Jennifer Jinot

Utrecht University, Utrecht, Utrecht, Netherlands

Are you Jennifer Jinot?

Claim your profile

Publications (18)74.95 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Benzene, a ubiquitous environmental pollutant, causes acute myeloid leukemia (AML). Recently, through transcriptome profiling of peripheral blood mononuclear cells (PBMC), we reported dose-dependent effects of benzene exposure on gene expression and biochemical pathways in 83 workers exposed across four airborne concentration ranges (from <1 ppm to >10 ppm) compared with 42 subjects with non-workplace ambient exposure levels. Here, we further characterize these dose-dependent effects with continuous benzene exposure in all 125 study subjects. We estimated air benzene exposure levels in the 42 environmentally-exposed subjects from their unmetabolized urinary benzene levels. We used a novel non-parametric, data-adaptive model selection method to estimate the change with dose in the expression of each gene. We describe non-parametric approaches to model pathway responses and used these to estimate the dose responses of the AML pathway and 4 other pathways of interest. The response patterns of majority of genes as captured by mean estimates of the first and second principal components of the dose-response for the five pathways and the profiles of 6 AML pathway response-representative genes (identified by clustering) exhibited similar apparent supra-linear responses. Responses at or below 0.1 ppm benzene were observed for altered expression of AML pathway genes and CYP2E1. Together, these data show that benzene alters disease-relevant pathways and genes in a dose-dependent manner, with effects apparent at doses as low as 100 ppb in air. Studies with extensive exposure assessment of subjects exposed in the low-dose range between 10 ppb and 1 ppm are needed to confirm these findings.
    PLoS ONE 05/2014; 9(5):e91828. DOI:10.1371/journal.pone.0091828 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Ramazzini Institute (RI) has completed nearly 400 cancer bioassays on over 200 compounds. Study design and protocol differences between RI and other laboratories have been suggested by the European Food Safety Authority (EFSA) and others to contribute to controversy regarding cancer hazard findings, principally lymphoma/leukemia diagnoses. Evaluate RI study design, protocol differences, and accuracy of tumor diagnoses for their impact on carcinogenic hazard characterization. We analyzed the findings from a recent Pathology Working Group (PWG) review of RI procedures and tumor diagnoses, evaluated consistency of RI and other laboratory findings for chemicals identified by RI as positive for lymphoma/leukemia, and examined evidence for a number of other issues raised regarding RI bioassays. The RI cancer bioassay design and protocols were evaluated in the context of relevant risk assessment guidance from International authorities. Although the PWG identified close agreement with RI diagnoses for most tumor types, it did not for lymphoma/leukemia of the respiratory tract and neoplasms of the inner ear and cranium. We discuss (1) the implications of the PWG findings, particularly lymphoma diagnostic issues, (2) differences between RI and other laboratory studies that are relevant to evaluating RI cancer bioassays and (3) future work that may help resolve some concerns. We conclude that (1) issues related to respiratory tract infections have complicated diagnoses at that site (i.e., lymphoma/leukemia) and for neoplasms of the inner ear and cranium, and (2) there is consistency and value in RI studies for identification of other chemical-related neoplasia.
