns of mRNA level of key genes associated with antioxidant (HO-1, Ucp-2 and CoxI), proapoptotic gene (TP53), and antiapoptotic gene (Bcl-2). To our knowledge, this is the first report on the effects of environmentally relevant Pb levels from Kabwe, Zambia and their adverse neurobehavioural effects and subcellular molecular oxidative responses in larval zebrafish acutely exposed within a 30 min period. The current results would be beneficial in our understanding of the effects of low Pb levels acutely discharged into an aquatic environment and the life of aquatic organisms.
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http://dx.doi.org/10.1016/j.aquatox.2020.105607DOI Listing
October 2020

Comparison of two reducing agents dithiothreitol and tris(3-hydroxypropyl)phosphine for kinetic assay of vitamin K epoxide reductase.

Vet Anim Sci 2020 Jun 15;9:100095. Epub 2020 Feb 15.

Department of Environmental Sciences, Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, Kita-18 Nishi-9, Kita-ku, Sapporo 060-0818, Japan.

Vitamin K epoxide reductase (VKOR) is a target enzyme for anticoagulants, such as warfarin, that are used as medicines or rodenticides. Assessing VKOR activity is required to ensure the proper usage of these drugs. Dithiothreitol (DTT) is a typical disulfide reductant that is used as a substrate for VKOR assays. However, DTT is considered problematic because of its side effects. Tris(3-hydroxypropyl)phosphine (THP) has been found to be a reliable alternative to DTT, as shown by kinetic analyses of the VKOR with them. THP showed significantly lower and values than those of DTT; however, there was no significant difference in their / and IC for warfarin.
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http://dx.doi.org/10.1016/j.vas.2020.100095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386777PMC
June 2020

Trophic transfer of pollutants within two intertidal rocky shore ecosystems in different biogeographic regions of South Africa.

Mar Pollut Bull 2020 Aug 5;157:111309. Epub 2020 Jun 5.

Water Research Group, Unit for Environmental Sciences and Management, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa; Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

Tsitsikamma and Sheffield Beach are two relatively pristine sites along the South African east coast representing warm temperate and subtropical biogeographic rocky shore intertidal ecosystems, respectively. Stable isotopes (δN and δC), metals and organochlorine pesticides (OCPs) were measured in 38 intertidal components to study biomagnification or biodilution of metals and OCPs in these marine food webs. Comparison of the four species common to both sites revealed that the highest Al, Fe and OCP concentrations were measured in intertidal organisms from Sheffield Beach and was attributed to diffuse input into the nearshore marine environment sources via estuaries and groundwater. All other metals were higher in intertidal organisms from Tsitsikamma and were attributed to the metal-rich phytoplankton blooms during upwelling events. There was no correlation between metal and OCP accumulation and dietary source (δC) or trophic level (δN). The application of trophic magnification factors (TMFs) using a relatively short benthic food chain indicated biomagnification for As, Cd, Cu, Se and Zn and biodilution of OCPs at both sites. Since these food chains represent only a small portion of the intertidal ecosystems we found limited evidence of biomagnification or biodilution of metals and OCPs across species. This was attributed to different dietary sources in the same food web and similar trophic levels being occupied by the same species in different food chains. We found that food web composition rather than temperature-based biogeographical distribution influenced trophic transfer of metals and OCPs.
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http://dx.doi.org/10.1016/j.marpolbul.2020.111309DOI Listing
August 2020

Relationship between blood test values and blood lead (Pb) levels in Black-headed gull (Chroicocephalus ridibundus: Laridae).

J Vet Med Sci 2020 Aug 19;82(8):1124-1129. Epub 2020 Jun 19.

Laboratory of Wildlife Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan.

Few studies have evaluated immunosuppression due to lead accumulation below the overt toxicity threshold. If low levels of lead accumulation cause immunosuppression in birds, those birds could become more susceptible to pathogens. We aimed to determine if low levels of lead accumulation lead to immunosuppression in Black-headed gulls (Chroicocephalus ridibundus). Gulls were captured in Tokyo-bay and Mikawa-bay from January to April 2019. Their blood samples were analyzed for eight items. The data were analyzed to evaluate the correlation between lead concentrations and the variables from each bay. Lead was positively correlated with the percentage of heterophils and heterophil and lymphocyte ratio and negatively with lymphocytes. Thus, low lead accumulation levels may induce changes in percentage of the heterophils and lymphocyte.
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http://dx.doi.org/10.1292/jvms.20-0246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468077PMC
August 2020

Current situation regarding lead exposure in birds in Japan (2015-2018); lead exposure is still occurring.

