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At least 865 records · Page 48

Metals exposure and risk of small-for-gestational age birth in a Canadian birth cohort: The MIREC study

Background: Lead, mercury, cadmium and arsenic are some of the most common toxic metals to which Canadians are exposed. The effect of exposure to current low levels of toxic metals on fetal growth restriction is unknown. Objective: The aim of this study was to examine relationships between exposure to lead, mercury, cadmium and arsenic during pregnancy, and risk of small for gestational age (SGA) birth. Methods: Lead, mercury, cadmium and arsenic levels were measured in blood samples from the first and third trimesters in 1835 pregnant women from across Canada. Arsenic species in first trimester urine were also assessed. Relative risks and 95% confidence intervals were estimated using log binomial multivariate regression. Important covariates including maternal age, parity, pre-pregnancy BMI, and smoking, were considered in the analysis. An exploratory analysis was performed to examine potential effect modification of these relationships by single nucleotide polymorphisms (SNPs) in GSTP1 and GSTO1 genes. Results: No association was found between blood lead, cadmium or arsenic and risk for SGA. We observed an increased risk for SGA for the highest compared to the lowest tertile of exposure for mercury (>1.6 µg/L, RR=1.56.; 95% CI=1.04–2.58) and arsenobetaine (>2.25 µg/L, RR=1.65; 95% CI=1.10–2.47) after adjustment for the effects of parity and smoking. A statistically significant interaction was observed in the relationship between dimethylarsinic acid (DMA) levels in urinary arsenic and SGA between strata of GSTO1 A104A (p for interaction=0.02). A marginally significant interaction was observed in the relationship between blood lead and SGA between strata of GSTP1 A114V (p for interaction=0.06). Conclusions: These results suggest a small increase in risk for SGA in infants born to women exposed to mercury and arsenic. Given the conflicting evidence in the literature this warrants further investigation in other pregnant populations. - Highlights: • Metals measured in blood or urine of pregnant women. • No association between blood lead, cadmium or arsenic and SGA. • Small increased risk for highest tertile of blood mercury. • Small increased risk for highest tertile of urinary arsenobetaine. • Further research needed to confirm observed associations.

54 ENVIRONMENTAL SCIENCES↗

An approach to assess the Particulate Matter exposure for the population living around a cement plant: modelling indoor air and particle deposition in the respiratory tract

In this paper we studied the exposure to three size fractions of outdoor particulate matter (PM{sub 10}, PM{sub 2.5}, and PM{sub 1}) collected in an area influenced by a cement plant. For that purpose, three groups of population were evaluated (children, adults and retired) in two seasons (summer and winter). Outdoor measured PM concentrations, as well as physiological parameters and activity patterns of the three groups of population were used as input data in two different models. The first one was an indoor air quality model, used to elucidate indoor PM concentrations in different microenvironments. The second one was a dosimetry model, used to evaluate the internal exposure and the distribution of the different PM fractions in the respiratory tract. Results from the indoor air quality model showed that special attention must be paid to the finest particles, since they penetrate indoors in a greater degree. Highest pulmonary doses for the three PM sizes were reported for retired people, being this a result of the high amount of time in outdoor environments exercising lightly. For children, the exposure was mainly influenced by the time they also spend outdoors, but in this case due to heavy intensity activities. It was noticed that deposition of fine particles was more significant in the pulmonary regions of children and retired people in comparison with adults, which has implications in the expected adverse health effects for those vulnerable groups of population. - Highlights: • PM deposition in the respiratory tract was evaluated for three population groups. • Activity patterns and different microenvironments were used in our calculation. • Outdoor activities are the main contributors to PM deposited mass. • Children experienced the highest deposition dose in the pulmonary region. • Retired registered the highest deposited mass in the respiratory tract as a whole.

