Aortic Elasticity and Arsenic Exposure: A Step Function rather than a Linear Function.

While the dose-response relationship for the carcinogenic effects of arsenic exposure indicates nonlinearity with increases only above about 150 µg/L arsenic in drinking water, similar analyses of noncarcinogenic effects of arsenic exposure remain to be conducted. We present here an alternative analysis of data on a measure of aortic elasticity, a risk factor for hypertension, and its relationship to urinary arsenic levels. An occupational health study from Ankara, Turkey by Karakulak et al. compared urinary arsenic levels and a measure of aortic elasticity (specifically, aortic strain) in workers with a linear no-threshold model.  We have examined these data with three alternative models-a fitted step-function, a stratified, and a weighted linear regression model. Discontinuity within the data revealed two subsets of data, one for workers with urinary arsenic levels ≤ 160 µg/L whose mean aortic strain level was 11.3% and one for workers with arsenic levels > 160 µg/L whose mean aortic stain level was 5.33 % (p < 0.0001). Several alternative models were examined that indicated the best model to be the threshold model with a threshold at a urinary arsenic level of 160 µg/L. Observation of a discontinuity in the data revealed their better fit to a threshold model (at a urinary arsenic level of 160 µg/L) than to a linear-no threshold model.  Examinations with alternative models are recommended for studies of arsenic and hypertension and possibly other noncarcinogenic effects.

A review of low-dose arsenic risks and human cancers.

The linear no-threshold (LNT) model has historically been the default assumption in assessing carcinogenic risk from arsenic ingestion based on epidemiological studies. This contrasts with the threshold model used in assessing carcinogenic risk from arsenic ingestion derived from toxicological investigations of experimental animals. We present here a review of our epidemiological work that has examined models that may better explain the human cancer risk from the ingestion of arsenic, particularly from low level exposures, than does the LNT model. While previous epidemiology studies have demonstrated increased risks of bladder, lung, and skin cancers at arsenic exposures of 200 ug/L or greater, we seek here to examine the dose-response patterns at lower exposure levels. These include ecological, case/control, and cohort designs. Methodologic issues include choice of continuous or stratified analysis of exposure data, search for sources of non-conformity or variability, and distinctions in water sources and geography. Multiple studies have yielded useful data-based models, including threshold models, hockey-stick models, and "J-shaped" linear-quadratic models. These models have found that increased cancer risk may only begin at specific arsenic exposure levels greater than zero. These results provide guidance in seeking toxicological explanations and public health reference levels.

Maternal tobacco use: A third-trimester risk factor for small-for-gestational-age pregnancy outcome.

BACKGROUND: Small for gestational age (SGA) is a well-known consequence of maternal smoking. Here, we newly examine the magnitude of SGA risk by week of gestational age. METHODS: Singleton live births (N = 3,032,928) with recorded birth weight, gestational age (22-44 weeks), and maternal tobacco use (Y/N) were categorized as to SGA (Y/N), based on 10th percentile gender-specific weights-for-age. RESULTS: SGA prevalence among tobacco users (19.5%) and non-users (9.1%) yielded a significant SGA prevalence rate ratio of 2.15 (2.13-2.16) and a significant adjusted odds ratio of 2.36 (2.34-2.38). The tobacco non-users' rate was steadily near 9% across the week 22-44 gestational age range. The tobacco users' rate was steady until week 33 when it rose monotonically through week 37 to about 20% at week 38 and remained high. This pattern for SGA by gestational week was similar for prevalence rates and adjusted ORs. Tobacco use only through week 33 was not seen to be an SGA risk factor. The magnitude of tobacco use as an SGA risk factor for late third trimester births increased during the period of preterm birth and became fully evident with a two-fold risk for full term infants. CONCLUSION: We newly report the temporal pattern of tobacco-related SGA by week of gestational age. Tobacco-related SGA was only seen for late third trimester births - increasing during weeks 33-37 with a doubling during weeks 38-44. This pattern, informative for issues of mechanism, highlights the potential benefit of extending tobacco cessation programs through the third trimester of pregnancy.

Prostate Cancer Incidence in U.S. Counties and Low Levels of Arsenic in Drinking Water.

Background: Although inorganic arsenic in drinking water at high levels (100s-1000s µg/L [ppb]) increases cancer risk (skin, bladder, lung, and possibly prostate), the evidence at lower levels is limited. Methods: We conducted an ecologic analysis of the dose-response relationship between prostate cancer incidence and low arsenic levels in drinking water in a large study of U.S. counties (N = 710). County arsenic levels were <200 ug/L with median <100 ug/L and dependency greater than 10%. Groundwater well usage, water arsenic levels, prostate cancer incidence rates (2009-2013), and co-variate data were obtained from various U.S. governmental agencies. Poisson and negative-binomial regression analyses and stratified analysis were performed. Results: The best fitting polynomial analysis yielded a J-shaped linear-quadratic model. Linear and quadratic terms were significant (p < 0.001) in the Poisson model, and the quadratic term was significant (p < 0.05) in the negative binomial model. This model indicated a decreasing risk of prostate cancer with increasing arsenic level in the low range and increasing risk above. Conclusions: This study of prostate cancer incidence in US counties with low levels of arsenic in their well-water arsenic levels finds a j-shaped model with decreasing risk at very low levels and increasing risk at higher levels.

Lung Cancer Risk and Low (≤50 µg/L) Drinking Water Arsenic Levels for US Counties (2009⁻2013)-A Negative Association.

While epidemiologic studies clearly demonstrate drinking water with high levels of arsenic as a significant risk factor for lung cancer, the evidence at low levels (≤50 µg/L) is uncertain. Therefore, we have conducted an ecological analysis of recent lung cancer incidence for US counties with a groundwater supply of.