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Nodding syndrome (NS) is a neurologic disorder of unknown etiology characterized by vertical head nodding that has affected children aged 5-18 years in East Africa. Previous studies have examined relationships with biological agents (e.g., nematodes, measles, and fungi), but there is limited data on the possible contributions of neurotoxic environmental chemicals frequently used as pesticides/insecticides to the development and progression of this disorder. We examined the levels of persistent organochlorine pesticides (OCPs) in children (5-18 years old) from Kitgum District, Northern Uganda. These children previously lived in internally displaced people's (IDP) camps, where they were exposed to various health risks, including contaminated food and water. Exposure to OCPs through contaminated food and water is postulated here as a potential contributor to NS etiology. We analyzed serum (n = 75) and urine (n = 150) samples from children diagnosed with NS, and from seizure-free household controls (HC), and community controls (CC). Samples were extracted using solid-phase extraction (SPE) and extracts were analyzed for OCPs using gas chromatography with a triple quadrupole mass spectrometry (GC-MS/MS). Mean levels of total (∑) ∑OCPs in serum samples from NS, HC and CC subjects were 23.3 ± 2.82, 21.1 ± 3.40 and 20.9 ± 4.24 ng/mL, respectively, while in urine samples were 1.86 ± 1.03, 2.83 ± 1.42, and 2.14 ± 0.94 ng/mL, respectively. Correlation and linear regression analysis indicated that potential markers for ∑hexachlorocyclohexanes (HCHs), ∑chlordane compounds (CHLs), ∑endosulfan and ∑dichlorodiphenyltrichloroethanes (DDTs) were γ-HCH, heptachlor-exo-epoxide, endosulfan-α and p,p'-DDD in NS cases while in controls were α -HCH, heptachlor, endosulfan-α and p,p'-DDE, respectively. Since, in some instances, higher OCP levels were found in controls vs. NS cases, we conclude that exposure to organochlorine pesticides is unlikely to be associated with the etiology of NS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Some disinfection by-products (DBPs) are reproductive and developmental toxicants in laboratory animals. However, studies of trimester-specific DBP exposure on adverse birth outcomes in humans are inconsistent., Objective: We examined whether trimester-specific blood and urinary biomarkers of DBP were associated with small for gestational age (SGA), low birth weight (LBW), and preterm birth., Methods: A total of 4,086 blood and 3,951 urine samples were collected across pregnancy trimesters among 1,660 mothers from Xiaogan City, China. Blood samples were quantified for biomarkers of trihalomethanes (THMs): chloroform (TCM), bromodichloromethane, dibromochloromethane, and bromoform. Urine samples were quantified for biomarkers of haloacetic acids (HAA): dichloroacetic acid and trichloroacetic acid. Birth outcomes were abstracted at delivery from medical records. We used Poisson regression models with log link functions to estimate risk ratios (RRs) and 95% confidence intervals (CIs) for SGA, LBW, and preterm birth across tertiles (or categories) of DBP biomarker concentrations measured across pregnancy trimesters. We also examined the relative exposure differences across gestation comparing adverse outcomes with normal births using mixed-effects models., Results: Blood TCM concentrations in the second trimester were associated with an elevated risk of SGA comparing middle vs. lowest (RR, 2.34; 95% CI: 1.02, 5.35) and highest vs. lowest (RR, 2.47; 95% CI: 1.09, 5.58) exposure groups. Third-trimester blood TCM concentrations were also associated with an increased risk of SGA comparing the second tertile with the first (RR, 2.61; 95% CI: 1.15, 5.92). We found that maternal blood TCM concentrations were significantly higher for SGA compared with non-SGA births across the period from 23 to 34 wk gestation. Other blood and urinary DBP biomarkers examined were unrelated to SGA, LBW, or preterm birth., Conclusion: Blood TCM concentrations in mid to late pregnancy were associated with an increased risk of SGA, whereas other biomarkers of DBPs examined across pregnancy were not associated with birth outcomes. https://doi.org/10.1289/EHP7195.

