Concentrations of dialkyl phosphate metabolites of organophosphorus pesticides in the U.S. population

We report population-based concentrations, stratified by age, sex, and racial/ethnic groups, of dialkyl phosphate (DAP) metabolites of multiple organophosphorus pesticides. We measured dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP), diethylphosphate (DEP), diethylthiophosphate (DETP), and diethyldithiophosphate (DEDTP) concentrations in 1,949 urine samples collected in U.S. residents 6-59 years of age during 1999 and 2000 as a part of the ongoing National Health and Nutrition Examination Survey (NHANES). We detected each DAP metabolite in more than 50% of the samples, with DEP being detected most frequently (71%) at a limit of detection of 0.2 microg/L. The geometric means for the metabolites detected in more than 60% of the samples were 1.85 microg/L for DMTP and 1.04 microg/L for DEP. The 95th percentiles for each metabolite were DMP, 13 microg/L; DMTP, 46 microg/L; DMDTP, 19 micro g/L; DEP, 13 microg/L; DETP, 2.2 microg/L; and DEDTP, 0.87 microg/L. We determined the molar sums of the dimethyl-containing and diethyl-containing metabolites; their geometric mean concentrations were 49.4 and 10.5 nmol/L, respectively, and their 95th percentiles were 583 and 108 nmol/L, respectively. These data are also presented as creatinine-adjusted concentrations. Multivariate analyses showed concentrations of DAPs in children 6-11 years of age that were consistently significantly higher than in adults and often higher than in adolescents. Although the concentrations between sexes and among racial/ethnic groups varied, no significant differences were observed. These data will be important in evaluating the impact of organophosphorus pesticide exposure in the U.S. population and the effectiveness of regulatory actions.     

Arsenic speciation analysis of urine samples from individuals living in an arsenic-contaminated area in Bangladesh

Objectives

Chronic inorganic arsenic (iAs) exposure currently affects tens of millions of people worldwide. To accurately determine the proportion of urinary arsenic metabolites in residents continuously exposed to iAs, we performed arsenic speciation analysis of the urine of these individuals and determined whether a correlation exists between the concentration of iAs in drinking water and the urinary arsenic species content.

Methods

The subjects were 165 married couples who had lived in the Pabna District in Bangladesh for more than 5 years. Arsenic species were measured using high-performance liquid chromatography and inductively coupled plasma mass spectrometry.

Results

The median iAs concentration in drinking water was 55 μgAs/L (range <0.5–332 μgAs/L). Speciation analysis revealed the presence of arsenite, arsenate, monomethylarsonic acid (MMA), and dimethylarsinic acid in urine samples with medians (range) of 16.8 (7.7–32.3), 1.8 (<0.5–3.3), 13.7 (5.6–25.0), and 88.6 μgAs/L (47.9–153.4 μgAs/L), respectively. No arsenobetaine or arsenocholine was detected. The concentrations of the 4 urinary arsenic species were significantly and linearly related to each other. The urinary concentrations of total arsenic and each species were significantly correlated with the iAs concentration of drinking water.

Conclusions

All urinary arsenic species are well correlated with each other and with iAs in drinking water. The most significant linear relationship existed between the iAs concentration in drinking water and urinary iAs + MMA concentration. From these results, combined with the effects of seafood ingestion, the best biomarker of iAs exposure is urinary iAs + MMA concentration.     

Urinary Dialkyl Phosphate Concentrations and Lung Function Parameters in Adolescents and Adults: Results from the Canadian Health Measures Survey

Background:

Epidemiological studies have reported associations between lung function parameters and organophosphate (OP) pesticide exposures in agricultural occupations, but to our knowledge associations have not been evaluated in general populations.

Objectives:

We examined associations between OP metabolite dialkyl phosphates (DAPs) and lung function using data from the Canadian Health Measures Survey (CHMS) Cycle 1.

Methods:

Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), FEV1/FVC ratio, and forced expiratory flow between 25% and 75% of FVC (FEF25%–75%) were measured for 4,446 CHMS participants. Urinary concentrations of six DAP metabolites (DMP, DMTP, DMDTP, DEP, DETP, and DEDTP), smoking status, and other predictors of lung function were also measured in the CHMS-Cycle 1. Multiple linear regression analyses were used to examine the relationship between total DAP concentrations (ΣDAPs) and lung function in adolescents (12–19 years) and adults (20–79 years).

