PIECEWISE POLYNOMIAL APPROXIMATIONS TO THE ICRP 116 EFFECTIVE DOSE COEFFICIENTS: PHOTONS AND NEUTRONS.

We present fitting equations for estimating effective dose per unit fluence at any photon energy between 10 keV and 10 GeV and any neutron energy between 0.001 eV and 10 GeV. These new equations are based on the latest radiation protection quantities for external radiation exposure found in International Commission on Radiological Protection (ICRP) Publication 116 and incorporate the latest definition of effective dose as described in ICRP Publication 103. The ICRP 116 dose coefficients were fit to piecewise polynomial functions. A total of 8 irradiation geometries were considered: the six in ICRP 116 and two additional geometries presented elsewhere in the literature. The fitting functions generally reproduce the ICRP 116 data to within 3% or better. The functions were used to modify the Monte Carlo N-Particle radiation transport code version 6 (MCNP6) and were applied to a sample problem. The results are intended to be used as a basis for revising the American National Standards Institute/American Nuclear Society 6.1.1-1991 standard.

Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma.

BACKGROUND: We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs). METHODS: A total of 231 patients with GBM at first recurrence from 21 institutions in 10 countries were enrolled. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 600 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIAEDs. The primary end point was radiographic response rate and secondary end points were safety, progression-free survival at 6 months (PFS-6), and overall survival (OS). RESULTS: The radiographic response rate after centralised review was 3.4%. Progression-free survival at 6 months and median OS were 10.6% and 26.0 weeks, respectively. Outcome did not appear to differ based on EIAED status. The most common grade 3 or greater adverse events were fatigue (7%), neutropaenia (7%), and thrombocytopaenia (7%). CONCLUSIONS: Imatinib in addition to hydroxyurea was well tolerated among patients with recurrent GBM but did not show clinically meaningful anti-tumour activity.

Combined effects of embolization and hypofractionated conformal stereotactic radiotherapy in arteriovenous malformations of the brain.

SUMMARY: There are three major treatment options for cerebral AVMs; surgery, embolization and radiosurgery. Embolization may be effective to reduce the size and density but completely obliterates AVMs only in a minority of cases. Radiosurgery may be an alternative to resection, especially in smaller AVMs. Large AVMs have been considered difficult to treat safely and effectively with single fraction radiosurgery. Hypofractionated conformal stereotactic radiotherapy (HCSRT) alone or in combination with embolization may be an alternative treatment. Embolization may reduce the volume and density of AVMs, followed by HCSRT, allowing a safe delivery of a higher total dose of radiation than possible with a single fraction. Sixteen patients with AVMs were treated with embolization and HCSRT. Embolization was performed in 1-6 (median 2) sessions. HCSRT was delivered in 5 fractions with 6-7 Gy each to the total dose of 30-35 Gy. Cerebral angiographies before and after embolization were digitally compared for calculation of volume reduction and luminescence as a measure of AVM density. The mean AVM volume in 15 patients was reduced from 11.9 +/- 2.1 (1-29, median 10.0) ml to 6.5 +/- 2.0 (0.5-28, median 3) ml by embolization. The luminescence for all AVMs was significantly higher after than before embolization, indicating that all AVMs were less dense after embolization. Thirteen out of 16 patients (13/16, 81%) treated with embolization and HCSRT have so far shown obliteration of their AVMs 2-9 (median 4) years after HCSRT. Three patients experienced neurological sequele after embolization, and three patients developed radionecrosis after HCSRT. Using a new method to compare cerebral angiographies in AVMs we report reduction in density and volume after embolization. The obliteration rate of a combined treatment with embolization and HCSRT seems comparable with single fraction radiosurgery although the AVMs in our series are larger than reported in most series treated with single fraction radiosurgery.

Description and dosimetric verification of the PEREGRINE Monte Carlo dose calculation system for photon beams incident on a water phantom.

