Adverse Effects Of Long-term Exposure Research Articles

Long-term lithium treatment in bipolar disorder: effects on glomerular filtration rate and other metabolic parameters

BackgroundConcerns about potential adverse effects of long-term exposure to lithium as a mood-stabilizing treatment notably include altered renal function. However, the incidence of severe renal dysfunction; rate of decline over time; effects of lithium dose, serum concentration, and duration of treatment; relative effects of lithium exposure vs. aging; and contributions of sex and other factors all remain unclear.MethodsAccordingly, we acquired data from 12 collaborating international sites and 312 bipolar disorder patients (6142 person-years, 2669 assays) treated with lithium carbonate for 8–48 (mean 18) years and aged 20–89 (mean 56) years. We evaluated changes of estimated glomerular filtration rate (eGFR) as well as serum creatinine, urea–nitrogen, and glucose concentrations, white blood cell count, and body-mass index, and tested associations of eGFR with selected factors, using standard bivariate contrasts and regression modeling.ResultsOverall, 29.5% of subjects experienced at least one low value of eGFR (<60 mL/min/1.73 m2), most after ≥15 years of treatment and age > 55; risk of ≥2 low values was 18.1%; none experienced end-stage renal failure. eGFR declined by 0.71%/year of age and 0.92%/year of treatment, both by 19% more among women than men. Mean serum creatinine increased from 0.87 to 1.17 mg/dL, BUN from 23.7 to 33.1 mg/dL, glucose from 88 to 122 mg/dL, and BMI from 25.9 to 26.6 kg/m2. By multivariate regression, risk factors for declining eGFR ranked: longer lithium treatment, lower lithium dose, higher serum lithium concentration, older age, and medical comorbidity. Later low eGFR was also predicted by lower initial eGFR, and starting lithium at age ≥ 40 years.LimitationsControl data for age-matched subjects not exposed to lithium were lacking.ConclusionsLong-term lithium treatment was associated with gradual decline of renal functioning (eGFR) by about 30% more than that was associated with aging alone. Risk of subnormal eGFR was from 18.1% (≥2 low values) to 29.5% (≥1 low value), requiring about 30 years of exposure. Additional risk factors for low eGFR were higher serum lithium level, longer lithium treatment, lower initial eGFR, and medical comorbidity, as well as older age.

Chronic adverse effects of long-term exposure of children to dichlorodiphenyltrichloroethane (DDT) through indoor residual spraying: a systematic review

Malaria remains a significant public health problem in endemic regions of the world, most especially in sub-Saharan Africa. As part of the global efforts to control malaria, dichlorodiphenyltrichloroethane (DDT), a cheap and effective chemical, was endorsed by the World Health Organization for use in indoor residual spraying (IRS). However, in the light of evidence on the acute toxicity of DDT, concerns have grown about the safety or the possible chronic health effects from the continued use of this persistent chemical, generating much debate and research efforts over the years. The purpose of this study was to identify, appraise and synthesise evidence about the chronic adverse effects of long-term exposure to DDT in children, 0-18 years, in zones where IRS is practised, in order to contribute to informing policy decisions. Twenty-seven electronic databases were systematically searched using pre-defined inclusion/exclusion criteria. Two were trial registers while 25 others indexed studies of various designs. Other complementary methods were also employed in searching for both published and grey literature. Eligible studies were critically appraised using amended versions of available validated guidelines (and in a case, an improvised guideline) and a narrative synthesis was undertaken. Only nine studies met the inclusion/exclusion criteria out of 3281 hits generated. Five of the studies are of high quality while four are of moderate quality. For the three studies on neurodevelopment, evidence suggestive of negative impact of DDT was found. For the three studies on endocrine/congenital disorders, ambivalent evidence existed. In the case of the immunity-related outcome, there was growing but insufficient evidence of negative effect. The only study on survival outcome was inconclusive. Empirically, insufficient evidence exists with regard to the chronic adverse effects of long-term exposure of children to DDT through IRS. Considering the dearth of studies and the fact that many adverse effects might take much longer time to manifest, inferences drawn are weak. It would therefore require a series of well-coordinated observational studies done in the context of IRS to adequately address this evidence gap in the future.

