Human Health Risk Assessment from Mercury-Contaminated Soil and Water in Abu Hamad Mining Market, Sudan.

Artisanal and small-scale gold mining (ASGM) poses a significant global threat due to mercury emissions and resulting health hazards. This study focuses on assessing these risks in the Abu Hamad ASGM community in Sudan. Utilizing the Mercury Analyzer 3000 (NIC), analyses of twelve soil samples (including one tailings sample) and seven water samples revealed the highest concentrations near amalgam burning locations: 34.8 mg/kg in soil (S06) and 3.26 µg/L in water (W03). Concentrations decrease with distance, with soil near burning exceeding tailings (S05 = 19.0 mg/kg). Hazard quotients indicate mercury vapor inhalation as the primary exposure route from soil, with the Hazard Index reaching 5.34 for adults and 33.4 for children close to amalgam burning sites. Water samples generally pose little risk except for W03, where children face potential danger via ingestion (HI = 1.74). These findings emphasize the urgent need for adopting retorts and eco-friendly practices to reduce mercury emissions and protect ASGM communities.

Adverse effects of contamination by fipronil and its derivatives on growth, molting, and gene expression in the mysid crustacean, Americamysis bahia, in Japanese estuaries.

Concentrations of fipronil (Fip) and several of its derivatives were detected in samples from four rivers and four estuaries in Japan. LC-MS/MS analysis detected Fip and its derivatives, except for fipronil detrifluoromethylsulfinyl, in almost all samples. The total concentrations of the five compounds were approximately two-fold greater in river water (mean: 21.2, 14.1, and 9.95 ng/L in June, July, and September, respectively) compared to those in estuarine water (mean: 10.3, 8.67, and 6.71 ng/L, respectively). Fipronil, fipronil sulfone (Fip-S), and fipronil sulfide (Fip-Sf) represented more than 70 % of all compounds. This is the first report to demonstrate the contamination of estuarine waters of Japan by these compounds. We further investigated the potentially toxic effects of Fip, Fip-S, and Fip-Sf on the exotic mysid, Americamysis bahia (Crustacea: Mysidae). The lowest effective concentrations of Fip-S (10.9 ng/L) and Fip-Sf (19.2 ng/L) on mysid growth and molting was approximately 12.9- and 7.3-fold lower than Fip (140.3 ng/L), suggesting they had higher toxicity. Quantitative reverse transcription polymerase chain reaction analysis revealed that ecdysone receptor and ultraspiracle gene expression were not affected after 96-h of exposure to Fip, Fip-S, and Fip-Sf, suggesting that these genes may not be involved in the molting disruption induced by Fip, Fip-S, and Fip-Sf. Our findings suggest that environmentally relevant concentrations of Fip and its derivatives can disrupt the growth of A. bahia by promoting molting. However, further studies are required to elucidate its molecular mechanism.

Evaluation of neurotoxicity of anticancer drugs using nematode Caenorhabditis elegans as a model organism.

It is well established that platinum-based drugs, including oxaliplatin (L-OHP) and cisplatin (CDDP), as well as microtubule inhibitors paclitaxel (PTX) and vincristine (VCR), are associated with chemotherapy-induced peripheral neuropathy (CIPN). In this study, we examined and compared the characteristics of neuropathies induced by L-OHP, CDDP, PTX, and VCR to evaluate whether Caenorhabditis elegans (C. elegans) could serve as a model organism for human CIPN. Worms were cultured on nematode growth medium plates, and L1 larvae synchronized by gel filtration were employed. We then performed bioassays and examined motility. In the motility test, exposure was performed for 2, 24, and 48 hr, and time-dependent effects were measured for each exposure time and 24 hr after terminating exposure. Herein, we observed that L-OHP and CDDP exerted concentration-dependent effects above a certain concentration, and PTX and VCR exerted concentration-dependent negative effects in the bioassay. Motility recovered in L-OHP-, PTX-, and VCR-treated worms on terminating exposure. However, CDDP exposure tended to reduce motility even 24 hr after terminating exposure. L-OHP exposure could decrease motility 2 hr after exposure, with a trend toward recovery 24 hr after terminating drug exposure. The findings of the present study revealed that C. elegans could exhibit neuropathy characteristics suggested to be similar to those observed in humans, indicating that this organism could be a suitable model to explore human CIPN.