Background: Pregnant women are exposed to a mixture of endocrine disrupting chemicals (EDCs). Gestational EDC exposures may be associated with changes in fetal growth that elevates the risk for poor health later in life, but few studies have examined the health effects of simultaneous exposure to multiple chemicals. This study aimed to examine the association of gestational exposure to five chemical classes of potential EDCs: phthalates and bisphenol A, perfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs) with infant birth weight., Methods: Using data from the Health Outcomes and Measures of Environment (HOME) Study, we examined 272 pregnant women enrolled between 2003-2006. EDC concentrations were quantified in blood and urine samples collected at 16 and 26 weeks gestation. We used Bayesian Hierarchical Linear Models (BHLM) to examine the associations between newborn birth weight and 53 EDCs, 2 organochlorine pesticides (OPPs) and 2 heavy metals., Results: For a 10-fold increase in chemical concentration, the mean differences in birth weights (95% credible intervals (CI)) were 1 g (-20, 23) for phthalates, -11 g (-52, 34) for PFAS, 0.2 g (-9, 10) for PCBs, -4 g (-30, 22) for PBDEs, and 7 g (-25, 40) for OCPs., Conclusion: Gestational exposure to phthalates, PFAS, PCBs, PBDEs, OCPs or OPPs had null or small associations with birth weight. Gestational OPP, Pb, and PFAS exposures were most strongly associated with lower birth weight.

In this work, the potential of layered double hydroxide/graphene (LDH-G) hybrid as a sorbent for extraction and preconcentration of fifteen organochlorine pesticides (OCPs) in urine samples was evaluated. The LDH-G hybrid was synthesized by co-precipitation method and it was then characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy and X-ray diffraction. The sorbent was then employed in membrane-protected stir-bar supported micro-solid-phase extraction (SB-μ-SPE) of OCPs in urine samples. This extraction approach is highly suitable for the samples representing matrix complexity such as urine because the sorbent is effectively protected inside the membrane. The extracted samples were analyzed by gas chromatography mass spectrometry. The factors that affect the performance of SB-μ-SPE were suitably optimized. This method demonstrated good linearity with coefficients of determination up to 0.9996. The limits of detection ranged between 0.22 and 1.38ngmL -1 . The RSD values for intra and inter-day precision were also in a satisfactory range (2.7-9.5%)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Several studies have suggested that exposure to DDT may be related to changes in thyroid hormone levels in animals and humans, even though results across studies are inconsistent. The aim of this study was to assess the association between exposure to p,p'-DDE (a stable metabolite of DDT) and serum levels of thyroid hormones in floriculture workers. A longitudinal study was conducted on 136 male subjects from the States of Mexico and Morelos, Mexico, who were occupationally exposed to pesticides, during agricultural periods of high (rainy season) and low (dry season) levels of pesticide application. Using a structured questionnaire, a survey was carried out on socio-demographic characteristics, anthropometry, clinical history, alcohol and tobacco consumption, residential chemical exposure, and occupational history. Blood and urine samples were collected to determine serum levels of TSH, total T3, total T4, and p,p'-DDE, and metabolites of organophosphate pesticides (OP), respectively. The analysis of the associations between p,p'-DDE levels and thyroid hormone profile adjusting by potential confounding variables including urinary OP metabolites was carried out using multivariate generalized estimating equation (GEE) models. Our results showed that the geometric means of p,p'-DDE levels were 6.17 ng/ml and 4.71 ng/ml in the rainy and dry seasons, respectively. We observed positive associations between the serum levels of p,p'-DDE and those of total T3 (β=0.01, 95% CI: -0.009, 0.03), and total T4 (β=0.08, 95% CI:0.03, 0.14) and negative but no significant changes in TSH in male floricultural workers, supporting the hypothesis that acts as thyroid disruptor in humans., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Short-chain chlorinated paraffins (SCCPs) have attracted considerable attention for their characteristic of persistent organic pollutants. However, very limited information is available for their toxicokinetic characteristics, limiting the evaluation of their health risks. In this study, we performed a toxicokinetics study to explore the absorption and excretion processes of SCCPs (a mixture of C10-, C11-, C12- and C13-CPs) after a single oral administration to the Sprague-Dawley rats. The toxicokinetic results showed that peak blood concentration of total SCCPs was attained at 2.8 day with Cmax value of 2.3 mg L(-1). The half-lives of total SCCPs in blood for the absorption t1/2 (ka), distribution t1/2 (α) and elimination phases t1/2 (β) were calculated to be 1.0, 1.7 and 6.6 days, respectively. During the 28 days post-dosing, about 27.9% and 3.5% of orally administrated SCCPs were excreted through feces and urine without metabolism, respectively. Congener group abundance profiles indicate a relative increase of Cl5-SCCPs in blood and urine in the elimination stage, and a higher accumulation of Cl8-10-SCCPs in feces. The distribution discrepancies of SCCPs congener groups in blood and excreta were more dependent on chlorine contents than on carbon chain lengths., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Organochlorine pesticides (OCPs) have caused increasing global concern due to their high toxicity, persistence, bioaccumulation, and significant adverse effects on human health. This study was to explore the interaction effects between OCPs and isoflavones. Six kinds of OCPs and 2 kinds of isoflavones-genistein and daidzein were included to study their effect on MCF-7 cells in vitro. Eighty-one female Sprague-Dawley rats were randomized to 9 groups according to factorial design to study the interaction effect between isoflavones and γ-HCH. Compared to organochlorine pesticides alone group, proliferation rate of MCF-7 cells was lower in 100 μmol/L genistein + organochlorine pesticides and 100 μmol/L daidzein + organochlorine pesticides group (p < 0.05). In vivo study showed that there are interaction effects on kidney weight and liver weight when treated with isoflavones and γ-HCH. The changes in uterine morphology and positive expression of ERα showed inhibition effects between isoflavones and γ-HCH. In conclusion, the data suggests that there are interactions between isoflavones and OCPs in vitro and in vivo.