Long-Term Effects of Traffic Particles on Lung Function Decline in the Elderly

Few studies have been performed on air pollution effects on lung function in the elderly, a vulnerable population with low reserve capacity, and even fewer have looked at changes in the rate of lung function decline. We evaluated the effect of long-term exposure to black carbon on levels and rates of decline in lung function in the elderly. FVC and FEV1 were measured one to six times during the period 1995-2011 in 858 men participating in the Normative Aging Study. Exposure to black carbon, a tracer of traffic emissions, was estimated by a spatiotemporal land use regression model. We investigated the effects of moving averages of black carbon of 1-5 years before the lung function measurement using linear mixed models. A 0.5 μg/m(3) increase in long-term exposure to black carbon was associated with an additional rate of decline in FVC and FEV1 of between 0.5% and 0.9% per year, respectively, depending on the averaging time. In addition, black carbon exposure before the baseline visit was associated with lower levels of both FVC and FEV1, with effect estimates increasing up to 6-7% with a 5-year average exposure. Our results support adverse effects of long-term exposure to traffic particles on lung function level and rate of decline in the elderly and suggest that functionally significant differences in health and risk of disability occur below the annual Environmental Protection Agency National Air Quality Standards.

Adverse effects of long-term exposure to bisphenol A during adulthood leading to hyperglycaemia and hypercholesterolemia in mice.

Bisphenol A (BPA) is a suspected endocrine disruptor highly prevalent in our environment since it is used as monomer of polycarbonate plastics and epoxy resins. Recent epidemiological and animal studies have suggested that BPA exposure may influence the development of obesity and related pathologies such as type 2 diabetes, and cardiovascular diseases. However, experimental studies have often focused on short-term exposures. In this study, we investigated the effect of several months of BPA exposure on hepatic and plasma metabolic markers in adult mice. Male CD1 mice were exposed during 8 months to five different BPA doses below or equivalent to the current no observed adverse effect level (NOAEL: 5000 μg/kg/day) through drinking water. Plasma lipid profiles and liver transcriptomic analysis were performed in control and BPA-treated animals. We report a specific impact of BPA exposure on glycaemia, glucose tolerance and cholesterolemia. Consistent with the hypercholesterolemia in BPA-treated animals, RT-qPCR performed on hepatic mRNA from same animals demonstrated an overexpression of key genes involved in cholesterol biosynthesis, namely, Mvd, Lss Hmgcr, and Sqle. BPA also induced the expression of the sterol regulatory element-binding proteins 2, a master regulator of hepatic cholesterol biosynthesis. As shown by the plasma lathosterol to cholesterol ratio, a surrogate marker for cholesterol biosynthesis, whole body cholesterol de novo synthesis was also increased in BPA-exposed animals. These original results are consistent with many epidemiological studies reporting on a link between BPA exposure and the onset of cardiovascular diseases.

Metabolomic analysis of the toxic effects of chronic exposure to low-level dichlorvos on rats using ultra-performance liquid chromatography–mass spectrometry

