NTP monograph最新文献

{"title":"NTP monograph on the state of the science concerning fluoride exposure and neurodevelopment and cognition: a systematic review.","authors":"","doi":"10.22427/NTP-MGRAPH-8","DOIUrl":"https://doi.org/10.22427/NTP-MGRAPH-8","url":null,"abstract":"<p><strong>Background: </strong>Fluoride is a common exposure in our environment that comes from a variety of sources and is widely promoted for its dental and overall oral health benefits. Contributions to an individual's total exposure come primarily from fluoride in drinking water, food, beverages and dental products. A 2006 evaluation by the National Research Council (NRC) found support for an association between consumption of high levels of naturally occurring fluoride in drinking water and adverse neurological effects in humans and recommended further investigation. The evidence reviewed at that time was from dental and skeletal fluorosis-endemic regions of China. Since the NRC evaluation, the number and location of studies examining cognitive and neurobehavioral effects of fluoride in humans have grown considerably, including several recent North American prospective cohort studies evaluating prenatal fluoride exposure. In 2016, the National Toxicology Program (NTP) published a systematic review of the evidence from experimental animal studies on the effects of fluoride on learning and memory. That systematic review found a low-to-moderate level of evidence that deficits in learning and memory occur in non-human mammals exposed to fluoride.</p><p><strong>Objective: </strong>To conduct a systematic review of the human, experimental animal, and mechanistic literature to evaluate the extent and quality of the evidence linking fluoride exposure to neurodevelopmental and cognitive effects in humans.</p><p><strong>Method: </strong>A systematic review protocol was developed and utilized following the standardized OHAT systematic review approach for conducting literature-based health assessments. This monograph presents the current state of evidence associating fluoride exposure with cognitive or neurodevelopmental health effects and incorporated predefined assessments of study quality and confidence levels. Benefits of fluoride with respect to oral health are not addressed in this monograph.</p><p><strong>Results: </strong>The bodies of experimental animal studies and human mechanistic evidence do not provide clarity on the association between fluoride exposure and cognitive or neurodevelopmental human health effects. Human mechanistic studies were too heterogenous and limited in number to make any determination on biological plausibility. This systematic review identified studies that assessed the association between estimated fluoride exposure and cognitive or neurodevelopmental effects in both adults and children, which were evaluated separately. The most common exposure assessment measures were drinking water concentrations and estimates of total fluoride exposure, as reflected in biomarkers such as urinary fluoride. In adults, only two high-quality cross-sectional studies examining cognitive effects were available. The literature in children was more extensive and was separated into studies assessing intelligence quotient (IQ) and studies a","PeriodicalId":87331,"journal":{"name":"NTP monograph","volume":" 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NTP monograph on the systematic review of traffic-related air pollution and hypertensive disorders of pregnancy.","authors":"","doi":"10.22427/NTP-MGRAPH-7","DOIUrl":"10.22427/NTP-MGRAPH-7","url":null,"abstract":"<p><strong>Introduction: </strong>Traffic-related air pollution (TRAP) contributes significantly to ambient air pollution, especially in urban settings. Air pollution has been established as a risk factor for hypertension and cardiovascular disease in adults, but this effect is less studied in other susceptible populations. There is increasing evidence that air pollution may adversely affect hypertensive disorders of pregnancy (e.g., gestational hypertension, preeclampsia, eclampsia).</p><p><strong>Objective: </strong>Because reports indicate that air pollution may be linked to hypertensive disorders, the National Toxicology Program (NTP) conducted a systematic review to evaluate whether exposure to TRAP during pregnancy is associated with hypertensive disorders of pregnancy.