Moderate Exposure Levels Research Articles

Microplastic burial potential and ecological risks in mangrove forests of the Amazon River delta

Coastal mangrove ecosystems have been shown to be important microplastic (MP) sinks. Yet, information regarding their MP sequestration capacity is scant. Here, we characterized the spatial and vertical distribution of MPs in mangrove ecosystems of the Amazon River delta and quantified, for the first time, their MP burial and potential economic value related to their surface water filtering capacity. Furthermore, we assessed the ecotoxicological risks considering differing effect mechanisms for benthic organisms (i.e., food dilution and translocation-mediated effects). Soil core samples (up to 3 m) were taken from seven locations in the northern part of the Amazon River delta and analyzed for MP contamination. MPs in the 100–5000 μm range were measured and the polymer type was characterized using Fourier Transform Infrared Spectroscopy. The collected soil samples were dated based on a radionuclide analysis, and a burial analysis was done based on the sediment mass accumulation rates and the mass concentration of MPs. The outcomes of this study show that MPs are ubiquitous contaminants in mangroves of the Amazon River delta (present in 30 out of the 35 analyzed samples). The largest MP concentration was found in the upper soil layer (0–15 cm), 138 MPs/kg dw, which has been deposited and reworked during the time of the soil core collection. However, moderate exposure levels were also found in older samples (71–138 MPs/kg dw), and in samples taken before the plastic era (≈ 1870–1930), suggesting a downward MP migration. We estimated a mean burial rate of 0.32 ± 0.17 kg of MPs km2/year, which corresponds to 0.55 ± 0.28 tons per year in the Amazon River delta. Based on the estimated burial rate, we valued the removal of MPs from surface waters by these mangroves at 0.3–1.1 million USD per year. Our study shows that the exposure levels of MPs in mangroves of the Amazon River delta are relatively low when compared to other mangrove ecosystems and ecotoxicological risks for benthic organisms are not expected given the current exposure levels.

Air pollution exposure during pregnancy and lung function in childhood: The LUIS study.

The adverse effects of high air pollution levels on childhood lung function are well-known. Limited evidence exists on the effects of moderate exposure levels during early life on childhood lung function. We investigated the association of exposure to moderate air pollution during pregnancy, infancy, and preschool time with lung function at school age in a Swiss population-based study. Fine-scale spatiotemporal model estimates of particulate matter with a diameter <2.5 µm (PM2.5) and nitrogen dioxide (NO2) were linked with residential address histories. We compared air pollution exposures within different time windows (whole pregnancy, first, second, and third trimester of pregnancy, first year of life, preschool age) with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) measured cross-sectionally using linear regression models adjusted for potential confounders. We included 2182 children, ages 6-17 years. Prenatal air pollution exposure was associated with reduced lung function at school age. In children aged 12 years, per 10 µg·m-3 increase in PM2.5 during pregnancy, FEV1 was 55 mL lower (95% CI -84 to -25 mL) and FVC 62 mL lower (95% CI -96 to -28 mL). Associations were age-dependent since they were stronger in younger and weaker in older children. PM2.5 exposure after birth was not associated with reduced lung function. There was no association between NO2 exposure and lung function. In utero lung development is most sensitive to air pollution exposure, since even modest PM2.5 exposure during the prenatal time was associated with reduced lung function, most prominent in younger children.

Potential lethality of organochlorine pesticides: Inducing fatality through inflammatory responses in the organism