The purpose of the current study was to assess the effects of long-term exposure to low levels of DDVP on the biochemical parameters and metabolic profiles of rats. Three different doses (2.4, 7.2, and 21.6mg/kgbody weight/day) of DDVP were administered to rats through their drinking water over 24 weeks. Significant changes in blood cholinesterase, creatinine, urea nitrogen, aspartate aminotransferase, alanine aminotransferase, and albumin concentrations were observed in the middle and high dose groups. Changes in the concentration of some urine metabolites were detected via ultra performance liquid chromatography–mass spectrometry (UPLC–MS). Dimethyl phosphate (DMP), which was exclusively detected in the treated groups, can be an early, sensitive biomarker for DDVP exposure. Moreover, DDVP treatment resulted in an increase in the lactobionic acid, estrone sulfate, and indoxyl sulfic concentrations, and a decrease in citric acid, suberic acid, gulonic acid, urea, creatinine, and uric acid. These results suggest that chronic exposure to low-level DDVP can cause a disturbance in carbohydrate and fatty acid metabolism, the antioxidant system, etc. Therefore, an analysis of the metabolic profiles can contribute to the understanding of the adverse effects of long-term exposure to low doses of DDVP.

Distinct Impact of Imatinib on Growth In Prepubertal and Pubertal Children with Chronic Myeloid Leukemia

AbstractAbstract 2277Imatinib is now widely used for treating chronic-phase chronic myeloid leukemia (CML) in children as well as in adults, and long-term adverse effects of imatinib therapy in children are now gaining attention. One of its adverse effects is the negative impact on growth in children, suggested by 3 recently published case reports. However, the incidence or prospect of growth impairment resulting from imatinib treatment has not been fully elucidated.In this study, we retrospectively analyzed the clinical records of 48 children with chronic-phase CML who were treated with imatinib as a first-line therapy between 2001 and 2006. The median age at diagnosis was 9 years (2 to 15 years). Cumulative change in height while on imatinib was assessed using the height standard deviations score (height-SDS), the converted height data from age- and sex-adjusted Japanese norms. Our data indicated that growth impairment (decrease in height-SDS) was observed in 72.9% of the patients, with median maximum reduction in height-SDS of 0.61 during imatinib treatment. Growth impairment was noticeable in children who were prepubertal at the commencement of imatinib treatment, while only mild or no growth impairment (with no decrease of height-SDS) was observed in most patients who were pubertal at the commencement of imatinib treatment. Furthermore, in prepubertal children with growth impairment, growth velocity tended to recuperate concomitant with pubertal maturation, suggesting that imatinib has little impact on growth during puberty. To our knowledge, this is the first report to describe and compare the distinct inhibitory effect of imatinib on growth in prepubertal and pubertal children with CML.Although the introduction of imatinib was a breakthrough in CML therapy, the possibility of continuous remission after discontinuation of imatinib remains uncertain. Thus, the possibility of adverse effects of long-term exposure to imatinib has become a huge issue, especially when treating children. We consider that it is important to promote awareness of growth deceleration in children, especially in young children who started imatinib treatment before puberty and are inevitably going to be subject to prolonged exposure. Disclosures:No relevant conflicts of interest to declare.

Multiple Sclerosis, Cannabinoids, and Cognition

Multiple Sclerosis, Cannabinoids, and Cognition

Longitudinal surveys on effects of changes in road traffic noise-annoyance, activity disturbances, and psycho-social well-being.

The adverse effects of long-term exposure to a high volume of road traffic were studied in socio-acoustic surveys in 1997 and in 1999 after a substantial reduction in road traffic. The results obtained in 1997 showed a similar response pattern as in previously performed studies in the area in 1986 [Ohrström, J. Sound Vib. 122, 277-290 (1989)]. In 1999, road traffic had been reduced from 25000 to 2400 vehicles per day, and this resulted not only in a large decrease in annoyance and activity disturbances, but also in a better general well-being. The results suggest that a reduction in both noise and other pollutants from road traffic contribute to these effects. To be able to use the outdoor environment and to have the possibility to keep windows open is essential for general well-being and daily behavior, which implies that access both to quiet indoor and outdoor sections of the residency is of importance for achievement of a healthy sound environment. More knowledge of long-term health consequences of exposure to noise and simultaneous pollutants from road traffic is needed. Studies should focus more on "softer" health outcomes and well-being than hitherto and preferably be performed in connection with traffic abatement measures.

