7 research outputs found
Do Interactions Between Environmental Chemicals and the Human Microbiome Need to Be Considered in Risk Assessments?
One of the most dynamic and fruitful areas of current healthârelated research concerns the various roles of the human microbiome in disease. Evidence is accumulating that interactions between substances in the environment and the microbiome can affect risks of disease, in both beneficial and adverse ways. Although most of the research has concerned the roles of diet and certain pharmaceutical agents, there is increasing interest in the possible roles of environmental chemicals. Chemical risk assessment has, to date, not included consideration of the influence of the microbiome. We suggest that failure to consider the possible roles of the microbiome could lead to significant error in risk assessment results. Our purpose in this commentary is to summarize some of the evidence supporting our hypothesis and to urge the risk assessment community to begin considering and influencing how results from microbiomeârelated research could be incorporated into chemical risk assessments. An additional emphasis in our commentary concerns the distinct possibility that research on chemicalâmicrobiome interactions will also reduce some of the significant uncertainties that accompany current risk assessments. Of particular interest is evidence suggesting that the microbiome has an influence on variability in disease risk across populations and (of particular interest to chemical risk) in animal and human responses to chemical exposure. The possible explanatory power of the microbiome regarding sources of variability could reduce what might be the most significant source of uncertainty in chemical risk assessment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151980/1/risa13316_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151980/2/risa13316.pd
The IARC Monographs: Updated procedures for modern and transparent evidence synthesis in cancer hazard identification
The Monographs produced by the International Agency for Research on Cancer (IARC) apply rigorous procedures for the scientific review and evaluation of carcinogenic hazards by independent experts. The Preamble to the IARC Monographs, which outlines these procedures, was updated in 2019, following recommendations of a 2018 expert Advisory Group. This article presents the key features of the updated Preamble, a major milestone that will enable IARC to take advantage of recent scientific and procedural advances made during the 12 years since the last Preamble amendments. The updated Preamble formalizes important developments already being pioneered in the Monographs Programme. These developments were taken forward in a clarified and strengthened process for identifying, reviewing, evaluating and integrating evidence to identify causes of human cancer. The advancements adopted include strengthening of systematic review methodologies; greater emphasis on mechanistic evidence, based on key characteristics of carcinogens; greater consideration of quality and informativeness in the critical evaluation of epidemiological studies, including their exposure assessment methods; improved harmonization of evaluation criteria for the different evidence streams; and a single-step process of integrating evidence on cancer in humans, cancer in experimental animals and mechanisms for reaching overall evaluations. In all, the updated Preamble underpins a stronger and more transparent method for the identification of carcinogenic hazards, the essential first step in cancer prevention
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Monocrotaline toxicity and pulmonary arteries
Monocrotaline is a pyrrolizidine alkaloid found in plants implicated in livestock and human poisoning. Laboratory rats given monocrotaline develop pulmonary hypertension and right heart hypertrophy in the weeks following administration of the chemical. Lung weight increases and right heart hypertrophy correlate with increased pulmonary artery pressure. Rats which consumed monocrotaline drinking water (20 mg/l) for only 4 days developed significant increases in lung and heart weights 14 days after exposure began. This exposure was equivalent to a dose of 15 mg/kg. Other treatment combinations of time (0-10 days exposure) and monocrotaline concentration (5-60 mg/l in drinking water) were tested. The accumulative dose calculated for each of the treatment combinations which produced toxicity was in the range of 15 to 20 mg/kg. Monocrotaline injury appears to be cumulative, but organ weight increases reverse once exposure is stopped. As pulmonary hypertension develops and pulmonary arteries hypertrophy, the force with which isolated pulmonary artery segments contract decreases. This is a loss of efficacy rather than potency to the contracting agents KCl, norepinephrine, and 5-hydroxytryptamine. Relaxation of arteries under conditions of potassium-return (a measure of Naâș/Kâș ATPase activity) was also altered by monocrotaline treatment. In vivo monocrotaline treatment had little effect on the force of Kâș-return relaxation. However, the rate at which arteries relaxed was significantly decreased following 4 days ingestion of monocrotaline drinking water (20 mg/l). In vitro ouabain treatment and endothelial injury also decreased the rate of Kâș-return relaxation. Another Naâș/Kâș ATPase activity, âžâ¶Rbâș uptake, was decreased following monocrotaline treatment only when 5-hydroxytryptamine was present and only uptake associated with the endothelium was affected. These studies utilized a very low exposure to monocrotaline (4 days ingestion of 20 mg/l monocrotaline drinking water or 15 mg/kg) to produce toxicity in rats. Monocrotaline-induced toxicity measured 20 days after treatment included right heart and lung hypertrophy and decreased contractions of isolated pulmonary arteries. Monocrotaline treatment decreased the rate of Naâș/Kâș ATPase-dependent relaxation of isolated pulmonary arteries 4 days after treatment began
The IARC Monographs: Updated procedures for modern and transparent evidence synthesis in cancer hazard identification
The Monographs produced by the International Agency for Research on Cancer (IARC) apply rigorous procedures for the scientific review and evaluation of carcinogenic hazards by independent experts. The Preamble to the IARC Monographs, which outlines these procedures, was updated in 2019, following recommendations of a 2018 expert Advisory Group. This article presents the key features of the updated Preamble, a major milestone that will enable IARC to take advantage of recent scientific and procedural advances made during the 12 years since the last Preamble amendments. The updated Preamble formalizes important developments already being pioneered in the Monographs Programme. These developments were taken forward in a clarified and strengthened process for identifying, reviewing, evaluating and integrating evidence to identify causes of human cancer. The advancements adopted include strengthening of systematic review methodologies; greater emphasis on mechanistic evidence, based on key characteristics of carcinogens; greater consideration of quality and informativeness in the critical evaluation of epidemiological studies, including their exposure assessment methods; improved harmonization of evaluation criteria for the different evidence streams; and a single-step process of integrating evidence on cancer in humans, cancer in experimental animals and mechanisms for reaching overall evaluations. In all, the updated Preamble underpins a stronger and more transparent method for the identification of carcinogenic hazards, the essential first step in cancer prevention