PEREGRINE is a three-dimensional Monte Carlo dose calculation system written specifically for radiotherapy. This paper describes the implementation and overall dosimetric accuracy of PEREGRINE physics algorithms, beam model, and beam commissioning procedure. Particle-interaction data, tracking geometries, scoring, variance reduction, and statistical analysis are described. The BEAM code system is used to model the treatment-independent accelerator head, resulting in the identification of primary and scattered photon sources and an electron contaminant source. The magnitude of the electron source is increased to improve agreement with measurements in the buildup region in the largest fields. Published measurements provide an estimate of backscatter on monitor chamber response. Commissioning consists of selecting the electron beam energy, determining the scale factor that defines dose per monitor unit, and describing treatment-dependent beam modifiers. We compare calculations with measurements in a water phantom for open fields, wedges, blocks, and a multileaf collimator for 6 and 18 MV Varian Clinac 2100C photon beams. All calculations are reported as dose per monitor unit. Aside from backscatter estimates, no additional, field-specific normalization is included in comparisons with measurements. Maximum discrepancies were less than either 2% of the maximum dose or 1.2 mm in isodose position for all field sizes and beam modifiers.

Consistency of care with national guidelines for children with asthma in managed care.

OBJECTIVE: To evaluate the consistency of pediatric asthma care with the National Asthma Education and Prevention Program Guidelines. DESIGN: Cross-sectional survey at 2 managed care organizations in the United States (winter 1997-1998). The participants were parents of children (n = 318) age 5 to 17 years with asthma. There were no interventions. The outcome measures were indicators of care in 4 domains: (1) periodic physiologic assessment, (2) proper use of medications, (3) patient education, and (4) control of factors contributing to asthma severity. RESULTS: Of 533 eligible patients with asthma, 318 (60%) parents responded; 59% of children were male, 76% were white, and 60% were aged 5 to 10 years. Deficiencies in care were identified in all care domains including, for patients with moderate and severe persistent symptoms, only 55% used long-term control medication daily, 49% had written instructions for handling asthma attacks, 44% had instructions for adjustment of medication before exposures, 56% had undergone allergy testing, and 54% had undergone pulmonary function testing. CONCLUSIONS: There are significant opportunities to improve the quality of care for children with asthma enrolled in managed care. A comprehensive approach to improving care may be necessary to address multiple aspects of care where opportunities exist.

Acute side effects after dose-escalation treatment of prostate cancer using the new urethral catheter BeamCath technique.

Acute side effects after dose-escalated radiotherapy for prostate cancer with different treatment techniques were evaluated, using a daily diary recorded by the patients. Dose escalation was performed using the urethral catheter BeamCath' technique. Side effects were evaluated in 267 patients by means of a daily diary during the treatment and at 3-months' follow-up. The patients' evaluations were compared with those of patients treated with conventional or conformal techniques. Looser stools were reported in the conventional (placebo) and 76 Gy groups at 3-months' follow-up compared with at week 1. No other obvious increase in rectal or bladder morbidity was seen in the 76 Gy group. The catheter did not increase the urinary frequency in comparison to the other groups. The reported urgency and starting problems at the beginning of treatment seemed to improve in all groups at 3-months' follow-up. External beam radiotherapy dose escalation using the BeamCath technique did not result in a dose-dependent increase in acute side effects.

Nocturnal asthma in children affects school attendance, school performance, and parents' work attendance.

CONTEXT: Asthma symptoms that occur at night may signal worse asthma control, but the nighttime occurrence may have additional clinical significance. To date, however, there have been few studies of the impact of nocturnal awakening from asthma on children with the disease, including problems with daytime functioning. OBJECTIVE: To determine if school absenteeism and school performance in children and work absenteeism in their parents are associated with nocturnal awakenings from asthma. DESIGN: Cross-sectional survey during the winter of 1997 through 1998. SETTING: Three managed care organizations in the United States. PARTICIPANTS: Parents of 438 children with asthma, aged 5 to 17 years, who were enrolled in managed care organizations. INTERVENTION: None. MAIN OUTCOME MEASURES: Parent's reports of number of days their child missed school and parent missed work and how often the child's education suffered because of asthma in the past 4 weeks. RESULTS: Overall, more than 40% of children had nocturnal awakenings from asthma in the past 4 weeks. Multivariate analyses were performed that adjusted for child age, race, overall symptom severity, and use of reliever medications. Compared with children who did not awaken from asthma, there were greater odds of missed school days in children who awakened 1 to 3 nights (odds ratio [OR], 3.6; 95% confidence interval [CI], 2.1-6.2), 4 to 7 nights (OR, 4.4; 95% CI, 2.0-10.0), and more than 7 nights (OR, 14.7; 95% CI, 5.9-37.0). Similarly, there were greater odds of education suffering in children who awakened 1 to 3 nights (OR, 2.3; 95% CI, 1.4-3.7), 4 to 7 nights (OR, 2.1; 95% CI, 0.9-4.6), and more than 7 nights (OR, 2.3; 95% CI, 1. 0-5.4), and parents missing work in children who awakened 1 to 3 nights (OR, 4.0; 95% CI, 2.2-7.1), 4 to 7 nights (OR, 6.5; 95% CI, 2.7-16), and more than 7 nights (OR, 3.2; 95% CI, 1.3-7.9). Greater overall symptom severity and high use of reliever mediation were also associated with missed school, education suffering, and parent absenteeism. CONCLUSIONS: Nighttime awakenings in children with asthma may affect school attendance and performance, as well as work attendance by parents. Nighttime symptoms have independent prognostic value, even when overall asthma symptom severity is accounted for. By addressing whether there are nighttime awakenings in children with asthma, clinicians may be able to tailor the therapeutic regimen to counter these symptoms.