In the Czech Republic, the Human Biomonitoring Project (CZ-HBM) was launched in 1994 as an integral part of the nationwide Environmental Health Monitoring System (EHMS). Until now, the HBM covers two time periods: the first covered 1994-2003 and the second, 2005-2009. Altogether three population groups were included in the HBM: adults (blood donors aged 18-58 years), children aged 8-10 years, and breastfeeding primiparas. Sampling is organized on a yearly basis. Altogether three groups of biomarkers were analyzed: (a) selected heavy metals (Pb, Cd, Hg) and essential elements (Cu, Se, Zn) in blood and urine of adults and children, (b) indicator PCBs, DDT, DDE, HCB and HCHs in human milk and blood serum of adults and (c) cytogenetic changes in peripheral lymphocytes in blood of adults and children. This paper is focused on the general design of the CZ-HBM, the trends over time, and reference values. A significant downward time trend was observed for the blood lead levels in adults and children. Increased urinary cadmium levels were observed in Czech children compared to German children. The blood and urinary mercury levels were higher in women than in men. The levels of indicator PCB congeners in the Czech human milk samples were still higher than in most other European countries, because of existing hot spots. The levels of organochlorine pesticides showed a substantial continuous downward trend., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

Human biomonitoring is an important indicator and measure of exposure to environmental chemicals and provides information to support health protection policies and programs. Cycle 1 (2007-2009) of the Canadian Health Measures Survey (CHMS) collected and analyzed biological samples from over 5600 males and females aged 6-79 years, which established national representative blood and urine concentrations for a number of environmental chemicals including metals, organophosphate insecticide metabolites, polychlorinated biphenyls (PCBs), organochlorines (OCs), perfluorinated compounds (PFCs), bisphenol A (BPA), and cotinine. The results of CHMS Cycle 1 indicate that while some organophosphate insecticide metabolites were below limits of detection for most participants, metals, PCBs, OCs, PFCs and BPA were detected in almost all blood or urine samples. Significant differences (p<0.05) in blood concentrations between males and females were also determined for several metals (e.g., lead for males and females was 15.1 and 11.8 μg/L, respectively), PFCs (e.g., PFOS for males and females was 11.13 and 7.07 μg/L, respectively), and OCs (e.g., p,p'-DDE for males and females was 134.43 and 172.07 μg/kg lipid, respectively) and in urine concentrations for BPA (1.29 and 1.04 μg/L for males and females, respectively). Future cycles of the CHMS will permit temporal trend analysis for a number of these chemicals., (Crown Copyright © 2011. Published by Elsevier GmbH. All rights reserved.)