BackgroundOrganochlorine pesticides, with their environmental persistence and bioaccumulation potential, have gained significant attention. This study explores the impact of organochlorine pesticides on mortality and chronic diseases, investigates their link to inflammatory states, and examines the role of anti-inflammatory diets in mitigating adverse reactions to these pesticides. MethodsThis study, with 2,847 participants, used gas chromatography and mass spectrometry to measure organochlorine pesticide exposure in NHANES data. Conventional statistical methodologies, encompassing survival curves, Cox proportional hazards regression, regression analysis, and restricted quadratic spline analysis, were employed to investigate the association between pesticides and mortality, chronic ailments, and inflammation. Furthermore, machine learning techniques, comprising RF, AdaBoost, Extra-Trees, LightGBM, and BPNN, were leveraged to evaluate the impact of pesticides on chronic disease and mortality prognostication. ResultsOrganochlorine pesticides were significantly and positively correlated with increased mortality (p<0.05). Additionally, these pollutants were linked to the incidence of chronic diseases such as chronic kidney disease, diabetes, and hypertension (p< 0.05). Our study, utilizing various machine learning models, also showed a notable increase in the Area Under the Curve when incorporating organochlorine pesticide indicators into the model as opposed to excluding them. Furthermore, strong correlations were observed between serum c-reactive protein (CRP) and CRP to serum albumin ratio (CAR) concentrations with these substances, demonstrating their pro-inflammatory effects at specific concentrations. Interestingly, cutting down on dietary inflammation through changes in diet effectively reduced the risk of death at high organochlorine pesticide exposure levels, but the effect was less noticeable at low to moderate exposure levels. ConclusionsExposure to organochlorine pesticides was linked to a higher risk of mortality, likely due to an increased prevalence of chronic diseases. In this context, inflammation played a crucial role, and adopting an anti-inflammatory diet significantly reduced the mortality risk associated with these pesticides.

Evaluation of health risk experienced by urban taxi drivers to whole-body vibration and multiple shocks

This cross-sectional study was done aiming at determining the exposure of taxi drivers to vibration on 35 safe taxis (19 cars with engine volume of 1.325 L, 9 cars with engine volume of 1.645 L, and 7 cars with engine volume of 1.761 L). Measurements were based on ‘ISO 2631-1’ on seats’ pans, by Castel GA2005 vibrometer. The results through two different evaluative methods indicated moderate exposure levels, corresponding to suggestive Health Guidance Caution Zone (HGCZ) in ‘ISO 2631-1’. Evaluation of exposure to the WBV among taxi drivers, in the taxis with low and high mean acceleration values, using the VDV method is preferred over the R.M.S method. In lower accelerations, in all conditions, the mean of the reckoned values in the VDV method was less than the R.M.S method, and in higher accelerations, where there are more differences, and the CF values were higher (PAIK 1761 cars), again the assessed mean duration in the VDV method is less than R.M.S method. In higher accelerations and with fewer crest factors, this matter didn’t hold, and the allowed time in the R.M.S method became lower.

Uptake, depuration, and behavioural effects of oxazepam on activity and foraging in a tropical snail (Melanoides tuberculata)

Pharmaceuticals are increasingly being detected in surface waters around the globe, giving rise to concerns that they may alter the physiology and behaviour of aquatic organisms exposed in the wild. Invertebrates represent important components of many ecosystems and bear a high potential for transmitting pharmaceutical contaminants to higher trophic levels. Here, we present a laboratory study in which we exposed a freshwater tropical snail, Melanoides tuberculata, to a serial dilution of the benzodiazepine oxazepam ranging from 50 ng/L to 5 mg/L. We tested for subsequent behavioural effects, including locomotor activity and foraging propensity, at two diurnal time points (day and night), and across three days. We found that the snails displayed a high level of behavioural tolerance to all treatments of oxazepam except at the highest exposure, where locomotor and foraging activity declined. We also detected a weak non-monotonic response curve suggestive of behavioural disinhibition at moderate exposure levels. Regardless of treatment, the snails were also less active after three days of exposure and more active during nighttime observations. We measured the uptake of oxazepam in tissues across treatments, showing that it bioconcentrated at up to 29 times the water exposure level (BCF range: 7 - 29). Finally, we characterized the uptake/depuration pharmacokinetics of oxazepam in snail tissues across time, which revealed that the snails reach a steady state equilibrium in < 8 hours of exposure and depurate at a similar rate. Overall, our study suggests that snails such as M. tuberculata, due to their behavioural resilience and high bioconcentration potential, could act as vectors for pharmaceutical transfer throughout the food web in pharmaceutical-polluted habitats (e.g., wastewater outfalls).