Developmental toxicity and transcriptome analysis of equine estrogens in developing medaka (Oryzias latipes) using nanosecond pulsed electric field incorporation.

Equine estrogens (EQs) are steroidal hormones isolated from the urine of pregnant mares and are used in the formulation of human medications. This study initially investigated the embryonic developmental toxicity of equilin (Eq) and equilenin (Eqn) in medaka (Oryzias latipes). Malformations were observed in embryos exposed to nominal concentrations of 1 and 10 mg/L of Eq and Eqn. Delayed hatching was observed at 1 mg/L of Eq. To further investigate the molecular mechanism of developmental toxicity caused by Eq and Eqn, transcriptome and bioinformatics analyses were performed. Among 2016 and 3855 total differentially expressed genes (DEGs), 1117 DEGs overlapped between Eq. (55.4 % of total DEGs) and Eq. (29.0 % of total DEGs). Gene ontology indicated effects in terms related to blood circulation and cell junctions. Pathway analyses using DEGs revealed that both Eq and Eqn treatments at 10 mg/L affected various KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, such as neuroactive ligand-receptor interaction, mitogen-activated protein kinase signaling, retinol metabolism, and cytokine-cytokine receptor interaction. These results suggest that the disruption of these KEGG pathways is involved in the developmental toxicity of EQs in medaka embryos.

Mercury waste from artisanal and small-scale gold mining facilities: a risk to farm ecosystems-a case study of Obuasi, Ghana.

Frequent discharge of mercury waste from artisanal and small-scale gold mining (ASGM) facilities into nearby farms may contaminate foodstuffs and the entire farms. High contamination levels may result in ecological risks to the soil, plants, animals, humans, and the entire farm ecosystem. This original research is the first study within the catchment areas that describes the effects of mercury waste on the entire farm ecosystem. In this study, the contamination levels and the associated ecological risks of farmland soils, plantains, and cassavas from farms sited near ASGM facilities in four communities around Obuasi, Ghana, were evaluated using the Hakanson (1980) model. Results showed that all samples except for the edible parts of plantains from Tweapease, Nyamebekyere, and Ahansonyewodea and plantain peels from Nyamebekyere and Ahansonyewodea were contaminated and may pose moderate to very high ecological risks. All farms were also contaminated and may pose considerable to very high ecological risks. The farms at Odumase were the highest contaminated with degree of contamination (Cdeg) above 20, while those at Ahansonyewodea were the least contaminated with Cdeg = 8.1. This meant that farms at Odumase may pose the highest potential ecological risk (Per) to plants, animals, humans, and the entire farm ecosystem since Per > 600, while the farms at Ahansonyewodea may pose the least ecological risks with Per = 324. There is, therefore, the need for strict control of ASGM activities in these study areas to preserve the integrity of the ecosystem.

Mercury Pollution from Artisanal and Small-Scale Gold Mining in Myanmar and Other Southeast Asian Countries.

Mercury (Hg) is one of the most harmful metals and has been a public health concern according to the World Health Organization (WHO). Artisanal and small-scale gold mining (ASGM) is the world's fastest-growing source of Hg and can release Hg into the atmosphere, hydrosphere, and geosphere. Hg has been widely used in ASGM industries throughout Southeast Asia countries, including Cambodia, Indonesia, Laos, Malaysia, Myanmar, the Philippines, and Thailand. Here, 16 relevant studies were systematically searched by performing the PRISMA flow, combining the keywords of "Hg", "ASGM", and relevant study areas. Mercury concentrations exceeding the WHO and United States Environmental Protection Agency guideline values were reported in environmental (i.e., air, water, and soil) and biomonitoring samples (i.e., plants, fish, and human hair). ASGM-related health risks to miners and nonminers, specifically in Indonesia, the Philippines, and Myanmar, were also assessed. The findings indicated severe Hg contamination around the ASGM process, specifically the gold-amalgamation stage, was significantly high. To one point, Hg atmospheric concentrations from all observed studies was shown to be extremely high in the vicinity of gold operating areas. Attentions should be given regarding the public health concern, specifically for the vulnerable groups such as adults, pregnant women, and children who live near the ASGM activity. This review summarizes the effects of Hg in Myanmar and other Southeast Asian countries. In the future, more research and assessment will be required to investigate the current and evolving situation in ASGM communities.