Results:

In adults, estimates from multiple regression analyses suggested that a 1-unit increase on natural logarithmic scale (171% increase on the original scale) in the creatinine-corrected urinary concentration (nanomoles per gram creatinine) of ΣDAP was associated with a 32.6-mL (95% CI: –57.2, –8.1) reduction in FVC, 32.6-mL (95% CI: –59.0, –6.3) reduction in FEV1, 0.2% (95% CI: –0.6, 0.2) reduction in FEV1/FVC ratio, and 53.1-mL/sec (95% CI: –113.9, 7.7) reduction in FEF25%–75%. In adolescents, associations between ΣDAP and FEV1 were closer to the null and positive for FVC, whereas associations with FEV1/FVC and FEF25%–75% were negative, as in adults. However, none of the associations were significant in adolescents.

Conclusions:

The negative association between ΣDAP and lung function in adult participants suggests a detrimental effect of OP pesticides on lung function in the adult general population. Further studies using prospective designs are warranted to confirm the findings reported in this study.

Citation:

Ye M, Beach J, Martin JW, Senthilselvan A. 2016. Urinary dialkyl phosphate concentrations and lung function parameters in adolescents and adults: results from the Canadian Health Measures Survey. Environ Health Perspect 124:491–497; http://dx.doi.org/10.1289/ehp.1509745     

Organophosphate pesticide exposure and attention in young Mexican-American children: the CHAMACOS study

Background

Exposure to organophosphate (OP) pesticides, well-known neurotoxicants, has been associated with neurobehavioral deficits in children.

Objectives

We investigated whether OP exposure, as measured by urinary dialkyl phosphate (DAP) metabolites in pregnant women and their children, was associated with attention-related outcomes among Mexican-American children living in an agricultural region of California.

Methods

Children were assessed at ages 3.5 years (n = 331) and 5 years (n = 323). Mothers completed the Child Behavior Checklist (CBCL). We administered the NEPSY-II visual attention subtest to children at 3.5 years and Conners’ Kiddie Continuous Performance Test (K-CPT) at 5 years. The K-CPT yielded a standardized attention deficit/hyperactivity disorder (ADHD) Confidence Index score. Psychometricians scored behavior of the 5-year-olds during testing using the Hillside Behavior Rating Scale.

Results

Prenatal DAPs (nanomoles per liter) were nonsignificantly associated with maternal report of attention problems and ADHD at age 3.5 years but were significantly related at age 5 years [CBCL attention problems: β = 0.7 points; 95% confidence interval (CI), 0.2–1.2; ADHD: β = 1.3; 95% CI, 0.4–2.1]. Prenatal DAPs were associated with scores on the K-CPT ADHD Confidence Index > 70th percentile [odds ratio (OR) = 5.1; 95% CI, 1.7–15.7] and with a composite ADHD indicator of the various measures (OR = 3.5; 95% CI, 1.1–10.7). Some outcomes exhibited evidence of effect modification by sex, with associations found only among boys. There was also limited evidence of associations between child DAPs and attention.

Conclusions

In utero DAPs and, to a lesser extent, postnatal DAPs were associated adversely with attention as assessed by maternal report, psychometrician observation, and direct assessment. These associations were somewhat stronger at 5 years than at 3.5 years and were stronger in boys.     

Prenatal Exposure to Organophosphorous Pesticides and Fetal Growth: Pooled Results from Four Longitudinal Birth Cohort Studies

Background:

Organophosphorous (OP) pesticides are associated with reduced fetal growth in animals, but human studies are inconsistent.

Objectives:

We pooled data from four cohorts to examine associations of prenatal OP exposure with birth weight (n = 1,169), length (n = 1,152), and head circumference (n = 1,143).

Methods:

Data were from the CHAMACOS, HOME, Columbia, and Mount Sinai birth cohorts. Concentrations of three diethyl phosphate (ΣDEP) and three dimethyl phosphate (ΣDMP) metabolites of OP pesticides [summed to six dialkyl phosphates (ΣDAPs)] were measured in maternal urine. Linear regression and mixed-effects models were used to examine associations with birth outcomes.

Results:

We found no significant associations of ΣDEP, ΣDMP, or ΣDAPs with birth weight, length, or head circumference overall. However, among non-Hispanic black women, increasing urinary ΣDAP and ΣDMP concentrations were associated with decreased birth length (β = –0.4 cm; 95% CI: –0.9, 0.0 and β = –0.4 cm; 95% CI: –0.8, 0.0, respectively, for each 10-fold increase in metabolite concentration). Among infants with the PON1192RR genotype, ΣDAP and ΣDMP were negatively associated with length (β = –0.4 cm; 95% CI: –0.9, 0.0 and β = –0.5 cm; 95% CI: –0.9, –0.1).

