Sielken and Associates Consulting Inc.

Bryan, TX, United States

Sielken and Associates Consulting Inc.

Bryan, TX, United States
SEARCH FILTERS
Time filter
Source Type

Hard G.C.,Private Consultant | Banton M.I.,LyondellBasell | Bretzlaff R.S.,Sielken and Associates Consulting Inc. | Dekant W.,University of Würzburg | And 7 more authors.
Toxicological Sciences | Year: 2013

Chronic progressive nephropathy (CPN) is a spontaneous renal disease of rats which can be a serious confounder in toxicology studies. It is a progressive disease with known physiological factors that modify disease progression, such as high dietary protein. The weight of evidence supports an absence of a renal counterpart in humans. There is extensive evidence that advanced CPN, particularly end-stage kidney, is a risk factor for development of a background incidence of atypical tubule hyperplasia and renal tubule tumors (RTT). The likely cause underlying this association with tubule neoplasia is the long-term increased tubule cell proliferation that occurs throughout CPN progression. As a variety of chemicals are able to exacerbate CPN, there is a potential for those exacerbating the severity up to and including end-stage kidney to cause a marginal increase in RTT and their precursor lesions. Extensive statistical analysis of National Toxicology Program studies shows a strong correlation between high-grade CPN, especially end-stage CPN, and renal tumor development. CPN as a mode of action (MOA) for rat RTT has received attention from regulatory authorities only recently. In the absence of toxic effects elsewhere, this does not constitute a carcinogenic effect of the chemical but can be addressed through a proposed MOA approach for regulatory purposes to reach a decision that RTT, developing as a result of CPN exacerbation in rats, have no relevance for human risk assessment. Guidelines are proposed for evaluation of exacerbation of CPN and RTT as a valid MOA for a given chemical. © The Author 2012. Published by Oxford University Press on behalf of the Society of Toxicology.


Haney Jr. J.T.,Texas Commission on Environmental Quality TCEQ | Erraguntla N.,Texas Commission on Environmental Quality TCEQ | Sielken Jr. R.L.,Sielken and Associates Consulting Inc. | Valdez-Flores C.,Sielken and Associates Consulting Inc.
Regulatory Toxicology and Pharmacology | Year: 2014

A unit risk factor (URF) was developed for hexavalent chromium (CrVI). The URF is based on excess lung cancer mortality in two key epidemiological studies of chromate production workers. The Crump et al. (2003) study concerns the Painesville, OH worker cohort, while Gibb et al. (2000) regards the Baltimore, MD cohort. A supporting assessment was also performed for a cohort from four low-dose chromate plants (Leverkusen and Uerdingen, Germany, Corpus Christi, TX, Castle Hayne, NC). For the Crump et al. (2003) study, grouped observed and expected number of lung cancer mortalities along with cumulative CrVI exposures were used to obtain the maximum likelihood estimate and asymptotic variance of the slope (β) for the linear multiplicative relative risk model using Poisson regression modeling. For the Gibb et al. (2000) study, Cox proportional hazards modeling was performed with optimal exposure lag and adjusting for the effect of covariates (e.g., smoking) to estimate β values. Life-table analyses were used to develop URFs for each of the two key studies, as well as for supporting and related studies. The two key study URFs were combined using weighting factors relevant to confidence to derive the final URF for CrVI of 2.3E-03 per μgCrVI/m3. © 2013 Elsevier Inc.