J Vet Med Sci 2020 Aug 18;82(8):1118-1123. Epub 2020 Jun 18.

Laboratory of Toxicology, Department of Environmental Veterinary Sciences, School of Veterinary Medicine, Hokkaido University, Kita18, Nishi9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.

Birds of a number of species have died as a result of lead (Pb) poisoning, including many Steller's sea eagles (Haliaeetus pelagicus) and white-tailed sea eagles (Haliaeetus albicilla) in Hokkaido, the northernmost island of Japan. To address this issue, the use of any type of Pb ammunition for hunting of large animals was prohibited in Hokkaido in 2004. However, Pb poisoning is still being reported in this area, and there are few regulations regarding the use of Pb ammunition in other parts of Japan, where it has been reported that eagles and water birds have been exposed to Pb. This study was performed to accurately determine the current level of Pb exposure of birds found dead in the field or dead in the wild bird centers in Japan (June 2015-May 2018) and to identify the sources of Pb. Pb exposure was found to still be occurring in raptors and water birds in various parts of Japan. Twenty-six point five % and 5.9% of the recorded deaths of Steller's sea eagles and white-tailed sea eagles, respectively, were found to have been poisoned by Pb. In addition, Pb isotope ratio analysis showed that both Pb rifle bullets and Pb shot pellets cause Pb exposure in birds, and these endangered eagles are also exposed to Pb in Hokkaido due to the illegal use of Pb ammunition. Changing to Pb-free ammunition, such as copper (Cu) rifle bullets, steel shot pellets, or bismuth shot pellets, will be essential for the conservation of avian species in Japan.
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http://dx.doi.org/10.1292/jvms.20-0104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468064PMC
August 2020

Blood lead levels and aberrant DNA methylation of the ALAD and p16 gene promoters in children exposed to environmental-lead.

Environ Res 2020 09 5;188:109759. Epub 2020 Jun 5.

Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan. Electronic address:

Background: Lead (Pb) is a well-known toxic heavy metal which can have serious public health hazards. As of today, there is no safe threshold for Pb exposure, especially for children. Lead exposure has been associated with adverse health outcomes involving epigenetic mechanisms, such as aberrant DNA methylation. The objective of the present study was to elucidate the associations between blood lead levels (BLLs) and gene-specific promoter DNA methylation status in environmental Pb-exposed children from Kabwe, Zambia.

Methods: A cross-sectional study was conducted using 2 to 10-year-old children from high Pb exposed area (N = 102) and low Pb exposed area (N = 38). We measured BLLs using a LeadCare II analyzer and investigated the methylation status of the ALAD and p16 gene promoters by methylation-specific PCR.

Results: The mean BLLs were 23.7 μg/dL and 7.9 μg/dL in high Pb exposed and low Pb exposed children, respectively. Pb exposure was correlated with increased methylation of the ALAD and p16 genes. The promoter methylation rates of ALAD and p16 in high Pb exposed children were 84.3% and 67.7%, and 42.1% and 44.7% in low Pb exposed children, respectively. Significantly increased methylation was found in both genes in high Pb exposed children compared with low Pb exposed children (p < 0.05). Children with methylated ALAD and p16 genes showed an increased risk of Pb poisoning (odd ratio >1) compared to the unmethylated status.

Conclusions: This study for the first time tries to correlate promoter methylation status of the ALAD and p16 genes in environmental Pb-exposed children from Kabwe, Zambia as a representative. The result suggests that Pb exposure increases aberrations in ALAD and p16 gene methylation, which may be involved in the mechanism of Pb toxicity.
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http://dx.doi.org/10.1016/j.envres.2020.109759DOI Listing
September 2020

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

Environ Sci Technol 2020 11 26;54(22):14474-14481. Epub 2020 Oct 26.

Laboratory of Toxicology, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.

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 (). 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.
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http://dx.doi.org/10.1021/acs.est.0c00150DOI Listing
November 2020

Altered hepatic cytochrome P450 expression in cats after chronic exposure to decabromodiphenyl ether (BDE-209).