54 ENVIRONMENTAL SCIENCES↗

CO-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women

Background: Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy Objectives: We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New York City using weighted quantile sum (WQS) regression. Methods: We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (±2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. Results: Individual analyte concentrations in urine were significantly correlated (Spearman's r 0.4–0.5, p<0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. Conclusions: Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy. - Highlights: • Perchlorate, nitrate, thiocyanate and iodide measured in maternal urine. • Thyroid function (TSH and Free T4) measured in maternal blood. • Weighted quantile sum (WQS) regression examined complex mixture effect. • WQS identified an inverse association between the exposure mixture and maternal TSH. • Perchlorate indicated as the ‘bad actor’ of the mixture.

54 ENVIRONMENTAL SCIENCES↗

Association of cadmium and arsenic exposure with salivary telomere length in adolescents in Terai, Nepal

Background: Cadmium and arsenic are ubiquitous metals commonly found in the environment which can harm human health. A growing body of research shows telomere length as a potential biomarker of future disease risk. Few studies have examined the effects of metals on telomere length and none have focused on adolescents. Objectives: In this study, the impact of cadmium and arsenic on salivary telomere length was studied in adolescents in Terai, Nepal. Methods: Adolescents aged 12–16 years old (n=351)were recruited where questionnaire interviews and both saliva and urine collection took place. Telomere length was determined by quantitative polymerase chain reaction using DNA extracted from saliva. Urinary cadmium and arsenic concentration were measured by inductively coupled plasma mass spectrometry. Multivariable linear regression was used to examine associations between urinary metals and salivary telomere length. Results: The geometric means and standard deviations of cadmium and arsenic were 0.33±0.33 μg/g creatinine and 196.0±301.1 μg/g creatinine, respectively. Urinary cadmium concentration was negatively associated with salivary telomere length after adjustment for confounders (β=−0.24, 95% CI −0.42,−0.07). Arsenic showed positive associations with telomere length but did not reach statistical significance. Conclusions: This is the first study to demonstrate that cadmium may shorten adolescent telomeres, even at exposure levels that may be considered low. These results agree with prior experimental and adult epidemiological studies, and also help identify the mechanism of DNA damage by cadmium. This study expanded current evidence on the harmful effects of cadmium exposure on telomere length even to adolescents. - Highlights: • This is the first study examining metal exposure on telomere length in adolescents. • Urinary cadmium levels were similar to non-industrially polluted levels in Asia. • Urinary arsenic levels were as high as groundwater arsenic polluted areas in Asia. • Urinary cadmium was negatively associated with salivary telomere length. • Urinary arsenic was not significantly associated with salivary telomere length.

54 ENVIRONMENTAL SCIENCES↗

Dietary exposure and human risk assessment of phthalate esters based on total diet study in Cambodia

Phthalate esters are used in a wide variety of consumer products, and human exposure to this class of compounds is widespread. Nevertheless, studies on dietary exposure of human to phthalates are limited. In this study, to assess the daily intakes of phthalate esters and the possible adverse health impacts, different food samples were collected from three areas of Cambodia, one of the poorest countries in the world. The ∑phthalate ester concentrations in Kampong Cham, Kratie and Kandal provinces ranged from 0.05 to 2.34 (median 0.88) μg g{sup −1}, 0.19–1.65 (median 0.86) μg g{sup −1} and 0.24–3.05 (median 0.59) μg g{sup −1} wet weight (ww), respectively. Di-2-Ethylhexyl phthalate (DEHP) and diisobutyl phthalate (DiBP) were the predominant compounds among all foodstuffs. The estimated daily intake (EDI) of phthalate esters for the general population in Kampong Cham, Kratie and Kandal was 34.3, 35.6 and 35.8 μg kg{sup −1} bw d{sup −1}, respectively. The dietary daily intake of DEHP, benzylbutyl phthalate (BBP) and di-n-butyl phthalate (DBP) in Kampong Cham, Kratie and Kandal were below the tolerable daily intakes (TDI) imposed by the European Food Safety Authority (EFSA) and reference doses (RfD) imposed by The United States Environmental Protection Agency (USEPA). Rice contributed the greatest quantity of DEHP to the daily intake in Cambodia so may deserve further exploration. To our knowledge, this is the first study to investigate the occurrence and the daily intakes of phthalate esters in Cambodia. - Highlights: • Phthalate esters concentration in daily foodstuffs collected from Cambodia. • Investigate the bioaccessbility of phthalate esters via the foodstuffs consumption. • Health risk evaluation of dietary exposure to phthalate esters.

