Environmental Research

Published by Elsevier
Online ISSN: 1096-0953
Publications
Article
Nitrogen dioxide (NO2) is a common oxidant air pollutant. Animal studies have suggested that NO2 exposure causes a decrease in the numbers of some splenic lymphocyte subtypes and impairs lymphocyte-dependent immune responses. To investigate whether ambient levels of NO2 alter circulating and bronchoalveolar lavage fluid (BALF) human lymphocytes, we studied five healthy nonsmoking adult volunteers. In each subject, blood and bronchoalveolar lavage fluid was obtained and then, more than 2 weeks later, volunteers were exposured to 0.60 ppm NO2 for 2 hr with intermittent light to moderate exercise on 4 separate days within a 6-day period. We measured standard tests of pulmonary function (airway resistance, thoracic gas volume, maximal expiratory flow) and had the subjects rate the severity of respiratory symptoms before and after each NO2 exposure. Circulating and BALF lymphocytes were labeled with fluorochrome-conjugated monoclonal antibodies to human lymphocyte antigens and a flow cytometer was used to count lymphocyte subtypes. Neither any single day's exposure nor all four exposures caused a change in symptoms or in the results of tests of pulmonary function. The total number of circulating lymphocytes obtained after NO2 exposure was slightly greater than at baseline (1792 +/- 544 vs 1598 +/- 549 cells/mm3 at baseline; P = not significant) but the proportions of lymphocyte subtypes did not differ. In the BALF obtained after NO2 exposure and in the baseline state, the total number of lymphocytes and the percentages of T cells (CD 3), B cells (CD 20), T cytotoxic-suppressor cells (CD 8), T helper-inducer cells (CD 4), and large granular lymphocytes (CD 57) also did not differ after NO2 exposure. A slightly but significantly greater proportion of natural killer cells (CD 16) was found in the BALF obtained after NO2 exposure (7.2 +/- 3.1 vs 4.2 +/- 2.4% of total lymphocytes). We conclude that repeated exposures of healthy nonsmoking adults to 0.60 ppm NO2 are not associated with clinically significant symptoms, changes in airway caliber, or alterations in circulating and BALF lymphocyte subtypes. We suggest that brief, daily exposures to NO2 at levels higher than those achieved in urban atmosphere are unlikely to provoke acute respiratory impairment in healthy, nonsmoking adults.
 
Article
Cardiopulmonary and metabolic responses of three groups, each consisting of five adult males (aged 20–25), were determined before, during, and after a 2-hr exposure to 0.62 ± 0.12 ppm NO2 at 25°C and 45% RH. The three groups exercised during exposure at 40% of V̇O2 max for either 15, 30, or 60 min for Groups A, B, and C, respectively. During the exercise periods the ventilation was about 33 liter/min, a fourfold increase over the resting level. There were no physiologically significant cardiovascular, metabolic, or pulmonary function changes which could be attributed to exposure to this level of NO2 (0.62 ppm). There were no differences between the groups in their response despite the fact that Groups A and B received more NO2 as a result of 28% and 84% greater ventilations, respectively.
 
Article
A rat model of chronic pulmonary infection (CPI) initiated by Pseudomonas aeruginosa embedded in agar beads was used to test the effect of ozone on lysosomal enzyme levels in alveolar macrophages (AM). CPI was induced by intratracheal instillation of a 0.1-ml suspension of infected beads into the left lung. Ten days after infection half the rats were exposed to atmospheres of air and half to 0.64 ppm ozone for 4 weeks. Enzyme levels were measured using a scanning cytospectrophotometer linked to PDP/11 computer. Measurement of lysozyme in individual rat AM in situ showed a significant decrease in cell size and enzyme content in ozone-exposed uninfected animals. Cell size and enzyme content of ozone-exposed animals with CPI were further reduced, suggesting a synergistic effect between ozone exposure and chronic infection.
 
Article
To determine the influence of mouthpiece breathing on respiratory responses to sulfur dioxide (SO2), 23 young adult asthmatic volunteers were exposed in a chamber to 0.75 ppm SO2 during heavy exercise, once with breathing unencumbered and once while they wore noseclips and mouthpieces. These conditions (more severe than in typical ambient exposures) were deliberately chosen to produce significant physiological and clinical responses. Similar exposures to clean air served as controls. Exposure studies were separated by 1-week intervals and order was randomized. The protocol consisted of 10 min on a bicycle ergometer (mean load 650 kg-m/min, mean ventilation 40 liter/min), preceded and followed by response testing (body plethysmography, symptom questionnaires, and forced expiratory function tests; the last were performed only postexposure). During clean-air exposures, specific airway resistance (SRaw) and symptoms increased significantly, but no meaningful differences between mouthpiece breathing and unencumbered breathing were observed. Exposures to SO2 under these relatively severe conditions produced greater increases in SRaw than clean-air exposures regardless of the mode of breathing, but the excess increase was significantly greater with mouthpiece than with unencumbered breathing. Symptom changes and postexposure forced expiratory function showed qualitatively the same pattern of decrements with SO2 ad did SRaw, but the excess responses attributable to mouthpiece breathing did not attain statistical significance. Mouthpiece breathing can compromise upper-respiratory defenses against SO2 to the extent that responses are greater than with more natural breathing. The mode of breathing should be taken in account when applying laboratory human exposure data to air-quality risk assessment.
 
Article
Cytoplasmic inclusions known as Lewy bodies, a hallmark of Parkinson's disease (PD) pathology, may protect against cytotoxic proteins. Since the ubiquitin-proteasome system (UPS) degrades cytotoxic proteins, dysfunction in the UPS may contribute to PD etiology. Our goal in this study was to screen pesticides for proteasome inhibition and investigate (i) whether ambient exposures to pesticides that inhibit the UPS increase PD risk and (ii) whether genetic variation in candidate genes of the UPS pathway modify those increased risks. We assessed 26S UPS activity in SK-N-MC(u) cells by fluorescence. We recruited idiopathic PD cases (n=360) and population-based controls (n=816) from three counties in California with considerable commercial agriculture. We determined ambient pesticide exposure by our validated GIS-based model utilizing residential and workplace address histories. We limited effect measure modification assessment to Caucasians (287 cases, 453 controls). Eleven of 28 pesticides we screened inhibited 26S UPS activity at 10µM. Benomyl, cyanazine, dieldrin, endosulfan, metam, propargite, triflumizole, and ziram were associated with increased PD risk. We estimated an odds ratio of 2.14 (95% CI: 1.42, 3.22) for subjects with ambient exposure to any UPS-inhibiting pesticide at both residential and workplace addresses; this association was modified by genetic variation in the s-phase kinase-associated protein 1 gene (SKP1; interaction p-value=0.005). Our results provide evidence that UPS-inhibiting pesticides play a role in the etiology of PD and suggest that genetic variation in candidate genes involved in the UPS pathway might exacerbate the toxic effects of pesticide exposures.
 