Comparing asthma care for Medicaid and non-Medicaid children in a health maintenance organization.

OBJECTIVE: To compare ambulatory visit patterns, rates of medication use, and emergency department and hospital utilization for children with asthma covered under Medicaid and commercial payers within the same health maintenance organization (HMO). DESIGN: Retrospective cohort study. SETTING: Eleven staff-model pediatric departments of an HMO. PATIENTS: A total of 1928 Medicaid and 11007 non-Medicaid children aged 2 to 18 years with at least 1 encounter with a diagnosis of asthma between October 1, 1991, and September 30, 1996. METHODS: We linked patient-level data from the HMO's automated medical record system for ambulatory encounters, a claims system for emergency department and hospital care, and an automated pharmacy dispensing database. Medicaid and non-Medicaid patients were compared for all encounter types and for prescribing and dispensing of beta-agonist and controller medications (inhaled corticosteroids and cromolyn sodium). Incidence rate ratios were calculated from Poisson regression models to control for age, sex, and, when appropriate, beta-agonist dispensing rate. The number of refills authorized on each prescription and the fraction of medications dispensed as refills compared with new prescriptions were compared for Medicaid and non-Medicaid patients. RESULTS: Medicaid-insured children in the HMO were 1.4 times (95% confidence interval, 1.2-1.5) more likely to receive care in emergency departments and 1.3 times (95% confidence interval, 1.1-1.5) more likely to be hospitalized for their asthma compared with non-Medicaid members. Medicaid and non-Medicaid enrollees had similar yearly rates of nonurgent (1.32 vs 1.17) and urgent (0.38 vs 0.31) ambulatory visits. Beta-agonists were dispensed roughly equally to Medicaid and non-Medicaid members. Although Medicaid patients were less likely to have controller medications dispensed (relative risk, 0.72; 95% confidence interval, 0.69-0.74), they were equally likely to have them prescribed. CONCLUSIONS: Differences in ambulatory contact for Medicaid members do not explain the higher rates of emergency department visits and hospitalization in this population. Reasons for lower rates of dispensing of controller medications should continue to be investigated as one cause of increased morbidity for low-income children with asthma.

Patient-dependent beam-modifier physics in Monte Carlo photon dose calculations.

Model pencil-beam on slab calculations are used as well as a series of detailed calculations of photon and electron output from commercial accelerators to quantify level(s) of physics required for the Monte Carlo transport of photons and electrons in treatment-dependent beam modifiers, such as jaws, wedges, blocks, and multileaf collimators, in photon teletherapy dose calculations. The physics approximations investigated comprise (1) not tracking particles below a given kinetic energy, (2) continuing to track particles, but performing simplified collision physics, particularly in handling secondary particle production, and (3) not tracking particles in specific spatial regions. Figures-of-merit needed to estimate the effects of these approximations are developed, and these estimates are compared with full-physics Monte Carlo calculations of the contribution of the collimating jaws to the on-axis depth-dose curve in a water phantom. These figures of merit are next used to evaluate various approximations used in coupled photon/electron physics in beam modifiers. Approximations for tracking electrons in air are then evaluated. It is found that knowledge of the materials used for beam modifiers, of the energies of the photon beams used, as well as of the length scales typically found in photon teletherapy plans, allows a number of simplifying approximations to be made in the Monte Carlo transport of secondary particles from the accelerator head and beam modifiers to the isocenter plane.