Ca2+ imaging with two-photon microscopy to detect the disruption of brain function in mice administered neonicotinoid insecticides.

Neonicotinoid pesticides are a class of insecticides that reportedly have harmful effects on bees and dragonflies, causing a reduction in their numbers. Neonicotinoids act as neuroreceptor modulators, and some studies have reported their association with neurodevelopmental disorders. However, the precise effect of neonicotinoids on the central nervous system has not yet been identified. Herein, we conducted in vivo Ca2+ imaging using a two-photon microscope to detect the abnormal activity of neuronal circuits in the brain after neonicotinoid application. The oral administration of acetamiprid (ACE) (20 mg/kg body weight (BW) in mature mice with a quantity less than the no-observed-adverse-effect level (NOAEL) and a tenth or half of the median lethal dose (LD50) of nicotine (0.33 or 1.65 mg/kg BW, respectively), as a typical nicotinic acetylcholine receptor (nAChR) agonist, increased anxiety-like behavior associated with altered activities of the neuronal population in the somatosensory cortex. Furthermore, we detected ACE and its metabolites in the brain, 1 h after ACE administration. The results suggested that in vivo Ca2+ imaging using a two-photon microscope enabled the highly sensitive detection of neurotoxicant-mediated brain disturbance of nerves.

Combination of Vortex Agitation and Ultrasonic Irradiation for Mercury Removal from Sediment by Acid Extraction.

The removal of Hg from solid waste plays a key role in environmental protection. In this study, a fast, simple, and effective method for the removal of Hg by acid extraction, using a combination of vortex agitation and ultrasonic irradiation along with hydrobromic acid (HBr), was established using Hg-containing solid wastes. The optimal durations of vortex agitation and ultrasonic irradiation with 48% v/v of HBr were 5 and 6 min, respectively, and total Hg (T-Hg) extraction was achieved within 21 min. The proposed method was validated using the Certified Reference Material (CRM) ERM CC580 (estuarine sediment) and CRM NMIJ 7302-a (marine sediment). Under the optimized conditions, the efficiency rates of T-Hg extraction in both CRMs were 99.5% and 94.2%, with repeatabilities of 3.21% RSD and 2.31% RSD, respectively. The proposed extraction method can also be used for the remediation of Hg in other environmental matrices.

Human health risk of mercury in street dust: A case study of children in the vicinity of compact fluorescence lamp factory, Hanoi, Vietnam.

Urban dust has been contaminated with toxic heavy metals from various diffused sources. On August 28, 2019, the compact fluorescence lamp (CFL) factory that generates light for Rang Dong Light Source and Vacuum Flask in Hanoi City in Vietnam was accidentally fired. The assessment for Hg contamination and its human health impact 2 months after the incident was conducted in autumn 2019. The heavy Hg pollution is still found near CFL. Additionally, localized Hg pollution by air and wind direction was identified at sites in the northeast direction from CFL. Namely, in the area located downstream of the southwest monsoon wind, Hg had a trend higher than other directions. The hazard quotient (HQ) and the hazard index (HI) were evaluated by four routes of Hg exposure pathways. The HI values for children and adults in the most polluted site (Site 15) were 0.968 and 0.468, respectively. This meant that children who lived around this site and commuted to schools were the most at risk regarding the potential adverse health effects of Hg in street dust around the polluted areas. This study also showed that Hg levels were affected by wind direction and that the higher Hg levels in the most polluted sites resulted from the wind flow to the sites. This study revealed that street dust may be a useful tool for the assessment of human and environmental health.

The human health risks assessment of mercury in soils and plantains from farms in selected artisanal and small-scale gold mining communities around Obuasi, Ghana.