Article
One etiologic model for narcolepsy suggests that some environmental toxin selectively and irreversibly destroys hypocretin-producing cells in individuals with human leukocyte antigen (HLA) DQB1(*)0602. Between 2001 and 2005, the authors conducted a population-based case-control study in King County, Washington to examine narcolepsy risk in relation to toxins found in jobs, hobbies, and other non-vocational activities. Sixty-seven cases and 95 controls were enrolled; all were between ages 18 and 50 and positive for HLA DQB1(*)0602. All were administered in-person interviews about jobs, hobbies or other non-vocational activities before age 21. All analyses were adjusted for African-American race and income. Risk increased significantly for jobs involving heavy metals (odds ratio [OR]=4.7; 95% confidence interval [CI]: 1.5, 14.5) and for highest levels of exposure to woodwork (OR: 3.0; 95% CI: 1.0, 8.9), fertilizer (OR=3.1; 95% CI: 1.1, 9.1), and bug or weed killer (OR=4.5; 95% CI: 1.5, 13.4). Associations were of borderline significance for activities involving ceramics, pesticides, and painting projects. Significant dose-response relationships were evident for jobs involving metals (p<0.03), paints (p<0.03), and bug or weed killer (p<0.02). Additional studies are needed to replicate these findings and continue the search for specific toxins that could damage hypocretin neurons in genetically susceptible people.
 
Article
Recent data suggest that prenatal exposure to p,p'-DDE may reduce height and increase body mass index (BMI) in childhood, thus potentially raising the risk of adult health problems. The association between prenatal DDE exposure and growth was evaluated in 788 boys from Chiapas, an area of Mexico where DDT was recently used. The median DDE levels in maternal serum at birth (2002-2003) were 2.7 microg/g lipid. 2633 measurements of height (cm) and weight (kg) were obtained in 2004-2005. The median age of the children during follow-up was 18 months (quartiles 14 and 22 months). Height and body mass index (kg/m(2)) were age-standardized and expressed as standard deviation scores (SDS). Multivariate random-effect models for longitudinal data were fitted and predicted height and BMI SDS were estimated from the adjusted models. Overall, associations between prenatal DDE level and height or BMI SDS at any given age were not observed. For example, the predicted values showed that children with the highest exposure (DDE: >9.00 microg/g) compared to those least exposed (DDE: <3.01 microg/g) grew similarly and they had a BMI SDS similar to the referent group. The results do not support the prior findings of an association of DDE exposure with childhood height or BMI.
 
Article
Fertile white Leghorn chicken eggs were exposed via intravitelline injections to dosages of 5.0, 10.0, or 20 mg 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT) in olive oil prior to incubation. Control embryos received only the olive oil vehicle. Eggs were placed in a forced-draft incubator for either 5 or 12 days. Embryos were removed and their gonadal areas prepared for histological or histochemical evaluation. Histological examination of DDT-exposed 5-day embryos revealed no significant differences in the number of primordial germ cells aggregating in the gonadal area and in the localization of acid and alkaline phosphatase activity. Embryos exposed to DDT for 12 days revealed significant alterations in both ovaries and testes. The testes of DDT-exposed embryos consisted of mostly stroma with fewer seminiferous cords than controls while ovaries of exposed embryos contained a larger number of distended medullary cords as well as a difference in the distribution of these cords when compared to controls. There was an increased alkaline phosphatase activity in the stromal cells of female gonads. Increased amounts of alkaline phosphatase activity found in the stroma at 12 days might be due to a DDT-induced stimulation of these cells to differentiate more rapidly. Acid phosphatase activity was found in the secondary sex cords of control 12-day ovaries, but was much reduced or absent in those of pesticide-exposed embryos. These results indicate that a single dosage of DDT administered to a chick embryo prior to incubation does not affect early stages of gonadal development but that effects on both ovaries and testes occur 12 days following exposure.
 
Article
Dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs) are persistent organochlorine compounds bioaccumulating in human tissues. Body burden of organochlorines may be influenced by individual characteristics such as age, weight variations, breastfeeding, dietary habits and place of residence. To assess the current serum concentrations of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), the main DDT breakdown product, and of PCBs in women from two French administrative areas (Ille-et-Vilaine and Côte d'Or). To identify determinants of the current serum levels among individual characteristics related to intake, metabolism, and excretion of organochlorines. We measured serum p,p'-DDE and PCB levels in 1055 general population women who were recruited in 2005-2007 to serve as controls in a case-control study on breast cancer. Associations between organochlorine levels and age, current body mass index (BMI), BMI change during the last 10 years, dietary habits, breastfeeding history, residence area and education were assessed in multivariate analyses. Median concentrations of p,p'-DDE and total PCBs were 85 and 240ng/g lipid, respectively. Based on multivariate analyses, the main predictors of high p,p'-DDE levels included age and frequent consumption of saltwater fish in women below 50 years, and high BMI in older women. Total PCB levels increased markedly with age. Among older women, other important predictors of high PCB levels included frequent consumption of saltwater fish and low BMI. Our results are also suggestive of an inverse association between PCB levels and BMI gain during the last ten years. Women in Côte d'Or had significantly higher PCB levels than women in Ille-et-Vilaine. The patterns of associations between determinants and serum organochlorine concentrations suggest that human PCB contamination is still ongoing in France. The most important predictors of serum p,p'-DDE and PCB concentrations among French women include age, body mass index, dietary habits, and place of residence.
 