An in-school CD-ROM asthma education program.

Computer-based education in schools is not novel. However, only a few computer games have been introduced into school-based health education programs. This study describes inclusion of an asthma education space adventure game into fourth-grade classrooms. Using the game improved asthma knowledge in the intervention classes. Children in the active participation classroom gained significantly more asthma knowledge over the observation period compared to the classroom that did not play the computer game. Knowledge gained was retained over a four-week period and the addition of physician-led talks appeared to add little to the knowledge gained. "Air Academy: The Quest for Airtopia" is an easy and successful tool for elementary grade asthma-related health education in schools.

Measurement of lung density by photon transmission for monitoring intravascular and extravascular fluid volume changes in the lungs.

Left ventricular (LV) heart failure increases pulmonary blood volume (PBV) and interstitial fluid volume. Continuous measurements of lung density may be a simple non-invasive method for monitoring of the LV function as the lung density should reflect the changes in the PBV and extravascular lung water. The purpose of the study was to optimize transmission measurements of the lung with a gamma camera and a planar source. Another aim was to assess the possibility of transmission monitoring in normal subjects at rest and during exercise and to compare the results with simultaneous measurements of PBV changes. Transmission measurements were made in a water-filled phantom containing lungs of different density. A gamma camera and a planar 57Co source were used. The coefficient of variation in density determination owing to counting statistics in a lung area was calculated for different energy windows, acquisition times and collimation. Dynamic measurements in normal subjects were carried out in a sitting and a supine position at rest and during exercise. Pulmonary blood volume was monitored simultaneously using 99mTc-labelled red blood cells and the registered blood pool activity was corrected for attenuation. Highest precision in relative density determination was obtained with large energy window and uncollimated source. A precision of 1.0% was obtained with 1 min measuring time. About 10% change in transmission corresponding to a 15% change in density was observed during exercise. Changes in blood pool and lung density covariated. We conclude that lung density changes can be monitored with a high degree of statistical precision in a few minutes and with a low radiation dose of radiation using a gamma camera and a planar source.

Correlated histogram representation of Monte Carlo derived medical accelerator photon-output phase space.

We present a method for condensing the photon energy and angular distributions obtained from Monte Carlo simulations of medical accelerators. This method represents the output as a series of correlated histograms and as such is well-suited for inclusion as the photon-source package for Monte Carlo codes used to determine the dose distributions in photon teletherapy. The method accounts for the isocenter-plane variations of the photon energy spectral distributions with increasing distance from the beam central axis for radiation produced in the bremsstrahlung target as well as for radiation scattered by the various treatment machine components within the accelerator head. Comparison of the isocenter energy fluence computed by this algorithm with that of the underlying full-physics Monte Carlo photon phase space indicates that energy fluence errors are less than 1% of the maximum energy fluence for a range of open-field sizes. Comparison of jaw-edge penumbrae shows that the angular distributions of the photons are accurately reproduced. The Monte Carlo sampling efficiency (the fraction of generated photons which clear the collimator jaws) of the algorithm is approximately 83% for an open 10x10 field, rising to approximately 96% for an open 40x40 field. Data file sizes for a typical medical accelerator, at a given energy, are approximately 150 kB, compared to the 1 GB size of the underlying full-physics phase space file.

Effects of amifostine on cisplatin induced DNA adduct formation and toxicity in malignant glioma and normal tissues in rat.