Fragment-based lead discovery of indazole-based compounds as AXL kinase inhibitors

AXL is a member of the TAM (TYRO3, AXL, MER) subfamily of receptor tyrosine kinases. It is upregulated in a variety of cancers and its overexpression is associated with poor disease prognosis and acquired drug resistance. Utilizing a fragment-based lead discovery approach, a new indazole-based AXL inhibitor was obtained. The indazole fragment hit 11, identified through a high concentration biochemical screen, was expeditiously improved to fragment 24 by screening our in-house expanded library of fragments (ELF) collection. Subsequent fragment optimization guided by docking studies provided potent inhibitor 54 with moderate exposure levels in mice. X-ray crystal structure of analog 50 complexed with the I650M mutated kinase domain of Mer revealed the key binding interactions for the scaffold. The good potency coupled with reasonable kinase selectivity, moderate in vivo exposure levels, and availability of structural information for the series makes it a suitable starting point for further optimization efforts.

Ovarian cancer risk in relation to blood lipid levels and hyperlipidemia: a systematic review and meta-analysis of observational epidemiologic studies.

Epidemiologic evidence regarding association of ovarian cancer risk with blood lipid level and hyperlipidemia is inconsistent. We aimed to synthesize available epidemiologic studies to disentangle associations of cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and hyperlipidemia with ovarian cancer risk. We searched PubMed, EMBASE, and Web of Science for eligible studies. A random-effects model was applied for synthesis. Heterogeneity was evaluated by a Chi-squared test for the Cochran Q statistic and the I-squared value. Subgroup analysis was conducted by design, study locale, and ovarian cancer case number. Sensitivity analysis was conducted for studies adjusting for certain covariates or with superior quality. To explore the potential dose-response relationship, we further synthesized effect measures of moderate levels of cholesterol, triglycerides, HDL-C, and LDL-C. Twelve studies (five cohort and seven case-control studies) were included. In primary meta-analysis, the synthesized risk ratio (RRpool) and 95% confidence interval (CI) suggested that high cholesterol was associated with an increased ovarian cancer risk (RRpool 1.22, 95% CI 1.01-1.48, Cochran P value: 0.40, I2: 0.5%). High HDL-C was associated with a lower ovarian cancer risk (RRpool 0.61, 95% CI 0.40-0.94, Cochran P value: 0.06, I2: 63.7%). We obtained nonsignificant associations for other exposures. Subgroup and sensitivity analyses yielded consistent results as the primary analysis. Only cholesterol showed marginally significant association in synthesis using moderate exposure levels (RRpool 1.18, 95% CI 0.99-1.42, Cochran P value: 0.51, I2: 0.0%). Our study suggests that high blood cholesterol is associated with an increased ovarian cancer risk, whereas the etiological significance of other exposures deserves more investigations.

Reprint of: Spatial–temporal human exposure modeling based on land-use at a regional scale in China

Regional human exposure to the hazard is an important basis of decision support for more efficient and effective emergency management especially pre-event. Due to the diverse locations of human activities and the displacements they induce, the spatial distribution of population is inhomogeneous and strongly time-dependent. Hence, in the present work, land use pattern was introduced to reflect the distribution characteristics of human exposure in hazard affected regions both in daytime and nighttime. Human activities that contribute to spatial distribution variance were considered to establish the correlation between human types and land-use patterns at a regional scale. Furthermore, hypergraph was used to model the regional human exposure in order to benefit the analysis of spatial–temporal distribution characteristics of population, and variance algorithms for disaggregating different styles of human to the regional land were constructed. What’s more, the model was applied to the analysis of potential human exposure in the built district of Dalian City. Results show that a great amount of area and population are beyond moderate exposure levels on urban construction land of Dalian City, and the population potentially exposed significantly increases from nighttime to daytime periods, especially in the zones with diverse human activities. The presented approach in this study can not only be of utmost importance for vulnerability assessment or risk evaluation, but also for regional and environmental planning as well as local development.

