NTP has made a commitment to studying noncancer health effects. As part of that commitment, NTP assesses the evidence that environmental chemicals, physical substances, or mixtures—collectively referred to as substances—cause adverse health effects. NTP also provides opinions on whether these substances might be of concern, given what is known about current human exposure levels. The Office of Health Assessment and Translation (OHAT) conducts health hazard assessments and scoping reviews or state-of-the-science evaluations, which are published as NTP monographs, NTP research reports, and journal publications. OHAT also hosts workshops to address important issues in environmental health sciences. Andrew Rooney, Ph.D., served as acting director of OHAT in FY 2017.
In FY 2017, NTP published the NTP Monograph on Immunotoxicity Associated with Exposure to Perfluorooctanoic Acid or Perfluorooctane Sulfonate, the first evaluation reaching hazard conclusions using the OHAT Approach to Systematic Review and Evidence Integration. OHAT began using a new data visualization format—an interactive systematic evidence map—that allows readers to search and explore evidence categorized by health effect, exposure, and type such as the literature collected in the state-of-the-science evaluation of transgenerational inheritance.
As part of efforts to promote harmonization in development of systematic review methods, OHAT hosted the 4th International Symposium on Systematic Review and Meta-Analysis of Laboratory Studies in April 2017. OHAT also published several reports in the new NTP research report series, including a pilot study on tin and organotin levels in Danish women, a systematic review of biological activity of bisphenol A structural analogues, and a systematic review of the effects of fluoride on learning and memory in animal studies.
Study Scientist: Andrew Rooney
Sarin is a highly toxic organophosphorus nerve agent developed for chemical warfare during World War II that continues to be used as a weapon today. The immediate, or acute, effects of sarin exposure are serious and well known, including constriction of the pupils, muscle paralysis, seizures, cardiorespiratory depression, and death due to respiratory failure. Although there are reports of potential long-term neurological effects from sarin exposure, the evidence has not been evaluated with the increased objectivity, rigor, and transparent process of a systematic review methodology. In partnership with the NIH Countermeasures Against Chemical Threats (CounterACT) Program, NTP is conducting a systematic review to evaluate the evidence for long-term neurological effects in humans following acute exposure to sarin. The protocol was posted in April 2017, and this evaluation is ongoing.
Study Scientist: Andrew Rooney and Brandy Beverly
Evidence is growing that the environment plays a role in a wide range of diseases that involve inflammation. The extent to which environmental exposures ultimately lead to these adverse health effects through an inflammatory pathway remains unclear. This evaluation will examine the evidence that environmental substances contribute to inflammation, which ultimately leads to atherosclerosis, and will identify biomarkers of the inflammation involved. Atherosclerosis was selected for investigation because of the significant public health impact of the disease, and the well-established role for inflammation in the disease process that leads to it. The concept was reviewed at the December 2014 Board of Scientific Counselors meeting, and the evaluation has been initiated.
Study Scientist: Kyla Taylor
Concern has been raised about the endocrine-disrupting potential of some chemicals found in personal care and other consumer products. Given the large number of co-occurring chemicals in these products, new strategies and techniques need to be developed. NIEHS is collaborating with EPA to perform a small-scale, longitudinal pilot study to evaluate the performance of existing survey, measurement, and modeling methods for assessing exposures to chemicals in several consumer product categories, including personal and child care, household cleaning, lawn and garden, home improvement, and food packaging products. The pilot study addresses several research needs related to the measurement and modeling of human exposures. The concept was reviewed at the June 2015 Board of Scientific Counselors meeting, and the NIEHS Institutional Review Board (IRB) for the Protection of Human Subjects in Research has approved the project. This study is currently open for enrollment.
Study Scientist: Vickie Walker
Transgenerational inheritance is the phenomenon in which an individual’s exposures have far-reaching consequences, affecting multiple generations removed from the original insult. NTP conducted a state-of-the-science or scoping review to examine the evidence for transgenerational inheritance of health effects associated with exposure to a wide range of stressors (e.g., environmental chemicals, drugs of abuse, nutrition and diet, pharmaceuticals, infectious agents, stress) in humans and animals. The report systematically compiled and categorized the literature to develop an evidence map for transgenerational inheritance by broad health-effect categories, exposures, and types of evidence, and identified areas of consistency, uncertainty, data gaps, and research needs. Evidence mapping illustrated that risk of bias, having generally few studies, and heterogeneity in exposures and endpoints examined present serious limitations to available bodies of evidence for assessing transgenerational effects. This report was accepted for publication in Environment International in December 2017.
Study Scientist: Kembra Howdeshell and Brandy Beverly
Research on traffic-related air pollution and children’s health has increased in the past decade, reflecting improvement in air monitoring technology and exposure methodology. Traffic-related air pollution has been measured in multiple ways, including direct traffic measures (such as traffic proximity or density) and surrogate measures of traffic-related air pollution (such as particulate matter, oxides of nitrogen, and other products of fossil-fuel combustion generated by motor vehicles including benzene, diesel exhaust, and polycyclic aromatic hydrocarbons). This topic is the subject of a series of evaluations on the evidence for an association between traffic-related air pollution and health outcomes impacting the fetus and children, beginning with hypertensive disorders of pregnancy and neurological development and function in children. The concept was reviewed at the April 2014 Board of Scientific Counselors meeting. The protocol was posted in June 2016, and the evaluation is ongoing.
