Biological Monitoring of Human Exposure to Neonicotinoids Using Urine Samples, and Neonicotinoid Excretion Kinetics.

BACKGROUND: Neonicotinoids, which are novel pesticides, have entered into usage around the world because they are selectively toxic to arthropods and relatively non-toxic to vertebrates. It has been suggested that several neonicotinoids cause neurodevelopmental toxicity in mammals. The aim was to establish the relationship between oral intake and urinary excretion of neonicotinoids by humans to facilitate biological monitoring, and to estimate dietary neonicotinoid intakes by Japanese adults. METHODOLOGY/PRINCIPAL FINDINGS: Deuterium-labeled neonicotinoid (acetamiprid, clothianidin, dinotefuran, and imidacloprid) microdoses were orally ingested by nine healthy adults, and 24 h pooled urine samples were collected for 4 consecutive days after dosing. The excretion kinetics were modeled using one- and two-compartment models, then validated in a non-deuterium-labeled neonicotinoid microdose study involving 12 healthy adults. Increased urinary concentrations of labeled neonicotinoids were observed after dosing. Clothianidin was recovered unchanged within 3 days, and most dinotefuran was recovered unchanged within 1 day. Around 10% of the imidacloprid dose was excreted unchanged. Most of the acetamiprid was metabolized to desmethyl-acetamiprid. Spot urine samples from 373 Japanese adults were analyzed for neonicotinoids, and daily intakes were estimated. The estimated average daily intake of these neonicotinoids was 0.53-3.66 µg/day. The highest intake of any of the neonicotinoids in the study population was 64.5 µg/day for dinotefuran, and this was <1% of the acceptable daily intake.

Associations between levels of hydroxylated PCBs and PCBs in serum of pregnant women and blood thyroid hormone levels and body size of neonates.

The purpose of this study was to investigate possible associations between concentrations of hydroxylated PCBs (OH-PCBs) and PCBs in the serum of women in the first trimester of pregnancy and thyroid hormone levels and body size of newborn infants in 79 mother-neonate pairs. We measured 16 OH-PCB isomers and 29 PCB isomers in the serum of Japanese women sampled at 11.1±1.9 weeks of gestation. The concentrations of free thyroxine (fT4) and thyroid stimulating hormone (TSH) were measured in whole blood spots on filter papers sampled from the neonates. Dietary and lifestyle information of the mothers were obtained by self-administered questionnaires. Geometric mean (GM) concentrations of the sum of 16 OH-PCB isomers and of 29 PCB isomers were 1.2×10(2)pg/g wet wt. and 69ng/g lipid wt., respectively, in maternal serum. The GM concentrations of neonatal fT4 and TSH were 2.21ng/dL and 1.37µIU/mL, respectively. Multiple regression analysis was performed using measures of neonatal thyroid hormones as dependent variable and serum levels of OH-PCBs/PCBs and other potential covariates (age, pre-pregnancy weight, smoking status, etc.) as independent variables. The results demonstrated a significant positive association between the concentrations of some OH-PCB isomers and that of neonatal TSH. There were no significant associations between levels of PCBs and neonatal fT4, or between OH-PCBs/PCBs and body size of neonates. We conclude that exposure to/body burden of OH-PCBs, but not PCBs, at environmental levels during the first trimester of pregnancy can affect neonatal thyroid hormone status.

Serum levels of hydroxylated PCBs, PCBs and thyroid hormone measures of Japanese pregnant women.