The relationship between the environment and human fecundity and fertility remains virtually unstudied from a couple-based perspective in which longitudinal exposure data and biospecimens are captured across sensitive windows. In response, we completed the LIFE Study with methodology that intended to empirically evaluate a priori purported methodological challenges: implementation of population-based sampling frameworks suitable for recruiting couples planning pregnancy; obtaining environmental data across sensitive windows of reproduction and development; home-based biospecimen collection; and development of a data management system for hierarchical exposome data. We used two sampling frameworks (i.e., fish/wildlife licence registry and a direct marketing database) for 16 targeted counties with presumed environmental exposures to persistent organochlorine chemicals to recruit 501 couples planning pregnancies for prospective longitudinal follow-up while trying to conceive and throughout pregnancy. Enrolment rates varied from <1% of the targeted population (n = 424,423) to 42% of eligible couples who were successfully screened; 84% of the targeted population could not be reached, while 36% refused screening. Among enrolled couples, ∼ 85% completed daily journals while trying; 82% of pregnant women completed daily early pregnancy journals, and 80% completed monthly pregnancy journals. All couples provided baseline blood/urine samples; 94% of men provided one or more semen samples and 98% of women provided one or more saliva samples. Women successfully used urinary fertility monitors for identifying ovulation and home pregnancy test kits. Couples can be recruited for preconception cohorts and will comply with intensive data collection across sensitive windows. However, appropriately sized sampling frameworks are critical, given the small percentage of couples contacted found eligible and reportedly planning pregnancy at any point in time., (© Published 2011. This article is a US Government work and is in the public domain in the USA.)

A new solid-phase microextraction fiber based on alumina/titania sol-gel-coated on copper wire for headspace sampling of chlorinated organic solvents (chloroform, carbon tetrachloride, trichloroethene, and tetrachloroethene) from urine samples is introduced. The influences of fiber coating composition and microextraction conditions (extraction temperature, extraction time, and ionic strength of the sample matrix) on the fiber performance were investigated. Also, the influence of temperature and time on desorption of analytes from fiber was studied. The proposed fiber has high capacity and demonstrates fast sampling of chlorinated organic solvents from urine samples with high sensitivity. The relative standard deviation (RSD, n=5) for all analytes was below 6.5%., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Pesticides have been shown to disrupt neurodevelopment in laboratory animals and in human populations. To date, there have been no studies on exposure to pesticides in pregnant women in Israel, despite reports of widespread exposure in other populations of pregnant women and the importance of evaluating exposure in this susceptible sub-population., Methods: We measured urinary concentrations of organophosphorus (OP) insecticide metabolites and plasma concentrations of OP and other pesticides in 20 pregnant women, recruited in Jerusalem, Israel in 2006, and collected questionnaire data on demographic factors and consumer habits from these women. We compared geometric mean concentrations in subgroups using the Mann-Whitney U-test for independent samples. We compared creatinine-adjusted OP pesticide metabolite concentrations, as well as plasma pesticide concentrations, with other populations of pregnant women., Results: Creatinine-adjusted total dimethyl (DM) metabolite concentrations were between 4 and 6 times higher in this population compared to other populations of pregnant women in the United States while total diethyl (DE) metabolite concentrations were lower. Dimethylphosphate (DMP) was detected in 74% of the urine samples whereas dimethylthiophosphate (DMTP) was detected in 90% of the urine samples. The carbamate bendiocarb was detected in 89% of the plasma samples, while the OP insecticide chlorpyrifos was detected in 42% of the samples. Mean plasma concentrations of bendiocarb and chlorpyrifos in our sample were 4.4 and 3.9 times higher, respectively, than that of an urban minority cohort from New York City. Twelve women (63%) reported using some form of household pest control during their pregnancy and five (26%) reported using household pest control during the past month. Women with a graduate degree had significantly higher geometric mean concentrations of total urinary DM metabolite concentrations compared to other women (P=0.006). Finally, one woman in the study had exceptionally high concentrations of DMP, DMTP, DMDTP compared to the other women in the study, despite reporting no current occupational exposure to OP pesticides and no other significant exposure sources., Conclusions: Pregnant women in the Jerusalem area are exposed to OP pesticides and to the carbamate pesticide bendiocarb. It is unclear why total DM metabolites concentrations were much higher in this population compared to other populations of pregnant women in the United States and Netherlands. Finally, the finding of very high DM metabolite concentrations in one woman who reported being moved from her regular laboratory work to administrative work upon becoming pregnant, raises questions about the adequacy of measures to protect pregnant women from pesticide exposures during pregnancy., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Chlorinated hydrocarbon solvents are often used for dry-cleaning clothes in the laundry industry. The object of this study was to monitor the occupational exposure of dry-clean employees coming into contact with VOXs. Twenty five workers collected their urine samples before the work shift, after 4 h of work and after the work shift. The analyses of urine samples and solvents used in dry-cleaning were performed using TLHS-DAI-GC-ECD. Chloroform was detected in all urine samples, and dichloromethane and tetrachloroethene in nearly all urine samples collected before and after the work shift. The concentrations of the compounds determined in urine samples were higher at the end of the workday in directly exposed individuals. Concentrations of the compounds determined in urine samples depended mainly on the type of activities carried out at the dry-cleaning establishments.