54 ENVIRONMENTAL SCIENCES↗

Basophil mediated pro-allergic inflammation in vehicle-emitted particles exposure

Despite of the fact that engine manufacturers develop a new technology to reduce exhaust emissions, insufficient attention given to particulate emissions. However, diesel exhaust particles are a major source of air-borne pollution, contain vast amount of polycyclic aromatic hydrocarbons (PAHs) and may have deleterious effects on the immune system, resulting in the induction and enhancement of pro-allergic processes. In the current study, vehicle emitted particles (VEP) from 2 different types of cars (diesel - D and gasoline - G) and locomotive (L) were collected. Overall, 129 four-week-old, male SPF-class Kunming mice were subcutaneously instilled with either low dose 100, 250 or high dose, 500 mg/kg VEP and 15 mice were assigned as control group. The systemic toxicity was evaluated and alterations in the percentages of the CD3, CD4, CD8, CD16, CD25 expressing cells, basophils, eosinophils and neutrophils were determined. Basophil percentages were inversely associated with the PAH content of the VEPs, however basophil sensitization was more important than cell count in VEP exposure. Thus, the effects of VEP-PAHs emerge with the activation of basophils in an allergen independent fashion. Despite the increased percentage of CD4+ T cells, a sharp decrease in basophil counts at 500 mg/kg of VEP indicates a decreased inhibitory effect of CD16+ monocytes on the proliferation of CD4+ T cell and suppressed polarization into a Th2 phenotype. Therefore, although the restrictions for vehicles emissions differ between countries, follow up studies and strict regulations are needed. - Highlights: • Basophil sensitization is more important than cell count in VEP exposure. • CD16+ cells are more effective than basophils on CD4+ T cell proliferation. • CD16+ and CD16- monocytes respond to VEP exposure in opposite directions. • CD8+ T cell proliferation is inhibited by all doses of VEPs. • Globally, more stringent standards are needed for vehicle particle emissions.

54 ENVIRONMENTAL SCIENCES↗

Potential human exposure to halogenated flame-retardants in elevated surface dust and floor dust in an academic environment

Most households and workplaces all over the world possess furnishings and electronics, all of which contain potentially toxic flame retardant chemicals to prevent fire hazards. Indoor dust is a recognized repository of these types of chemicals including polybrominated diphenyl ethers (PBDEs) and non-polybrominated diphenyl ethers (non-PBDEs). However, no previous U.S. studies have differentiated concentrations from elevated surface dust (ESD) and floor dust (FD) within and across microenvironments. We address this information gap by measuring twenty-two flame-retardant chemicals in dust on elevated surfaces (ESD; n=10) and floors (FD; n=10) from rooms on a California campus that contain various concentrations of electronic products. We hypothesized a difference in chemical concentrations in ESD and FD. Secondarily, we examined whether or not this difference persisted: (a) across the studied microenvironments and (b) in rooms with various concentrations of electronics. A Wilcoxon signed-rank test demonstrated that the ESD was statistically significantly higher than FD for BDE-47 (p=0.01), BDE-99 (p=0.01), BDE-100 (p=0.01), BDE-153 (p=0.02), BDE-154 (p=0.02), and 3 non-PBDEs including EH-TBB (p=0.02), BEH-TEBP (p=0.05), and TDCIPP (p=0.03). These results suggest different levels and kinds of exposures to flame-retardant chemicals for individuals spending time in the sampled locations depending on the position of accumulated dust. Therefore, further research is needed to estimate human exposure to flame retardant chemicals based on how much time and where in the room individuals spend their time. Such sub-location estimates will likely differ from assessments that assume continuous unidimensional exposure, with implications for improved understanding of potential health impacts of flame retardant chemicals. - Highlights: • Brominated flame retardants used in electronic products accumulate in room dust • Various chemical moieties of flame retardants leach differently into room dust • Flame retardant concentrations in dust differ in elevated surfaces compared to floors.

