Jane Ellen Simmons

United States Environmental Protection Agency, Washington, Washington, D.C., United States

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Publications (90)265.23 Total impact

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    ABSTRACT: Current strategies for predicting adverse health outcomes of environmental chemicals are centered on early key events in toxicity pathways. However, quantitative relationships between early molecular changes in a given pathway and later health effects are often poorly defined. The goal of this study was to evaluate short-term key event indicators using qualitative and quantitative methods in an established pathway of mouse liver tumorigenesis mediated by peroxisome proliferator-activated receptor-alpha (PPARα). Male B6C3F1 mice were exposed for 7 days to di (2-ethylhexyl) phthalate (DEHP), di-n-octyl phthalate (DNOP), and n-butyl benzyl phthalate (BBP), which vary in PPARα activity and liver tumorigenicity. Each phthalate increased expression of select PPARα target genes at 7 days, while only DEHP significantly increased liver cell proliferation labeling index (LI). Transcriptional benchmark dose (BMDT) estimates for dose-related genomic markers stratified phthalates according to hypothetical tumorigenic potencies, unlike BMDs for non-genomic endpoints (relative liver weights or proliferation). The 7-day BMDT values for Acot1 as a surrogate measure for PPARα activation were 29, 370, and 676 mg/kg-d for DEHP, DNOP, and BBP, respectively, distinguishing DEHP (liver tumor BMD of 35 mg/kg-d) from non-tumorigenic DNOP and BBP. Effect thresholds were generated using linear regression of DEHP effects at 7 days and 2-year tumor incidence values to anchor early response molecular indicators and a later phenotypic outcome. Thresholds varied widely by marker, from 2-fold (Pdk4 and proliferation LI) to 30-fold (Acot1) induction to reach hypothetical tumorigenic expression levels. These findings highlight key issues in defining thresholds for biological adversity based on molecular changes.
    Toxicological Sciences 10/2015; DOI:10.1093/toxsci/kfv236 · 3.85 Impact Factor
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    ABSTRACT: The introduction of drinking water disinfection greatly reduced waterborne diseases. However, the reaction between disinfectants and natural organic matter in the source water leads to an unintended consequence, the formation of drinking water disinfection byproducts (DBPs). The haloacetaldehydes (HALs) are the third largest group by weight of identified DBPs in drinking water. The primary objective of this study was to analyze the occurrence and comparative toxicity of the emerging HAL DBPs. A new HAL DBP, iodoacetaldehyde (IAL) was identified. This study provided the first systematic, quantitative comparison of HAL toxicity in Chinese hamster ovary cells. The rank order of HAL cytotoxicity is tribromoacetaldehyde (TBAL) ≈ chloroacetaldehyde (CAL) > dibromoacetaldehyde (DBAL) ≈ bromochloroacetaldehyde (BCAL) ≈ dibromochloroacetaldehyde (DBCAL) > IAL > bromoacetaldehyde (BAL) ≈ bromodichloroacetaldehyde (BDCAL) > dichloroacetaldehyde (DCAL) > trichloroacetaldehyde (TCAL). The HALs were highly cytotoxic compared to other DBP chemical classes. The rank order of HAL genotoxicity is DBAL > CAL ≈ DBCAL > TBAL ≈ BAL > BDCAL > BCAL ≈ DCAL > IAL. TCAL was not genotoxic. Because of their toxicity and abundance, further research is needed to investigate their mode of action to protect the public health and the environment.
    Environmental Science & Technology 05/2015; DOI:10.1021/es506358x · 5.33 Impact Factor
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    Toxicology 03/2015; DOI:10.1016/j.tox.2015.03.009 · 3.62 Impact Factor
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    ABSTRACT: Considerable concern has been raised regarding research reproducibility both within and outside the scientific community. Several factors possibly contribute to a lack of reproducibility, including a failure to adequately employ statistical considerations during study design, bias in sample selection or subject recruitment, errors in developing data inclusion/exclusion criteria, and flawed statistical analysis. To address some of these issues, several publishers have developed checklists that authors must complete. Others have either enhanced statistical expertise on existing editorial boards, or formed distinct statistics editorial boards. Although the U.S. Environmental Protection Agency, Office of Research and Development, already has a strong Quality Assurance Program, an initiative was undertaken to further strengthen statistics consideration and other factors in study design and also to ensure these same factors are evaluated during the review and approval of study protocols. To raise awareness of the importance of statistical issues and provide a forum for robust discussion, a Community of Practice for Statistics was formed in January 2014. In addition, three working groups were established to develop a series of questions or criteria that should be considered when designing or reviewing experimental, observational, or modeling focused research. This article describes the process used to develop these study design guidance documents, their contents, how they are being employed by the Agency's research enterprise, and expected benefits to Agency science. The process and guidance documents presented here may be of utility for any research enterprise interested in enhancing the reproducibility of its science. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology.