Article
The effects of cadmium on the excretion and metabolism of DDT in rats were investigated. The excretion of DDT after a single parenteral administration was modified by the addition of a small amount of cadmium. The time pattern of DDT retention in the whole body was explained by a three-compartment model. An increased level of lipid content in the liver induced by cadmium was accompanied by a relative increase of DDT residue in the liver. This indicates that the effect of cadmium on the metabolism of DDT is mainly due to the change of lipid content in the liver. Since the effect of the cadmium was long-lasting, a significant elevation in the metabolic rate of DDT and a low level of DDT concentration in adipose tissue was observed after the dose of cadmium.
 
Article
Plastics are generally mixed with additives like plasticizers to enhance their flexibility, pliability, and elasticity proprieties. Plasticizers are easily released into the environment and are absorbed mainly through ingestion, dermal contact, and inhalation. One of the main classes of plasticizers, phthalates, has been associated with endocrine and reproductive diseases. In 2002, 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) was introduced in the market for use in plastic materials and articles intended to come into contact with food, and it received final approval from the European Food Safety Authority in 2006. At present, there is limited knowledge about the safety and potential metabolic and endocrine-disrupting properties of DINCH and its metabolites. The purpose of this study was to evaluate the biological effects of DINCH and its active metabolites, cyclohexane-1,2-dicarboxylic acid (CHDA) and cyclohexane-1,2-dicarboxylic acid mono isononyl ester (MINCH), on rat primary stromal vascular fraction (SVF) of adipose tissue. DINCH and its metabolite, CHDA, were not able to directly affect SVF differentiation. However, exposure of SVF to 50μM and 100μM concentrations of MINCH affected the expression of Cebpa and Fabp4, thus inducing SVF preadipocytes to accumulate lipids and fully differentiate into mature adipocytes. The effect of MINCH was blocked by the specific peroxisome proliferator-activated receptor (PPAR)-α antagonist, GW6471. Taken together, these results suggest that MINCH is a potent PPAR-α agonist and a metabolic disruptor, capable of inducing SVF preadipocyte differentiation, that may interfere with the endocrine system in mammals. Copyright © 2015 Elsevier Inc. All rights reserved.
 
Article
This study was initiated to investigate the possible perinatal carcinogenic effects of the colon carcinogen 1,2-dimethylhydrazine (DMH) in Fischer F344 inbred rats. Pregnant female animals during their 16-18th day of gestation were administered the chemical by intraperitoneal injections, and beginning at 4 months postparturition, the antitumor cell-mediated immunity (CMI) was delineated in the dams and pups as an indirect measure of carcinogenesis. The CMI status was established by the ability of peripheral blood lymphoid cells obtained from the rats to injure and kill target tumor cells derived from an X-ray-induced rat small bowel adenocarcinoma cell line with the degree of damage being reflected in the quantity of loss of radioiodinated peripheral and integral membrane proteins from the target cells. A significant antitumor CMI was observed in the exposed offsprings although there was no apparent difference between the immunoresponsiveness observed in either the males or the female siblings. Unexpectedly, the mothers exhibited little such antitumor cellular immunity following the carcinogenic insult; even though all previous investigations of adult animals always demonstrated such an immunological response following exposure to the quantities of DMH that were administered (0.1 to 20 mg per kg body wt). As a consequence, these findings tentatively implied that the state of pregnancy alters a female's response to chemical carcinogenic insults and may actually serve as a device for protection from environmentally caused cancer. The threshold detection level for DMH exposure utilizing immune measurements was found to be approximately 10 times smaller for the perinatal susceptibility to the chemical insult intimating that such tests might usefully be incorporated in those bioassays utilized for determining the cancer-causing potential of weak carcinogens. Our findings now suggest that DMH may indeed be a perinatal carcinogen and that immune responsiveness may be readily employed for identifying such substances. However, the definitive studies of actually identifying cancer following such in utero exposures remain to be accomplished.
 
Article
1,2-Cyclohexane dicarboxylic acid, diisononyl ester (DINCH) is a complex mixture of nine carbon branched-chain isomers. It has been used in Europe since 2002 as a plasticizer to replace phthalates such as di(2-ethylhexyl)phthalate (DEHP) and diisononyl phthalate (DINP). Urinary concentrations of the oxidative metabolites of DINCH, namely cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl ester (MCOCH); cyclohexane-1,2-dicarboxylic acid-mono(oxo-isononyl) ester (MONCH); and cyclohexane-1,2-dicarboxylic acid-mono(hydroxy-isononyl) ester (MHNCH), can potentially be used as DINCH exposure biomarkers. The concentrations of MCOCH, MONCH and MHNCH were measured by online solid phase extraction-high performance liquid chromatography-tandem mass spectrometry in urine collected in 2000 (n=114), 2001 (n=57), 2007 (n=23), 2009 (n=118), 2011 (n=94) and 2012 (n=121) from convenience groups of anonymous U.S. adult volunteers with no known DINCH exposure. None of the DINCH metabolites were detected in samples collected in 2000 and 2001. Only one sample collected in 2007 had measureable concentrations of DINCH metabolites. The detection rate for all three metabolites increased from 2007 to 2012. The presence of oxidative metabolites of DINCH in urine suggests that these oxidative metabolites can be used as DINCH biomarkers for exposure assessment even at environmental exposure levels.
 
Article
The oral administration of dieldrin (1.25, 2.50, or 5.00 mg/kg daily × 5) significantly reduced the total uptake and subsequent metabolism of labeled androgens in the mouse anterior prostate gland. The in vivo metabolism of testosterone-1,2-3H to dihydrotestosterone-3H (DHT-3H), androstanediol-3H, or androstenedione-3H by the mouse prostate gland was lowered by pretreatment with dieldrin. Similarly, the in vitro metabolism of testosterone-1,2-3H to these aforementioned radiometabolites was reduced by dieldrin at a treatment level of 5 mg/kg (daily × 5). This highest-dose regimen also reduced the formation of the metabolites of testosterone in mouse hepatic microsomes. Varying concentrations of dieldrin (4 × 10−7, 4 × 10−6, or 2 × 10−5m) in vitro effectively decreased the formation of DHT-H3 in the mouse anterior prostate gland and of androstanediol-3H in the rat ventral prostate gland.
 