High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile

BackgroundArsenic in drinking water has been associated with increases in lung disease, but information on the long-term impacts of early-life exposure or moderate exposure levels are limited. MethodsWe investigated pulmonary disease and lung function in 795 subjects from three socio-demographically similar areas in northern Chile: Antofagasta, which had a well-described period of high arsenic water concentrations (860μg/L) from 1958 to 1970; Iquique, which had long-term arsenic water concentrations near 60μg/L; and Arica, with long-term water concentrations ≤10μg/L. ResultsCompared to adults never exposed >10μg/L, adults born in Antofagasta during the high exposure period had elevated odds ratios (OR) of respiratory symptoms (e.g., OR for shortness of breath=5.56, 90% confidence interval (CI): 2.68–11.5), and decreases in pulmonary function (e.g., 224mL decrease in forced vital capacity in nonsmokers, 90% CI: 97–351mL). Subjects with long-term exposure to arsenic water concentrations near 60μg/L also had increases in some pulmonary symptoms and reduced lung function. ConclusionsOverall, these findings provide new evidence that in utero or childhood arsenic exposure is associated with non-malignant pulmonary disease in adults. They also provide preliminary new evidence that long-term exposures to moderate levels of arsenic may be associated with lung toxicity, although the magnitude of these latter findings were greater than expected and should be confirmed.

Long-term exposure to Ambient Air Pollution and Incidence of Lung Cancer: The Danish Nurse Cohort.

Introduction: In 2013, IARC classified outdoor air pollution as carcinogenic to humans. Evidence from several epidemiological studies suggests that exposure to particulate matter contributes the development of lung cancer, however some studies also indicate that the association may be restricted to or stronger in highly polluted areas, and less prominent in countries with moderate exposure levels. In this study we examine association between long-term exposure to air pollution and incidence of lung cancer in Denmark. Methods: For 28,731 nurses (age ≥ 44 years) from the Danish Nurse Cohort, recruited in 1993 or 1999, we obtained data on lung cancer incidence until 2013 from Danish Cancer Register, and estimated levels of particulate matter with diameter &lt; 2.5 (PM2.5), &lt; 10 (PM10), nitrogen oxides (NOx) and nitrogen dioxide (NO2) at residence since 1990 using a dispersion model. We examined association between 3-year running mean of pollutants and lung cancer incidence using time-varying Cox regression. Results: Of 23,892 cancer-free nurses at recruitment, 246 developed lung cancer during 15.6 years of follow-up. We found no association between the development of lung cancer and exposure to PM2.5 (Hazard Ratio: 0.86; 95% Confidence Interval: 0.78-1-18, per interquartile range (IQR) of 3.36 µg/m3), PM10 (0.98; 0.81-1.19, IQR 3.29 µg/m3), NO2 (0.97; 0.84-1.11, IQR 7.47 µg/m3) or NOx (1.01; 0.95-1.08 IQR 10.21 µg/m3). Conclusion: We found no evidence of an association between long-term exposure to PM2.5, PM10, NO2 or NOx and development of lung cancer in Danish adult women.

Spatial–temporal human exposure modeling based on land-use at a regional scale in China

Regional human exposure to the hazard is an important basis of decision support for more efficient and effective emergency management especially pre-event. Due to the diverse locations of human activities and the displacements they induce, the spatial distribution of population is inhomogeneous and strongly time-dependent. Hence, in the present work, land use pattern was introduced to reflect the distribution characteristics of human exposure in hazard affected regions both in daytime and nighttime. Human activities that contribute to spatial distribution variance were considered to establish the correlation between human types and land-use patterns at a regional scale. Furthermore, hypergraph was used to model the regional human exposure in order to benefit the analysis of spatial–temporal distribution characteristics of population, and variance algorithms for disaggregating different styles of human to the regional land were constructed. What’s more, the model was applied to the analysis of potential human exposure in the built district of Dalian City. Results show that a great amount of area and population are beyond moderate exposure levels on urban construction land of Dalian City, and the population potentially exposed significantly increases from nighttime to daytime periods, especially in the zones with diverse human activities. The presented approach in this study can not only be of utmost importance for vulnerability assessment or risk evaluation, but also for regional and environmental planning as well as local development.