    Environmental Health Perspectives 09/2013; 121(11-12). DOI:10.1289/ehp.1306661 · 7.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: In support of the Integrated Risk Information System (IRIS), the Environmental Protection Agency (EPA) completed a Toxicological Review of Trichloroethylene (TCE) in September, 2011, the result of an effort spanning over twenty years. OBJECTIVES: This article reviews key findings and scientific issues regarding the human health effects of TCE in EPA's Toxicological Review. METHODS: This assessment synthesized and characterized thousands of epidemiologic, experimental animal, and mechanistic studies, and addressed several key scientific issues through modeling of TCE toxicokinetics, meta-analyses of epidemiologic studies, and analyses of mechanistic data. DISCUSSION: Toxicokinetic modeling aided in characterizing the toxicological role of the complex metabolism and multiple metabolites of TCE. Meta-analyses of the epidemiologic data informed the conclusion that TCE causes kidney cancer in humans and provided strong evidence that TCE may also cause liver cancer and non-Hodgkin lymphoma. Mechanistic analyses support a key role for mutagenicity in TCE-induced kidney carcinogenicity. Recent evidence from both human and experimental animal studies indicates the involvement of TCE exposure in autoimmune disease and hypersensitivity. Recent avian and in vitro mechanistic studies provide biological plausibility that TCE plays a role in developmental cardiac toxicity, the subject of substantial debate due to mixed results from epidemiologic and rodent studies. CONCLUSIONS: TCE is carcinogenic to humans by all routes of exposure and poses a potential human health hazard for non-cancer toxicity to the central nervous system, kidney, liver, immune system, male reproductive system, and the developing embryo/fetus.
    Environmental Health Perspectives 12/2012; DOI:10.1289/ehp.1205879 · 7.26 Impact Factor
  • Source
    Environmental Health Perspectives 07/2012; 120(7):a264; author reply a264-5. DOI:10.1289/ehp.1205212 · 7.26 Impact Factor
  • Source
    Cheryl Siegel Scott, Jennifer Jinot
    [Show abstract] [Hide abstract]
    ABSTRACT: We conducted a meta-analysis focusing on studies with high potential for trichloroethylene (TCE) exposure to provide quantitative evaluations of the evidence for associations between TCE exposure and kidney, liver, and non-Hodgkin lymphoma (NHL) cancers. A systematic review documenting essential design features, exposure assessment approaches, statistical analyses, and potential sources of confounding and bias identified twenty-four cohort and case-control studies on TCE and the three cancers of interest with high potential for exposure, including five recently published case-control studies of kidney cancer or NHL. Fixed- and random-effects models were fitted to the data on overall exposure and on the highest exposure group. Sensitivity analyses examined the influence of individual studies and of alternative risk estimate selections. For overall TCE exposure and kidney cancer, the summary relative risk (RRm) estimate from the random effects model was 1.27 (95% CI: 1.13, 1.43), with a higher RRm for the highest exposure groups (1.58, 95% CI: 1.28, 1.96). The RRm estimates were not overly sensitive to alternative risk estimate selections or to removal of an individual study. There was no apparent heterogeneity or publication bias. For NHL, RRm estimates for overall exposure and for the highest exposure group, respectively, were 1.23 (95% CI: 1.07, 1.42) and 1.43 (95% CI: 1.13, 1.82) and, for liver cancer, 1.29 (95% CI: 1.07, 1.56) and 1.28 (95% CI: 0.93, 1.77). Our findings provide strong support for a causal association between TCE exposure and kidney cancer. The support is strong but less robust for NHL, where issues of study heterogeneity, potential publication bias, and weaker exposure-response results contribute uncertainty, and more limited for liver cancer, where only cohort studies with small numbers of cases were available.
    International Journal of Environmental Research and Public Health 11/2011; 8(11):4238-72. DOI:10.3390/ijerph8114238 · 1.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diverse environmental contaminants, including the plasticizer di(2-ethylhexyl)phthalate (DEHP), are hepatocarcinogenic peroxisome proliferators in rodents. Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) activation and its sequelae have been proposed to constitute a mode of action (MOA) for hepatocarcinogenesis by such agents as a sole causative factor. Further, based on a hypothesized lower sensitivity of humans to this MOA, prior reviews have concluded that rodent hepatocarcinogenesis by PPAR-alpha agonists is irrelevant to human carcinogenic risk. Herein, we review recent studies that experimentally challenge the PPAR-alpha activation MOA hypothesis, providing evidence that DEHP is hepatocarcinogenic in PPAR-alpha-null mice and that the MOA but not hepatocarcinogenesis is evoked by PPAR-alpha activation in a transgenic mouse model. We further examine whether relative potency for PPAR-alpha activation or other steps in the MOA correlates with tumorigenic potency. In addition, for most PPAR-alpha agonists of environmental concern, available data are insufficient to characterize relative human sensitivity to this rodent MOA or to induction of hepatocarcinogenesis. Our review and analyses raise questions about the hypothesized PPAR-alpha activation MOA as a sole explanation for rodent hepatocarcinogenesis by PPAR-alpha agonists and therefore its utility as a primary basis for assessing human carcinogenic risk from the diverse compounds that activate PPAR-alpha. These findings have broad implications for how MOA hypotheses are developed, tested, and applied in human health risk assessment. We discuss alternatives to the current approaches to these key aspects of mechanistic data evaluation.