    Toxicological Sciences 03/2015; 145(1). DOI:10.1093/toxsci/kfv020 · 3.85 Impact Factor
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    ABSTRACT: Trihalomethanes (THMs) and haloacetic acids (HAAs) are regulated disinfection by-products (DBPs); their joint reproductive toxicity in drinking water is unknown. We aimed to evaluate a drinking water mixture of the four regulated THMs and five regulated HAAs in a multigenerational reproductive toxicity bioassay. Sprague-Dawley rats were exposed via drinking water from gestation day 0 to postnatal day (PND) 6 of the F2 generation to a realistically proportioned mixture of THMs and HAAs at 0, 500×, 1000×, or 2000× of EPA's maximum contaminant levels (MCLs). Maternal water consumption was reduced at ≥1000×; body weights were reduced at 2000×. Pre- and postnatal survival were unaffected. F1 pup weights were unaffected at birth but reduced at 2000× on PND 6 and at ≥1000× on PND 21. Postweaning F1 body weights were reduced at 2000× while water consumption was reduced at ≥500×. Males at 2000× had a small but significantly increased incidence of retained nipples and compromised sperm motility. Onset of puberty was delayed at 1000× and 2000×. F1 estrous cycles and fertility were unaffected and F2 litters showed no effects on pup weight survival. Histologically, P0 dams had nephropathy and adrenal cortical pathology at 2000×. A mixture of regulated DBPs at up to 2000× the MCLs had no adverse effects on fertility, pregnancy maintenance, prenatal survival, postnatal survival, or birth weights. Delayed puberty at ≥1000× may have been secondary to reduced water consumption. Male nipple retention and compromised sperm motility at 2000× may have been secondary to reduced body weights.
    Environmental Health Perspectives 02/2015; 123(6). DOI:10.1289/ehp.1408579 · 7.98 Impact Factor

  • 01/2015: pages 25-43;
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    ABSTRACT: As the use of alternative drinking water treatment increases, it is important to understand potential public health implications associated with these processes. The objective of this study was to evaluate the formation of disinfection byproducts (DBPs) and cytotoxicity of natural organic matter (NOM) concentrates treated with chlorine, chloramine, and medium pressure ultraviolet (UV) irradiation followed by chlorine or chloramine, with and without nitrate or iodide spiking. The use of concentrated NOM conserved volatile DBPs and allowed for direct analysis of the treated water. Treatment with UV prior to chlorine in ambient (unspiked) samples did not affect cytotoxicity as measured using an in vitro normal human colon cell (NCM460) assay, compared to chlorination alone when toxicity is expressed on the basis of DOC. Nitrate-spiked UV+chlorine treatment produced greater cytotoxicity than nitrate-spiked chlorine alone or ambient UV+chlorine samples, on both a DOC and total organic halogen basis. Samples treated with UV+chloramine were more cytotoxic than those treated with only chloramine using either dose metric. This study demonstrated the combination of cytotoxicity and DBP measurements for process evaluation in drinking water treatment. The results highlight the importance of dose metric when considering the relative toxicity of complex DBP mixtures formed under different disinfection scenarios.
    Environmental Science and Technology 05/2014; 48(12). DOI:10.1021/es501412n · 5.33 Impact Factor
  • Article: Preface.