Conclusions:

This study confirms previously reported associations of prenatal OP exposure among black women with decreased infant size at birth, but finds no evidence of smaller birth weight, length, or head circumference among whites or Hispanics. Contrary to our hypothesis, we found stronger inverse associations of DAPs and birth outcome in infants with the less susceptible PON1192RR genotype. The large pooled data set facilitated exploration of interactions by race/ethnicity and PON1 genotype, but was limited by differences in study populations.

Citation:

Harley KG, Engel SM, Vedar MG, Eskenazi B, Whyatt RM, Lanphear BP, Bradman A, Rauh VA, Yolton K, Hornung RW, Wetmur JG, Chen J, Holland NT, Barr DB, Perera FP, Wolff MS. 2016. Prenatal exposure to organophosphorous pesticides and fetal growth: pooled results from four longitudinal birth cohort studies. Environ Health Perspect 124:1084–1092; http://dx.doi.org/10.1289/ehp.1409362     

PON1 and neurodevelopment in children from the CHAMACOS study exposed to organophosphate pesticides in utero

Background

Paraoxonase 1 (PON1) detoxifies oxon derivatives of some organophosphate (OP) pesticides, and its genetic polymorphisms influence enzyme activity and quantity. We previously reported that maternal urinary concentrations of dialkyl phosphate (DAP) metabolites, a marker of OP pesticide exposure, were related to poorer mental development and maternally reported symptoms consistent with pervasive developmental disorder (PDD) in 2-year-olds participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study.

Objective

We determined whether PON1 genotypes and enzyme measurements were associated with child neurobehavioral development and whether PON1 modified the association of in utero exposure to OPs (as assessed by maternal DAPs) and neurobehavior.

Methods

We measured DAP concentrations in maternal urine during pregnancy, PON1₁₉₂ and PON1₋₁₀₈ genotypes in mothers and children, and arylesterase (ARYase) and paraoxonase (POase) in maternal, cord, and 2-year-olds’ blood. We assessed 353 2-year-olds on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) of the Bayley Scales of Infant Development and queried their mothers on the Child Behavior Checklist to obtain a score for PDD.

Results

Children with the PON1_−108T allele had poorer MDI scores and somewhat poorer PDI scores. Children were less likely to display PDD when they or their mothers had higher ARYase activity and when their mothers had higher POase activity. The association between DAPs and MDI scores was strongest in children with PON1_−108T allele, but this and other interactions between DAPs and PON1 polymorphisms or enzymes were not significant.

Conclusion

PON1 was associated with child neurobehavioral development, but additional research is needed to confirm whether it modifies the relation with in utero OP exposure.     

Validation of the shake test for detecting freeze damage to adsorbed vaccines

Objective

To determine the validity of the shake test for detecting freeze damage in aluminium-based, adsorbed, freeze-sensitive vaccines.

Methods

A double-blind crossover design was used to compare the performance of the shake test conducted by trained health-care workers (HCWs) with that of phase contrast microscopy as a “gold standard”. A total of 475 vials of 8 different types of World Health Organization prequalified freeze-sensitive vaccines from 10 different manufacturers were used. Vaccines were kept at 5 °C. Selected numbers of vials from each type were then exposed to −25 °C and −2 °C for 24-hour periods.

Findings

There was complete concordance between HCWs and phase-contrast microscopy in identifying freeze-damaged vials and non-frozen samples. Non-frozen samples showed a fine-grain structure under phase contrast microscopy, but freeze-damaged samples showed large conglomerates of massed precipitates with amorphous, crystalline, solid and needle-like structures. Particles in the non-frozen samples measured from 1 μm (vaccines against diphtheria–tetanus–pertussis; Haemophilus influenzae type b; hepatitis B; diphtheria–tetanus–pertussis–hepatitis B) to 20 μm (diphtheria and tetanus vaccines, alone or in combination). By contrast, aggregates in the freeze-damaged samples measured up to 700 μm (diphtheria–tetanus–pertussis) and 350 μm on average.

Conclusion

The shake test had 100% sensitivity, 100% specificity and 100% positive predictive value in this study, which confirms its validity for detecting freeze damage to aluminium-based freeze-sensitive vaccines.     