J Vet Med Sci 2020 Jul 21;82(7):978-982. Epub 2020 May 21.

Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.

The knowledge of cytochrome P450 (CYP) expression involved in chemical exposure are necessary in clinical applications for the medication and prediction of adverse effects. The aim of this study was to evaluate the mRNA expression of CYP1-CYP3 families in cats exposed to BDE-209 for one year. All selected CYP isoforms showed no significant difference in mRNA expressions between control and exposure groups, however, CYP3A12 and CYP3A131 revealed tend to be two times higher in the exposure group compared to control group. The present results indicate that the chronic exposure of BDE209 could not alter CYP expression in the liver of cats. This result considered caused by the deficiency of CYP2B subfamily which is major metabolism enzyme of polybrominated diphenyl ethers (PBDEs) in cat.
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http://dx.doi.org/10.1292/jvms.20-0140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399315PMC
July 2020

In Vivo Accumulation of Plastic-Derived Chemicals into Seabird Tissues.

Curr Biol 2020 02 30;30(4):723-728.e3. Epub 2020 Jan 30.

Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.

Plastic debris is ubiquitous and increasing in the marine environment [1]. A wide range of marine organisms ingest plastic, and its impacts are of growing concern [2]. Seabirds are particularly susceptible to plastic pollution because of high rates of ingestion [3]. Because marine plastics contain an array of hazardous compounds, the chemical impacts of ingestion are concerning. Several studies on wild seabirds suggested accumulation of plastic-derived chemicals in seabird tissues [4-7]. However, to date, the evidence has all been indirect [4-7], and it is unclear whether plastic debris is the source of these pollutants. To obtain direct evidence for the transfer and accumulation of plastic additives in the tissues of seabirds, we conducted an in vivo plastic feeding experiment. Environmentally relevant exposure of plastics compounded with one flame retardant and four ultraviolet stabilizers to streaked shearwater (Calonectris leucomelas) chicks in semi-field conditions resulted in the accumulation of the additives in liver and adipose fat of 91 to 120,000 times the rate from the natural diet. Additional monitoring of six seabird species detected these chemical additives only in those species with high plastic ingestion rates, suggesting that plastic debris can be a major pathway of chemical pollutants into seabirds. These findings provide direct evidence of seabird exposure to plastic additives and emphasize the role of marine debris ingestion as a source of chemical pollution in marine organisms.
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http://dx.doi.org/10.1016/j.cub.2019.12.037DOI Listing
February 2020

Current trends of blood lead levels, distribution patterns and exposure variations among household members in Kabwe, Zambia.

Chemosphere 2020 Mar 19;243:125412. Epub 2019 Nov 19.

Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan. Electronic address:

Childhood lead (Pb) poisoning has devastating effects on neurodevelopment and causes overt clinical signs including convulsions and coma. Health effects including hypertension and various reproductive problems have been reported in adults. Historical Pb mining in Zambia's Kabwe town left a legacy of environmental pollution and childhood Pb poisoning. The current study aimed at establishing the extent of Pb poisoning and exposure differences among family members in Kabwe as well as determining populations at risk and identify children eligible for chelation therapy. Blood samples were collected in July and August 2017 from 1190 household members and Pb was measured using a portable LeadCare-II analyser. Participants included 291 younger children (3-months to 3-years-old), 271 older children (4-9-years-old), 412 mothers and 216 fathers from 13 townships with diverse levels of Pb contamination. The Blood Lead Levels (BLL) ranged from 1.65 to 162  μg/dL, with residents from Kasanda (mean 45.7  μg/dL) recording the highest BLL while Hamududu residents recorded the lowest (mean 3.3  μg/dL). Of the total number of children sampled (n = 562), 23% exceeded the 45  μg/dL, the threshold required for chelation therapy. A few children (5) exceeded the 100  μg/dL whereas none of the parents exceeded the 100  μg/dL value. Children had higher BLL than parents, with peak BLL-recorded at the age of 2-years-old. Lead exposure differences in Kabwe were attributed to distance and direction from the mine, with younger children at highest risk. Exposure levels in parents were equally alarming. For prompt diagnosis and treatment, a portable point-of-care devise such as a LeadCare-II would be preferable in Kabwe.
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http://dx.doi.org/10.1016/j.chemosphere.2019.125412DOI Listing
March 2020

Combined exposure to dinotefuran and chronic mild stress counteracts the change of the emotional and monoaminergic neuronal activity induced by either exposure singly despite corticosterone elevation in mice.