Behavioral and neurochemical effects induced by subchronic exposure to 40 ppm toluene in rats

Chronic toluene inhalation at concentrations above occupational exposure limits (e.g., 100 ppm; NIOSH) has been repeatedly shown to induce neurotoxic effects. In contrast, although few clinical and experimental data are available on the effects of toluene exposure at concentrations below occupational exposure standards, some of these data may support adverse effects of long-term exposure to low toluene concentrations. To test this hypothesis, we investigated the neurobehavioral and neurochemical effects of 40 ppm inhaled toluene in a rat model of 16-week subchronic exposure, examining locomotor and rearing activities; adaptation/sensitization to narcosis produced by acute exposure to toluene at high concentration; and tyrosine hydroxylase and tryptophan hydroxylase activities, and dopamine (DA) and serotonin (5-HT) turnovers in the caudate–putamen, nucleus accumbens, hippocampus, prefrontal cortex, and cerebellum. Our results mainly show that subchronic exposure to 40 ppm toluene significantly resulted in a sensitization to toluene-induced narcosis, a decrease in rearing activity, and alterations in DA and 5-HT transmissions. This demonstrates that subchronic toluene exposure at a low concentration may lead to adverse changes in neurobehavioral and neurochemical functioning, and further questions in a public health perspective the actual neurotoxic potential of toluene and other organic compounds, because deficits in functioning are generally viewed as precursors of more serious adverse effects.

Approach and issues relating to shield material design to protect astronauts from space radiation

One major obstacle to human space exploration is the possible limitations imposed by the adverse effects of long-term exposure to the space environment. Even before human spaceflight began, the potentially brief exposure of astronauts to the very intense random solar energetic particle (SEP) events was of great concern. A new challenge appears in deep space exploration from exposure to the low-intensity heavy-ion flux of the galactic cosmic rays (GCR) since the missions are of long duration and the accumulated exposures can be high. Since aluminum (traditionally used in spacecraft to avoid potential radiation risks) leads to prohibitively expensive mission launch costs, alternative materials need to be explored. An overview of the materials related issues and their impact on human space exploration will be given.

Adverse effects of low-level air pollution on the respiratory health of schoolchildren in Hong Kong.

To evaluate the respiratory effects of long-term exposure to air pollution, schoolchildren (ages 8 to 12 years) from two districts in Hong Kong with contrasting air quality were studied. Parents of 1660 children completed questionnaires on respiratory symptoms, and 1294 children had their ventilatory function tested with a spirometer. After adjustment for relevant covariates, children living in the more polluted district had increased odds ratios for frequent cough (1.74), frequent sputum (1.87), chronic sputum (1.84), and doctor-diagnosed asthma (1.98). Children of both sexes in the more polluted district had significantly poorer lung function, and the differences among girls were more marked. The study provides additional evidence for the adverse effects of long-term exposure to relatively low-level air pollution.

Radiation exposure for human Mars exploration.

One major obstacle to human space exploration is the possible limitations imposed by the adverse effects of long-term exposure to the space environment. Even before human space flight began, the potentially brief exposure of astronauts to the very intense random solar energetic particle events was of great concern. A new challenge appears in deep-space exploration from exposure to the low-intensity heavy-ion flux of the galactic cosmic rays since the missions are of long duration, and accumulated exposures can be high. Because cancer induction rates increase behind low to moderate thicknesses of aluminum shielding, according to available biological data on mammalian exposures to galactic cosmic ray-like ions, aluminum shield requirements for a Mars mission may be prohibitively expensive in terms of mission launch costs. Alternative materials for vehicle construction are under investigation to provide lightweight habitat structures with enhanced shielding properties. In the present paper, updated estimates for astronaut exposures on a Mars mission are presented and shielding properties of alternative materials are compared with aluminum.