Direct Impairment of Vascular Function by Diesel Exhaust Particulate through Reduced Bioavailability of Endothelium-Derived Nitric Oxide Induced by Superoxide Free Radicals

Background

Diesel exhaust particulate (DEP) is a key arbiter of the adverse cardiovascular effects of air pollution.

Objectives

We assessed the in vitro effects of DEP on vascular function, nitric oxide (NO) availability, and the generation of oxygen-centered free radicals.

Methods

We assessed the direct vascular effects of DEP (10–100 μg/mL) in isolated rat aortic rings using myography. We investigated NO scavenging and oxygen-centered free radical generation using an NO electrode and electron paramagnetic resonance (EPR) with the Tempone-H (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidine) spin trap, respectively.

Results

Acetylcholine-induced relaxation was attenuated by DEP (maximum relaxation reduced from 91 ± 4% to 49 ± 6% with 100 μg/mL DEP; p < 0.001) but was restored by superoxide dismutase (SOD; maximum relaxation, 73 ± 6%; p < 0.001). DEP caused a modest inhibition of relaxation to NO donor drugs, an effect that could be reversed by SOD (p < 0.01). At 10 μg/mL, DEP did not affect verapamil-induced relaxation (p = 0.73), but at 100 μg/mL DEP inhibited relaxation (p < 0.001) by a mechanism independent of SOD. NO concentrations generated by 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA/NO; 10 μM) were reduced by DEP (100 μg/mL; from 5.2 ± 0.4 to 3.3 ± 0.4 μM; p = 0.002). Free radical generation was increased by DEP (10 μg/mL; 9-fold increase in EPR spectra; p = 0.004) in a manner that could be attenuated by SOD (p = 0.015).

Conclusions

DEP caused oxidative stress through the generation of oxygen-centered free radicals that reduced the bioavailability of endothelium-derived NO without prior interaction with the lung or vascular tissue. These findings provide a mechanism for the adverse cardiovascular effects of particulate air pollution.     

Toxic effects of nicotinamide methylation on mouse brain striatum neuronal cells and its relation to manganese

Objective

It is well known that manganese (Mn) exposure is involved in parkinsonism. The aim of our study was to test the hypotheses that Mn affects nicotinamide N-methyltransferase (NNMT) activity, increases the metabolism of nicotinamide (NA) to 1-methylnicotinamide (MNA), and leads to neurocytotoxicity.

Methods

Following demonstration of the effects of Mn concentrations on the survival rate of Mouse CD1 brain striatum neuronal cells (MS cells), the effect of Mn on NNMT activity was investigated by comparing the difference in the amount of MNA produced after various Mn concentrations were added to mouse brain cytosol fractions as an enzyme solution. Toxicity induced by MNA and its precursor NA on MS cells was measured.

Results

The survival rate of MS cells decreased significantly with increasing concentrations of Mn in the culture medium. With respect to the influence of Mn on NNMT activity, NNMT activity increased significantly at Mn concentrations of 1 μmol/mg protein. MNA and NA neurotoxicity were compared by comparing cell survival rate. Cell survival rate dropped significantly when the cells were cultivated with 10 mM of MNA. There was also a tendency for the survival rate to fall following the addition of 10 mM NA; however, the difference with the control was not significant.

Conclusions

Our study suggests the possibility that Mn causes increased NNMT activity, thereby increasing MNA levels in the brain and bringing about neuron death. Daily absorption of Mn and NA may thus contribute to idiopathic Parkinson’s disease.     

Urinary dialkylphosphate metabolites and health symptoms among farmers in Thailand

Using a cross-sectional study, we investigated urinary DAPs levels and health symptoms related to the type of crop cultivation and farm tasks among 84 farmers in Phayao Province of northern Thailand. The results showed that the average of ∑DAPs levels was 10.93 ± 19.64 μg/g creatinine (range 1.48–163.90 μg/g creatinine). The compound found the most was DEP, followed by DETP, DEDTP, DMP, DMTP, and DMDTP, respectively. The type of crop cultivation may be associated with an increasing prevalence of respiratory tract, muscle system, and skin irritation. Farm tasks were associated with an increasing prevalence of muscle system and skin irritation. It was difficult to assess adverse health symptoms associated with urinary DAPs in low levels of exposure; therefore, further investigation is needed using more sensitive biomarkers and more sensitive health symptom measurement.     

Organophosphate pesticide residues in urine of farmworkers and their children in Fresno County, California.