Verbal learning and memory impairment in children with fetal alcohol spectrum disorders.

Previous studies using the California Verbal Learning Test-Children's Version (CVLT-C) to examine effects of heavy prenatal alcohol exposure on verbal learning and memory have reported impaired information acquisition (i.e., encoding), rather than retrieval, as the primary mechanism underlying learning and memory impairment. We administered the CVLT-C to 2 independent cohorts to determine whether (i) effects on encoding are also seen at moderate exposure levels, using both categorical (diagnostic/exposure group) and continuous exposure measures; (ii) these deficits are specific or secondary to alcohol-related impairment in IQ; (iii) effects on retrieval can be detected over and above effects on initial encoding; and (iv) effects on learning are attributable to less efficient learning strategy use. We administered the CVLT-C and Wechsler Intelligence Scale for Children to 151 Cape Town heavy and nonexposed children (M=10.3years), and 291 Detroit adolescents recruited to over-represent moderate-to-heavy prenatal alcohol exposure (M=14.4years). Effects on encoding in the heavily exposed Cape Town cohort and on retrieval in both cohorts were significant after adjustment for IQ. Although effects on retrieval were no longer significant in Cape Town after control for initial encoding, effects on recognition memory continued to be evident in Detroit. Children with full or partial fetal alcohol syndrome were less able to use the semantic cluster encoding strategy implicit in the CVLT-C. Effects on verbal learning were seen primarily in the more heavily exposed Cape Town cohort; effects on recall and recognition memory were also seen at moderate exposure levels in Detroit. These effects were not attributable to alcohol-related impairment in overall intellectual competence. The finding that effects on retention continued to be evident after statistical adjustment for initial encoding in Detroit suggests that a fetal alcohol-related deficit in retrieval is not secondary to a failure to encode the initial information. These data confirm that this impairment in initial learning is mediated, in part, by failure to use the semantic cluster learning strategy.

Tumor promotion by exposure to radiofrequency electromagnetic fields below exposure limits for humans

The vast majority of in vitro and in vivo studies did not find cancerogenic effects of exposure to electromagnetic fields (RF-EMF), i.e. emitted by mobile phones and base stations. Previously published results from a pilot study with carcinogen-treated mice, however, suggested tumor-promoting effects of RF-EMF (Tillmann et al., 2010). We have performed a replication study using higher numbers of animals per group and including two additional exposure levels (0 (sham), 0.04, 0.4 and 2 W/kg SAR). We could confirm and extend the originally reported findings. Numbers of tumors of the lungs and livers in exposed animals were significantly higher than in sham-exposed controls. In addition, lymphomas were also found to be significantly elevated by exposure. A clear dose–response effect is absent. We hypothesize that these tumor-promoting effects may be caused by metabolic changes due to exposure. Since many of the tumor-promoting effects in our study were seen at low to moderate exposure levels (0.04 and 0.4 W/kg SAR), thus well below exposure limits for the users of mobile phones, further studies are warranted to investigate the underlying mechanisms. Our findings may help to understand the repeatedly reported increased incidences of brain tumors in heavy users of mobile phones.

Quality of life in relation to the traffic pollution indicators NO2 and NOx: results from the Swedish GA2LEN survey

BackgroundAsthma is a chronic disease that may affect daily activities and quality of life. Asthmatics have higher incidence of chronic rhinosinusitis (CRS) and asthma is associated with sinonasal inflammation and...