</p><p><strong>Methods: </strong>A systematic review protocol was developed and utilized for this evaluation that followed the Office of Health Assessment and Translation approach for conducting literature-based health assessments. This evaluation considered a range of traffic-related air pollutant measurements (e.g., fine particulate matter [PM2.5]) and traffic measures (e.g., proximity to major roads) in the literature search. Confidence ratings and level-of-evidence conclusions were developed for bodies of evidence for a given exposure measure when there was sufficient evidence (i.e., more than three studies). Changes in blood pressure during pregnancy, gestational hypertension, preeclampsia, eclampsia, or hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) syndrome were considered as measures of hypertension. Hazard conclusions were developed using a two-step process. First, confidence ratings were developed for individual air pollutants (e.g., PM2.5, nitrogen oxides [NOx]) and traffic measures (traffic density and proximity to major roads). Overall hazard conclusions were then developed for TRAP, considering the combined bodies of evidence across different individual measures of traffic-related pollutants.</p><p><strong>Results and evidence synthesis: </strong>The literature search and screening process identified 18 relevant epidemiological studies and one relevant animal study (from 344 potentially relevant references) that met the objective and the inclusion criteria. The human bodies of evidence for traffic-related PM2.5 and NO2 present a consistent pattern of findings that exposure to these pollutants is associated with the development of hypertensive disorders of pregnancy. There is a similar pattern of findings, but a smaller effect size, for bodies of evidence that residing in high-traffic density regions or in close proximity to major roads are associated with developing hypertensive disorders during pregnancy. There is a moderate level of evidence in the combined human body of evidence based primarily on the TRAP air pollutant studies with support from the traffic measures studies. There is an inadequate level of evidence in the animal body ","PeriodicalId":87331,"journal":{"name":"NTP monograph","volume":" 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25347909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NTP monograph on the systematic review of long-term neurological effects following acute exposure to sarin.","authors":"","doi":"10.22427/NTP-MGRAPH-6","DOIUrl":"10.22427/NTP-MGRAPH-6","url":null,"abstract":"<p><strong>Introduction: </strong>Sarin (CASRN: 107-44-8) is a highly toxic organophosphorus nerve agent that was developed for chemical warfare during World War II and continues to be used in conflicts. Immediate effects of sarin exposure are well known, and although there are suggestions in the literature of neurological effects persisting after the initial signs have subsided, long-term neurological effects of acute exposure to sarin are not well characterized in humans.</p><p><strong>Objective: </strong>The National Toxicology Program (NTP), on behalf of the National Institutes of Health (NIH) Countermeasures Against Chemical Threats program, conducted a systematic review to evaluate the evidence for long-term neurological effects in humans and nonhuman animals following acute exposure to sarin. (The terms \"animal\" and \"animals\" refer to nonhuman animals.).</p><p><strong>Methods: </strong>A systematic review protocol was developed and utilized for this evaluation that followed the Office of Health Assessment and Translation approach for conducting literature-based health assessments. Any effect observed 24 hours after exposure (including days to years after exposure) was considered long term for this assessment. Because effects might vary based on time after exposure, the development of hazard conclusions was considered for three different time periods: initial (>24 hours-7 days after exposure), intermediate (8-364 days after exposure), and extended (greater than or equal to 1 year after exposure) periods.</p><p><strong>Results and evidence synthesis: </strong>The literature search and screening process identified 32 data sets within the 34 human studies and 47 data sets within the 51 animal studies (from 6,837 potentially relevant references) that met the objective and the inclusion criteria. Four main health effect categories of neurological response were identified as having sufficient data to reach hazard conclusions: (1) cholinesterase levels; (2) visual and ocular effects; (3) effects on learning, memory, and intelligence; and (4) morphology and histopathology in nervous system tissues. (This section of the abstract has been abridged.).