Valdez-Flores C.,Sielken and Associates Consulting Inc. | Sielken Jr. R.L.,Sielken and Associates Consulting Inc. | Teta M.J.,Exponent Health science
Regulatory Toxicology and Pharmacology | Year: 2010

The most recent epidemiological data on individual workers in the NIOSH and updated UCC occupational studies have been used to characterize the potential excess cancer risks of environmental exposure to ethylene oxide (EO). In addition to refined analyses of the separate cohorts, power has been increased by analyzing the combined cohorts. In previous SMR analyses of the separate studies and the present analyses of the updated and pooled studies of over 19,000 workers, none of the SMRs for any combination of the 12 cancer endpoints and six sub-cohorts analyzed were statistically significantly greater than one including the ones of greatest previous interest: leukemia, lymphohematopoietic tissue, lymphoid tumors, NHL, and breast cancer. In our study, no evidence of a positive cumulative exposure-response relationship was found. Fitted Cox proportional hazards models with cumulative EO exposure do not have statistically significant positive slopes. The lack of increasing trends was corroborated by categorical analyses. Cox model estimates of the concentrations corresponding to a 1-in-a-million extra environmental cancer risk are all greater than approximately 1 ppb and are more than 1500-fold greater than the 0.4 ppt estimate in the 2006 EPA draft IRIS risk assessment. The reasons for this difference are identified and discussed. © 2009 Elsevier Inc. All rights reserved.


Hovey R.C.,University of California at Davis | Coder P.S.,WIL Research Laboratories LLC | Wolf J.C.,Experimental Pathology Laboratories Inc. | Sielken Jr. R.L.,Sielken and Associates Consulting Inc. | And 2 more authors.
Toxicological Sciences | Year: 2011

In this study, we quantified the effects of in utero exposure to the herbicide atrazine on subsequent mammary gland development. Atrazine was administered to pregnant female Long Evans rats from gestation days 13-19 at doses of 0, 6.5, 50, or 100 mg/kg/day. A pair-fed control group was yoked to the high-dose atrazinetreated group. Litter size was standardized to 10 pups on postnatal day (PND) 4. Whole mounts of the left fourth mammary gland and histologic sections of the right fourth gland were obtained from a subgroup of offspring on PND1, 21, 33, on day of vaginal opening (VO), or around PND65 at diestrus. A blinded, quantitative analysis of key morphological features in mammary gland whole mounts (ductal elongation, ductal network area, epithelial area, terminal end bud [TEB] incidence, and epithelial density) as well as epithelial proliferation within different parenchymal structures was conducted. There was no effect of atrazine exposure on any of the measures of mammary gland development at the maternal dose of 6.5 mg/kg/day. On PND1, ductal elongation was increased by approximately 20% (p < 0.05) in the female offspring born to dams exposed to 50 and 100 mg/kg/day atrazine, coincident with decreased epithelial proliferation in the 100 mg/kg/day group at this age. These differences were not present on PND21, or thereafter. An increased incidence of TEB in the mammary glands from females that were born to both the pair-fed and 50 mg/kg/day-treated dams at the time of VO indicated that this response was a specific result of maternal caloric restriction. Collectively, these data indicate that maternal atrazine exposure has no long-term effects on mammary gland development in female offspring beyond a transitory response to high doses at PND1. © The Author 2010. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.


Sielken R.L.,Sielken and Associates Consulting Inc. | Valdez-Flores C.,Sielken and Associates Consulting Inc.
Regulatory Toxicology and Pharmacology | Year: 2011

Cox regression is used to estimate exposure-response models (with cumulative 1,3-butadiene (BD) ppm-years as the exposure metric) based on the most recent data and validated exposure estimates from UAB's study of North American workers in the styrene-butadiene-rubber industry. These data are substantially updated from those in USEPA's 2002 risk assessment. The slope for cumulative BD ppm-years is not statistically significantly different than zero for CML, AML, or, when any one of eight exposure covariates is added to the model, for all leukemias combined (total leukemia).For total leukemia, the EC(1/100,000) is approximately 0.15 BD environmental ppm and the corresponding unit risk factor is approximately 0.00007 per BD environmental ppm. The excess risk for CML is approximately 15-fold less than for total leukemia. The maximum likelihood estimates suggest that there is no excess risk for AML from cumulative BD ppm-years. For CLL, the slope is statistically significantly different than zero. The excess risk for CLL is approximately 2.5-fold less than for total leukemia. For both total leukemia and CLL, the slope is not statistically significantly different than zero when the exposure-response modeling is based on the person-years with cumulative BD ppm-years less than or equal to 300. ppm-years. © 2011 Elsevier Inc.