Environmental policies in Mexico have contributed to the reduction in the production or use of some persistent organic pollutants (POPs) and metals. However, monitoring of POPs concentrations in humans living in hot spots is lacking. Therefore, the objective of this study was to conduct a screening for POPs and metals first in Mexican children living in high-risk areas. During the year 2004, we analyzed a total of 229 healthy children (aged 6-12 years old) who resided in communities located in nine Mexican states. Organochlorine insecticides, PCBs and metals were quantified in plasma and urine samples. We detected p'p-DDE in all the children; moreover, p'p-DDT, lindane and hexachlorobenzene were detected respectively in 14%, 85% and 10% of the children studied. Measurable levels of PCBs were recorded in only one community, where six of 14 PCB congeners assayed were detected (numbers 52, 118, 138, 153, 170 and 180). All the children had detectable levels of lead in their blood (mean level, 4.6 microg dL(-1)); furthermore, 57% of the children studied had levels higher than 5.0 microg/dL. The mean level of urinary arsenic (UAs) for all the children was 22.35 microg g(-1) creatinine and 15% of those children had concentrations of UAs above 50 microg g(-1) creatinine. For cadmium, the mean urinary level was 0.78 microg g(-1) creatinine, and only one percent of the children had values above 2.0 microg g(-1) creatinine. The results cannot be generalized since the communities selected are not representative of the Mexican population; however, they indicate that Mexican children are exposed to chemicals and some at risk levels.

We analyzed data from a prospective study of menstrual cycle function and early pregnancy loss to explore further the effects of trihalomethanes (THM) on reproductive end points. Premenopausal women ((italic)n(/italic) = 403) collected urine samples daily during an average of 5.6 cycles for measurement of steroid metabolites that were used to define menstrual parameters such as cycle and phase length. Women were asked about consumption of various types of water as well as other habits and demographics. A THM level was estimated for each cycle based on residence and quarterly measurements made by water utilities during a 90-day period beginning 60 days before the cycle start date. We found a monotonic decrease in mean cycle length with increasing total THM (TTHM) level; at > 60 microg/L, the adjusted decrement was 1.1 days [95% confidence interval (CI), -1.8 to -0.40], compared with less than or equal to 40 microg/L. This finding was also reflected as a reduced follicular phase length (difference -0.94 day; 95% CI, -1.6 to -0.24). A decrement in cycle and follicular phase length of 0.18 days (95% CI, -0.29 to -0.07) per 10 microg/L unit increase in TTHM concentration was found. There was little association with luteal phase length, menses length, or cycle variability. Examining the individual THMs by quartile, we found the greatest association with chlorodibromomethane or the sum of the brominated compounds. Incorporating tap water consumption showed a similar pattern of reduced cycle length with increasing TTHM exposure. These findings suggest that THM exposure may affect ovarian function and should be confirmed in other studies.