Dopamine-dependent behavior in adult rats after perinatal exposure to purity-controlled polychlorinated biphenyl congeners (PCB52 and PCB180)

Since knowledge about toxic effects of non-dioxinlike (NDL) PCBs is fragmentary, regulatory panels have concluded that risk assessment of these congeners is hampered or impossible. As the dopaminergic system is one of the main targets in PCB-related neurotoxic effects after developmental exposure, we selected catalepsy induced by the dopamine receptor blocker haloperidol to characterize effects of the NDL congeners PCB52 and PCB180 in adult offspring from exposed rat dams. Rat dams were treated with PCB congeners by gavage using six dose levels (total doses: PCB52 – 0, 30, 100, 300, 1000 or 3000mg/kg body wt.; PCB180 – 0, 10, 30, 100, 300, or 1000mg/kg body wt.) to allow benchmark dose analysis of the results. Testing of adult offspring (starting at 180 days of age) for catalepsy induced by injection with haloperidol revealed slightly prolonged latencies to movement onset in female offspring exposed to PCB52. Exposure to PCB180 resulted in more pronounced effects, with generally reduced latencies in male offspring. These results indicate reduced dopaminergic activity after PCB52 exposure, whereas the outcome for PCB180 may be related to increased extracellular dopamine as reported in the literature. Benchmark dose analyses revealed that both PCB congeners exerted effects mainly at moderate exposure levels. Together, these results underline the importance of effects on the dopaminergic system as indicated by studies in human females after occupational PCB exposure.

Commentary on Day and Colleagues : The Association Between Prenatal Alcohol Exposure and Behavior at 22 Years of Age-Adverse Effects of Risky Patterns of Drinking Among Low to Moderate Alcohol-Using Pregnant Women

Day and colleagues have presented the first data showing that the behavioral effects of low to moderate prenatal alcohol exposure seen in childhood and adolescence persist into adulthood. Using the Achenbach Adult Self-Report, they found dose-dependent effects of prenatal exposure on internalizing, externalizing, and attention problems that persist in young adults and, thus, appear to be permanent. To date, few studies have attempted to identify thresholds at which prenatal alcohol exposure is harmful, although the animal literature suggests that even 1 to 2 binge episodes can result in adverse effects in the offspring. Four prospective longitudinal studies have reported adverse effects at what can be characterized as moderate exposure levels based on NIAAA criteria, but moderate drinking women often concentrate their alcohol use on 1 to 2 days per week, thereby engaging in binge drinking. In this study, binge drinking was not a strong predictor of adverse outcome when average daily dose was held constant, a conclusion that the authors note runs "counter to studies that have reported that binge drinking has a greater effect." This inconsistency may be due to the difficulty of allocating variance that is shared (overlapping) between average daily dose and binge drinking (i.e., dose/occasion). Data from laboratory animal studies, in which dosage can be manipulated experimentally, demonstrate that a higher dose per occasion, the key feature of binge drinking, leads to more severe adverse effects. Day and colleagues' findings of adverse effects at low levels of exposure provides clear evidence that there is no safe level of drinking during pregnancy and that, even at low levels, drinking results in irreversible behavioral impairment. On the other hand, given the evidence from the animal and most human studies, it is important for all women who drink during pregnancy, even at light to moderate levels, to recognize that minimizing their intake per occasion and refraining from binge drinking can reduce risk to the fetus.

Rejoinder: Arsenic Exposure and Prevalence of Type 2 Diabetes

Rejoinder: Arsenic Exposure and Prevalence of Type 2 Diabetes

Evaluation of Tumor Necrosis Factor-Alpha and Granulocyte Colony-Stimulating Factor Serum Levels in Lead-Exposed Smoker Workers