Materials for Shielding Astronauts from the Hazards of Space Radiations

AbstractOne major obstacle to human space exploration is the possible limitations imposed by the adverse effects of long-term exposure to the space environment. Even before human spaceflight began, the potentially brief exposure of astronauts to the very intense random solar energetic particle (SEP) events was of great concern. A new challenge appears in deep space exploration from exposure to the low-intensity heavy-ion flux of the galactic cosmic rays (GCR) since the missions are of long duration and the accumulated exposures can be high. Because cancer induction rates increase behind low to rather large thickness of aluminum shielding according to available biological data on mammalian exposures to GCR like ions, the shield requirements for a Mars mission are prohibitively expensive in terms of mission launch costs. Preliminary studies indicate that materials with high hydrogen content and low atomic number constituents are most efficient in protecting the astronauts. This occurs for two reasons: the hydrogen is efficient in breaking up the heavy GCR ions into smaller less damaging fragments and the light constituents produce few secondary radiations (especially few biologically damaging neutrons). An overview of the materials related issues and their impact on human space exploration will be given.

Urinary N‐acetyl‐β‐D‐glucosaminidase activity in lead‐exposed workers

The adverse effects of long-term exposure to lead dust on renal tubular functions were studied in 39 male and 7 female workers in a secondary lead refinery. Laboratory examinations showed low or moderate lead absorption levels. The N-acetyl-beta-D-glucosaminidase (NAG) activity in urine showed significant correlation with each of the lead exposure indices. NAG activity increased remarkably in lead workers with blood lead (PbB) above 80 micrograms 100g-1. Blood urea nitrogen (BUN) showed significant correlation with PbB and logarithmic urine delta-amino-levulinic acid (log(ALAU)), but not with urine lead (PbU) and logarithmic urine coproporphyrin (log(CPU)). All the other indices of renal function were almost within the normal range and showed no correlation with lead indices. This study suggests that moderate lead absorption may cause renal tubular impairment, and NAG can be one of the most sensitive indices for estimating renal dysfunction due to lead poisoning.

Recommendations for Protecting Human Health Against Potential Adverse Effects of Long-term Exposure to Low Doses of Chemical Warfare Agents

Recommendations for Protecting Human Health Against Potential Adverse Effects of Long-term Exposure to Low Doses of Chemical Warfare Agents

Leads from the MMWR. Recommendations for protecting human health against potential adverse effects of long-term exposure to low doses of chemical warfare agents

Leads from the MMWR. Recommendations for protecting human health against potential adverse effects of long-term exposure to low doses of chemical warfare agents

THE UCLA POPULATION STUDIES OF CHRONIC OBSTRUCTIVE RESPIRATORY DISEASE. I. METHODOLOGY AND COMPARISON OF LUNG FUNCTION IN AREAS OF HIGH AND LOW POLLUTION

The prevalence of symptoms of chronic obstructive respiratory disease and of functional respiratory impairment was determined in 3465 residents (70 per cent of enumerated) of an area historically exposed to photochemical/oxidant pollutants and 4509 residents (79 per cent of enumerated) of an area exposed to low levels of chemical pollutants. Tests administered included the NHLI questionnaire, electronic volume spirometry, whole body plethysmography, and the single-breath nitrogen test (deltaN2750-1250 and closing volume). Cough and cough with sputum were more frequently reported in the low-pollution area. Lung function was better among residents of the low-pollution area according to FEV1, FVC, maximal expiratory flow rates, closing volume fraction, thoracic gas volume, and airway resistance. Maximal mid-expiratory flow rate, considered to be a sensitive spirometric test for detection of small airways disease, was similar in residents of both areas. Mean deltaN2750-1250 was slightly worse among residents of the low-pollution area. Findings suggest that adverse effects of long-term exposure to photochemical/oxidant pollutants may occur primarily in the larger airways both among smokers and never smokers. The greatest differences between areas were observed in residents 18-59 years of age, suggesting that long-term exposure may be required to cause measurable impairment and that these differnces may be obliterated by such factors as smoking, differential out-migration and differential survival.