54 ENVIRONMENTAL SCIENCES↗

Low-level arsenic exposure via drinking water consumption and female fecundity - A preliminary investigation

High level arsenic exposure is associated with reproductive toxicity in experimental and observational studies; however, few data exist to assess risks at low levels. Even less data are available to evaluate the impact of low level arsenic exposure on human fecundity. Our aim in this pilot study was a preliminary evaluation of associations between low level drinking water arsenic contamination and female fecundity. This retrospective study was conducted among women previously recruited to a hospital-based case-control study of spontaneous pregnancy loss in Timiá¹£ County, Romania. Women (n=94) with planned pregnancies of 5–20 weeks gestation completed a comprehensive physician-administered study questionnaire and reported the number of menstrual cycles attempting to conceive as the time to pregnancy (TTP). Drinking water samples were collected from residential drinking water sources and we determined arsenic levels using hydride generation-atomic absorption spectrometry (HG-AAS). Multivariable Cox-proportional hazards regression with Efron approximation was employed to evaluate TTP as a function of drinking water arsenic concentrations among planned pregnancies, adjusted for covariates. There was no main effect for drinking water arsenic exposure, yet the conditional probability for pregnancy was modestly lower among arsenic exposed women with longer TTPs, relative to women with shorter TTPs, and relative to unexposed women. For example, 1 µg/L average drinking water arsenic conferred 5%, 8%, and 10% lower likelihoods for pregnancy in the 6th, 9th, and 12th cycles, respectively (P=0.01). While preliminary, our results suggest that low level arsenic contamination in residential drinking water sources may further impair fecundity among women with longer waiting times; however, this hypothesis requires confirmation by a future, more definitive study. - Highlights: • We assessed low level drinking water arsenic as a predictor of fecundability. • Arsenic did not affect time to pregnancy among women conceiving quickly. • Arsenic increased time to pregnancy among women taking longer to conceive. • Low level drinking water arsenic may adversely impact women with lower fecundity.

54 ENVIRONMENTAL SCIENCES↗

Urinary biomarkers of polycyclic aromatic hydrocarbons in pre- and peri-pubertal girls in Northern California: Predictors of exposure and temporal variability

Highlights: • PAHs, potential endocrine disruptors, were detected in the majority of young girls. • Multiple exposure sources predicted urinary PAH metabolites concentrations. • Most PAH metabolites had fair to moderate reproducibility over four years. Polycyclic aromatic hydrocarbons (PAHs), a class of chemicals produced as combustion by-products, have been associated with endocrine disruption. To understand exposure in children, who have been less studied than adults, we examined PAH metabolite concentrations by demographic characteristics, potential sources of exposure, and variability over time, in a cohort study of pre- and peri-pubertal girls in Northern California.

54 ENVIRONMENTAL SCIENCES↗

Development of hypertension after long-term exposure to static magnetic fields among workers from a magnetic resonance imaging device manufacturing facility

Highlights: • High cumulative exposure to MRI-related static magnetic fields is associated with hypertension. • No association was apparent for low cumulative exposure to static magnetic fields. • New association pointing at long term effects of static magnetic fields needs corroboration. To assess the association between long-term exposure to static magnetic fields (SMF) in a magnetic resonance imaging (MRI)-manufacturing environment and hypertension.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

