Role of metabolism in the endocrine-disrupting effects of chemicals in aquatic and terrestrial systems

2003 ◽  
Vol 75 (11-12) ◽  
pp. 1917-1932 ◽  
Author(s):  
M. van den Berg ◽  
T. Sanderson ◽  
N. Kurihara ◽  
A. Katayama
Keyword(s):  
Risk Assessment ◽  
Estrogen Receptor ◽  
Parent Compound ◽  
Water Soluble ◽  
Assessment Process ◽  
Endocrine Disrupting ◽  
Pcb Metabolites ◽  
Hydroxy Groups ◽  
Active Substances

This review describes the role of metabolism with endocrine active substances. Many modern synthetic compounds are readily metabolized to more polar forms that often contain hydroxy groups. This presence of polar groups and aromatic moieties in the parent compound or metabolite can play an important role in the mechanism of endocrine disruption. In addition, phase II metabolism (e.g., glucuronidation) can also lead to deactivation of the endocrine properties. In the case of bisphenol A and alkylphenols, metabolism can be considered as a detoxification mechanism as glucuronides decrease of inhibit binding to the estrogen receptors. In the case of phthalate esters, the primary metabolites, the monoesters, and further degraded metabolites do not interact with the estrogen receptor either. In contrast, the demethylation of methoxychlor in fish and other vertebrate species leads to metabolites with an increased affinity for the estrogen receptor. Certain PCB metabolites with hydroxy groups on the para position without vicinal chlorines have estrogenic activity, but these metabolites are not relevant for the environment. PCB metabolites with methylsulfonyl groups are commonly found in environmental biota and have been associated with several endocrine, developmental, and reproductive effects. Some DDT metabolites bind weakly to the estrogen receptor, but the major biotransformation product p,p-DDE is an androgen receptor (AR) antagonist. Vinclozolin is an anti-androgen and this effect appears to caused by two of its more water-soluble metabolites. The chloro-s-triazines exhibit an in vitro induction of aromatase, but their dealkylated metabolites show a decrease or lack of this effect. It is recognized that common metabolic processes can differ strongly among species that complicates ecotoxicological risk assessment of endocrine active substances. In conclusion, the testing of metabolites for endocrine-disrupting properties should be encouraged in the future to establish a better risk assessment process. An appendix containing levels and half-lives of various endocrine-disrupting chemicals in the environment and in wildlife is included at the end of this article.

scholarly journals The Alginate Immobilization of Metabolic Enzymes Platform Retrofits an Estrogen Receptor Transactivation Assay With Metabolic Competence

2020 ◽  
Vol 178 (2) ◽  
pp. 281-301
Author(s):  
Chad Deisenroth ◽  
Danica E DeGroot ◽  
Todd Zurlinden ◽  
Andrew Eicher ◽  
James McCord ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Biological Effects ◽  
Parent Compound ◽  
False Negative ◽  
Metabolic Enzymes ◽  
Vitro Assay ◽  
Transactivation Assay ◽  
Alginate Immobilization ◽  
Active Substances ◽  
Receptor Transactivation

Abstract The U.S. EPA Endocrine Disruptor Screening Program utilizes data across the ToxCast/Tox21 high-throughput screening (HTS) programs to evaluate the biological effects of potential endocrine active substances. A potential limitation to the use of in vitro assay data in regulatory decision-making is the lack of coverage for xenobiotic metabolic processes. Both hepatic- and peripheral-tissue metabolism can yield metabolites that exhibit greater activity than the parent compound (bioactivation) or are inactive (bioinactivation) for a given biological target. Interpretation of biological effect data for both putative endocrine active substances, as well as other chemicals, screened in HTS assays may benefit from the addition of xenobiotic metabolic capabilities to decrease the uncertainty in predicting potential hazards to human health. The objective of this study was to develop an approach to retrofit existing HTS assays with hepatic metabolism. The Alginate Immobilization of Metabolic Enzymes (AIME) platform encapsulates hepatic S9 fractions in alginate microspheres attached to 96-well peg lids. Functional characterization across a panel of reference substrates for phase I cytochrome P450 enzymes revealed substrate depletion with expected metabolite accumulation. Performance of the AIME method in the VM7Luc estrogen receptor transactivation assay was evaluated across 15 reference chemicals and 48 test chemicals that yield metabolites previously identified as estrogen receptor active or inactive. The results demonstrate the utility of applying the AIME method for identification of false-positive and false-negative target assay effects, reprioritization of hazard based on metabolism-dependent bioactivity, and enhanced in vivo concordance with the rodent uterotrophic bioassay. Integration of the AIME metabolism method may prove useful for future biochemical and cell-based HTS applications.

scholarly journals The Allergen Bureau VITAL Program

2018 ◽  
Vol 101 (1) ◽  
pp. 77-82 ◽  
Author(s):  
Simon Brooke Taylor ◽  
Georgina Christensen ◽  
Kirsten Grinter ◽  
Robin Sherlock ◽  
Lisa Warren
Keyword(s):  
Risk Assessment ◽  
Food Industry ◽  
Assessment Process ◽  
Food Allergens ◽  
Multiple Stakeholders ◽  
Risk Assessment Process ◽  
Scientific Principles ◽  
Consumer Organizations ◽  
Allergen Labelling