The chemoprotective effect of amifostine (WR2721) was studied in a BDIX rat model with intracerebral BT4C glioma implants. Twenty-one rats were given cisplatin 5 mg/kg i.p., 21 were given amifostine 200 mg/kg i.p. + cisplatin 5 mg/kg i.p. Ten rats served as untreated controls. An immunohistochemical method for analysis of cisplatin-DNA adducts was used to elucidate the adduct formation in tumor, normal brain and kidney. Tumor volume and serum creatinine level were analysed 10 days after treatment. In animals pretreated with amifostine there was a delayed adduct formation rate in the normal brain, and in the kidney cortex the number of tubular cells with extremely high adduct level was reduced. No difference in adduct formation was seen in tumors. Tumor volume was significantly larger following amifostine + cisplatin (66% of controls) compared to cisplatin alone (38% of controls). Weight loss was, however, severe in rats given cisplatin alone. In the tumor growth study only 3 out of 11 rats treated with cisplatin 5 mg/kg alone survived until time of sacrifice at 10 days, whereas all those pretreated with amifostine survived. Mean serum creatinine was 48 micromol/l (controls), 146 micromol/l (cisplatin) and 59 micromol/l (amifostine + cisplatin). A marked reduction of histopathological renal changes was found when amifostine was added. Amifostine thus significantly reduced general and renal toxicity of cisplatin. The tumor growth retardation was stronger when cisplatin was given alone but this is probably related to general toxicity and malnutrition indirectly supported by the fact that amifostine did not significantly reduce cisplatin-DNA adduct formation in tumors. The results of the present study suggest that amifostine may have a role in increasing the therapeutic ratio of cisplatin, also in the treatment of malignant glioma.

Characterisation of the functional alpha-adrenoceptor subtype in the isolated female pig urethra.

The aim of the present study is to characterise the contraction-mediating functional alpha-adrenoceptor of the female pig urethra. Alpha-adrenoceptor reference agonists were used to contract the isolated female pig urethra. The relative intrinsic activity was noradrenaline (1.0), phenylephrine (0.91), methoxamine (0.74), (+/-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethane-sulfonanilid e hydrochloride (NS-49) (0.68), oxymetazoline (0.60), dopamine (0.50), clonidine (0.43), midodrine (0.32), ephedrine (0.30), 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK 14,304) (0.11), and phenylpropanolamine (0.11). The 21 competitive antagonists used caused parallel rightward shifts in the alpha-adrenoceptor agonist concentration-response curves, giving linear Schild-plots with slopes not significantly different from unity, suggesting that contraction was mediated by a single receptor. The antagonist pK(B) values calculated were R(-)-tamsulosin (9.68), risperidone (9.19), 2-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-4,4-dimethyl-1,3(2H,4H)-+ ++isoquinolinedione (AR-C 239) (9.09), 2-([2,6-dimethoxyphenoxyethyl]aminomethyl)-1,4-benzodioxane (WB-4101) (8.87), N-[3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl]-3-methyl-4-oxo-2-phenyl- 4H-1-benzopyran-8-carboxamide monomethanesulfonate (Rec 15/2739/3) (8.81), 5-methylurapidil (8.59), prazosin (8.57), benoxathian (8.56), S(+)-tamsulosin (8.27), indoramin (8.11), doxazosin (7.96), alfuzosine (7.82), phentolamine (7.70), terazosin (7.52), spiperone (7.48), oxymetazoline (7.40), 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]deca ne-7,9-dione dihydrochloride (BMY 7378) (7.05), corynanthine (6.98), rauwolscine (6.40), yohimbine (6.22), and N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha,alpha-dime thyl-1H-indole-3-ethanamine hydrochloride (RS 17053) (6.07). Correlation of subtype-selective antagonist pK(B) values was best with published values for the alpha1a/1A-adrenoceptor subtype. Therefore, the present results suggest that contraction of the female pig urethra is caused by activation of the alpha1A-adrenoceptor.

Aspects on reducing gastrointestinal adverse effects associated with radiotherapy.

Patients receiving cancer therapy are afflicted with a diversity of side effects. Radiotherapy for cancer affecting the head and neck, oesophagus and pelvis is associated with a marked toxicity, specifically encountered as mucosal toxicity. Pain and diarrhoea as well as nausea and vomiting are the most common symptoms, with subsequent problems such as malnutrition and decreased quality of life. These side effects need to be reduced if we are to optimize radiotherapy and to cure patients. Because there is no straightforward way of obviating these side effects, every effort to prevent aggravation and to induce healing of mucosal changes is of prime importance. Numerous agents including antimicrobials, local and systemic analgesics, anti-inflammatory drugs, anti-diarrhoeal drugs, and mucosal protectors alone or in combination with dietetic care have been used and/or are under evaluation in order to palliate the symptoms and increase the quality of life for the patients subjected to radiotherapy. In this article we summarize some aspects within the field that were discussed at the Annual Meeting of the Swedish Society for Oncology in Gavle, 1997.