BACKGROUND: Childhood cancer, notably leukemia, brain cancer, non-Hodgkin's lymphoma, soft tissue sarcoma, and Hodgkin's disease, has been associated with pesticide exposure, often with greater relative risks than among exposed adults, suggesting greater susceptibility in children. These differences in risk may be due to developmental factors or differences in pesticide exposure. METHODS: A feasibility study was conducted to determine levels of pesticide metabolites in urine of adults (n = 18) and children (n = 9) in Fresno County, California, an intensely agricultural county in the Central San Joaquin Valley. Spot urine samples were obtained and analyzed for six metabolites of organophosphate (OP) pesticides using gas chromatography with flame photometric detection methods. The metabolites of OP pesticides included DMP, DEP, DMTP, DMDTP, DETP, and DEDTP. RESULTS: Levels were generally low for both adults and children for most metabolites tested. Frequencies of detection ranged from 0 to 37%, with mean levels ranging from non-detectable to 13.22 ppb. However, levels of several metabolites were higher in children than in adults. The most frequently detected metabolite, DMP, was found among 44% of the children and 33% of the adults. DMTP was detected among 33% of the children and 28% of the adults. CONCLUSIONS: These results are difficult to interpret given the sampling variation associated with the small sample size. Nevertheless, because OP pesticides have been associated with increased cancer risk in animal and human studies, these results indicate a need to closely monitor children's exposure to environmental chemicals.     

Biomonitoring of mercury,cadmium, and lead exposure in Japanese children: a cross-sectional study

Objectives

To measure current Hg, Cd, and Pb exposure in Japanese children, and to estimate dietary intakes of foods responsible for high body burden.

Methods

Blood, hair, and urine samples were collected from 9 to 10-year-old 229 children in Asahikawa and measured for Hg, Cd, and Pb in these matrices. Diet history questionnaire was used to estimate intake of marine foods and other food items. Hg level was measured by cold vapor atomic absorption spectrometry. Cd and Pb levels were determined with inductively coupled plasma mass spectrometry.

Results

Geometric mean (GM) of blood Hg, Cd, and Pb was 4.55 μg/L, 0.34 μg/L, and 0.96 μg/dL, respectively. Urinary Cd level was 0.34 μg/g creatinine (GM) and hair Hg was 1.31 μg/g (GM). Approximately one-third (35 %) of blood samples had Hg level above the U.S. EPA reference dose (RfD; 5.8 μg/L). Hair Hg level exceeded U.S. EPA RfD (1.2 μg/g) in 59 % samples. Children in the upper quartile of blood Hg level had significantly higher intake of large predatory fish species compared to those in the lower quartile of blood Hg.

Conclusions

Those with high blood Hg level may be explained by more frequent intake of big predatory fish. Cd and Pb exposure is generally low among Japanese children. As no safety margin exists for Pb exposure and high exposure to MeHg is noted in Japanese population; periodic biomonitoring and potential health risk assessment should continue in high-risk populations, notably among children.     

Simultaneous changes in high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis and those underlying molecular mechanisms in novel SHRSP5/Dmcr rat

Objectives

The aim of this study was to identify the molecular mechanisms underlying high-fat and high-cholesterol (HFC) diet-induced steatohepatitis and associated liver fibrosis progression in a novel stroke-prone, spontaneously hypertensive 5/Dmcr (SHRSP5/Dmcr) rat model.

Methods

SHRSP5/Dmcr rats were given the control or HFC-diet for 2, 8, and 16 weeks. Plasma and hepatic gene expression of key molecules involved in fatty acid oxidation, inflammation, oxidative stress, and fibrosis were subsequently analyzed.

Results

Rats fed the HFC-diet showed increased plasma tumor necrosis factor-α (TNF-α) and hepatic p50/p65 signals, but reduced hepatic Cu²⁺/Zn²⁺-superoxide dismutase across the treatment period and reduced plasma total adiponectin at 8 weeks. In HFC-diet-fed rats, transforming growth factor-β1 (TGF-β1) was elevated prior to the appearance of obvious liver fibrosis pathology at 2 weeks, followed by elevations in platelet-derived growth factor-B (PDGF-B) and α-smooth muscle actin (α-SMA), corresponding to evident liver fibrosis, at 8 weeks and by α₁ type I collagen production at 16 weeks. The HFC-diet increased hepatic total cholesterol accumulation, although hepatic triglyceride declined by 0.3-fold from 2 to 16 weeks due to reduced hepatic triglyceride synthesis, as suggested by the diacylglycerol acyltransferase 1 and 2 measurements.