OBJECTIVES: The purpose of this study was to investigate the associations between serum concentrations of hydroxylated PCBs (OH-PCBs) and PCBs and measures of thyroid hormone status of Japanese pregnant women. METHODS: The concentrations of free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroxine binding globulin (TBG) as well as 16 OH-PCB isomers and 29 PCB isomers were analyzed in the serum of 129 women sampled in the first trimester of gestation. Dietary and lifestyle information of the subjects was obtained by self-administered questionnaire. Multiple regression analysis was performed using measures of thyroid hormones as the dependent variable and serum levels of OH-PCBs/PCBs, urinary iodine concentration, and other potential covariates (age, BMI, smoking, etc.) as independent variables. RESULTS: Geometric mean (GM) concentration of the sum of 16 isomers of OH-PCBs was 120 pg/g wet wt. and that of 29 isomers of PCBs was 68 ng/g lipid wt., respectively, in the serum of the subjects. Iodine nutrition was considered adequate to high from urinary iodine level (GM, 370 µg/g creatinine). The mean concentration of TSH, fT4 and TBG was 1.34 ± 1.37 µIU/mL, 1.22 ± 0.16 ng/dL and 33.0 ± 6.4 µg/mL, respectively, with a small number of subjects who were outside the reference range. Multiple regression analysis revealed that serum concentrations of OH-PCBs/PCBs were not significantly associated with any of the measures of thyroid hormone status. CONCLUSIONS: Exposure/body burden of OH-PCBs and PCBs at environmental levels does not have a measurable effect on thyroid hormones.

Levels of perfluorooctane sulfonate and perfluorooctanoic acid in female serum samples from Japan in 2008, Korea in 1994-2008 and Vietnam in 2007-2008.

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have recently received attention owing to their widespread contamination in the environment. One of major manufacturers, 3M Company voluntarily phased out PFOS production in 2002. We measured the PFOS and PFOA concentrations in serum samples from Japan (Sendai, Takayama and Osaka), Korea (Busan and Seoul) and Vietnam (Hanoi) to evaluate the possible effects of the phase-out on the serum levels. There were spatial differences in both the serum PFOS and PFOA concentrations. The serum PFOS concentrations (ngmL(-1)) evaluated as the geometric mean (geometric standard deviation) in 2007-2008 ranged from 4.86 (1.45) in Sendai, Japan, to 9.36 (1.42) in Busan, Korea. The serum PFOA concentrations ranged from 0.575 (2.32) in Hanoi, Vietnam, to 14.2 (1.73) in Osaka, Japan. Historically archived samples collected from Korea in 1994-2008 revealed that the serum PFOA concentrations increased by 1.24-fold in Busan from 2000 to 2008 and 1.41-fold in Seoul from 1994 to 2007. On the other hand, the serum PFOS concentrations did not change from 1994 to 2007/2008. The serum PFOS levels in Japan in 2008 were significantly decreased compared with previously reported values (22.3-66.7% of the values in 2003/2004). However, the serum PFOA levels showed a clear decline from 2003 to 2008 in a high-exposed area, Osaka, but not in low-exposed areas in Japan. The trends toward decreases were not uniformly observed in Asian countries, unlike the case for the United States, suggesting that local factors associated with the production and introduction histories in each country overwhelm the effects of the phase-out.

[Host risk factors for acquirement of antimicromial resistant gene in Haemophilus influenzae].

The present study investigated the host risk factors for carriage of Haemophilus influenzae (H. influenzae) with resistant gene (s) against antibiotics. From September 2001 to January 2004, 174 strains of H. influenzae were isolated from the nasopharynx of children with respiratory tract infections. We classified these strains on the basis of the MIC to Ampicillin and the presence of resistant gene (s) for antibiotics resistance (gene for beta-lactams and altered pbp gene (s)). The patients' background such as previous antibiotic usage, age, daycare attendance, siblings and underlying diseases was investigated. The risk factor for carriage of strains with altered pbp gene (s) was the usage of beta-lactams within the last 3 months. Controlled usage of oral beta-lactams might be an important issue for preventing the spread of resistant H. influenzae strains such as beta-lactamase non-producing ampicillin resistant H. influenzae. We have to reconsider a therapeutic approach for the treatment of young children with respiratory tract infection.

Analysis of UNEP priority POPs using HRGC-HRMS and their contamination profiles in livers and eggs of great cormorants (Phalacrocorax carbo) from Japan.