    Jane Ellen Simmons ·

    Toxicology 11/2013; 313(2-3):71-2. DOI:10.1016/j.tox.2013.11.001 · 3.62 Impact Factor
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    ABSTRACT: Recent efforts to update cumulative risk assessment procedures to incorporate nonchemical stressors ranging from physical to psychosocial, reflect increased interest in consideration of the totality of variables affecting human health and the growing desire to develop community-based risk assessment methods. A key roadblock is uncertainty as to how nonchemical stressors behave in relationship to chemical stressors. Physical stressors offer a reasonable starting place for measuring the effects of nonchemical stressors and their modulation of chemical effects (and vice versa), as they clearly differ from chemical stressors; and, "doses" of many physical stressors are more easily quantifiable than psychosocial stressors. There is a commonly held belief that virtually nothing is known about the impact of nonchemical stressors on chemically-mediated toxicity or the joint impact of co-exposure to chemical and nonchemical stressors. While this is generally true, there are several instances where a substantial body of evidence exists. A workshop titled "Cumulative Risk: Toxicity and Interactions of Physical and Chemical Stressors" held at the 2013 Society of Toxicology Annual Meeting, provided a forum for discussion of research addressing the toxicity of physical stressors and what is known about their interactions with chemical stressors, both in terms of exposure and effects. Physical stressors including sunlight, heat, radiation, infectious disease, and noise were discussed in reference to identifying pathways of interaction with chemical stressors, data gaps, and suggestions for future incorporation into cumulative risk assessments.
    Toxicological Sciences 10/2013; 137(1). DOI:10.1093/toxsci/kft228 · 3.85 Impact Factor
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    ABSTRACT: Some epidemiological studies report associations between drinking water disinfection by-products (DBPs) and adverse reproductive/developmental effects, e.g., low birth weight, spontaneous abortion, stillbirth, and birth defects. Using a multigenerational rat bioassay, we evaluated an environmentally relevant "whole" mixture of DBPs representative of chlorinated drinking water, including unidentified DBPs as well as realistic proportions of known DBPs at low-toxicity concentrations. Source water from a water utility was concentrated 136 fold, chlorinated, and provided as drinking water to Sprague-Dawley rats. Timed-pregnant females (P0 generation) were exposed during gestation and lactation. Weanlings (F1 generation) continued exposures and were bred to produce an F2 generation. Large sample sizes enhanced statistical power, particularly for pup weight and prenatal loss. No adverse effects were observed for pup weight, prenatal loss, pregnancy rate, gestation length, puberty onset in males, growth, estrous cycles, hormone levels, immunological endpoints, and most neurobehavioral endpoints. Significant, albeit slight, effects included delayed puberty for F1 females, reduced caput epidydimal sperm counts in F1 adult males, and increased incidences of thyroid follicular cell hypertrophy in adult females. These results highlight areas for future research while the largely negative findings, particularly for pup weight and prenatal loss, ease concerns raised by some epidemiological studies.
    Environmental Science & Technology 08/2013; 47(18). DOI:10.1021/es402646c · 5.33 Impact Factor
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    ABSTRACT: Mixture risk assessment is often hampered by the lack of dose response information on the mixture being assessed, forcing reliance on component formulas such as dose addition. We present a four step approach for evaluating chemical mixture data for consistency with dose addition for use in supporting a component based mixture risk assessment. Following the concepts in the U.S. EPA mixture risk guidance (EPA 2000), toxicological interaction for a defined mixture (all components known) is departure from a clearly articulated definition of component additivity. For the common approach of dose additivity, the EPA guidance identifies three desirable characteristics, foremost of which is that the component chemicals are toxicologically similar. The other two characteristics are empirical: the mixture components have toxic potencies that are fixed proportions of each other (throughout the dose range of interest), and the mixture dose term in the dose additive prediction formula, which we call the combined prediction model (CPM), can be represented by a linear combination of the component doses. A consequent property of the proportional toxic potencies is that the component chemicals must share a common dose response model, where only the dose coefficients depend on the chemical components. A further consequence is that the mixture data must be described by the same mathematical function ("mixture model") as the components, but with a distinct coefficient for the total mixture dose. The mixture response is predicted from the component dose response curves by using the dose additive CPM and the prediction is then compared with the observed mixture results. The four steps are to evaluate: 1) toxic proportionality by determining how well the CPM matches the single chemical models regarding mean and variance; 2) fit of the mixture model to the mixture data; 3) agreement between the mixture data and the CPM prediction; and 4) consistency between the CPM and the mixture model. Because there are four evaluations instead of one, some involving many parameters or dose groups, there are more opportunities to reject statistical hypotheses about dose addition, thus statistical adjustment for multiple comparisons is necessary. These four steps contribute different pieces of information about the consistency of the component and mixture data with the two empirical characteristics of dose additivity. We examine this four step approach in how it can show empirical support for dose addition as a predictor for an untested mixture in a screening level risk assessment. The decision whether to apply dose addition should be based on all four of those evidentiary pieces as well as toxicological understanding of these chemicals and should include interpretations of the numerical and toxicological issues that arise during the evaluation. This approach is demonstrated with neurotoxicity data on carbamate mixtures.