Conclusions

TNF-α and p50/p65 molecular signals appeared to be major factors for HFC-diet-induced hepatic inflammation and oxidative stress facilitating liver disease progression. While the up-regulation of TGF-β1 prior to the appearance of any evident liver fibrosis could be an early signal for progressive liver fibrosis, elevated PDGF-B and α-SMA levels signified evident liver fibrosis at 8 weeks, and subsequent increased α₁ type I collagen production and reduced triglyceride synthesis indicated extensive liver fibrosis at 16 weeks in this novel SHRSP5/Dmcr model.

Electronic supplementary material

The online version of this article (doi:10.1007/s12199-012-0273-y) contains supplementary material, which is available to authorized users.     

Population-based inorganic mercury biomonitoring and the identification of skin care products as a source of exposure in New York City

Background

Mercury is a toxic metal that has been used for centuries as a constituent of medicines and other items.

Objective

We assessed exposure to inorganic mercury in the adult population of New York City (NYC).

Methods

We measured mercury concentrations in spot urine specimens from a representative sample of 1,840 adult New Yorkers in the 2004 NYC Health and Nutrition Examination Survey. Cases with urine concentrations ≥ 20 μg/L were followed up with a telephone or in-person interview that asked about potential sources of exposure, including ritualistic/cultural practices, skin care products, mercury spills, herbal medicine products, and fish.

Results

Geometric mean urine mercury concentration in NYC was higher for Caribbean-born blacks [1.39 μg/L; 95% confidence interval (CI), 1.14–1.70] and Dominicans (1.04 μg/L; 95% CI, 0.82–1.33) than for non-Hispanic whites (0.67 μg/L; 95% CI, 0.60–0.75) or other racial/ethnic groups. It was also higher among those who reported at least 20 fish meals in the past 30 days (1.02 μg/L; 95% CI, 0.83–1.25) than among those who reported no fish meals (0.50 μg/L; 95% CI, 0.41–0.61). We observed the highest 95th percentile of exposure (21.18 μg/L; 95% CI, 7.25–51.29) among Dominican women. Mercury-containing skin-lightening creams were a source of exposure among those most highly exposed, and we subsequently identified 12 imported products containing illegal levels of mercury in NYC stores.

Conclusion

Population-based biomonitoring identified a previously unrecognized source of exposure to inorganic mercury among NYC residents. In response, the NYC Health Department embargoed products and notified store owners and the public that skin-lightening creams and other skin care products that contain mercury are dangerous and illegal. Although exposure to inorganic mercury is not a widespread problem in NYC, users of these products may be at risk of health effects from exposure.     

Age-related effects of fasting on ketone body production during lipolysis in rats

Objective

The age-related effects of fasting on lipolysis, the production of ketone bodies, and plasma insulin levels were studied in male 3-, 8-, and 32-week-old Sprague–Dawley rats.

Methods

The rats were divided into fasting and control groups. The 3-, 8- and 32-week-old rats tolerated fasting for 2, 5, and 12 days, respectively.

Results

Fasting markedly reduced the weights of perirenal and periepididymal white adipose tissues in rats in the three age groups. The mean rates of reduction in both these adipose tissue weights during fasting periods were higher in the order of 3 > 8 > 32-week-old rats. Fasting transiently increased plasma free fatty acid (FFA), total ketone body, β-hydroxybutyrate, and acetoacetate concentrations in the rats in the three age groups. However, plasma FFA, total ketone body, β-hydroxybutyrate, and acetoacetate concentrations in the 3-week-old rats reached maximal peak within 2 days after the onset of fasting, although these concentrations in the 8- and 32-week-old rats took more than 2 days to reach the maximal peak. By contrast, the augmentation of plasma FFA, total ketone body, β-hydroxybutyrate, and acetoacetate concentrations in the rats in the three age groups had declined at the end of each experimental period. Thus, the capacity for fat mobilization was associated with tolerance to fasting. Plasma insulin concentrations in the rats in the three age groups were dramatically reduced during fasting periods, although basal levels of insulin were higher in the order of 32 > 8 > 3 week-old rats.

Conclusion

These results suggest that differences in fat metabolism patterns among rats in the three age groups during prolonged fasting were partly reflected the metabolic turnover rates, plasma insulin levels, and amounts of fat storage.     

