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Siler City, North Carolina, United States

An approach to identify causal components of complex air pollution mixtures was explored. Rats and mice were exposed by inhalation 6h daily for 1 week or 6 months to dilutions of simulated downwind coal emissions, diesel and gasoline exhausts and wood smoke. Organ weights, hematology, serum chemistry, bronchoalveolar lavage, central vascular and respiratory allergic responses were measured. Multiple additive regression tree (MART) analysis of the combined database ranked 45 exposure (predictor) variables for importance to models best fitting 47 significant responses. Single-predictor concentration-response data were examined for evidence of single response functions across all exposure groups. Replication of the responses by the combined influences of the two most important predictors was tested. Statistical power was limited by inclusion of only four mixtures, albeit in multiple concentrations each and with particles removed for some groups. Results gave suggestive or strong evidence of causation of 19 of the 47 responses. The top two predictors of the 19 responses included only 12 organic and 6 inorganic species or classes. An increase in red blood cell count of rats by ammonia and pro-atherosclerotic vascular responses of mice by inorganic gases yielded the strongest evidence for causation and the best opportunity for confirmation. The former was a novel finding; the latter was consistent with other results. The results demonstrated the plausibility of identifying putative causal components of highly complex mixtures, given a database in which the ratios of the components are varied sufficiently and exposures and response measurements are conducted using a consistent protocol. © 2014 Informa Healthcare USA, Inc.

Seilkop S.K.,SKS Consulting Services | Lightfoot N.E.,Laurentian University | Berriault C.J.,Occupational Cancer Research Center | Conard B.R.,Consulting Inc.
Archives of Environmental and Occupational Health | Year: 2016

Respiratory cancer mortality and incidence were examined in an updated cohort of >56,000 Canadian nickel mining and refining workers. There was little evidence to suggest increased lung cancer risk in workers who had no experience in high-risk sintering operations that were closed by 1972, apart from that which would be expected from probable increased smoking prevalence relative to the comparison population. There was no substantive evidence of increased laryngeal cancer risk in the cohort, nor was there evidence of increased pharyngeal cancer risk in nonsinter workers. Nasal cancer incidence was elevated in nonsinter workers, but excess risks appeared to be confined to those hired prior to 1960. These findings lead us to tentatively conclude that occupationally-related respiratory risks in workers hired over the past 45 years are either very low or nonexistent. © 2016 Taylor & Francis

Lightfoot N.E.,Laurentian University | Berriault C.J.,Occupational Cancer Research Center | Seilkop S.K.,SKS Consulting Services | Conard B.R.,Consulting Inc.
Archives of Environmental and Occupational Health | Year: 2016

Mortality and cancer incidence were examined for an updated cohort of nonsinter nickel workers in Sudbury and Port Colborne, Ontario, Canada. Abstract results are provided for those with ≥ 15 years since first exposure. For circulatory disease mortality, significant elevations were observed overall in many Sudbury work areas and in Port Colborne staff. Underground miners, with first exposure before 1960, displayed significant elevations for pneumoconiosis, as well as silicosis and anthrasilicosis, likely due to crystalline silica. Significant elevations in colorectal cancer incidence were observed in Sudbury underground mining, mining maintenance, and maintenance work areas. Given a case-control study is not practical, the next cohort update should include more detailed occupational exposure assessment, including dust exposure, diesel engine emissions, solvents, various metals, silica, and sulphur dioxide. © 2016 Taylor & Francis

Conard B.R.,BRConard Consulting Inc. | Seilkop S.K.,SKS Consulting Services
Human and Ecological Risk Assessment | Year: 2011

Both animal and human exposure-response data are used to estimate the incremental unit risks (IURs) of lung cancer for Ni3S2 and NiO, which are constituent compounds of nickel refinery dust. The animal experiments are used to determine relative lung cancer potencies for Ni3S2 and NiO, and the human epidemiological data are used as the best estimate of overall risk for refinery dust exposure. The animal data for Ni3S2 are fit with a linear model, while the nonlinear animal data for NiO are fit with a Weibull model. The lower 95% confidence limit at a 5% point of departure is used to calculate a tumorigenic potency ratio of Ni3S2 to NiO of 5.6. Analyses of actual nickel refinery dust indicate the weight% of Ni3S2 and NiO to be 82% and 9%, respectively. This information is used with the previously determined IUR for nickel refinery dust to calculate IURNiO = 5.1 × 10 -5 (μg Ni/m3) -1 and IURNi3S2 = 2.9 × 10-4 (μg Ni/m3) -1. © Taylor & Francis Group, LLC.

Seilkop S.K.,SKS Consulting Services | Seilkop S.K.,Lovelace Respiratory Research Institute | Campen M.J.,University of New Mexico | Lund A.K.,Lovelace Respiratory Research Institute | And 2 more authors.
Inhalation Toxicology | Year: 2012

Combustion emissions cause pro-atherosclerotic responses in apolipoprotein E-deficient (ApoE /-) mice, but the causal components of these complex mixtures are unresolved. In studies previously reported, ApoE -/- mice were exposed by inhalation 6h/day for 50 consecutive days to multiple dilutions of diesel or gasoline exhaust, wood smoke, or simulated "downwind" coal emissions. In this study, the analysis of the combined four-study database using the Multiple Additive Regression Trees (MART) data mining approach to determine putative causal exposure components regardless of combustion source is reported. Over 700 physicalchemical components were grouped into 45 predictor variables. Response variables measured in aorta included endothelin-1, vascular endothelin growth factor, three matrix metalloproteinases (3, 7, 9), metalloproteinase inhibitor 2, heme-oxygenase-1, and thiobarbituric acid reactive substances. Two or three predictors typically explained most of the variation in response among the experimental groups. Overall, sulfur dioxide, ammonia, nitrogen oxides, and carbon monoxide were most highly predictive of responses, although their rankings differed among the responses. Consistent with the earlier finding that filtration of particles had little effect on responses, particulate components ranked third to seventh in predictive importance for the eight response variables. MART proved useful for identifying putative causal components, although the small number of pollution mixtures (4) can provide only suggestive evidence of causality. The potential independent causal contributions of these gases to the vascular responses, as well as possible interactions among them and other components of complex pollutant mixtures, warrant further evaluation. © 2012 Informa Healthcare USA, Inc.

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