Article
The possible maternal hepatic and reproductive effects of 1,2,4-trichlorobenzene (TCB) were assessed in rats given 0, 36, 120, 360, and 1200 mg/kg/day of TCB on Days 9-13 of gestation. The animals were sacrificed on Day 14 of pregnancy. Maternal deaths (2/9 rats, 6/6 rats) were recorded in the 360 and 1200 mg/kg/day treatment groups and body weight gain was significantly decreased in the 360 mg/kg/day TCB group. Maternal liver weight, liver/body weight ratio, and hepatic microsomal protein content were unaffected by TCB treatment. Although Day 14 NADPH-cytochrome c reductase activity was affected only at 360 mg/kg/day TCB, the maternal hepatic microsomal cytochrome P-450 content was significantly increased by administration of both 120 and 360 mg/kg/day of TCB. Hepatic microsomal aminopyrine N-demethylase, ethoxyresorufin O-deethylase, and UDP-glucuronyl transferase activity towards p-nitrophenol were also increased at 120 and 360 mg/kg TCB. Glutathione S-transferase activity to 1-chloro-2,4-dinitrobenzene and 1,2 dichloro-4-nitrobenzene were both increased by pretreatment with TCB. Although pretreatment with 360 mg/kg/day TCB did not increase resorptions, embryolethality, or teratogenicity, embryonic development was significantly retarded by all four growth criteria used (head length, crown-rump length, somite number, and protein content).
 
Article
Interactions between dietary calcium (Ca) and lead (Pb) which influence serum levels of the vitamin D hormone, 1,25-dihydroxyvitamin D (1,25(OH)2D), intestinal Ca and Pb absorption, and body Pb retention were investigated in chicks. In a 5 x 5 (levels of Ca and Pb) design, response surface modeling was used to describe and compare the various interactions. Lead ingestion and Ca deficiency alone or in combination generally increased serum 1,25(OH)2D levels over most of the range of dietary Ca and Pb. However, in severe Ca deficiency, Pb ingestion resulted in marked decreases in hormone concentration. Overall similarities in response profiles for 1,25(OH)2D, intestinal Ca absorption and calbindin-D suggest that major interactions between Pb and Ca are mediated via changes in circulating 1,25(OH)2D concentration, rather than direct effects on the intestine. The response profiles for Ca and Pb absorption differed, in part, suggesting that intestinal transport of the two cations may not be identical. Kidney and bone Pb content also differed in response to varying Ca and Pb levels, providing evidence for additional tissue-specific interactions not related to 1,25(OH)2D. The present study provides a comprehensive basis on which to interpret the results of previous clinical and experimental results.
 
Article
Cadmium is a widespread environmental pollutant, which is associated with increased risk of osteoporosis. It has been proposed that cadmium's toxic effect on bone is exerted via impaired activation of vitamin D, secondary to the kidney effects. To test this, we assessed the association of cadmium-induced bone and kidney effects with serum 1,25-dihydroxyvitamin D (1,25(OH)(2)D); measured by enzyme immunoassay. For the assessment, we selected 85 postmenopausal women, based on low (0.14-0.39 microg/L) or high (0.66-2.1 microg/L) urinary cadmium, within a cross-sectional population-based women's health survey in Southern Sweden. We also measured 25-hydroxy vitamin D, cadmium in blood, bone mineral density and several markers of bone remodeling and kidney effects. Although there were clear differences in both kidney and bone effect markers between women with low and high cadmium exposure, the 1,25(OH)(2)D concentrations were not significantly different (median, 111 pmol/L (5-95th percentile, 67-170 pmol/L) in low- and 125 pmol/L (66-200 pmol/L) in high-cadmium groups; p=0.08). Also, there was no association between 1,25(OH)(2)D and markers of bone or kidney effects. It is concluded that the low levels of cadmium exposure present in the studied women, although high enough to be associated with lower bone mineral density and increased bone resorption, were not associated with lower serum concentrations of 1,25(OH)(2)D. Hence, decreased circulating levels of 1,25(OH)(2)D are unlikely to be the proposed link between cadmium-induced effects on kidney and bone.
 
Article
Eight adult healthy male volunteers were exposed to 1.0 ppm nitric oxide (NO) with intermittent light exercise for 2 hr. No one showed any symptoms during NO exposure. A small, but significant, decrease of specific airway conductance was observed in half of the subjects. As a group, a significant reduction of the percentage increase of maximal expiratory flow at 50% of forced vital capacity while breathing a He-O/sub 2/ gas mixture as compared with air was observed among various pulmonary function tests. These results suggested that some physiological response to NO exposure might be observed in some subjects when performing exercise.
 
Article
Bouwman and coauthors present data and analyses of DDT and other halogenated pollutants in environmental samples and based on their data and analyses thereof, argue against the use of DDT for malaria control. Regrettably, the analyses, presentations, and interpretations of data presented by Bouwman and coauthors are biased and erroneous.
 
Article
Measurements of ultra-low ambient blood lead (PbB) concentrations (mean +/- SD = 0.13 +/- 0.06 micrograms/dL) in Northern elephant seal (Mirounga angustirostris) validate previous estimates of ultra-low PbB levels in preindustrial humans. These estimates had been unsubstantiated, since PbB levels in this range had never been measured in any organisms prior to this study. Similarities in PbB levels among these contemporary and preindustrial mammals are consistent with similarities in their measured and estimated lead exposures, respectively. The marginally higher PbB levels and rates of lead exposure in contemporary marine mammals are, also, consistent with lead isotopic composition analyses that indicate their PbB levels have been elevated from exposure to industrial lead. Consequently, these analyses substantiate concerns that current baseline PbB levels in humans, which are estimated to be two to three orders of magnitude above natural levels, may still constitute public health risks.
 
Article
The retention, tissue distribution, and excretion of 103Pd in adult rats was determined following oral, intravenous (iv), and intratracheal admission. The highest retention was obtained following iv dosing, and lowest retention (less than 0.5%) occurred after oral dosing. Tissues containing the highest concentrations of 103Pd were the kidney, spleen, liver, lung, and bone. Following a single oral dose, almost all of the 103Pd was excreted in the feces due to nonabsorption, whereas after iv dosing, similar quantities were excreted in both the urine and feces. In pregnant rats following iv dosing, 103Pd did not readily move across the placental barrier, and statistically significant amounts of 103Pd were not found in all the fetuses. Furthermore, 103Pd was transferred to suckling rats via the dam's milk.
 