J Vet Med Sci 2020 Mar 27;82(3):350-359. Epub 2020 Jan 27.

Laboratory of Animal Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Nada, Kobe, Hyogo 657-8501, Japan.

Dinotefuran (DIN) belongs to the neonicotinoids (NNs), a class of globally applied pesticides originally developed to exhibit selective toxicity in insects. However, several reports have suggested that NNs also exert neurotoxic effects in mammals. We previously demonstrated neurobehavioral effects of DIN on mice under non-stressful conditions. For further toxicity assessments in the present study, we investigated the effects of DIN on mice exposed to stressful conditions. After subacutely administering a no-observed-effect-level (NOEL) dose of DIN and/or chronic unpredictable mild stress (CUMS) to mice, we conducted three behavioral tests (i.e., open field test [OFT], tail suspension test [TST] and forced swimming test [FST]). In addition, serotonin (5-HT) and tryptophan hydroxylase 2 (TPH2) of the dorsal raphe nuclei (DRN) and median raphe nuclei (MRN) and tyrosine hydroxylase (TH) of the ventral tegmental area and substantia nigra (SN) were evaluated immunohistochemically. A NOEL dose of DIN or CUMS alone increased of the total distance in OFT, decreased or increased the immobility time in TST or FST, respectively, and increased the positive intensity of 5-HT and TPH2 in the DRN/MRN, and TH in the SN. These changes were suppressed under the conditions of combined exposure to DIN and CUMS, though the blood corticosterone level was increased depending on the blood DIN values and the presence of CUMS. The present study suggests the multifaceted toxicity of the neurotoxin DIN.
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http://dx.doi.org/10.1292/jvms.19-0635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118473PMC
March 2020

Factors associated with lead (Pb) exposure on dogs around a Pb mining area, Kabwe, Zambia.

Chemosphere 2020 May 13;247:125884. Epub 2020 Jan 13.

Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Japan. Electronic address:

Lead (Pb)-poisoning is a serious public health concern and dogs have been useful as a sentinel-animal for Pb exposure of humans. In the present study, the blood Pb concentrations (BLC), isotope ratios (208 Pb/206 Pb and 207 Pb/206 Pb), and biochemistry of 120 domestically owned dogs living around a Pb mining area, in Kabwe, Zambia were analyzed to determine factors associated with Pb exposure. The overall mean value of Pb in dog blood in the present study was 271.6 μg/L. The BLC in the dogs from sites near the mine were significantly higher than those in the dogs from a site 4 km from the mine (352.9 ± 205.1 μg/L versus 28.0 ± 13.9 μg/L). BLC significantly decreased with both increasing age of the dogs and distance from the mine. The Pb isotope ratios in the dog that resided near the mine showed values similar to those reported at the galena mine in Kabwe, which is considered to be the source of Pb exposure. In contrast to the high metal exposure that was determined in these dogs, the mean values of most analyzed parameters in the blood biochemical analysis were surprisingly within or close to the standard reference values. Moreover, none of the dogs showed overt signs of Pb-poisoning or other clinical symptoms. The results of analysis of Pb exposure of the dogs obtained in the present study, which are similar to the previously reported results in human in this location, suggest that dogs could be useful as a sentinel animal for Pb exposure of humans in Kabwe.
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http://dx.doi.org/10.1016/j.chemosphere.2020.125884DOI Listing
May 2020

Quantitative elucidation of maternal-to-fetal transfer of neonicotinoid pesticide clothianidin and its metabolites in mice.

Toxicol Lett 2020 Apr 7;322:32-38. Epub 2020 Jan 7.