High-precision conformal radiotherapy (HPCRT) of prostate cancer--a new technique for exact positioning of the prostate at the time of treatment.

PURPOSE: Biopsies taken 2 years after radiotherapy of localized prostate cancer indicate residual tumor cells in 20-60% of cases, and the prognosis for these patients is unfavorable. More precise methods of localization of the prostate are desirable to increase the dose to the prostate tumor and minimize the volume of adjacent sensitive tissues that are currently included in the planning target volume. We have sought a method to more accurately locate the prostate at the time of treatment, allowing a reduction of the volume of rectum and bladder included in the high dose region during dose escalation. METHODS AND RESULTS: We have developed a new technique using a special urethral catheter (patent pending), containing markers that can be visualized by the radiotherapy machine for accurate positioning of the prostate. The catheter is used throughout the treatment planning procedure and the isocenter is placed on one of the markers. On the treatment couch the markers are visualized on port-films and with portal imaging immediately before dose delivery. A beam-center-marker on the accelerator makes it possible to adjust the isocenter position to within 1 mm, giving very high precision, independent of external fixation. The technique involves a simple patient setup. The method has been tested in five patients with conventional dose level (70 Gy) and in 24 patients in the first Scandinavian dose escalation study with external beam radiotherapy. No increase in acute side-effects was observed. CONCLUSION: With the new high precision conformal radiotherapy (HPCRT) technique we have developed a technique that allows us to increase the dose to the prostate without excessive side effects. The method reduces the uncertainties in prostate localization, is easy to handle, and feasible in routine treatment.

Apoptotic tumor cell death induced by estramustine in patients with malignant glioma.

Estramustine phosphate (EMP), a cytotoxic drug used in the treatment of prostatic carcinoma, is metabolized and exerts specific cytotoxic effects in malignant glioma in vitro and in vivo. In the present study, we have evaluated the cytotoxic effect of EMP in the clinical situation with regard to appearance of DNA damage and its correlation to the uptake of estramustine (EaM) in human malignant astrocytoma tissue. Ten patients were given 280 mg of EMP p.o. 12 h before surgery. Specimens from brain tumor tissue were collected during surgery and used for detection of fragmented DNA, a hallmark of apoptosis, with in situ end labeling (ISEL) and agarose gel techniques. The main metabolite of EMP in glioma tissue, EaM, was analyzed with gas chromatography. It was demonstrated that EMP induced clusters of ISEL-positive tumor cells and fragmentation of DNA on agarose gels in patients treated with EMP. In the same patients, a significant uptake of EaM in tumor tissue was demonstrated. In control patients, who were not treated with EMP, and in two EMP-treated patients with no uptake of EaM, no signs of fragmented DNA and only a few scattered ISEL-positive cells were seen in the tumor tissue. Signs of apoptosis were also seen in two different experimental models, i.e., in vitro cell cultures of rat glioma cells and an in vivo rat glioma model. It is suggested that EaM can induce apoptosis by a direct effect on a subpopulation of glioma cells in human brain tumors in the clinical situation.

Issues in setting health-based cleanup levels for arsenic in soil.

Health risk assessments often do not take into account the unique aspects of evaluating exposures to arsenic in soil. For example, risks from ingestion of arsenic in soil are often based on toxicity factors derived from studies of arsenic (soluble arsenate or arsenite) in drinking water. However, the toxicity of arsenic in drinking water cannot be directly extrapolated to toxicity of soil arsenic because of differences in chemical form, bioavailability, and excretion kinetics. Because of the differences between soil arsenic and water arsenic, we conclude that risks from arsenic in soil are lower than what would be calculated using default toxicity values for arsenic in drinking water. Site-specific risk assessments for arsenic in soil can be improved by characterizing the form of arsenic in soil, by conducting animal feeding or in vitro bioavailability studies using site soils, and by conducting studies to evaluate the relationship between urinary arsenic and soil arsenic levels. Such data could be used to more accurately measure the contribution that soil arsenic makes to total intake of arsenic. Available data suggest that arsenic usually makes a small contribution to this total.