    Toxicology 11/2012; 313(2-3). DOI:10.1016/j.tox.2012.10.016 · 3.62 Impact Factor
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    ABSTRACT: A developmental toxicity bioassay was used in three experiments to evaluate water concentrates for suitability in multigenerational studies. First, chlorinated water was concentrated 135-fold by reverse osmosis; select lost disinfection by-products were spiked back. Concentrate was provided as drinking water to Sprague-Dawley and F344 rats from gestation day 6 to postnatal day 6. Maternal serum levels of luteinizing hormone on gestation day 10 were unaffected by treatment for both strains. Treated dams had increased water consumption, and increased incidences of polyuria, diarrhea, and (in Sprague-Dawley rats) red perinasal staining. Pup weights were reduced. An increased incidence of eye defects was seen in F344 litters. Chemical analysis of the concentrate revealed high sodium (6.6 g/l) and sulfate (10.4 g/l) levels. To confirm that these chemicals caused polyuria and osmotic diarrhea, respectively, Na₂SO₄ (5-20 g/l) or NaCl (16.5 g/l) was provided to rats in drinking water. Water consumption was increased at 5- and 10-g Na₂SO₄/l and with NaCl. Pup weights were reduced at 20-g Na₂SO₄/l. Dose-related incidences and severity of polyuria and diarrhea occurred in Na₂SO₄-treated rats; perinasal staining was seen at 20 g/l. NaCl caused polyuria and perinasal staining, but not diarrhea. Subsequently, water was concentrated ∼120-fold and sulfate levels were reduced by barium hydroxide before chlorination, yielding lower sodium (≤1.5 g/l) and sulfate (≤2.1 g/l) levels. Treatment resulted in increased water consumption, but pup weight and survival were unaffected. There were no treatment-related clinical findings, indicating that mixtures produced by the second method are suitable for multigenerational testing.
    Birth Defects Research Part B Developmental and Reproductive Toxicology 06/2012; 95(3):202-12. DOI:10.1002/bdrb.21004 · 0.77 Impact Factor
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    ABSTRACT: Statistical design and environmental relevance are important aspects of studies of chemical mixtures, such as pesticides. We used a dose-additivity model to test experimentally the default assumptions of dose additivity for two mixtures of seven N-methylcarbamates (carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl, and propoxur). The best-fitting models were selected for the single-chemical dose-response data and used to develop a combined prediction model, which was then compared with the experimental mixture data. We evaluated behavioral (motor activity) and cholinesterase (ChE)-inhibitory (brain, red blood cells) outcomes at the time of peak acute effects following oral gavage in adult and preweanling (17 days old) Long-Evans male rats. The mixtures varied only in their mixing ratios. In the relative potency mixture, proportions of each carbamate were set at equitoxic component doses. A California environmental mixture was based on the 2005 sales of each carbamate in California. In adult rats, the relative potency mixture showed dose additivity for red blood cell ChE and motor activity, and brain ChE inhibition showed a modest greater-than additive (synergistic) response, but only at a middle dose. In rat pups, the relative potency mixture was either dose-additive (brain ChE inhibition, motor activity) or slightly less-than additive (red blood cell ChE inhibition). On the other hand, at both ages, the environmental mixture showed greater-than additive responses on all three endpoints, with significant deviations from predicted at most to all doses tested. Thus, we observed different interactive properties for different mixing ratios of these chemicals. These approaches for studying pesticide mixtures can improve evaluations of potential toxicity under varying experimental conditions that may mimic human exposures.
    Toxicological Sciences 05/2012; 129(1):126-34. DOI:10.1093/toxsci/kfs190 · 3.85 Impact Factor
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    ABSTRACT: In rodent bioassays where chemicals are administered in the drinking water, water consumption data for individual animals are needed to estimate chemical exposures accurately. If multiple animals share a common water source, as occurs in some studies, only the total amount of drinking water consumed by all animals utilizing the common source is directly measurable, and water consumption rates for individual animals are not available. In the Four Lab Study of the US Environmental Protection Agency, which included a multigenerational rodent bioassay, a complex mixture of drinking water disinfection by-products was delivered to multiple Sprague-Dawley rats from a common drinking water container. To estimate disinfection by-product mixture exposure for each animal, authors developed four log-linear regression models to allocate water consumption among rats sharing a common water container. The four models represented three animal lifestages: Gestation, Lactation, and Postweaning, with separate Postweaning models for male and female. Authors used data from six Sprague-Dawley rat bioassays to develop these models from available individual cage data for the Postweaning models, and available individual animal data for the Gestation and Lactation models. The r(2) values for the model fits were good, ranging from 0.67 to 0.92. The Gestation and Lactation models were generally quite accurate in predicting average daily water consumption whereas the Postweaning models were less robust. These models can be generalized for use in other reproductive and developmental bioassays where common water sources are used and data on the explanatory variables are available.