    Environmental Health Perspectives 11/2009; 117(11). DOI:10.1289/ehp.0900758 · 7.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Our objective was to examine experimental and epidemiologic studies pertaining to immune-related, and specifically autoimmune-related, effects of trichloroethylene (TCE). We performed a literature search of PubMed and reviewed bibliographies in identified articles. We then systematically reviewed immune-related data, focusing on clinical and immunologic features and mechanistic studies. Studies conducted in MRL+/+ lupus mice report an accelerated autoimmune response in relation to exposure to TCE or some metabolites. Effects have been reported after 4 weeks of exposure to TCE at doses as low as 0.1 mg/kg/day in drinking water and have included increased antinuclear antibodies and interferon-gamma (IFN-gamma) and decreased secretion of interleukin-4 (IL-4), consistent with an inflammatory response. Autoimmune hepatitis, inflammatory skin lesions, and alopecia have been found after exposures of 32-48 weeks. Recent mechanistic experiments in mice examined oxidative stress and, specifically, effects on lipid-peroxidation-derived aldehydes in TCE-induced autoimmune disease. Two studies in humans reported an increase in IL-2 or IFN-gamma and a decrease in IL-4 in relation to occupational or environmental TCE exposure. Occupational exposure to TCE has also been associated with a severe, generalized hypersensitivity skin disorder accompanied by systemic effects, including hepatitis. In three case-control studies of scleroderma with a measure of occupational TCE exposure, the combined odds ratio was 2.5 [95% confidence interval (CI), 1.1-5.4] in men and 1.2 (95% CI, 0.58-2.6) in women. The consistency among the studies and the concordance between the studies in mice and humans support an etiologic role of TCE in autoimmune disease. Multisite collaborations and studies of preclinical immune markers are needed to further develop this field of research.
    Environmental Health Perspectives 06/2009; 117(5):696-702. DOI:10.1289/ehp.11782 · 7.26 Impact Factor
  • Source
    Environmental and Molecular Mutagenesis 01/2009; DOI:10.1002/em.20464 · 2.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The European Food Safety Authority (EFSA) released a 2006 report questioning the relationship of aspartame exposure with increased incidence of lymphomas/leukemias in a European Ramazzini Foundation (ERF) rat study. The EFSA report suggested that the lymphoma/leukemia findings were most likely explained by infection in the rat colony. The ERF has also conducted the only available long-term oral study of methyl tertiary-butyl ether (MTBE). Thus, using the EFSA report as support, some have now raised questions about the human relevance of MTBE-associated hemolymphoreticular tumors reported by the ERF in female rats as well as whether their incidence was elevated above background levels. In this report, we discuss the hypothesized mode of action (MOA) of infection-induced lymphoma and its relevance to MTBE-associated lymphomas. We address the relationship of rat strain and study duration to lymphoma susceptibility and review evidence of low background rates of this tumor in control animals at the ERF, similar survival rates for female rats at the ERF and National Toxicology Program (NTP), and chemical- and gender-specificity of tumor induction for this type of tumor in studies at the ERF. We find that the background incidence of hemolymphoreticular tumors in female rats in the MTBE study is consistent with contemporaneous studies at the ERF and that there is an exposure-related effect, which is unlikely to be due to infections. We examine more recent tumor classification schemes for lymphomas, which support the combination of lymphoblastic leukemias and lymphomas reported by Belpoggi et al. ([1995] Toxicol Ind Health 11:119-149; [1998] Eur J Oncol 3:201-206).