Article
Understanding the gender similarities and differences in how organisms respond following exposure to environmental chemicals is important if we are to determine the relative risk of these agents to wildlife and human populations. In this paper, we have chosen to focus on the sex determination and differentiation of fishes, amphibians, and reptiles, because of their close association with the environment and the number of environmental factors (e.g., temperature and endocrine disrupting chemicals) that are known to affect these phenomena in these taxa. We have discussed examples of gender differences in response to exposure to endocrine disrupting chemicals and found gender similarities about as often as we found differences. We found that most studies examined either one sex exclusively, or the experimental design did not include examining the effect of sex as a variable. Given the central role of sex steroid hormones in the sex determination and sexual differentiation of fishes, amphibians, and reptiles, we recommend that future research purposefully include sex as a factor, so that risk assessment by government agencies can address the probable gender differences in effects from exposure to chemicals in the environment.
 
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Clinical Features and Treatment of Patients Sex Total Male Female n (%)
Article
The present study reports a thorough investigation of the sociodemographic characteristics, clinical findings, and treatment of persons affected acutely by chlorine gas exposure from a chlorine tank belonging to the municipality of Diyarbakir. One hundred six persons were assessed. In this cross-sectional study, 58 patients were male and 48 were female. Children and adolescents younger than 18 years constituted more than half of the patients (60 cases, 56.6%). The age of patients ranged between 3 months and 75 years. Among the cases evaluated in emergency rooms, 7 patients had mild poisoning and were discharged after first examinations and symptomatic treatments, 62 patients were moderately affected and were taken under observation, and the remaining 37 were severely affected and were hospitalized. In physical examinations, 29 patients had expiratory wheezing, and 1 had tachycardia and extrasystoles. There were no deaths among these patients, acute chlorine intoxication affected mostly children. Respiratory tract findings were predominant in most of the patients. Steroid and bicarbonate applications were inadequate supportive therapies. Humidified O(2) and beta-agonist applications were most useful in the therapy of acute chlorine intoxication.
 
Article
The Seychelles Child Development Study has been unable to confirm any relationship between maternal exposure to MeHg during pregnancy and adverse developmental outcomes. In this report, 87 children from a pilot cohort were evaluated at 9 years of age. Each child was given a battery testing specific cognitive, visual motor, and motor skills using standardized psychometric and neuro-psychological tests. The results indicated no adverse association between maternal MeHg exposure and any developmental outcome measure. For three endpoints (Boston Naming Test and two tests of visual motor coordination), enhanced performance in males was associated with increasing prenatal MeHg exposure. A secondary analysis including both prenatal MeHg and postnatal MeHg exposure was done even though we lacked postnatal hair for about 35% of the cohort. The results of the secondary analysis mirrored the outcomes of the primary analysis regarding prenatal exposure but were less robust. The results of this study are consistent with earlier findings from the 66-month evaluations of the SCDS Main cohort. Since MeHg is neurotoxic, this effect is likely due to other factors associated with consumption of fish.
 
Article
Sequential injections of 109Cd on mice were performed to demonstrate the accumulation patterns of cadmium in various organs in mammals at tracer level. During the experimental period of 130 days, slow and upward accumulation of the tracer continued in most organs except gonads in which the equilibrium was attained. These linear increments showed slightly downward projection as sigmoid, which suggested the fitness to the two-compartment-model. More than a thousandfold difference of 109Cd concentrations among different organs was observed, and these striking differences of tissue levels manifested the strong tissue specificity of cadmium distribution. Sexual variation was also demonstrated; in blood, stomach, liver, spleen and kidneys the tracer concentrations in females were from 1.1 to 1.5 times those of the males, while in the skeletons males kept a 1.5-fold higher concentration of the tracer.
 
Article
Independent experiments have been performed at two centers, to evaluate the dosimetric properties of their respective 109Cd K X-ray fluorescence (XRF) bone lead measurement systems. Measurements were made of the dose to several points on the skin on the lower leg, at the surface of the tibia, in the red marrow tibia cavity, at the midcalf, and in the abdominal region occupied by the conceptus. Overall agreement between the two data sets was found. Similarities and differences are discussed. The effective dose values for an in vivo measurement of tibia lead concentration in 1-, 5-, and 10-year-old and adult subjects were calculated from one data set to be 1100, 420, 190, and 34/38 (male/female) nSv, respectively, for an in vivo median precision (one standard deviation) of 4.9 micrograms Pb (g bone mineral)-1 for a 30-min adult measurement.
 
Article
Adult and neonatal rats and neonatal pigs were gavaged with solutions of metal radionuclides to determine gastrointestinal absorption. Zinc-65 and technetium-95m were well-absorbed by both age groups; chromium-51, cadmium-109, tin-113, promethium-147, and plutonium-238 were not. The quantities of the poorly absorbed metals that were absorbed by neonates were between 4 and 100 times higher than those absorbed by adult rats. Autoradiograms prepared from the entire small intestine of the neonatal rat showed that 109Cd was retained in the duodenum. In contrast, measurements in the piglets showed much higher 109Cd retention in the ileum than in the duodenum. Autoradiograms and radiochemical measurements of 147Pm and 238Pu in both neonatal rats and swine showed the highest level of retention in the ileum. The results indicate that, for most of the metals studied, absorption from the gastrointestinal tract is substantially higher for neonatal than for adult rats.
 