Food consumption remains the commonest pathway through which humans ingest higher levels of mercury (Hg). Long-term exposure to Hg through Hg-contaminated food may result in acute or chronic Hg toxicity. Incessant discharge of Hg waste from ASGM facilities into nearby farms contaminates food crops. Ingestion of such food crops by residents may lead to detrimental human health effects. The human health risks upon exposure to total mercury (THg) and methylmercury (MeHg) in farmland soils and plantains from farms sited near ASGM facilities were studied in four communities around Obuasi, Ghana. The human health risk assessment was evaluated using hazard quotient (HQ), estimated average daily intake (e AvDI), hazard index (HI) and Hg elimination and retention kinetics. Tweapease, Nyamebekyere and Ahansonyewodea had HQ, e AvDI and HI for THg of plantains for both adults and children below the recommended USEPA limit of 1, 3 × 10-4 mg/kg/day and 1, respectively. Odumase had HQ, e AvDI and HI for THg of plantains for both adults and children, higher than the guideline values. This meant that only Odumase may cause non-carcinogenic human health effects upon repeated exposure. The HQ, e AvDI and HI values of MeHg for all the study areas were far below guideline values, hence may not pose any non-carcinogenic human health risks to residents even upon repeated exposure. Retention and elimination kinetics of Hg also showed that only plantains from Odumase may pose significant non-carcinogenic human health risks to residents because the final amount of inorganic mercury exceeded the extrapolated USEPA guideline value of 0.393 µg/kg/year.

Mercury, cadmium, and lead in cigarettes from international markets: concentrations, distributions and absorption ability of filters.

Mercury (Hg), cadmium (Cd), and lead (Pb) concentrations in marketed cigarettes from South Korea, Vietnam, Japan, Indonesia, Taiwan, Thailand, the United Kingdom (UK), Belgium, Italy, Finland, and France were investigated. The cigarettes from Vietnam and Thailand had the highest trend of Hg. Meanwhile, Cd was found higher in cigarettes from Thailand, the UK, and Belgium. Pb concentrations in cigarettes from Belgium, the UK, and Korea were higher than others. The average of these heavy metals concentrated in cigarettes was in the order of Pb > Cd > Hg. Furthermore, the contents of these heavy metals in cigarette leaves were much higher than in filter and rolling paper. There was a significant positive correlation between Hg and Cd, but no correlation between Cd and Pb and between Hg and Pb. Significant positive correlations of nicotine with Hg and Cd but not Pb in the cigarette were observed. Activated carbon filters (Ce-C) absorb Cd and Pb from cigarette leaves and rolling paper indicated a higher trapping trend than cellulose acetate filter without activated carbon (Ce). The trapping ratios of Ce-C (Cd: 5.53%, Pb:5.41%) were higher than Ce (Cd:3.09%, Pb:5.49%). On the other hand, Hg had lower absorption by both types of filters (Ce:0.15%, Ce-C:0.02%). This revealed that Hg, Cd and Pb absorption ability by both filters was relatively lower to the total concentration of these metals in tobacco leaves and rolling paper. The concern was that the higher concentrations of metals such as Hg, Cd and Pb in cigarettes might exist in mainstream smoke.

Urinary neonicotinoids level among pregnant women in Japan.

Neonicotinoids (NEOs) are the most important globally available class of chemical insecticides since the introduction of synthetic pyrethroids. The adverse effects of NEOs for early development have been reported via in vivo and epidemiological studies. Therefore, prenatal NEOs exposure is highly concerning. This study aimed to determine the level of NEOs exposure during daily life among pregnant women in Japan, as well as the sources of exposure. Spot urine samples were collected during the first, second, and third trimesters from 109 pregnant women who delivered their infants at obstetrics and gynecology clinics in Kumamoto city, Japan, between 2014 and 2016. Additional data were obtained from medical records and self-administered questionnaires. thiamethoxam and clothianidin (CLO) were detected in most participants (83.4% and 80.9%, respectively), and at higher concentrations than those in other areas of Japan. Multiple logistic regression analysis showed a statistical significant association of pulses in CLO (1.01 [1.00-1.02]). In conclusion, pregnant women in Japan appear to be exposed to NEOs in their daily lives, and pulses intake may be a source of NEOs exposure. These findings may further the assessment of human NEOs exposure risk.