Inorganic lead (Pb) is able to modulate the immune response even at low to moderate exposure levels. It inhibits in vitro and in vivo activities of neutrophil leucocytes and influences their blood count in humans. Neutrophil functions are governed by a number of cytokines. Pb has been shown to affect leukocyte production of some of these cytokines in vitro. The objective of this study is to assess serum tumor necrosis factor-alpha (TNF-alpha) and granulocyte colony-stimulating factor (G-CSF) levels of thirty-three male lead-exposed (E) workers at a lead recycling plant as compared with twenty-eight male non-exposed (NE) workers at a food processing plant, whose current smoking habit was known. Serum TNF-alpha and G-CSF levels were measured by a quantitative sandwich enzyme immunoassay. Blood lead levels (Pb-B) were significantly higher in E (geometric mean (GM) 30.7 microg/dl, GSD 1.7; min-max: 9.1-81.6 microg/dl) workers than controls (GM 3.6 microg/dl, GSD 1.7; min-max: 1.0-11.0 microg/dl). E workers had significantly higher serum TNF-alpha (median: 107.1; min-max: 11.1-623.0 pg/ml) and G-CSF levels (median: 53.0, min-max: 31.1-197.0 pg/ml) than NE workers (TNF-alpha: median: 12.0; min-max: 9.4-18.8 pg/ml; G-CSF: median: 34.3, min-max: 25.1-52.2 pg/ml). In particular, the TNF-alpha level was shown to be significantly influenced by lead exposure and smoking habit, as well as by interaction between these two factors. Both serum TNF-alpha and G-CSF levels were correlated with Pb-B and absolute neutrophil count. This study is the first to detect higher serum levels of G-CSF in E over NE workers. Our data confirm that exposure to low to medium doses of lead may interfere in the complex cytokine network involved in inflammation, especially in workers who are current smokers.

The effects of recall errors and of selection bias in epidemiologic studies of mobile phone use and cancer risk

This paper examines the effects of systematic and random errors in recall and of selection bias in case-control studies of mobile phone use and cancer. These sensitivity analyses are based on Monte-Carlo computer simulations and were carried out within the INTERPHONE Study, an international collaborative case-control study in 13 countries. Recall error scenarios simulated plausible values of random and systematic, non-differential and differential recall errors in amount of mobile phone use reported by study subjects. Plausible values for the recall error were obtained from validation studies. Selection bias scenarios assumed varying selection probabilities for cases and controls, mobile phone users, and non-users. Where possible these selection probabilities were based on existing information from non-respondents in INTERPHONE. Simulations used exposure distributions based on existing INTERPHONE data and assumed varying levels of the true risk of brain cancer related to mobile phone use. Results suggest that random recall errors of plausible levels can lead to a large underestimation in the risk of brain cancer associated with mobile phone use. Random errors were found to have larger impact than plausible systematic errors. Differential errors in recall had very little additional impact in the presence of large random errors. Selection bias resulting from underselection of unexposed controls led to J-shaped exposure-response patterns, with risk apparently decreasing at low to moderate exposure levels. The present results, in conjunction with those of the validation studies conducted within the INTERPHONE study, will play an important role in the interpretation of existing and future case-control studies of mobile phone use and cancer risk, including the INTERPHONE study.

The role of indoor allergen exposure in the development of sensitization and asthma

The role of indoor allergen exposure in the development of sensitization and asthma remains a subject of controversy. From a number of cross-sectional and longitudinal studies we can conclude that there is a very close association between allergen exposure and the sensitization of an individual. The dose-response relationships seem to differ between allergens; house dust mite and cockroach allergens appear to have a positive linear relationship, whereas cat allergens appear to act quite differently, with maximum sensitization developing at moderate exposure levels. Very low levels of cat allergen exposure are likely to induce no response and very high levels are likely to develop a form of tolerance, with a modified T helper cell type 2 response and the production of IgG4 antibodies and but not IgE. The relationship between indoor allergen exposure and asthma is, however, less clear. The proposed mechanism for the development of disease is that allergen exposure causes sensitization, and continued exposure leads to airway responsiveness and inflammation. As yet, the evidence for allergen exposure being a primary cause of asthma remains weak, and the results of ongoing prospective, randomized allergen avoidance trials are awaited to clarify this issue.