Laboratory of Animal Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657-8501, Japan. Electronic address:

Neonicotinoids (NNs), a widely used class of systemic pesticides, are regarded as exhibiting selective toxicity in insects. However, NNs are suspected of exerting adverse effects on mammals as well, including humans. To date, only adult male animal models have been subjected to general toxicity studies of NNs; fetuses have yet to be considered in this context. Here, we focused on the NN clothianidin (CLO) for the first quantitative LC-MS/MS analysis of maternal-to-fetal transfer and residual property of once-daily (single or multiple days), orally administered CLO and its metabolites in mice. The results revealed the presence of CLO and its five metabolites at approximately the same respective blood levels in both dams and fetuses. In the dams, CLO showed a peak value 1 h after administration, after which levels rapidly decreased at 3 and 6 h. In the fetuses of each group, levels of CLO were almost the same as those observed in the corresponding dams. The present results clearly demonstrated rapid passage of CLO through the placental barrier. However, metabolite-dependent differences observed in blood pharmacokinetics and residual levels. This is the first quantitative demonstration of the presence of CLO and its metabolites in fetal mouse blood.
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http://dx.doi.org/10.1016/j.toxlet.2020.01.003DOI Listing
April 2020

Occurrence and concentrations of chemical additives in plastic fragments on a beach on the island of Kauai, Hawaii.

Mar Pollut Bull 2020 Jan 20;150:110732. Epub 2019 Nov 20.

Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.

In the ocean, plastic debris containing chemical additives is fragmented into smaller pieces that can be ingested by a wide range of organisms, potentially exposing them to additives. However, the levels of additives retained in marine plastic fragments have rarely been assessed. In this study, 141 plastic fragments from a beach in Kauai were analyzed piece-by-piece for 12 compounds, including UV stabilizers and brominated flame retardants. UV stabilizers (UV-326, UV-328, UV-327, and BP-12) were found in 13% of "small" fragments (4-7 mm) with levels of up to 315 μg/g and in 33% of "large" fragments (15-80 mm) with levels of up to 1130 μg/g. This observation suggests that exhaustive leaching of additives does not occur during fragmentation and that significant levels of additives, comparable to those of the original products, can be retained in fragments of marine plastic, indicating their importance as a vector of chemical additive exposure.
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http://dx.doi.org/10.1016/j.marpolbul.2019.110732DOI Listing
January 2020

Effects of PCB exposure on serum thyroid hormone levels in dogs and cats.

Sci Total Environ 2019 Oct 23;688:1172-1183. Epub 2019 Jun 23.

Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama, Ehime 790-8577, Japan. Electronic address:

Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) might disrupt thyroid function. However, there is no clear evidence of PCB exposure disrupting thyroid hormone (TH) homeostasis in dogs and cats. The present study conducted in vivo experiments to evaluate the effects of a mixture of 12 PCB congeners (CB18, 28, 70, 77, 99, 101, 118, 138, 153, 180, 187 and 202, each congener 0.5 mg/kg BW, i.p. administration) on serum TH levels in male dogs (Canis lupus familiaris) and male cats (Felis silvestris catus). In PCB-exposed dogs, the time courses of higher-chlorinated PCBs and L-thyroxine (T4)-like OH-PCBs (4-OH-CB107 and 4-OH-CB202) concentrations were unchanged or tended to increase, whereas those of lower-chlorinated PCBs and OH-PCBs tended to decrease after 24 h. In PCB-exposed cats, concentrations of PCBs increased until 6 h and then remained unchanged. The levels of lower-chlorinated OH-PCBs including 4'-OH-CB18 increased until 96 h and then decreased. In PCB-exposed dogs, free T4 concentrations were higher than those in the control group at 48 and 96 h after PCB administration and positively correlated with the levels of T4-like OH-PCBs, suggesting competitive binding of T4 and T4-like OH-PCBs to a TH transporter, transthyretin. Serum levels of total T4 and total 3,3',5-triiodo-L-thyronine (T3) in PCB-exposed dogs were lower than in the control group at 24 and 48 h and negatively correlated with PCB concentrations, implying that PCB exposure enhanced TH excretion by increasing TH uptake and TH conjugation enzyme activities in the dog liver. In contrast, no obvious changes in TH levels were observed in PCB-exposed cats. This could be explained by the lower levels of T4-like OH-PCBs and lower hepatic conjugation enzyme activities in cats compared with dogs. Different effects on serum TH levels in PCB-exposed dogs and cats are likely to be attributable to species-specific PCB and TH metabolism.
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http://dx.doi.org/10.1016/j.scitotenv.2019.06.300DOI Listing
October 2019