Biomarkers of chlorpyrifos exposure and effect in Egyptian cotton field workers

Background

Chlorpyrifos (CPF), a widely used organophosphorus pesticide (OP), is metabolized to CPF-oxon, a potent cholinesterase (ChE) inhibitor, and trichloro-2-pyridinol (TCPy). Urinary TCPy is often used as a biomarker for CPF exposure, whereas blood ChE activity is considered an indicator of CPF toxicity. However, whether these biomarkers are dose related has not been studied extensively in populations with repeated daily OP exposures.

Objective

We sought to determine the relationship between blood ChE and urinary TCPy during repeated occupational exposures to CPF.

Methods

Daily urine samples and weekly blood samples were collected from pesticide workers (n = 38) in Menoufia Governorate, Egypt, before, during, and after 9–17 consecutive days of CPF application to cotton fields. We compared blood butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) activities with the respective urinary TCPy concentrations in each worker.

Results

Average TCPy levels during the middle of a 1- to 2-week CPF application period were significantly higher in pesticide applicators (6,437 μg/g creatinine) than in technicians (184 μg/g) and engineers (157 μg/g), both of whom are involved in supervising the application process. We observed a statistically significant inverse correlation between urinary TCPy and blood BuChE and AChE activities. The no-effect level (or inflection point) of the exposure–effect relationships has an average urinary TCPy level of 114 μg/g creatinine for BuChE and 3,161 μg/g creatinine for AChE.

Conclusions

Our findings demonstrate a dose–effect relationship between urinary TCPy and both plasma BuChE and red blood cell AChE in humans exposed occupationally to CPF. These findings will contribute to future risk assessment efforts for CPF exposure.     

Assessment of long-term subacute exposure to dimethoate by hair analysis of dialkyl phosphates DMP and DMTP in exposed rabbits: The effects of dose, dose duration and hair colour

Hair analysis for dialkyl phosphates’ (DAPs) residues could provide a measure of chronic exposure to organophosphate pesticides (OPs). The aim of this study was to determine whether these metabolites can be internally incorporated into the hair of rabbits exposed to dimethoate and also to investigate the influence of dose and dose duration of this OP, as well as the effect of hair colour on the concentrations of its DAPs in hair. Two-coloured rabbits were daily exposed to dimethoate (0, 12 or 24 mg kg⁻¹ body weight) via their drinking water. Hair samples of both colours were obtained 4 and 6 months after the beginning of exposure from the back of all treated rabbits, and each hair colour sample was analyzed for dimethyl phosphate (DMP) and dimethyl thiophosphate (DMTP) by gas chromatography-mass spectrometry (GC-MS). Analysis revealed the incorporation of these metabolites into the rabbit hair in a dose-dependent manner. The mean concentrations found ranged from 0.18 to 0.77 ng mg⁻¹ for DMP and from 0.43 to 1.53 ng mg⁻¹ for DMTP. Mixed results for the significance of the relationship between dose duration and the levels of the two DAPs in hair are observed. Hair pigmentation does not appear to affect the concentration values of DMTP, whereas it seems to be a critical factor in the incorporation of DMP into hair. These data confirm the ability of hair testing to assess chronic OP exposure by the detection of DAPs.     

Association of renal function and delta-aminolevulinic acid dehydratase polymorphism among Vietnamese and Singapore workers exposed to inorganic lead

Objectives

To investigate the effect of δ‐aminolevulinic acid dehydratase (ALAD) polymorphisms on the association between blood lead and renal function among Vietnamese and Singaporean workers who were exposed to low to medium levels of inorganic lead, and to study the distribution of ALAD polymorphism among Vietnamese, Chinese, Malays and Indians.

Methods

A total of 459 male and female workers were studied. Blood and urine were collected for each worker in order to determine ALAD genotype, blood lead, and urinary δ‐aminolevulinic acid (ALAU). Renal function tests included urine albumin (Ualb), urine β2 microglobulin (Uβ2m), urinary α1 microglobulin (Uα1m), N‐acetyl‐glucosaminidas (NAG), and urine retinol blinding protein (RBP). A multiple regression model with interaction term was applied to fit the entire data and to explore the modifying effect of ALAD polymorphism on the relation of blood lead to each renal function parameter.