Sielken R.L.,Sielken and Associates Consulting Inc. | Valdez-Flores C.,Sielken and Associates Consulting Inc.
Regulatory Toxicology and Pharmacology | Year: 2013

The excess risks due to 1,3-butadiene (BD) inhalation in EU occupational settings are quantified for leukemia, AML, CLL, CML, lymphoid neoplasms, and myeloid neoplasms. The most recent data from the University of Alabama at Birmingham epidemiological study of North American workers in the styrene-butadiene rubber industry are modeled.The number of high-intensity tasks (HITs) and other exposure covariates may be more important predictors than cumulative BD ppm-years alone. For example, all of the 71 leukemia decedents in the UAB study who were exposed to BD had some BD HITs. None of the 1192 exposed workers without BD HITs had leukemia mortalities.The authors' best estimate (consolidated over all endpoints) of the average occupational BD exposure concentration for 45. years of exposure starting at age 20 corresponding to an added risk of 1/10,000 by age 70 is 7.2. ppm.Cumulative BD ppm-years is not statistically significantly associated with CML, AML, or myeloid neoplasms or (after any one of eight exposure covariates is included in the modeling) leukemia. The statistical significance of the slopes for leukemia, CLL, and lymphoid neoplasms unadjusted for covariate effects disappears when modeling is restricted to person years with less than 200 cumulative BD ppm-years. © 2012 Elsevier Inc.


Haney J.T.,Texas Commission on Environmental Quality TCEQ | McCant D.D.,Texas Commission on Environmental Quality TCEQ | Sielken R.L.,Sielken and Associates Consulting Inc. | Valdez-Flores C.,Sielken and Associates Consulting Inc. | Grant R.L.,Texas Commission on Environmental Quality TCEQ
Regulatory Toxicology and Pharmacology | Year: 2012

The TCEQ has developed a URF for nickel based on excess lung cancer in two epidemiological studies of nickel refinery workers with nickel species exposure profiles most similar to emissions expected in Texas (i.e., low in sulfidic nickel). One of the studies (Enterline and Marsh, 1982) was used in the 1986 USEPA assessment, while the other (Grimsrud et al., 2003) is an update to an earlier study (Magnus et al., 1982) used by USEPA. The linear multiplicative relative risk model with Poisson regression modeling was used to obtain maximum likelihood estimates and asymptotic variances for cancer potency factors (β) using cumulative nickel exposure levels versus observed and expected lung cancer mortality (Enterline and Marsh, 1982) or lung cancer incidence cases (Grimsrud et al., 2003). Life-table analyses were then used to develop URFs from these two studies, which were combined using weighting factors relevant to confidence to derive the final URF for nickel of 1.7E-04perμg/m 3. The de minimis air concentration corresponding to a 1 in 100,000 extra lung cancer risk level is 0.059μg/m 3. The TCEQ will use this conservative value to protect the general public in Texas against the potential carcinogenic effects from chronic exposure to nickel. © 2011.


Erraguntla N.K.,Texas Commission on Environmental Quality TCEQ | Sielken Jr. R.L.,Sielken and Associates Consulting Inc. | Valdez-Flores C.,Sielken and Associates Consulting Inc. | Grant R.L.,Texas Commission on Environmental Quality TCEQ
Regulatory Toxicology and Pharmacology | Year: 2012