The genomic effects of cell phone exposure on the reproductive system

Highlights: • Electromagnetic fields (EMF) causes an imbalance between pro-oxidant and antioxidant mechanismsEMF increases reactive oxygen species production. • Exposure to EMF leads to disruptions in spermatogenic cells. • Exposure to GSM-modulated EMF causes an increase in superoxide formation levels in human spermatozoa. Humans are exposed to increasing levels of electromagnetic fields (EMF) at various frequencies as technology advances. In this context, improving understanding of the biological effects of EMF remains an important, high priority issue. Although a number of studies in this issue and elsewhere have focused on the mechanisms of the oxidative stress caused by EMF, the precise understanding of the processes involved remains to be elucidated. Due to unclear results among the studies, the issue of EMF exposure in the literature should be evaluated at the genomic level on the reproductive system. Based on this requirement, a detail review of recently published studies is necessary. The main objectives of this study are to show differences between negative and positive effect of EMF on the reproductive system of animal and human. Extensive review of literature has been made based on well known data bases like Web of Science, PubMed, MEDLINE, Google Scholar, Science Direct, Scopus. This paper reviews the current literature and is intended to contribute to a better understanding of the genotoxic effects of EMF emitted from mobile phones and wireless systems on the human reproductive system, especially on fertility. The current literature reveals that mobile phones can affect cellular functions via non-thermal effects. Although the cellular targets of global system for mobile communications (GSM)-modulated EMF are associated with the cell membrane, the subject is still controversial. Studies regarding the genotoxic effects of EMF have generally focused on DNA damage. Possible mechanisms are related to ROS formation due to oxidative stress. EMF increases ROS production by enhancing the activity of nicotinamide adenine dinucleotide (NADH) oxidase in the cell membrane. Further detailed studies are needed to elucidate DNA damage mechanisms and apoptotic pathways during oogenesis and spermatogenesis in germ cells exposed to EMF.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

Exposure to tetrachloroethylene-contaminated drinking water and time to pregnancy

Highlights: • Cape Cod residents were exposed to PCE through contaminated drinking water. • Cumulative PCE exposure was not associated with increased risk of infertility. • High PCE exposure around the pregnancy attempt may be associated with infertility. The synthetic solvent tetrachloroethylene (PCE), commonly used in dry cleaning operations, is a human neurotoxicant and carcinogen. However, its effect on reproduction is poorly understood, as prior studies have been limited to small occupational cohorts. We examined the association between PCE exposure from contamination of the public drinking water supply and time-to-pregnancy (TTP) in a cohort of mothers from Cape Cod, Massachusetts.

54 ENVIRONMENTAL SCIENCES↗

Prenatal nitrate air pollution exposure and reduced child lung function: Timing and fetal sex effects

Highlights: • Prenatal nitrate exposure is associated with reduced lung function at age 7 years • Link between prenatal nitrate exposure and lung function deficits is male-specific • Significant effects occur during early sensitive window of 6-12 weeks gestation Prenatal particulate air pollution exposure may alter lung growth and development in utero in a time-sensitive and sex-specific manner, resulting in reduced lung function in childhood. Such relationships have not been examined for nitrate (NO{sub 3}{sup -}).

54 ENVIRONMENTAL SCIENCES↗

Pregnancy exposure to wind turbine noise and adverse birth outcomes: a nationwide cohort study

Highlights: • We identified all Danes exposed to wind turbine noise (WTN) from 1982 to 2013. • We then identified all live born singletons from mothers in this population. • We investigated preterm birth, low birth weight and small for gestational age. • We found no associations between WTN and the adverse birth outcomes. • Few women had high levels of WTN and independent replication is called for. Noise from wind turbines (WTs) is reported as more annoying than traffic noise at similar levels, raising concerns as to whether WT noise (WTN) may negatively affect health, as reported for traffic noise. We aimed to investigate whether residential WTN is associated with adverse birth outcomes. Based on national registries, we identified all Danish dwellings situated within ≤ 20 wt heights radius and a random selection of 25% of dwellings situated within 20–40 wt heights radius of a WT. We identified 135,795 pregnant women living in the dwellings from 1982 to 2013, and collected information on gestational age and birth weight from a national birth registry. Using data on WT type and simulated hourly wind at each WT, we estimated hourly outdoor and low frequency (LF) indoor WTN at the dwellings of the pregnant women and aggregated as mean nighttime WTN during pregnancy. We used logistic regression with adjustment for individual and area-level covariates for the analyses. We did not find evidence suggesting that mean pregnancy or trimester-specific exposure to outdoor or indoor LF WTN were associated with any of the three adverse birth outcomes investigated: preterm birth (n = 13,003), term small for gestational age (n = 12,220) or term low birth weight (n = 1127). However, the number of cases in the highest exposure categories of ≥ 42 dB outdoor WTN or ≥ 15 dB indoor LF WTN were low for all outcomes (n between 0 and 31). The present study does not support an association between nighttime WTN and adverse birth outcomes. However, there were few cases in the high exposure groups and the results call for reproduction.