Article
Arsenic (As) is a common element in the environment with many industrial uses, but it also can be a contaminant in drinking water and present serious health concerns. Earlier studies on the quality of drinking water in the city of Hermosillo, Sonora, México, showed high levels of As (> 0.05 ppm) in water from wells located in the northern part of the city. Additionally a high positive correlation between the levels of Fluoride (F) and As in the same wells was found. Therefore, the objective of this study was to determine the excretion of As in children, 7-11 years of age, that had been exposed to elevated levels of As in their drinking water. Twenty-four-hour urine samples and a water sample taken directly in the home were collected from school age children living in two different areas with known high levels of As in their drinking water. A control group with normal levels of As in their water was also included. As was determined by an atomic absorption-hydride generator, verified with the use of NBS certified standards (SRM 1643a and SRM 2670). None of the water samples exceeded the limit established for drinking water; however, there was a significant difference between the intake of As and the As in drinking water among the three areas of the study. Average As in water was 0.009 +/- 0.002 and 0.030 +/- 0.011 micrograms/ml between the control and high areas. Intake (in micrograms/day) was 15 +/- 3 and 54 +/- 18. In the group consuming water with high levels of As, 65% of the children exceeded the recommended dose of < 1 micrograms/kg/day (EPA, 1988). Several children in this study also had high levels of As in their urine. Even though As levels in the drinking water are within the norms, it appears that children exposed to high levels of As in their drinking water may have a health risk.
 
Article
Maternal consumption of fish during the gestational period exposes the fetus to both nutrients, especially the long-chain polyunsaturated fatty acids (LCPUFAs), believed to be beneficial for fetal brain development, as well as to the neurotoxicant methylmercury (MeHg). We recently reported that nutrients present in fish may modify MeHg neurotoxicity. Understanding the apparent interaction of MeHg exposure and nutrients present in fish is complicated by the limitations of modeling methods. In this study we fit varying coefficient function models to data from the Seychelles Child Development Nutrition Study (SCDNS) cohort to assess the association of dietary nutrients and children's development. This cohort of mother-child pairs in the Republic of Seychelles had fish consumption averaging 9 meals per week. Maternal nutritional status was assessed for five different nutritional components known to be present in fish (n-3 LCPUFA, n-6 LCPUFA, iron status, iodine status, and choline) and associated with children's neurological development. We also included prenatal MeHg exposure (measured in maternal hair). We examined two child neurodevelopmental outcomes (Bayley Scales Infant Development-II (BSID-II) Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI)), each administered at 9 and at 30 months. The varying coefficient models allow the possible interactions between each nutritional component and MeHg to be modeled as a smoothly varying function of MeHg as an effect modifier. Iron, iodine, choline, and n-6 LCPUFA had little or no observable modulation at different MeHg exposures. In contrast the n-3 LCPUFA docosahexaenoic acid (DHA) had beneficial effects on the BSID-II PDI that were reduced or absent at higher MeHg exposures. This study presents a useful modeling method that can be brought to bear on questions involving interactions between covariates, and illustrates the continuing importance of viewing fish consumption during pregnancy as a case of multiple exposures to nutrients and to MeHg. The results encourage more emphasis on a holistic view of the risks and benefits of fish consumption as it relates to infant development.
 
Article
The apparent fractional absorption of cadmium (Cd) from sunflower kernels (SFK) was determined in women volunteers by using kernels labeled with a stable isotope of Cd ((113)Cd) by injecting it into the flowering head. Fourteen women who were between the ages of 30 and 70 years, who did not use tobacco products, who were in good health, and who had been consuming a self-selected diet low in Cd content participated in the study. The volunteers were fed a breakfast composed primarily of cereal, milk, and fruit juice. The breakfast also contained a portion of (113)Cd-labeled SFK processed into a buttery spread. Each volunteer collected individual stool samples for 21 days beginning immediately after they had consumed the labeled kernels. The total amounts of Cd and (113)Cd excreted in each stool were determined by isotope dilution inductively coupled plasma mass spectrometry. Mean fecal Cd excretion was 14.1+/-4.1 microg/day and mean (113)Cd absorption was 10.6+/-4.4%. In agreement with previous studies, no significant (P>0.3) correlation between Cd absorption and serum ferritin concentrations was found in women whose serum ferritin concentrations were >25 ng/mL. These data suggest that the availability of Cd from highly processed sunflower kernels to humans is similar to that reported for other types of food.
 
Article
Whole body retention studies of 115mCd were carried out on rats following four different routes of administration: oral, inhalation, intraperitoneal, and intravenous. The retention curve for each route of administration was divided into two components. The first component reflected the initial rapid clearance of 115mCd primarily by the gastrointestinal tract and the second component indicated the absorption and turnover of 115mCd. Extrapolation of the second component to the intercept gave initial absorption values of 93%, 91%, 41%, and 2.3% for intraperitoneal, intravenous, inhalation, and oral routes, respectively. Immediately after inhalation exposure, 9.7% of the total inhaled Cd was present in the lungs. The route of administration did not significantly influence the rate of elimination and biological half-life of the second component of the whole body retention curve.
 
Article
The absorption and retention of three different compounds of 115mcadmium and the effects of variations in concentration were studied in female rats. After a single oral dose, the chloride, sulfate, and acetate forms of 115mCd did not significantly influence the absorption, retention, or distribution of the 115mCd in the tissues. The only organs containing significant amounts of 115mCd were the liver, kidney, and gastrointestinal tract. Increases in concentration of cadmium resulted in more cadmium being absorbed from the gastrointestinal tract, although the amount absorbed was not proportional to the increase in concentration.
 
Article
Six-day-old suckling rats were artificially fed over 8 hr with cow's milk or rat's diet labeled with 85Sr, 115mCd, or 203Hg. The whole-body radioactivity was determined in a double-crystal scintillation counter every 24 hr over a 6-day period. Rat's diet caused a reduction in the whole-body retention of all radioisotopes which was highest for 203Hg and lowest for 85Sr. All sucklings were killed 6 days after the radioisotope administration and the radioactivity was determined in the carcass and in the gut. Rat's diet reduced carcass retention by about 10% for 85Sr, and two and three times for 115mCd and 203Hg, respectively. Rat's diet also reduced gut retention by about 20% for 85Sr, two times for 115mCd and eight times for 203Hg. It is concluded that dietary factors are partly responsible for the high metal absorption in sucklings. This specially applies to mercury because rat's diet caused a considerable reduction in the whole-body retention of this metal primarily by decreasing its gut retention.
 