Results

ALAD1‐1 was the predominant genotype for all the ethnic groups while ALAD2‐2 was the rarest. The frequency of ALAD2 allele was higher among Malays (8.8%) and Indians (10.6%) compared to the Chinese (5.0%) and Vietnamese (4.3%). The geometric mean of blood lead for all workers was 19.0 μg/dl. The models for Uβ2m, Uα1m, and NAG showed that the ALAD1‐2/2‐2 group had higher β coefficients than the ALAD1‐1 group. Corresponding to 10 μg/dl blood lead, ALAD1‐1 homozygotes had an increment of 1.288 μg/g Cr, 1.175 mg/g Cr, and 1.995 U/g Cr for Uβ2m, Uα1m, and NAG, respectively. ALAD1‐2/2‐2 subjects had higher increments of 3.802 μg/g Cr, 2.138 mg/g Cr, and 3.89 U/g Cr for Uβ2m, Uα1m, and NAG, respectively.

Conclusion

The frequency of the ALAD2 allele is as low in Vietnamese workers as in Chinese. Workers with the ALAD2 allele appeared more susceptible to the effects of lead (especially at higher levels) on renal function.     

High human exposure to pyrene (polycyclic aromatic hydrocarbon) in Kinshasa,a capital of the Democratic Republic of Congo

Background

Data on human exposure to chemicals in Africa are scarce. A biomonitoring study was conducted in a representative sample of the population in Kinshasa (Democratic Republic of Congo) to document exposure to polycyclic aromatics hydrocarbons.

Methods

1-hydroxypyrene (1-OHP) was measured by HPLC fluorescence in spot urine samples from 220 individuals (50.5% women), aged 6–70 years living in the urban area and from 50 additional subjects from the sub-rural area of Kinshasa. Data were compiled as geometric means and selected percentiles, expressed without (μg/L) or with creatinine adjustment (μg/g cr). Multiple regression analyses were applied to factors (creatinine, grilled meat habits and smoking habits) influencing 1-OHP (stepwise procedure, criteria: probability F to enter ≤ 0.05 and probability F to remove ≥ 0.10).

Results

According to the regression models, creatinine, grilled meat habits and smoking habits contribute to explain 45% of the variation in population’s urinary 1-OHP by the environmental exposure. Overall, living in urban area of Kinshasa was associated with increased levels of 1-OHP in urine as compared to a population living in the sub-rural area [GM: 1.8 μg/L (n = 220) versus 1.4 μg/L (n = 50), p < 0.01] as well as compared to the reference values from databases involving American or German populations.

Conclusion

This study reveals the high pyrene (PAH) exposure of the Kinshasa population. However, more work, with a rigorous design in the exposed population (monitoring of air concentrations and identifying other sources of pyrene –PAH exposure), is needed to establish further documentation.     

Lithium in drinking water and thyroid function

Background

High concentrations of lithium in drinking water were previously discovered in the Argentinean Andes Mountains. Lithium is used worldwide for treatment of bipolar disorder and treatment-resistant depression. One known side effect is altered thyroid function.

Objectives

We assessed associations between exposure to lithium from drinking water and other environmental sources and thyroid function.

Methods

Women (n = 202) were recruited in four Andean villages in northern Argentina. Lithium exposure was assessed based on concentrations in spot urine samples, measured by inductively coupled plasma mass spectrometry. Thyroid function was evaluated by plasma free thyroxine (T₄) and pituitary gland thyroid-stimulating hormone (TSH), analyzed by routine immunometric methods.

Results

The median urinary lithium concentration was 3,910 μg/L (5th, 95th percentiles, 270 μg/L, 10,400 μg/L). Median plasma concentrations (5th, 95th percentiles) of T₄ and TSH were 17 pmol/L (13 pmol/L, 21 pmol/L) and 1.9 mIU/L, (0.68 mIU/L, 4.9 mIU/L), respectively. Urine lithium was inversely associated with T₄ [β for a 1,000-μg/L increase = −0.19; 95% confidence interval (CI), −0.31 to −0.068; p = 0.002] and positively associated with TSH (β = 0.096; 95% CI, 0.033 to 0.16; p = 0.003). Both associations persisted after adjustment (for T₄, β = −0.17; 95% CI, −0.32 to −0.015; p = 0.032; for TSH: β = 0.089; 95% CI, 0.024 to 0.15; p = 0.007). Urine selenium was positively associated with T₄ (adjusted T₄ for a 1 μg/L increase: β = 0.041; 95% CI, 0.012 to 0.071; p = 0.006).

Conclusions

Exposure to lithium via drinking water and other environmental sources may affect thyroid function, consistent with known side effects of medical treatment with lithium. This stresses the need to screen for lithium in all drinking water sources.