The United States Environmental Protection Agency (USEPA) developed an inhalation unit risk factor (URF) of 4.3E-03 per μg/m3 for arsenic in 1984 for excess lung cancer mortality based on epidemiological studies of workers at two smelters: the Asarco smelter in Tacoma, Washington and the Anaconda smelter in Montana. Since the USEPA assessment, new studies have been published and exposure estimates were updated at the Asarco and Anaconda smelters and additional years of follow-up evaluated. The Texas Commission on Environmental Quality (TCEQ) has developed an inhalation URF for lung cancer mortality from exposures to arsenic and inorganic arsenic compounds based on a newer epidemiology study of Swedish workers and the updates of the Asarco and Anaconda epidemiology studies. Using a combined analysis approach, the TCEQ weighted the individual URFs from these three epidemiology cohort studies, to calculate a final inhalation URF of 1.5E-04 per μg/m3. In addition, the TCEQ also conducted a sensitivity analysis, in which they calculated a URF based on a type of meta-analysis, and these results compared well with the results of the combined analysis. The no significant concentration level (i.e., air concentration at 1 in 100,000 excess lung cancer mortality) is 0.067μg/m3. This value will be used to evaluate ambient air monitoring data so the general public in Texas is protected against adverse health effects from chronic exposure to arsenic. © 2012 Elsevier Inc.


Haney J.T.,Texas Commission on Environmental Quality TCEQ | Erraguntla N.,Texas Commission on Environmental Quality TCEQ | Sielken R.L.,Sielken and Associates Consulting Inc. | Valdez-Flores C.,Sielken and Associates Consulting Inc.
Regulatory Toxicology and Pharmacology | Year: 2012

The carcinogenicity of hexavalent chromium(CrVI) is of significant interest to regulatory agencies for the protection of public health and to industry. Additionally, the mode of action (MOA) and conditions under which CrVI may induce carcinogenicity (e.g., reductive capacity considerations) have recently been the subject of significant scientific debate. Epidemiological data supported by data relevant to the carcinogenic MOA support considering nonlinear-threshold carcinogenic assessments for comparison to default linear low-dose extrapolation approaches. This study reviews epidemiological studies available in the scientific literature and conducts additional statistical dose-response analyses to identify potential carcinogenic thresholds and points of departure (PODs) in the context of supportive MOA information for a nonlinear-threshold inhalation carcinogenic assessment. Dosimetric adjustments and application of appropriate uncertainty factors (total UF of 30) to the selected cumulative exposure POD results in a cancer-based chronic inhalation reference value (ReV) of 0.24μgCrVI/m 3. This chronic ReV is 300 times higher than the 1 in 100,000 excess cancer risk air concentration of 8E-04μg/m 3 based on USEPA's unit risk factor. © 2012 Elsevier Inc.


Valdez-Flores C.,Sielken and Associates Consulting Inc. | Sielken Jr. R.L.,Sielken and Associates Consulting Inc. | Jane Teta M.,Exponent Health science
Archives of Toxicology | Year: 2011

The estimated occupational ethylene oxide (EO) exposure concentrations corresponding to specified extra risks are calculated for lymphoid mortality as the most appropriate endpoint, despite the lack of a statistically significant exposure-response relationship. These estimated concentrations are for occupational exposures-40 years of occupational inhalation exposure to EO from age 20 to age 60 years. The estimated occupational inhalation exposure concentrations (ppm) corresponding to specified extra risks of lymphoid mortality to age 70 years in a population of male and female EO workers are based on Cox proportional hazards models of the most recent updated epidemiology cohort mortality studies of EO workers and a standard life-table calculation. An occupational exposure at an inhalation concentration of 2.77 ppm EO is estimated to result in an extra risk of lymphoid mortality of 4 in 10,000 (0.0004) in the combined worker population of men and women from the two studies. The corresponding estimated concentration decreases slightly to 2.27 ppm when based on only the men in the updated cohorts combined. The difference in these estimates reflects the difference between combining all of the available data or focusing on only the men and excluding the women who did not show an increase in lymphoid mortality with EO inhalation exposure. The results of sensitivity analyses using other mortality endpoints (all lymphohematopoietic tissue cancers, leukemia) support the choice of lymphoid tumor mortality for estimation of extra risk. © 2011 Springer-Verlag.

Loading Sielken and Associates Consulting Inc. collaborators
Loading Sielken and Associates Consulting Inc. collaborators