Article
The influence of age on whole-body retention and organ distribution of intraperitoneally applied 115mCdCl2 was studied in 1-, 3-, 6-, and 52-week-old rats. The mean percent values of 115mCd retention in the whole body decreased with increasing age. The distribution of 115mCd in the body on the 14th day after application shows that in all age groups most of the cadmium is accumulated in the liver (45–56%) and kidneys (4–6%). In younger rats the percentage of cadmium in the kidney and blood was always higher than in older animals in contrast to the liver where it was lower. The percentage of the dose in the liver, kidneys, and blood represents however, a considerably lower fraction of the total whole-body retention in younger animals than in older rats. It is therefore concluded that age bears a significant influence on cadmium metabolism. This might be important for estimating cadmium body burden and critical organ exposure in the youngest age group.
 
Article
Twenty-four pairs of adult mallards were fed a diet containing 0 or 150 ppm of the PCB Aroclor 1242 for 12 weeks during which egg laying was induced. Laying started in both groups an average of 33 days after PCB treatment began. All hens were allowed to lay a 20-egg clutch; 15 eggs from each clutch were artificially incubated. Eleven hens from each group completed the clutch. There was no difference between the two groups in the time taken to lay the clutch, nor was there a difference in fertility, embryo mortality, or hatching success. Eggshell thickness decreased 8.9% with PCB ingestion; eggs from hens fed PCB contained an average of 105 ppm PCB wet wt. No difference in survival or weight gain to 3 weeks of age was observed between young mallards from eggs laid by PCB-treated hens and control hens.
 
Article
Adult male rhesus monkeys (Macaca mulatta) were given oral treatment of either Aroclor 1242 or vehicle (corn oil and glycerol) at a dose of 200 microg/kg body wt/day for 6 months to investigate the effects of the pollutant on plasma testosterone and the morphology of testes and accessory glands. Aroclor 1242 treatment significantly decreased testicular size and testosterone levels in plasma and adversely affected spermatogenic activity by disrupting epithelial organization. All components of the germinal epithelium were greatly reduced. The spermatogonia were either hypertrophied or had shrunken vesiculated cytoplasm with distorted mitochondria and nuclear pyknosis. Changes were milder in the Sertoli cells, where nuclear infoldings were reduced. Characteristic features of treated Leydig cells were the presence of electron-dense and electron-opaque zones, appearing as plaques, cell membrane abnormalities, and high variability in nuclear shape and heterochromatin distribution. All the Aroclor 1242-treated accessory glands contained more connective tissue than their vehicle-treated counterparts. The epithelium contained many layers of irregularly shaped necrotic cells possessing stereocilia in the epididymides, either hypochromic and hypertrophied or hyperchromic and hypotrophied cells in the prostate and shrunken cuboidal cells with elongated nuclei in the seminal vesicles. In conclusion, Aroclor 1242 treatment causes severe structural alterations on gonads and accessory organs in adult male rhesus monkeys, and these effects could be mediated through both estrogen and Ah receptors.
 
Article
The effects of a 21-week exposure to Aroclor 1242 (1mg per day in feed) on plasma concentrations of vitamins A(1) (retinol) and A(2) (3,4-didehydroretinol) and their principal fatty acyl esters (A(1)-16:0, A(2)-16:0 (palmitates), A(1)-18:1n-9; A(2)-18:1n-9 (oleates), and A(1)-18:0; A(2)-18:0 (stearates)) were studied in young female mink (Mustela vison) fed a diet based on freshwater smelt. These vitamin levels were also examined in mink fed diets containing Baltic herring or fatty marine fish. In the Aroclor-exposed smelt-fed mink, the plasma concentrations of A(1) and A(2) esters were significantly lower than the levels in controls fed the uncontaminated smelt diet. In addition, the A(2) esters reacted more sensitively to the polychlorinated biphenyls than did A(1) esters. In contrast, in the plasma of the exposed mink the level of alcoholic A(1) was normal, and transport of thyroxine (T(4)) and nonspecific lipoprotein transport of major lipids were not impaired. Despite the large dietary supply of vitamin A(2) and high levels of plasma A(2) esters, the mink fed freshwater smelt had only trace amounts of alcoholic vitamin A(2) in their plasma. The concentrations of A(1) and A(2) esters in the plasma of all the mink studied correlated with the hepatic total concentrations of the vitamins. Thus, in carnivores that have nonspecific lipoprotein transport of vitamin A esters, determination of plasma levels of the esterified vitamins may be a useful nondestructive way to estimate stores of the vitamin A analogs in the body and to assess the organochlorine-induced decrease in the vitamin stores.
 
Article
Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that contribute to worldwide health problems. Despite data associating PCBs with adverse health effects, decisions to clean up contaminated sites remain controversial. Cleanup decisions are typically based on risk assessment methods that are not sensitive enough to detect subtle changes in health. We have recently shown that gene expression signatures can serve as sensitive molecular biomarkers of exposure and related health effects. Our initial studies were carried out with developing Xenopus laevis tadpoles that were exposed to the PCB mixture Aroclor 1254 (A1254) for 2 days. A1254 was dissolved in dimethyl sulfoxide and added to the aquarium water for rapid loading of PCBs into the tadpole tissue. These studies showed that increases in the expression of specific genes occurred independent of adverse health effects, and decreases in specific genes correlated with the appearance of observable health effects, including decreased survival and gross morphological and behavioral abnormalities. In this report, we extend our previous work to test the use of gene expression signatures as biomarkers in frogs exposed to PCBs through the diet from early tadpole stages through metamorphosis. This work showed that chronic low-dose exposure to A1254 (24 ppm) in food produced tissue levels of 17 ppm and increased gene expression of nerve growth factor and proopiomelanocortin independent of adverse health effects. Exposure to higher doses of A1254 (200 ppm) produced tissue levels of 80 ppm and increased expression of p450 1A1, also, independent of adverse health effects. This work provides further evidence for the use of gene expression changes as biomarkers of exposure to PCBs.
 
Article
Aroclor 1254 was administered intravenously at 30-minute intervals to anesthetized cats at a dosage of 100 mg/kg body weight. Arterial and venous blood samples were taken at 10-minute intervals for determination of oxygen tension (pO2), carbon dioxide tension (pCO2), and pH. Electrocardiograms, blood pressure, and respiration were recorded as well. The pO2 of the blood was reduced rapidly and markedly with concurrent changes in pCO2 and pH characterizing a respiratory acidosis. Respiratory rate increased to a sizable degree with development of cardiac arrhythmias. All animals died within 60 minutes following initial dosing. Severely hemorrhagic lungs in conjunction with edema were observed in all cats at necropsy.
 