54 ENVIRONMENTAL SCIENCES↗

Salinity exposure affects lower-canopy specific leaf area of upland trees in a coastal deciduous forest

Sea level rise and increasing storm surges are likely to affect the canopy physiology, ecology, and structure of coastal forests, even well in advance of tree mortality. Laboratory and greenhouse studies have documented that saltwater exposure can trigger changes in leaf-level physiology and morphology, but few in situ studies have examined how tree-specific leaf area (SLA), the ratio of leaf area to mass and a crucial trait and model parameter, is affected by saline soils. We conducted an observational study of SLA in a mid-Atlantic (USA) coastal deciduous forest, taking advantage of a natural gradient in salinity along a tidal creek. Measured SLA of the 239 trees and seven species sampled ranged from Carya glabra (N = 6 trees, mean SLA = 277.9±36.3cm 2 /g) to Fagus grandifolia (N=60, 321.9±62.9cm 2 g); as expected, trees species and canopy position (sun versus shade) significantly affected SLA. For trees (N=100) directly exposed to the tidal creek, salinity was highly significant after accounting for species (P<0.001), with trees in the lower reaches of the creek having lower SLA. Leaf area index (LAI), computed from SLA and litter traps, ranged from 4.8 to 15.8 and was inversely related to salinity exposure; the spatial variability in leaf litter production contributed much more to LAI uncertainty than did SLA variability. These in situ results are correlative but consistent with the hypothesis, based on previous greenhouse studies, that the stress of chronic salinity exposure changes species’ leaf morphology. Our findings are useful for understanding the growing effects of saltwater intrusion into upland forests, as well as parameterizing and testing ecosystem-scale models simulating forest stressors and disturbances at the terrestrial-aquatic interface.

54 ENVIRONMENTAL SCIENCES↗

High-flux plasma exposure of ultra-fine grain tungsten

Here we examine the response of an ultra-fine grained (UFG) tungsten material to high-flux deuterium plasma exposure. UFG tungsten has received considerable interest as a possible plasma-facing material in magnetic confinement fusion devices, in large part because of its improved resistance to neutron damage. However, optimization of the material in this manner may lead to trade-offs in other properties. Moreover, we address two aspects of the problem in this work: (a) how high-flux plasmas modify the structure of the exposed surface, and (b) how hydrogen isotopes become trapped within the material. The specific UFG tungsten considered here contains 100 nm-width Ti dispersoids (1 wt%) that limit the growth of the W grains to a median size of 960 nm. Metal impurities (Fe, Cr) as well as O were identified within the dispersoids; these species were absent from the W matrix. To simulate relevant particle bombardment conditions, we exposed specimens of the W-Ti material to low energy (100 eV), high-flux (> 10 22 m -2 s -1 ) deuterium plasmas in the PISCES-A facility at the University of California, San Diego. To explore different temperature-dependent trapping mechanisms, we considered a range of exposure temperatures between 200 °C and 500 °C. For comparison, we also exposed reference specimens of conventional powder metallurgy warm-rolled and ITER-grade tungsten at 300 °C. Post-mortem focused ion beam profiling and atomic force microscopy of the UFG tungsten revealed no evidence of near-surface bubbles containing high pressure D2 gas, a common surface degradation mechanism associated with plasma exposure. Thermal desorption spectrometry indicated moderately higher trapping of D in the material compared with the reference specimens, though still within the spread of values for different tungsten grades found in the literature database. Finally, for the criteria considered here, these results do not indicate any significant obstacles to the potential use of UFG tungsten as a plasma-facing material, although further experimental work is needed to assess material response to transient events and high plasma fluence.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Lifetime Increased Cancer Risk in Mice Following Exposure to Clinical Proton Beam–Generated Neutrons