</p><p><strong>Discussion and conclusions: </strong>Hazard conclusions were considered for the four main health effect categories at all three time periods after exposure. The conclusions with the highest level of evidence for each time period were used to reach the overall conclusions. NTP concludes that acute sarin exposure is known to be a neurological hazard to humans in the initial time period of >24 hours-7 days after exposure based on suppression of cholinesterase. NTP concludes that acute sarin exposure is suspected to be a neurological hazard to humans in the intermediate time period of 8 days-1 year after exposure based on multiple effects, including suppression of cholinesterase, visual and ocular effects, and morphological and histological changes in nervous system tissues. NTP concludes that ","PeriodicalId":87331,"journal":{"name":"NTP monograph","volume":" 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25344476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NTP monograph on the systematic review of occupational exposure to cancer chemotherapy agents and adverse health outcomes.","authors":"","doi":"10.22427/NTP-MGRAPH-5","DOIUrl":"10.22427/NTP-MGRAPH-5","url":null,"abstract":"<p><strong>Introduction: </strong>Many cancer chemotherapy agents are known carcinogens, genetic toxicants, and developmental toxicants. Secondary malignancies, such as therapy-related acute myeloid leukemia, are caused by cancer chemotherapy agents administered to patients for the treatment of cancer. Occupational exposure to these agents was first documented in the 1970s and continues to occur, despite the issuance of safe handling guidelines in 1980s.</p><p><strong>Objectives: </strong>Based on the evidence of carcinogenicity and genetic toxicity associated with direct administration of cancer chemotherapy agents and current evidence of occupational exposure, the National Toxicology Program (NTP) conducted a systematic review to: (1) evaluate whether occupational exposure (e.g., medical, manufacturing, research, and veterinary) is associated with any adverse health outcomes in humans, and (2) summarize the prevalence and levels of chemotherapy agents in the workplace as measured by environmental monitoring and biomonitoring for possible worker exposures.</p><p><strong>Methods: </strong>The evaluation was conducted following the Office of Health Assessment and Translation (OHAT) method. A literature search was performed up to February 23, 2017, using PubMed, Embase, Scopus, Toxline, and Web of Science. Relevant human studies were data extracted and assessed for risk of bias. Bodies of evidence were assessed to develop confidence ratings and level-of-evidence conclusions that reflect the certainty in the evidence that occupational exposure to cancer chemotherapy agents are associated with health effects on a per outcome basis.</p><p><strong>Results and evidence synthesis: </strong>The literature search and screening process identified 110 epidemiological studies relevant to assessing possible adverse health outcomes. Most studies addressing health outcomes evaluated potential DNA damage (n = 66; specifically, structural chromosomal aberrations (CA) and micronucleus (MN) induction and comet assay endpoints) and spontaneous abortion (n = 16). In addition to DNA damage, groups of studies were identified to evaluate the potential association between occupational exposure to cancer chemotherapy agents and adverse health outcomes, including cancer (three studies) and adverse effects on reproduction (30 studies). Additional health outcomes included acute effects, immune effects, and liver and kidney toxicity. One hundred seventy-one studies were identified to assess workplace exposure based on reporting of environmental contamination (107 studies) and urine and/or blood monitoring of these agents (82 studies).</p><p><strong>Discussion and conclusions: </strong>NTP concluded that there is a moderate level of evidence that occupational exposure to chemotherapy agents is associated with increased incidence of spontaneous abortion, particularly when evaluating studies of nursing and pharmacy personnel. NTP also concluded that there is a moderate level of e","PeriodicalId":87331,"journal":{"name":"NTP monograph","volume":" 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25344478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NTP Monograph: Developmental Effects and Pregnancy Outcomes Associated With Cancer Chemotherapy Use During Pregnancy.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The National Toxicology Program (NTP) Office of Health Assessment and Translation (OHAT) conducted an evaluation of the developmental effects and pregnancy outcomes associated with cancer chemotherapy use during pregnancy in humans. The final NTP monograph was completed in May 2013 (available at http:// ntp.niehs.nih.gov/go/36495). The incidence of cancer during pregnancy has been reported to occur from 17 to 100 per 100,000 pregnant women. Chemotherapy is a common treatment for cancer; however, most chemotherapy agents are classified as known or suspected human teratogens. Cancer chemotherapy use during pregnancy was selected for evaluation by the NTP because of the: (1) paucity of comprehensive reviews on the pregnancy outcomes following cancer chemotherapy use during pregnancy in humans, including