Simultaneous quantification of imidacloprid and its metabolites in tissues of mice upon chronic low-dose administration of imidacloprid.

This study aimed to (i) develop a sensitive method for simultaneous detection and quantification of imidacloprid (IMI) and seven of its metabolites in tissue specimens, and to (ii) determine the biodistribution of the IMI compounds in tissues of C57BL/6J male mice; after exposure to 0.6 mg/kg bw/day of IMI (10% of no observable adverse effect level of IMI) through a powdered diet for 24 weeks. We successfully developed a method which was accurate (recoveries were ≥ 70% for most compounds), sensitive (LODs ≤ 0.47 ng/mL and LOQs ≤ 1.43 ng/mL were recorded for all detected compounds, R2 ≥ 0.99) and precise (RSDs ≤ 20%) for routine analysis of IMI and seven of its metabolites in blood and various tissue matrices. After bio-distributional analysis, IMI and five of its metabolites were detected in mice. Brain, testis, lung, kidney, inguinal white adipose tissue and gonadal white adipose tissue mainly accumulated IMI, blood and mesenteric white adipose tissue mainly accumulated IMI-olefin; liver mainly accumulated desnitro-IMI; pancreas predominately accumulated 4-hydroxy-IMI. The desnitro-dehydro-IMI and the desnitro-IMI metabolites recorded tissue-blood concentration ratios ≥ 1.0 for testis, brain, lung and kidney. The cumulative levels of the six detected IMI compounds (Σ6 IMI compounds) were found in the decreasing order: blood > testis > brain > kidney > lung > iWAT > gWAT > mWAT > liver > pancreas. Altogether, this study provided essential data needed for effective mechanistic elucidation of compound-specific adverse outcomes associated with chronic exposures to IMI in mammalian species.

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

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.

In vivo and in silico analyses of estrogenic potential of equine estrogens in medaka (Oryzias latipes).

Equine estrogens (EEs) are widely used in hormone replacement therapy pharmaceuticals for postmenopausal women. Previous studies have shown that EEs occur in the aquatic environment; however, the potential estrogenicity and risk of EEs in aquatic organisms, including fish, have yet to be studied in detail. Therefore, we evaluated the estrogenic potential of major EEs, namely equilin (Eq), 17α-dihydroequilin (17α-Eq), 17ß-dihydroequilin (17ß-Eq), equilenin (Eqn), 17α-dihydroequilenin (17α-Eqn), and 17ß-dihydroequilenin (17ß-Eqn), on medaka (Oryzias latipes) using in vivo and in silico assays. Quantitative real-time RT-PCR analyses revealed that expression levels of choriogenin L (ChgL) and choriogenin H (ChgH) in medaka embryos responded to various types and concentrations of EEs in a concentration-dependent manner, whereas transcription levels of vitellogenin 1 were not significantly affected by any of the EEs in the concentration range tested. The order of the in vivo estrogenic potencies of EEs was as follows: 17ß-Eq > Eq > 17ß-Eqn > Eqn > 17α-Eqn > 17α-Eq. Additionally, the 50% effective concentrations (EC50) of 17ß-Eq was lower than that of 17ß-estradiol. We also investigated the interaction potential of EEs with medaka estrogen receptor (ER) subtypes in silico using a three-dimensional model of the ligand-binding domain (LBD) for each ER and docking simulations. All six EEs were found to interact with the LBDs of ERα, ERß1, and ERß2. The order of the in silico interaction potentials of EEs with each ER LBD was as follows: 17ß-Eq > 17α-Eq > Eq > 17ß-Eqn > 17α-Eqn > Eqn. Furthermore, we identified the key amino acids that interact with EEs in each ER LBD; our findings suggest that amino acids and/or their hydrogen bonding may be responsible for the ligand-specific interactions with each ER. This study is the first to comprehensively analyze the estrogenic potential of EEs in medaka both in vivo and in silico.

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

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.

[Analysis and Health Risk Assessment of Cadmium and Arsenic in Japanese, Vietnamese, and Indonesian Rice].

