Trimester-Specific Blood Trihalomethane and Urinary Haloacetic Acid Concentrations and Adverse Birth Outcomes: Identifying Windows of Vulnerability during Pregnancy.

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.

Gestational exposure to endocrine disrupting chemicals in relation to infant birth weight: a Bayesian analysis of the HOME Study.

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.

Evaluation of layered double hydroxide/graphene hybrid as a sorbent in membrane-protected stir-bar supported micro-solid-phase extraction for determination of organochlorine pesticides in urine samples.

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%).

Interaction Effects between Organochlorine Pesticides and Isoflavones In Vitro and In Vivo.

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.

Association between organochlorine pesticide exposure and thyroid hormones in floriculture workers.

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 (ß=0.01, 95% CI: -0.009, 0.03), and total T4 (ß=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.

Toxicokinetics of short-chain chlorinated paraffins in Sprague-Dawley rats following single oral administration.

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 (ß) 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.

Human biomonitoring in the Czech Republic: an overview.

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.

Human biomonitoring of environmental chemicals--early results of the 2007-2009 Canadian Health Measures Survey for males and females.

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.

Designing prospective cohort studies for assessing reproductive and developmental toxicity during sensitive windows of human reproduction and development--the LIFE Study.

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.

Preparation of Al2O3/TiO2 composite sol-gel fiber for headspace solid-phase microextraction of chlorinated organic solvents from urine.

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%.

Pesticide exposure among pregnant women in Jerusalem, Israel: results of a pilot study.

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.

Monitoring of occupational exposure to volatile organohalogen solvents (VOXs) in human urine samples of dry-cleaner workers by TLHS-DAI-GC-ECD procedure.

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.

Exposure assessment of persistent organic pollutants and metals in Mexican children.

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.

Chlorination by-products in drinking water and menstrual cycle function.

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.

Monitoring of occupational exposure to tetrachloroethene by analysis for unmetabolized tetrachloroethene in blood and urine in comparison with urinalysis for trichloroacetic acid.

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.

Comparative toxicokinetics of chlorinated and brominated haloacetates in F344 rats.

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).

Current status of the external quality assurance programmes of the German Society for Occupational and Environmental Medicine.

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.

Effects of exposure to low concentrations of chlorinated hydrocarbons on the kidney and liver of industrial workers.

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.