Purpose: To evaluate the life span and risk of cancer following whole-body exposure of mice to neutrons generated by a passively scattered clinical spread-out Bragg peak (SOBP) proton beam. Methods and Materials: Three hundred young adult female FVB/N mice, 152 test and 148 control, were entered into the experiment. Mice were placed in an annular cassette around a cylindrical phantom, which was positioned lateral to the mid-SOBP of a 165-MeV, clinical proton beam. The average distance from the edge of the mid-SOBP to the conscious active mice was 21.5 cm. The phantom was irradiated with once-daily fractions of 25 Gy, 4 days per week, for 6 weeks. The age at death and cause of death (ie, cancer and type vs noncancer causes) were assessed over the life span of the mice. Results: Exposure of mice to a dose of 600 Gy of proton beam–generated neutrons, reduced the median life span of the mice by 4.2% (Kaplan-Meier cumulative survival, P=.053). The relative risk of death from cancer in neutron exposed versus control mice was 1.40 for cancer of all types (P=.0006) and 1.22 for solid cancers (P=.09). For a typical 60 Gy dose of clinical protons, the observed 22% increased risk of solid cancer would be expected to decrease by a factor of 10. Conclusions: Exposure of mice to neutrons generated by a proton dose that exceeds a typical course of radiation therapy by a factor of 10, resulted in a statistically significant increase in the background incidence of leukemia and a marginally significant increase in solid cancer. The results indicate that the risk of out-of-field second solid cancers from SOBP proton-generated neutrons and typical treatment schedules, is 6 to 10 times less than is suggested by current neutron risk estimates.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Exposure Risks Among Children Undergoing Radiation Therapy: Considerations in the Era of Image Guided Radiation Therapy

Recent improvements in toxicity profiles of pediatric oncology patients are attributable, in part, to advances in the field of radiation oncology such as intensity modulated radiation (IMRT) and proton therapy (IMPT). While IMRT and IMPT deliver highly conformal dose to targeted volumes, they commonly demand the addition of 2- or 3-dimensional imaging for precise positioning—a technique known as image guided radiation therapy (IGRT). In this manuscript we address strategies to further minimize exposure risk in children by reducing effective IGRT dose. Portal X rays and cone beam computed tomography (CBCT) are commonly used to verify patient position during IGRT and, because their relative radiation exposure is far less than the radiation absorbed from therapeutic treatment beams, their sometimes significant contribution to cumulative risk can be easily overlooked. Optimizing the conformality of IMRT/IMPT while simultaneously ignoring IGRT dose may result in organs at risk being exposed to a greater proportion of radiation from IGRT than from therapeutic beams. Over a treatment course, cumulative central-axis CBCT effective dose can approach or supersede the amount of radiation absorbed from a single treatment fraction, a theoretical increase of 3% to 5% in mutagenic risk. In select scenarios, this may result in the underprediction of acute and late toxicity risk (such as azoospermia, ovarian dysfunction, or increased lifetime mutagenic risk) in radiation-sensitive organs and patients. Although dependent on variables such as patient age, gender, weight, body habitus, anatomic location, and dose-toxicity thresholds, modifying IGRT use and acquisition parameters such as frequency, imaging modality, beam energy, current, voltage, rotational degree, collimation, field size, reconstruction algorithm, and documentation can reduce exposure, avoid unnecessary toxicity, and achieve doses as low as reasonably achievable, promoting a culture and practice of “gentle IGRT.”.

62 RADIOLOGY AND NUCLEAR MEDICINE↗