Objective: The present study was initiated to examine a quantitative relationship between tetrachloroethene (TETRA) in blood and urine with TETRA in air, and to compare TETRA in blood or urine with trichloroacetic acid (TCA) in urine as exposure markers., Methods: In total, 44 workers (exposed to TETRA during automated, continuous cloth-degreasing operations), and ten non-exposed subjects volunteered to participate in the study. The exposure to vapor was monitored by diffusive sampling. The amounts of TETRA and TCA in end-of-shift blood and urine samples were measured by either head-space gas chromatography (HS-GC) or automated methylation followed by HS-GC. The correlation was examined by regression analysis., Results: The maximum time-weighted average (TWA) concentration for TETRA-exposure was 46 ppm. Regression analysis for correlation of TETRA in blood, TETRA in urine and TCA in urine, with TETRA in air, showed that the coefficient was largest for the correlation between TETRA in air and TETRA in blood. The TETRA in blood, in urine and in air correlated mutually, whereas TCA in urine correlated more closely with TETRA in blood than with TETRA in urine. The TCA values determined by colorimetry and by the GC method were very similar. The biological marker levels at a hypothetical exposure of 25 ppm TETRA were substantially higher in the present study than were the levels reported in the literature. Possible reasons are discussed., Conclusions: Blood TETRA is the best marker of occupational exposure to TETRA, being superior to the traditional marker, urinary TCA.

Chloro, bromo, and mixed bromochloro haloacetates (HAs) are by-products of drinking water disinfection and are hepatocarcinogenic in rodents. We compared the toxicokinetics of a series of di-HAs, dichloro (DCA), bromochloro (BCA), dibromo (DBA) and tri-HAs: trichloro (TCA), bromodichloro (BDCA), chlorodibromo (CDBA), and tribromo (TBA) after iv and oral dosing (500 micrometer/kg) in male F344 rats. The blood concentrations of the HAs after iv injection declined in a bi-exponential manner with a short but pronounced distributive phase. The structural features that had the greatest influence on the disposition of HAs were substitution of a halogen for a hydrogen and the degree of bromine substitution. All di-HAs had blood elimination half-lives of less than 4 h (DCA > DBA, BCA) compared to the tri-HAs, which had half-lives that varied from 0.6 to 8.0 h (TCA > BDCA > CDBA > TBA). The urinary excretion of all di-HAs was low and accounted for less than 3% of the dose in contrast to the tri-HAs, where urinary excretion accounted for at least 30% of the dose. Toxicokinetic analysis indicated the steady-state apparent volume of distribution varied between 301 and 881 ml/kg among the HAs, but the variation was not statistically significant (P > 0.17). The blood concentration-time profiles for all di-HAs after oral dosing was complex and exhibited multiple peaks. This did not appear to be due to enterohepatic recirculation, as bile duct cannulated animals also displayed similar profiles. In contrast, the profiles for the tri-HAs did not exhibit multiple peaking after oral dosing and could be described using a one-compartment pharmacokinetic model. The oral bioavailability of the HAs varied between 30% (DBA) and 116% (TCA), depending on the number of halogen substituents and the degree of bromine substitution. In general, three patterns of elimination for the HAs can be broadly described: low metabolism with moderate renal clearance (TCA), high metabolism and renal clearance (BDCA, CDBA, TBA), and high metabolism, low renal clearance (DCA, BCA, DBA)., (Copyright 1999 Academic Press.)

Due to a technical rule issued by the Ministry of Labour, in Germany toxicological analysis in blood and urine for biological monitoring must be carried out under quality assurance. Since 1982 the German Society for Occupational and Environmental Medicine has offered 13 intercomparison programmes. The 1994 round robin considered 7 metals and 5 solvents in blood, 12 organochlorine compounds in plasma and 14 inorganic, as well as 11 organic, compounds in urine in the occupational and in the environmental exposure range. Reference values and tolerance ranges are established by reference laboratories. Successful participation was certified if the results for 2 concentration adjustments were in tolerance range (assigned value +/- 3 S.D.). In 1994 in 119 laboratories the percentage rate of accurate results was 59%. This mean success rate is in agreement with the last 12 round robins.