Herein, we quantified the concentrations of cadmium (Cd) and arsenic (As) in 63 milled rice (Oryza sativa L.) cultivated in Japan, Vietnam, and Indonesia. We estimated the daily intake of Cd and As by adults and children consuming this rice by inductively coupled plasma-mass spectrometer (ICP-MS). Cd and As were detected in all milled rice samples. No significant differences were observed in Cd concentrations between Japanese (50th percentile concentration: 0.036 mg/kg), Vietnamese (0.035 mg/kg), and Indonesian rice (0.022 mg/kg). However, As concentrations in Vietnamese rice (50th percentile concentration: 0.142 mg/kg) were significantly higher than those in Japanese (0.101 mg/kg, p<0.001) and Indonesian rice (0.038 mg/kg, p<0.0001). Target hazard quotients (THQs) were then calculated to evaluate the non-carcinogenic health risk from ingestion of individual heavy metals (Cd and As) by rice consumption. Results revealed that THQs of individual heavy metals for Japanese, Vietnamese, and Indonesian adults and children consuming this rice were all less than one, suggesting that no health risk is associated with the intake of a single heavy metal via rice consumption.

Choriogenin transcription in medaka embryos and larvae as an alternative model for screening estrogenic endocrine-disrupting chemicals.

This study assessed the transcription levels of estrogen-responsive genes, such as vitellogenins (Vtg1 and Vtg2), choriogenins (ChgL, ChgH, and ChgHm), cytochrome P450 aromatase (CYP19a1b), and ER subtypes (ERα, ERß1, and ERß2), in 7 days-post-fertilization (dpf) embryos and 9 and 12 dpf larvae of medaka (Oryzias latipes) exposed to estrogenic endocrine-disrupting chemicals (EDCs). The <5 h-post-fertilization embryos were exposed to EDCs such as 17ß-estradiol (E2), p-n-nonylphenol (NP), and bisphenol A (BPA). In E2 (0.10-222 nM)-treated 7 dpf embryos and 9 or 12 dpf larvae, ChgL, ChgH, and ChgHm expression was up-regulated in a concentration-dependent manner. By contrast, interestingly, Vtg1 and Vtg2 expression was not induced in E2-treated 7 dpf embryos but was significantly induced in 9 and 12 dpf larvae, suggesting a developmental-stage-specific regulatory mechanism underlying Vtg expression. The maximum concentrations of NP (0.09-1.5 µM) and BPA (1.8-30 µM) up-regulated Chg expression in 9 or 12 dpf larvae, and the relative estrogenic potencies (REPs) of E2, NP, and BPA were 1, 2.1 × 10-4, and 1.0 × 10-5, respectively. Chg messenger RNA (mRNA) in medaka embryos and larvae can be used as a sensitive biomarker for screening potential estrogenic EDCs. Our assay system using embryos and larvae can be used as an in vivo alternative model because independent feeding stages (e.g., embryonic and early larval stages) are suitable alternatives.

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

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.

Potential mechanisms underlying embryonic developmental toxicity caused by benzo[a]pyrene in Japanese medaka (Oryzias latipes).

Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are widely distributed in air, water, and sediments; however, limited data are available regarding their potential adverse effects on the early life stages of fish. In this study, we evaluated the embryonic teratogenicity and developmental toxicity of BaP in Japanese medaka (Oryzias latipes) using a nanosecond pulsed electric field (nsPEF) technique and predicted their molecular mechanisms via transcriptome analysis. The gas chromatography/mass spectrometry analyses revealed that the BaP was efficiently incorporated into the embryos by nsPEF treatment. The embryos incorporating BaP presented typical teratogenic and developmental effects, such as cardiovascular abnormalities, developmental abnormalities, and curvature of backbone. DNA microarray analysis revealed several unique upregulated genes, such as those involved in cardiovascular diseases, various cellular processes, and neural development. Furthermore, the gene set enrichment and network analyses found several genes and hub proteins involved in the developmental effects of BaP on the embryos. These findings suggest a potential mechanism of teratogenicity and developmental toxicity caused by exposure to BaP. The nsPEF and transcriptome analyses in combination can be effective for evaluating the potential effects of chemical substances on medaka embryos.