the integration of the developmental animal toxicology literature with the observational studies in humans, and (2) growing public interest in the developmental effects of chemotherapy on offspring exposed to cancer chemotherapy during gestation due to the expected incidence of cancer diagnosed during pregnancy as women delay pregnancy to later ages. Of the approximately 110 cancer chemotherapeutic agents currently in use, the NTP monograph includes data on 56 agents used during 1,261 pregnancies for which pregnancy outcomes were documented. Overall, the NTP evaluation found that treatment with chemotherapy for cancer appeared to be associated with: (1) a higher rate of major malformations following exposure during the first trimester compared to exposure in the second and/or third trimester; (2) an increase the rate of stillbirth following exposure in the second and/ or third trimester; abnormally low levels of amniotic fluid (primarily attributable to Trastuzumab); and (3), also data are insufficient, impaired fetal growth and myelosuppression. Treatment with chemotherapy for cancer during pregnancy did not appear to increase spontaneous preterm birth, or impair normal growth and development of offspring during early life. In addition, the NTP monograph provides background materials on individual cancer chemotherapeutic agents (e.g., evidence for placenta and breast milk transport, developmental toxicity in animals), and a brief review of the prevalence and prognosis of seven frequently diagnosed cancers in women during pregnancy. Finally, the NTP monograph identifies challenges in interpreting the health outcomes from this observational literature base and discussed possible actions to improve the understanding of the developmental effects of chemotherapy treatment for cancer administered during pregnancy. </p>","PeriodicalId":87331,"journal":{"name":"NTP monograph","volume":" 2","pages":"i-214"},"PeriodicalIF":0.0,"publicationDate":"2013-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32265052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NTP monograph on health effects of low-level lead.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Although reductions in lead (Pb) exposure for the U.S. population have resulted in lower blood Pb levels over time, epidemiological studies continue to provide evidence of health effects at lower and lower blood Pb levels. Low-level Pb was selected for evaluation by the National Toxicology Program (NTP) because of (1) the availability of a large number of epidemiological studies of Pb, (2) a nomination by the National Institute for Occupational Safety and Health for an assessment of Pb at lower levels of exposure, and (3) public concern for effects of Pb in children and adults. This evaluation summarizes the evidence in humans and presents conclusions on health effects in children and adults associated with low-level Pb exposure as indicated by less than 10 micrograms of Pb per deciliter of blood (< 10 microg/dL). The assessment focuses on epidemiological evidence at blood Pb levels < 10 microg/dL and < 5 microg/dL because health effects at higher blood Pb levels are well established. The NTP evaluation was conducted through the Office of Health Assessment and Translation (OHAT, formerly the Center for the Evaluation of Risks to Human Reproduction) and completed in April of 2012. The results of this evaluation are published in the NTP Monograph on Health Effects of Low-Level Lead. The document and appendices are available at http://ntp.niehs.nih.gov/go/evals. This document provides background on Pb exposure and includes a review of the primary epidemiological literature for evidence that low-level Pb is associated with neurological, immunological, cardiovascular, renal, and/or reproductive and developmental effects. The NTP Monograph presents specific conclusions for each health effect area. Overall, the NTP concludes that there is sufficient evidence that blood Pb levels < 10 microg/dL and < 5 microg/dL are associated with adverse health effects in children and adults. This conclusion was based on a review of the primary epidemiological literature, scientific input from technical advisors that reviewed pre-public release drafts of each chapter summarizing the evidence for specific health effects associated with low-level Pb, public comments received during the course of the evaluation, and comments from an expert panel of ad hoc reviewers during a public meeting to review the Draft NTP Monograph on November 17-18, 2011 (http://ntp.niehs.nih.gov/go/37090.</p>","PeriodicalId":87331,"journal":{"name":"NTP monograph","volume":" 1","pages":"xiii, xv-148"},"PeriodicalIF":0.0,"publicationDate":"2012-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31673175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}