An assessment has been made of biochemical alterations in renal and hepatic functions of 73 male operators employed for an average of 8.2 years (range 0.5-23 years) in a chemical plant producing chlorinated hydrocarbons. Exposure to allyl chloride (AC), 1,3-dichloropropene (DCP), epichlorohydrin (ECH), and hexachlorocyclopentadiene (HEX) has regularly been determined by personal air monitoring since 1980. Although exposures to DCP and ECH were well below currently accepted maximum allowable concentrations (MACs), relatively high exposures to AC and HEX, occasionally exceeding the MAC, have been measured. The results of the kidney and liver function tests were compared with those of a control group comprising 35 men employed at the materials division and not occupationally exposed to chemicals. Biochemical alterations of liver function were assessed by determination in serum of alanine and aspartate aminotransferases (ALAT, ASAT), alkaline phosphatase (AP), total bilirubin (BIL), gamma-glutamyltranspeptidase (GGT), lactate dehydrogenase (LDH), and total bile acids (SBA). No differences between the exposed group and the control group were found. Nor were differences found in biochemical tests for renal tubular damage (urinary alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG) and renal tubular function (urinary retinol binding protein (RBP). Total urinary protein and albumin excretion were measured to assess the integrity of the glomerulus. Urinary total protein did not differ between the groups, but urinary albumin, although within normal limits in both groups, was significantly higher (p < 0.02) in the exposed group. This difference in urinary albumin could not simply be explained by exposure to chlorinated hydrocarbons because albumin concentrations did not correlate with the duration of employment. It is concluded that long term exposure to concentrations of AC, DCP, ECH, or HEX below or near the current limit threshold value does not lead to clinically significant effects on kidney and liver.

1. The metabolism of 1,2-dichloropropane in the rat has been investigated. The major urinary metabolite has been isolated and identified as N-acetyl-S-(2-hydroxypropyl)cysteine. Two minor metabolites of 1,2-dichloropropane have been identified as beta-chlorolactate and N-acetyl-S-(2,3-dihydroxypropyl)cysteine. 2. The fate of 1-chloro-2-hydroxypropane, a proposed intermediate metabolite of 1,2-dichloropropane, has been investigated. Apart from its known urinary metabolite, N-acetyl-S-(2-hydroxypropyl)cysteine, two oxidative metabolites were detected. These were identified as beta-chlorolactaldehyde and beta-chlorolactate. 3. A pathway is proposed for the metabolism and fate of 1,2-dichloropropane in the rat. This accounts for previous observations made for the fate of radioactivity from administration of 1,2-dichloro[1-14C]propane. 4. The microbial and mammalian metabolism of several halogen-containing foreign compounds is discussed.

A screening procedure based on solvent extraction with minimal clean up followed by examination with negative chemical ionization mass spectrometry has been developed for organochlorine residues and related compounds with masses greater than 130 daltons. The procedure has been made quantitative for analysis of pentachlorophenol residues. A limited survey of human urines indicated extensive contamination of the subjects, studied at parts per billion and higher levels, with pentachlorophenol, 2, 4, 5-trichlorophenoxy acetic acid, other polychlorophenoxy acids, and numerous unknown compounds. In an attempt to define the source of the contamination, the screening procedure was applied to samples of environmental substrates. The results suggest the food chain as one significant source of the contamination. A preliminary study of organochlorine compounds in human seminal fluid showed pentachlorophenol and other organochlorine residues in every sample, a result which suggests that this area may merit additional monitoring.

Quenched and sensitized room temperature phosphorescence techniques have been used for the detection of PCNs and PCBs after liquid chromatographic separation. The usefulness of these techniques to fingerprinting of commercial Aroclor and Halowax mixtures in complex matrices has been shown. The complementary nature of these detection modes yield valuable information in addition to UV detection. a signal inverter is proposed for linearization of the quenched RTPL signals. In this way linear calibration plots over more than two orders can be obtained. Detection limits are generally in the low nanogram or subnanogram concentration region. The application of RTPL detection techniques to the analysis of commercial PCN and PCB mixtures in surface water and urine is demonstrated. Pre-columns can be used to advantage for pre-concentration and clean-up of this type of samples.