Article
Adult male mallards were exposed to 0, 4, 20, 100, 250, and 500 mg/kg Aroclor 1254 by gavage twice per week for 5 weeks. Immunotoxic effects, as measured by antibody titers to sheep erythrocytes, natural killer cell activity and lymphocyte mitogenesis to phytohemagglutinin, were not detected as a consequence of polychlorinated biphenyl (PCB) exposure. Hepatic cytochrome P450 activities were measured as microsomal dealkylations of ethoxyresorufin (EROD) and pentoxyresorufin (PROD). Significant elevations in EROD and PROD were noted at 20 mg/kg and peaked in birds treated with 100 mg/kg. Total P450 was induced beginning at 100 mg/kg and peaked at 250 mg/kg. Relative liver weights were dose-dependently increased following treatment with 100 mg/kg or more. Thyroid weights were significantly increased in PCB-treated birds treated with 100 mg/kg or greater, but no significant histological abnormalities were observed, except at the highest dose. Plasma total triiodothyronine (T3) was decreased in a dose-dependent manner, with a significant lowest-observed-adverse-effect level (LOAEL) of 20 mg/kg. T3 was decreased following 7 days treatment with 100 mg/kg. The no-observed-adverse-effect level (NOAEL) was 4 mg/kg for decreased T3. Plasma glucose levels were decreased on days 28 and 35 in mallards treated with 500 mg/kg, while other clinical plasma biochemistry parameters were unaltered by PCB treatment. Plasma corticosterone levels were unchanged by PCB treatment. These results indicate that thyroid hormone levels and P450 activity in mallards are sensitive to subchronic PCB exposure in the absence of gross toxic effects and immunotoxicity.
 
Article
Male F344/NCr rats were exposed to low dietary concentrations of Aroclor 1254 (0-33 ppm) for 7 days, following which the induction of selected hepatic drug metabolizing enzymes was monitored. CYP1A1, measured indirectly by assaying the O-dealkylation of ethoxyresorufin in 9000 g supernatants, was increased 1.5-, 3-, 8-, and 37-fold following 7 days of exposure to 1.0, 3.3, 10, and 33 ppm Aroclor, respectively. In contrast, the O-dealkylation of benzyloxyresorufin, an indirect measure of CYP2B1 activity, was increased approximately 4-fold following exposure to 33 ppm dietary Aroclor. Measurement of the non-P450-mediated activities epoxide hydrolase, DT-diaphorase, and aldehyde dehydrogenase (NADP+, benzaldehyde) revealed < 4-fold inductions following feeding of 33 ppm Aroclor. In view of the relatively high sensitivity of the CYP1A-specific catalytic endpoint as a biomarker for Aroclor exposure, alternative endpoints for detecting induction of this subfamily of P450 were also examined. The extent of in vivo CYP1A induction was assessed by measuring serum concentrations of zoxazolamine 150 min following an intraperitoneal dose of 100 mg/kg body wt. Slight decreases in serum zoxazolamine concentration were observed in rats exposed to as little as 1.0 ppm dietary Aroclor 1254, while profound decreases were seen in rats exposed to > or = to 10 ppm Aroclor. Immunodetection of CYP1A1 protein, with a monoclonal antibody directed against this cytochrome, revealed a 2.9-fold increase in rats exposed to as little as 1.0 ppm Aroclor, and approximately 10- and 44-fold increases following exposure to 3.3 and 10 ppm dietary Aroclor, respectively. Increases in total hepatocellular RNA coding for CYP1A1 and CYP1A2, quantified by hybridization to specific oligonucleotide probes, corresponded well to the increases in hepatic O-dealkylase activity for ethoxyresorufin (CYP1A1) and methoxyresorufin (CYP1A2), respectively. Thus, CYP1A induction, directly or indirectly measured with a variety of endpoints, represents a highly sensitive biomarker for exposure to relatively low doses of Aroclor 1254 in the rat.
 
Article
The potential exposures of 127 preschool children to the pyrethroid insecticides, cis- and trans-permethrin, in their everyday environments were examined. Participants were recruited randomly from 127 homes and 16 daycare centers in six Ohio (OH) counties. Monitoring was performed over a 48-h period at the children's homes and/or daycare centers. Samples collected included soil, carpet dust, indoor air, outdoor air, diet, hand wipes, surface wipes, transferable residues, and urine. The environmental samples were analyzed for the cis and trans isomers of permethrin, and the urine samples were analyzed for the pyrethroid urinary metabolite, 3-phenoxybenzoic acid (3-PBA), by gas chromatography/mass spectrometry. The isomers were detected most often in the dust (100%) and hand wipe (>78%) samples collected at both homes and daycare centers. The median levels of cis-permethrin (470 and 1010 ng/g) were higher than the median levels of trans-permethrin (344 and 544 ng/g) in the dust samples at both the children's homes and daycare centers, respectively. In the children's hand wipe samples, the median levels of cis- and trans-permethrin were similar, ranging from 0.03 to 0.04 ng/cm(2), at both locations. The urinary metabolite 3-PBA was detected in 67% of the children's urine samples. The median urinary 3-PBA concentration for the children was 0.3 ng/mL, and the maximum value for one child was 33.8 ng/mL. The primary route of the children's exposure to the combined isomers was through dietary ingestion, followed by indirect ingestion. In addition, our calculated aggregate absorbed doses of permethrin accounted for about 60% of the excreted amounts of 3-PBA found in the children's urine. In conclusion, these children were potentially exposed to low levels of permethrin from several sources, and through several pathways and routes.
 
Top-cited authors
Charles James Moore
  • Algalita Marine Research and Education
Michael Brauer
  • University of British Columbia - Vancouver
Margarita Triguero-Mas
  • Instituto de Salud Global de Barcelona & BCNUEJ (ICTA-UAB, IMIM)
Adrian Barnett
  • Queensland University of Technology
Michael Jerrett
  • University of California, Los Angeles