    ILAR journal / National Research Council, Institute of Laboratory Animal Resources 03/2012; 53(1):99-112. DOI:10.1093/ilar.53.1.99 · 2.39 Impact Factor
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    ABSTRACT: The role of nonchemical stressors in modulating the human health risk associated with chemical exposures is an area of increasing attention. On 9 March 2011, a workshop titled "Approaches for Incorporating Nonchemical Stressors into Cumulative Risk Assessment" took place during the 50th Anniversary Annual Society of Toxicology Meeting in Washington D.C. Objectives of the workshop included describing the current state of the science from various perspectives (i.e., regulatory, exposure, modeling, and risk assessment) and presenting expert opinions on currently available methods for incorporating nonchemical stressors into cumulative risk assessments. Herein, distinct frameworks for characterizing exposure to, joint effects of, and risk associated with chemical and nonchemical stressors are discussed.
    Toxicological Sciences 02/2012; 127(1):10-7. DOI:10.1093/toxsci/kfs088 · 3.85 Impact Factor
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    ABSTRACT: Previously, we reported that acute treatment with propoxur or carbaryl decreased the duration of the photic after discharge (PhAD) of flash evoked potentials (FEPs). In the current studies, we compared the effects of acute or repeated exposure to a mixture of carbaryl and propoxur (1:1.45 ratio; propoxur:carbaryl) on the duration of the PhAD and brain ChE activity in Long Evans rats. Animals were exposed (po) either to a single dose (0, 3, 10, 45 or 75 mg/kg), or 14 daily dosages (0, 3, 10, 30, 45 mg/kg), of the mixture. Acute and repeated treatment with 3mg/kg (or greater) of the mixture produced dose-related inhibition of brain ChE activity. Compared to controls, the PhAD duration decreased after acute administration of 75 mg/kg or repeated treatment with 30 mg/kg of the mixture. The linear relationship between the percent of control brain ChE activity and the PhAD duration was similar for both exposure paradigms. Dose-response models for the acute and repeated exposure data did not differ for brain ChE activity or the duration of the PhAD. Repeated treatment with the mixture resulted in slightly less (13-22%) erythrocyte ChE inhibition than acute exposure. Both acute and repeated treatment resulted in dose-additive results for the PhAD duration and less than dose-additive responses (6-16%) for brain ChE activity for the middle range of dosages. Acute treatment resulted in greater than dose-additive erythrocyte ChE inhibition (15-18%) at the highest dosages. In contrast, repeated treatment resulted in less than dose-additive erythrocyte ChE inhibition (16-22%) at the middle dosages. Brain and plasma levels of propoxur and carbaryl did not differ between the acute and repeated dosing paradigms. In summary, a physiological measure of central nervous system function and brain ChE activity had similar responses after acute or repeated treatment with the carbamate mixture, and brain ChE showed only small deviations from dose-additivity. Erythrocyte ChE activity had larger differences between the acute and repeated treatment paradigms, and showed slightly greater deviations from dose-additivity. Because these treatments utilized larger dosages than anticipated environmental exposures, concern for non-additive effects in humans is minimized. The small magnitude of the deviations from dose-additivity also suggest that in the absence of repeated exposure data, results from an acute study of readily reversible carbamate toxicity can be used to estimate the response to repeated daily exposures.