The present investigation demonstrates establishment of United Nations Environment Programme (UNEP) priority Persistent Organic Pollutants (POPs) using high-resolution gas chromatography-high-resolution mass spectrometry. Particularly, POPs analytical methods were established using native and (13)C-labeled internal standards of HCHs, HCB, cyclodienes, chlordanes, DDTs, mirex, dioxin-like PCBs, PCDDs, and PCDFs by isotope dilution technique. The relative response factor for 6-point calibration curve native standards (18 replicate analysis) were in the ranges of 0.93-1.43 with relative standard deviation ranges from 1.68 to 4.96%. Instrument detection limit and instrument quantification limit was established for various POPs at femtograms. Concentrations of UNEP-POPs were measured in liver (n = 10) and egg (n = 10) of great cormorants and their major diet, gizzard shad (n = 2), collected in and around Tokyo, Japan. DDTs (ranges in liver and egg, respectively) were predominant accumulants (9800-310,000 and 9600-73,000) followed by dioxin-like PCBs (4500-69,000 and 7900-150,000), chlordanes (2600-16,000 and 700-4,800), cyclodienes (650-4600 and <1-1000), HCB (680-2800 and 180-590), HCHs (230-1800 and 120-490), PCDD/DFs (3.2-27 and 1.7-5.7) on nanogram per gram lipid basis. Concentrations (ranges) of POPs in gizzard shad were in the following order: DDTs (3900-16,000), chlordanes (3400-14,000), cyclodienes (340-1300), HCB (110-480), and HCHs (140-360) on nanogram per gram lipid basis.

Brominated organic contaminants in the liver and egg of the common cormorants (Phalacrocorax carbo) from Japan.

The contamination profiles of brominated flame retardants (BFRs) such as polybrominated diphenyl ethers (PBDEs), biphenyls (PBBs), dibenzo-p-dioxins (PBDDs), and dibenzofurans (PBDFs) were determined in the liver and egg of common cormorants from Japan. PBDEs and PBBs were detected in all the samples; especially the former were detected at elevated levels. PBDDs/PBDFs were also detected in cormorants, albeit the concentrations were lower than those of the PBBs. The total concentration of PBDEs ranged from 330 to 2600 in the liver and from 600 to 3300 in the egg on a nanogram per gram of lipid basis. The concentration of PBBs was in the range from 3.0 to 33 (in the liver) and from 3.4 to 82 (in the egg) on a nanogram per gram of lipid basis. The 2,2',4,4',5,5'-hexabromobiphenyl (BB-153) was the most predominant PBB congener in either organ, which corresponds to a major constituent of the BFR FireMaster BP-6. Concentrations of PBDDs/ PBDFs in the liver (range from 21 to 470) were slightly higher than in the egg (range from 31 to 160) on a picogram per gram of lipid basis. The results of this study imply that common cormorants accumulate a high level of PBDEs and PBBs. Comparing the concentrations of brominated organic compounds with those of chlorinated analogues, good relevance between PBBs and coplanar PCBs (r2 = 0.746 [liver] and 0.715 [egg]) was elucidated. To our knowledge, the present study demonstrates the first report of PBDEs, PBBs, and PBDDs/PBDFs in the common cormorant from Japan.

Remediation of soil contaminated with dioxins by subcritical water extraction.

The effectiveness of subcritical water extraction (SCWE) was examined for removing dioxins from contaminated soil. Most dioxins in the soil sample were reduced at 300 degrees C or more, but decreased dioxin concentrations were also observed at 150 degrees C. After 4 h of extraction, 99.4%, 94.5% and 60% of PCDDs were removed from samples at 350, 300 and 150 degrees C, respectively. It was also determined that degradation of dioxins had occurred, since the sum of dioxins in the soil plus water extracts after the experiments had considerably decreased. This study revealed that pressurizing is not essential for the removal of dioxins. Reduction was complete within 30 min at 350 degrees C; however, it took a much longer time at lower temperatures. The results of addition experiments in which OCDDs were added to different types of soil samples have shown that dechlorination is one of the major reaction pathways. After addition of OCDD to soil samples, experiments were carried out to examine in detail the degradation pathways of PCDDs. The removal rates and congener profiles varied among soil types. Although it was previously assumed that removal rates and congener profiles depended on the chemical components in soil, nonparametric statistical analysis revealed no significant relationship between the rate of reduction and elements present in the soil. It was confirmed from isomer patterns that dechlorination of the 2,3,7,8-positions in PCDDs takes place somewhat faster than for the 1,4,6,9-positions.