Abstract This paper sets out the role of the Allergen Bureau and the Voluntary Incidental Trace Allergen Labelling (VITAL) Program from its origin in 2007 to its current iteration, VITAL 2. Herewith are outlined the scientific principles that support the program; the program’s application in the food chain; and the benefits of the program’s use to the food industry, clinicians, and the allergic consumer. VITAL was developed by the Australian and New Zealand food industry in consultation with multiple stakeholders, including consumer organizations, industry bodies, regulators, and retailers, to provide a standardized, science-based risk assessment process for the investigation of the potential presence of food allergens due to cross-contact and to determine whether, for cases in which the allergen is unable to be removed or controlled consistently, precautionary statements are required. The aim of the program is to provide a consistent process, a standardized approach, and a relevant cross-contact statement to allow the allergic consumer to make an informed decision regarding consumption of food.

scholarly journals Role of Risk of Bias in Systematic Review for Chemical Risk Assessment: A Case Study in Understanding the Relationship Between Congenital Heart Defects and Exposures to Trichloroethylene

2018 ◽  
Vol 37 (2) ◽  
pp. 125-143 ◽  
Author(s):  
Daniele Wikoff ◽  
Jon D. Urban ◽  
Seneca Harvey ◽  
Laurie C. Haws
Keyword(s):  
Risk Assessment ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Risk Of Bias ◽  
Assessment Process ◽  
Chemical Risk ◽  
Chemical Risk Assessment

The National Academy of Science has recommended that a risk of bias (RoB; credibility of the link between exposure and outcome) assessment be conducted on studies that are used as primary data sources for hazard identification and dose–response assessment. Few applications of such have been conducted. Using trichloroethylene and congenital heart defects (CHDs) as a case study, we explore the role of RoB in chemical risk assessment using the National Toxicology Program’s Office of Health Assessment and Translation RoB tool. Selected questions were tailored to evaluation of CHD and then applied to 12 experimental animal studies and 9 epidemiological studies. Results demonstrated that the inconsistent findings of a single animal study were likely explained by the limitations in study design assessed via RoB (eg, lack of concurrent controls, unvalidated method for assessing outcome, unreliable statistical methods, etc). Such limitations considered in the context of the body of evidence render the study not sufficiently reliable for the development of toxicity reference values. The case study highlights the utility of RoB as part of a robust risk assessment process and specifically demonstrates the role RoB can play in objectively selecting candidate data sets to develop toxicity values.

Role of the precautionary principle in the EU risk assessment process on industrial chemicals

2003 ◽  
Vol 75 (11-12) ◽  
pp. 2535-2541 ◽  
Author(s):  
J. de Bruijn ◽  
Bjorn Hansen ◽  
S. Munn
Keyword(s):  
Risk Assessment ◽  
Precautionary Principle ◽  
Assessment Process ◽  
Practical Implementation ◽  
The European Union ◽  
Industrial Chemicals ◽  
The Precautionary Principle ◽  
Scientific Experts ◽  
General Guidance

This paper discusses the practical implementation of the precautionary principle in the area of management of industrial chemicals in the European Union. An analysis of a number of recent cases where the precautionary principle was invoked shows that the main reason for doing so were the uncertainties in the risk assessment (or the underlying effects or exposure data), which were, according to the scientific experts, so high that the "normal" level of certainty could not be obtained. The challenge for the future is to try to develop general guidance or rules that will support the policymakers in their decision as to whether this uncertainty is so large that action is warranted or whether it is acceptable to wait until further information has become available.

scholarly journals Rethinking risk: a narrative approach

2018 ◽  
Vol 13 (1) ◽  
pp. 54-62 ◽  
Author(s):  
Anne Felton ◽  
Theo Stickley
Keyword(s):  
Mental Health ◽  
Risk Assessment ◽  
Subjective Experience ◽  
Mental Health Problems ◽  
Assessment Process ◽  
Narrative Approach ◽  
Content Type ◽  
New Ways Of Working ◽  
Future Practice

Purpose The assessment and management of risk is central to contemporary mental health practice. The emergence of recovery has contributed to demands for more service user centred approaches to risk. The purpose of this paper is to examine the potential of narrative as a framework for understanding risk and safety in mental health care. Design/methodology/approach Narrative theory is adopted to structure a debate examining the potential role of a narrative approach to risk assessment and inform future practice. Findings There is a danger that even within services, people with mental health problems are understood in terms of their riskiness perpetuating an image of service users as “dangerous others”. This is confounded by a disconnection with individual context in the risk assessment process. Narrative centralizes the persons’ subjective experience and provides a contemporaneous self-account of their identity. This situates risk within a context and creates possibility for greater understanding of coping, strengths and resilience. Originality/value There has been a call for new ways of working with risk in mental health which facilitate safety and recovery. There is limited examination of what this might actually look like. This paper presents narrative as an approach that may achieve these aims.

1625: Role of Estrogen Receptor β in the Regulation of Sexual Behavior in Male Mice

2004 ◽  
Vol 171 (4S) ◽  
pp. 429-429
Author(s):  
Masayoshi Nomura ◽  
Naohiro Fujimoto ◽  
Donald W. Pfaff ◽  
Sonoko Ogawa ◽  
Tetsuro Matsumoto
Keyword(s):  
Estrogen Receptor ◽  
Sexual Behavior ◽  
Estrogen Receptor Β ◽  
Male Mice
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