    NeuroToxicology 02/2012; 33(3):332-46. DOI:10.1016/j.neuro.2012.02.006 · 3.38 Impact Factor
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    ABSTRACT: In complex mixture toxicology, there is growing emphasis on testing environmentally representative doses that improve the relevance of results for health risk assessment, but are typically much lower than those used in traditional toxicology studies. Traditional experimental designs with typical sample sizes may have insufficient statistical power to detect effects caused by environmentally relevant doses. Proper study design, with adequate statistical power, is critical to ensuring that experimental results are useful for environmental health risk assessment. Studies with environmentally realistic complex mixtures have practical constraints on sample concentration factor and sample volume as well as the number of animals that can be accommodated. This article describes methodology for calculation of statistical power for non-independent observations for a multigenerational rodent reproductive/developmental bioassay. The use of the methodology is illustrated using the U.S. EPA's Four Lab study in which rodents were exposed to chlorinated water concentrates containing complex mixtures of drinking water disinfection by-products. Possible experimental designs included two single-block designs and a two-block design. Considering the possible study designs and constraints, a design of two blocks of 100 females with a 40:60 ratio of control:treated animals and a significance level of 0.05 yielded maximum prospective power (~90%) to detect pup weight decreases, while providing the most power to detect increased prenatal loss.
    International Journal of Environmental Research and Public Health 10/2011; 8(10):4082-101. DOI:10.3390/ijerph8104082 · 2.06 Impact Factor
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    ABSTRACT: Reactions between chemicals used to disinfect drinking water and compounds present in source waters produce chemical mixtures containing hundreds of disinfection byproducts (DBPs). Although the results have been somewhat inconsistent, some epidemiological studies suggest associations may exist between DBP exposures and adverse developmental outcomes. The potencies of individual DBPs in rodent and rabbit developmental bioassays suggest that no individual DBP can account for the relative risk estimates reported in the positive epidemiologic studies, leading to the hypothesis that these outcomes could result from the toxicity of DBP mixtures. As a first step in a mixtures risk assessment for DBP developmental effects, this paper identifies developmentally toxic DBPs and examines data relevant to the mode of action (MOA) for DBP developmental toxicity. We identified 24 developmentally toxic DBPs and four adverse developmental outcomes associated with human DBP exposures: spontaneous abortion, cardiovascular defects, neural tube defects, and low birth weight infancy. A plausible MOA, involving hormonal disruption of pregnancy, is delineated for spontaneous abortion, which some epidemiologic studies associate with total trihalomethane and bromodichloromethane exposures. The DBP data for the other three outcomes were inadequate to define key MOA steps.
    Toxicology and Applied Pharmacology 02/2011; 254(2):100-26. DOI:10.1016/j.taap.2011.02.002 · 3.71 Impact Factor
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    ABSTRACT: Chlorination of drinking water yields hundreds of disinfection by-products (DBPs). Among the DBPs, four trihalomethanes (THMs; chloroform, bromodichloromethane, chlorodibromomethane, bromoform) and five haloacetic acids (HAAs; chloroacetic, dichloroacetic, trichloroacetic, bromoacetic, and dibromoacetic acid) are U.S. EPA regulated. We assessed the combined toxicity of these DBPs. F344 rats were treated with mixtures of the four THMs (THM4), the five HAAs (HAA5), or nine DBPs (DBP9; THM4+HAA5). Mixtures were administered in 10% Alkamuls(®) EL-620 daily by gavage on gestation days 6-20. Litters were examined postnatally. All three mixtures caused pregnancy loss at ≥ 613 μmol/kg/day. In surviving litters, resorption rates were increased in groups receiving HAA5 at 615 μmol/kg/day and DBP9 at 307 μmol/kg/day. HAA5 caused eye malformations (anophthalmia, microphthalmia) at ≥ 308 μmol/kg/day. Thus, both HAAs and THMs contributed to DBP9-induced pregnancy loss. The presence of THMs in the full mixture, however, appeared to reduce the incidence of HAA-induced eye defects.
    Reproductive Toxicology 01/2011; 31(1):59-65. DOI:10.1016/j.reprotox.2010.08.002 · 3.23 Impact Factor
  • Jane Ellen Simmons · Linda K. Teuschler ·

    Principles and Practice of Mixtures Toxicology, 12/2010: pages 401 - 419; , ISBN: 9783527630196

Publication Stats

2k Citations
265.23 Total Impact Points


  • 1987-2015
    • United States Environmental Protection Agency
      • Office of Research and Development
      Washington, Washington, D.C., United States
  • 2013
    • National Institute of Environmental Health Sciences
      Durham, North Carolina, United States
  • 2008-2010
    • Research Triangle Park Laboratories, Inc.
      Raleigh, North Carolina, United States
  • 2006
    • Virginia Commonwealth University
      • Department of Biostatistics
      Richmond, Virginia, United States
  • 2005
    • California Environmental Protection Agency (Cal/EPA)
      Sacramento, California, United States