    Environmental and Molecular Mutagenesis 03/2008; 49(2):155-64. DOI:10.1002/em.20356 · 2.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mode of action (MOA) information is increasingly being applied in human health risk assessment. The MOA can inform issues such as the relevance of observed effects in laboratory animals to humans, and the variability of response within the human population. Several collaborative groups have developed frameworks for analyzing and utilizing MOA information in human health risk assessment of environmental carcinogens and toxins, including the International Programme on Chemical Safety, International Life Sciences Institute, and U.S. Environmental Protection Agency. With the goal of identifying gaps and opportunities for progress, we critically evaluate several of these MOA frameworks. Despite continued improvement in incorporating biological data in human health risk assessment, several notable challenges remain. These include articulation of the significant role of scientific judgment in establishing an MOA and its relevance to humans. In addition, binary (yes/no) decisions can inappropriately exclude consideration of data that may nonetheless be informative to the overall assessment of risk. Indeed, the frameworks lack a broad consideration of known causes of human disease and the potential for chemical effects to act additively with these as well as endogenous background processes. No integrated analysis of the impact of multiple MOAs over the same dose range, or of varying MOAs at different life stages, is included. Separate consideration of each MOA and outcome limits understanding of how multiple metabolites, modes, and toxicity pathways contribute to the toxicological profile of the chemical. An extension of the analyses across outcomes with common modes is also needed.
    Journal of Toxicology and Environmental Health Part B 02/2008; 11(1):16-31. DOI:10.1080/10937400701600321 · 3.90 Impact Factor
  • Jennifer Jinot, Steven Bayard
    [Show abstract] [Hide abstract]
    ABSTRACT: After an extensive review and analysis of the scientific evidence on the respiratory health effects of passive smoking, the U.S. Environmental Protection Agency concluded that environmental tobacco smoke causes lung cancer in adult nonsmokers and increases the risk of a variety of non-cancer respiratory disorders, especially in children. This article is a response to claims in Dr. Gio Gori's article “Policy Against Science: The Case of Environmental Tobacco Smoke,” appearing in the same issue of this journal, that such conclusions are unwarranted. This response focuses only on the respiratory health effects of environmental tobacco smoke.
    Risk Analysis 05/2006; 15(1):91 - 96. DOI:10.1111/j.1539-6924.1995.tb00096.x · 2.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We model nicotine from environmental tobacco smoke (ETS) in office air and salivary cotinine in nonsmoking U.S. workers. We estimate that: an average salivary cotinine level of 0.4 ng/ml corresponds to an increased lifetime mortality risk of 1/1000 for lung cancer, and 1/100 for heart disease; >95% of ETS-exposed office workers exceed OSHA's significant risk level for heart disease mortality, and 60% exceed significant risk for lung cancer mortality; 4000 heart disease deaths and 400 lung cancer deaths occur annually among office workers from passive smoking in the workplace, at the current 28% prevalence of unrestricted smoking in the office workplace.
    Risk Analysis 05/2006; 18(1):71 - 83. DOI:10.1111/j.1539-6924.1998.tb00917.x · 2.28 Impact Factor
  • Steven Bayard, Jennifer Jinot
    Risk Analysis 07/1996; 16(3):301-4. DOI:10.1111/j.1539-6924.1996.tb01462.x · 1.97 Impact Factor
  • J Jinot, S Bayard
    [Show abstract] [Hide abstract]
    ABSTRACT: During the last 25 years, several hundred papers have been published on the respiratory health effects of environmental tobacco smoke (ETS). Various independent assessments have concluded that ETS causes lung cancer in adult nonsmokers and increases the risk of various noncancer effects, principally in children. The effects on children include pneumonia, bronchitis and bronchiolitis in young children; chronic middle ear effusion; increased frequency and severity of attacks among asthmatics; possible induction of asthma in previously asymptomatic individuals; small reductions in lung function; and symptoms of upper respiratory tract irritation. In nonsmoking adults, ETS exposure is associated with irritation of the eyes, nose, and throat, and with wheezing, symptoms of bronchitis, shortness of breath, and decreased lung function. The results of recent studies not only confirm and strengthen the above findings but also provide strong suggestive evidence that ETS causes sinonasal cancer and is a risk factor for sudden infant death syndrome. To mitigate such a preventable environmental health impact, public health measures to reduce involuntary ETS exposure are warranted.