Study Scientist: Kembra Howdeshell
Cancer chemotherapy agents are cytotoxic drugs, many of which are known mutagens and developmental toxicants. Occupational exposure to cancer chemotherapy agents can occur in various professions including medical, veterinary, and manufacturing. Although improved handling procedures and engineering controls have reduced contamination, surface contamination persists in pharmacy and nursing areas of some hospital-based cancer centers. This evaluation examined the evidence that occupational exposure to cancer chemotherapy agents is associated with adverse health effects, including genetic toxicity, cancer, reproductive and developmental effects, and acute effects. The concept was reviewed at the April 2014 Board of Scientific Counselors meeting and the protocol posted in October 2015. The draft NTP monograph has been completed and is undergoing peer review.
Study Scientist: Katie Pelch
Bisphenol A (BPA) is a high production volume chemical used in the manufacture of polycarbonate plastic, thermal paper, dental resins, and other composite materials used in consumer products. Recent studies report widespread use and exposure to a variety of chemicals with structural or functional similarity to BPA, referred to as BPA analogues. This study reviews human, animal, and in vitro evidence that the biological activity of BPA analogues is an emerging public health concern. The topic will be addressed further through in vitro laboratory experiments and external collaborations to evaluate in vivo activity in two model organisms, zebrafish and Caenorhabditis elegans. The concept was reviewed at the June 2015 Board of Scientific Counselors meeting. The protocol was finalized in August 2015, and the NTP research report was published in October 2017.
Study Scientist: Katie Pelch and Vickie Walker
NIEHS is interested in understanding the effects of the environment on epigenetic regulation of biological and pathological processes. Of the various epigenetic modifications, the alteration of DNA methylation patterns has been the most widely studied and highly funded modification to date. This evaluation will leverage newly developed text mining and machine learning tools to carry out scoping activities that will explore the evidence linking environmental exposures to health outcomes via genome-wide alterations in DNA methylation. The concept was reviewed at the June 2015 Board of Scientific Counselors meeting, and the evaluation is ongoing.
Study Scientist: Windy Boyd
Circadian disruption occurs when endogenous circadian rhythms, which are daily and predictable variations in biological, physiological, and behavioral processes, are out of phase with the external environment or with each other. Through their work, lifestyle choices, or residences, people are subjected to interruptions in the natural light-dark cycles, leading to the potential for circadian disruption. This project is being undertaken in conjunction with an analysis by the Office of the Report on Carcinogens for cancer hazard evaluation. The concept was reviewed at the April 2014 Board of Scientific Counselors meeting, and a public workshop/webinar was held at NIEHS in March 2016 to obtain expert opinion to inform potential health hazard assessments. The workshop report was published in Science of the Total Environment in December 2017. With the Office of the Report on Carcinogens, activity is underway to finalize the protocol and execute the cancer hazard evaluation.
Study Scientist: Windy Boyd
Neonicotinoid pesticides are a class of chemicals that act as insecticides by exerting neurotoxic effects through irreversible binding to insect nicotinic acetylcholine receptors. Nicotinic acetylcholine receptors are also present in the nervous systems of mammals, raising concern that neonicotinoids might affect animals other than their insect targets, including humans. In Spring 2015, neonicotinoid pesticides were nominated to NTP for possible evaluation of noncancer health outcomes. In response, OHAT is conducting a scoping review to identify the extent of evidence available to understand human health effects of seven neonicotinoid pesticides (acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, and thiamethoxam). The protocol was posted in November 2017, and the evaluation is ongoing.
Study Scientist: Windy Boyd
Parkinson’s disease is a group of motor system disorders including tremor of the extremities, rigidity of the limbs and body, slowness of movement, and postural instability. Although some Parkinson’s disease cases can be attributed to genetic factors, the causes of many cases remain unknown. Many studies report associations between environmental exposures and Parkinson’s disease or related symptoms. OHAT is conducting two scoping reviews on this topic. The first project is a scoping review to systematically map the evidence of the associations between exposures to environmental chemicals considered broadly and Parkinson’s disease. During scoping activities, hundreds of studies on the associations between exposure to the herbicide paraquat and Parkinson’s disease were identified, making paraquat a candidate chemical for further systematic review. Therefore, a more detailed scoping review is being developed to characterize reported associations between paraquat exposure and Parkinson’s disease. Both evaluations are ongoing.
Study Scientist: Kyla Taylor
NTP is currently conducting a systematic review to evaluate potential neurobehavioral effects from exposure to fluoride during development that includes consideration of human epidemiology, additional experimental animal studies, and mechanistic data. This update to NTP’s 2016 systematic review of published animal literature is examining neurobehavioral effects of exposure to fluoride during development and adulthood in rodents. The 2016 report concluded the evidence supporting adverse effects on learning and memory in animals exposed to fluoride in the diet or drinking water is low to moderate. The concept was approved at the December 2015 Board of Scientific Counselors meeting. The protocol was posted in July 2017, and the systematic review is ongoing.