The use of municipal wastewater treatment plants for the disposal of industrial wastes creates the potential for the exposure of treatment plant workers to hazardous chemical compounds that may be present in these wastes. Urine from workers and air and wastewater samples from a municipal wastewater treatment plant receiving wastes from a pesticide manufacturer were analyzed on several occasions by electron-capture gas chromatography for the presence of the compounds hexachlorocyclopentadiene (HEX) and hexachlorobicycloheptadiene (HEX-BCH) which are present in the waste stream from this industry. HEX-BCH was detected more frequently in urine from these workers than in urine from workers at another municipal wastewater treatment plant in the same city. Urine concentrations of HEX-BCH were found to be higher in specimens collected late in the work shift than in those collected earlier. The primary rate of exposure is thought to be by inhalation. This is the first known report of these compounds being detected in human urine and it demonstrates the potential for wastewater treatment plant worker exposure to industrial wastes.

Fifteen human volunteers were exposed to 1,1,1-trichloroethane (methyl chloroform) vapor at 72-495 mg/m3 for a period of 2 to 4 hours at rest (ten cases) and during light physical exercise (five cases). Subsequently 60 workers occupationally exposed to 1,1,1-trichloroethane in a refrigerator manufacturing plant were studied (median value: 178 mg/m3; geometrical standard deviation: 2.19 mg/m3). As expected, the relative uptake (R) of 1,1,1-trichloroethane decreased in the course of exposure at rest (R = 0.44 after 20 minutes of exposure; R = 0.26 after 240 minutes of exposure). Both in the experimentally exposed subjects and in the occupationally exposed workers, the urinary concentration of 1,1,1-trichloroethane showed a linear relationship to the corresponding environmental time-weighted average concentration. The correlation coefficients (r) were 0.95 in occupationally exposed subjects and more than 0.90 in experimentally exposed groups. A linear equation also existed between urinary concentration and amount of 1,1,1-trichloroethane absorbed (r = 0.88). The findings indicate that the urinary concentration of 1,1,1-trichloroethane can be used as an appropriate biological exposure indicator. In occupationally exposed subjects performing moderate work, the urinary 1,1,1-trichloroethane concentration corresponding to the time-weighted average of the threshold limit value was found to be 860 micrograms/L and its 95% lower confidence limit (biological threshold) 805 micrograms/L.

14C-Hexachlorocyclopentadiene (HEX, C56 ) was administered to adult rats and mice as a single oral dose (2.5 and 25 mg/kg) and as a component of the diet (1, 5 and 25 ppm) for a maximum of 30 days. The primary route of excretion was via the feces (-70% of dose) with low elimination in the urine (approximately 15%). Biliary excretion of only 16% with 66% still voided in the feces of bile duct cannulated rats suggested that the majority of orally consumed HEX was not absorbed. However, extensive degradation apparently occurred in the gut since little of the fecal material was of an apolar nature. The kidney, liver, ovaries and fat were the major sites of deposition of 14C-HEX equivalents. In rats, the kidney contained the highest levels of residues, whereas in mice the residues in the liver exceeded those in the kidney. Other than this difference, the fate of HEX in rats and mice, both male and female, was quite similar and in each case the tissue residues reached a plateau after about two weeks on the HEX-containing diets.

Ground water that was used as a source of potable water by residents of a small community became contaminated by leachate from a 300,000 barrel pesticide waste dump. An environmental health survey of the residents and an apparent control group was conducted to determine if any adverse health effects resulting from exposure to the toxic compounds, many of which were hepatotoxins, could be detected. The survey utilized a health questionnaire, a clinical examination, and a biochemical screening. The latter included analysis of serum for liver and kidney function parameters, determination of hepatitis A and B serology, and bile acid determinations on fasting and postprandial serum and urine specimens. Air and water from representative homes and urine from study participants were analyzed for selected organic compounds. The biochemical screening was conducted on two occasions 2 months apart. The initial hepatic profile testing revealed elevated concentrations of the serum enzymes, alkaline phosphatase and serum glutamic oxaloacetic transaminase, in residents who had used the contaminated water. During follow-up testing of these same persons 2 months later, these values were significantly reduced, as were postprandial serum concentrations of the bile acid of cholyglycine. Six individuals in the exposed group had slight hepatomegaly compared to one individual in the intermediate exposure group and none in the controls. Concentrations of carbon tetrachloride were as high as 18,700 microgram/L in the well water samples. The biochemical and clinical observations are suggestive of a transitory liver injury probably related to exposure to the contaminated drinking water.