    Reviews on environmental health 01/1996; 11(3):89-100. DOI:10.1515/REVEH.1996.11.3.89
  • Steven Bayard, Jennifer Jinot, George Flatman
    [Show abstract] [Hide abstract]
    ABSTRACT: This article is a rejoinder to the article by Gross in this issue, in which he claims that ‘any range [of estimates of lung cancer deaths attributable to environmental tobacco smoke (ETS)] must encompass an estimate of zero deaths, and that the uncertainties are so great as to cast serious doubt on the use of any quantitative estimate’.The U.S. Environmental Protection Agency's (EPA) conclusion that ETS is a human lung carcinogen was based on the total weight of evidence, not just the 11 U.S. epidemiology studies of ETS and lung cancer that Gross discusses with respect to the population risk estimates. This conclusion was unanimously endorsed by the Agency's independent Scientific Advisory Board and is in concurrence with the conclusions of other organizations.As for the population risk estimates, the EPA report acknowledges uncertainties in these estimates. However, we maintain that the estimate of 3000 lung cancer deaths per year in U.S. non-smokers is a reasonable point estimate. Furthermore, we have relatively high confidence in this estimate compared to cancer risk estimates for other environmental pollutants, because it is based on human data from actual environmental exposure levels.
    Environmetrics 07/1995; 6(4):413 - 418. DOI:10.1002/env.3170060410 · 1.49 Impact Factor
  • Source
    Tobacco Control 09/1994; DOI:10.1136/tc.3.3.263 · 5.15 Impact Factor
  • Source
    Jennifer Jinot, Steven Bayard
    [Show abstract] [Hide abstract]
    ABSTRACT: After an extensive review and assessment of the scientific evidence on the respiratory health effects of passive smoking, the U.S. Environmental Protection Agency has determined that the widespread exposure to environmental tobacco smoke in the United States presents a serious and substantial public health impact. The Environmental Protection Agency concluded that environmental tobacco smoke causes lung cancer in adult nonsmokers and increases the risk for a variety of noncancer respiratory disorders, especially in children. This article reviews evidence presented in the Environmental Protection Agency's 1992 report on the respiratory health effects of passive smoking and responds to critical allegations levied by Gio Gori in his article "Science, policy, and ethics: the case of environmental tobacco smoke", appearing in the same issue of this journal. Several recent studies appearing since the cutoff date for inclusion in the EPA report are also discussed.
    Journal of Clinical Epidemiology 05/1994; 47(4):339-49; discussion 351-3. DOI:10.1016/0895-4356(94)90154-6 · 5.48 Impact Factor
  • William Farland, Steven Bayard, Jennifer Jinot
    Journal of Clinical Epidemiology 05/1994; 47(4):335-7; discussion 351-3. DOI:10.1016/0895-4356(94)90153-8 · 5.48 Impact Factor

Publication Stats

275 Citations
74.95 Total Impact Points


  • 2014
    • Utrecht University
      • Institute for Risk Assessment Sciences (IRAS)
      Utrecht, Utrecht, Netherlands
  • 2009–2011
    • United States Environmental Protection Agency
      • National Center for Environmental Assessment
      Washington, D. C., DC, United States
  • 1994–2008
    • The Ohio Environmental Protection Agency
      Columbus, Ohio, United States