scholarly journals Endocrine Disruption by Mixtures in Topical Consumer Products

Cosmetics ◽  
2018 ◽  
Vol 5 (4) ◽  
pp. 61 ◽  
Author(s):  
Emiliano Ripamonti ◽  
Elena Allifranchini ◽  
Stefano Todeschi ◽  
Elena Bocchietto
Keyword(s):  
Endocrine Disruptors ◽  
Endocrine Disruption ◽  
Hormone Receptors ◽  
Health And Safety ◽  
Test Methods ◽  
Potential Interaction ◽  
Consumer Products ◽  
Cumulative Effects ◽  
Active Substances

Endocrine disruption has been gathering increasing attention in the past 25 years as a possible new threat for health and safety. Exposure to endocrine disruptor has been progressively linked with a growing number of increasing disease in the human population. The mechanics through which endocrine disruptors act are not yet completely clear, however a number of pathways have been identified. A key concern is the cumulative and synergic effects that endocrine disruptors could have when mixed in consumer products. We reviewed the available literature to identify known or potential endocrine disruptors, as well as endocrine active substances that could contribute to cumulative effects, in topical consumer products. The number of endocrine actives used daily in consumer products is staggering and even though most if not all are used in concentrations that are considered to be safe, we believe that the possibility of combined effects in mixtures and non-monotonic dose/response is enough to require further precautions. A combined in vitro approach based on existing, validated OECD test methods is suggested to screen consumer products and mixtures for potential interaction with estrogen and androgen hormone receptors, in order to identify products that could have cumulative effects or support their safety concerning direct endocrine disruption capabilities.

AFFECTING MECHANISMS AND EFFECTS OF ENDOCRINE DISRUPTOR PESTICIDES

2012 ◽  
pp. 66-74
Author(s):  
Ba Tiep Nguyen ◽  
Ngan Tam Bui
Keyword(s):  
Public Health ◽  
Endocrine Disruptors ◽  
Endocrine Disruption ◽  
Hormone Receptors ◽  
Endocrine Disrupting Chemicals ◽  
Endocrine System ◽  
Hormone Synthesis ◽  
Adverse Health Effects ◽  
Sustainable Agricultural Systems ◽  
Public Health Protection

Endocrine disrupting chemicals are compounds that alter the functioning of endocrine system and subsequently affect on different growth and development stages of human and animals. Endocrine disruptors including pesticides have gained a global attention in various fields like environment toxicology, reproduction, food safety and cancer. This article reviews affecting mechanisms of endocrine disruptors including (1) Interfering steroid hormone synthesis, release, transport and metabolism (2) Effecting via hormone receptors, (3) Effecting the action of thyroid hormones, and (4) affecting on central nervous system. Adverse health effects of pesticides via endocrine disruption pathways and recent discoveries in endocrine disruption mechanisms of common pesticides are also be discussed. The information is necessary for the development of safe and sustainable agricultural systems and public health protection in Vietnam. Key words: endocrine disruptors, affecting mechanisms, pesticides, public health

scholarly journals Scientific discrepancies in European regulatory proposals on endocrine disruptors—REACH regulation quo vadis?

2021 ◽  
Author(s):  
Andreas Natsch
Keyword(s):  
Low Dose ◽  
Endocrine Disrupting Chemicals ◽  
Test Methods ◽  
Consumer Products ◽  
In Vitro Tests ◽  
In Vitro Test ◽  
Animal Testing ◽  
European Regulatory ◽  
Quo Vadis

AbstractThe EU chemical strategy for sustainability places a high focus on endocrine-disrupting chemicals (ED), the importance of their identification with increased testing and a ban in consumer products by a generic approach. It is assumed that for ED no threshold and hence no safe dose exists, leading to this generic approach. This view appears to be linked to the claim that for ED ‘low-dose non-monotonic dose response’ (low-dose NMDR) effects are observed. Without this hypothesis, there are no scientific reasons why classical risk assessment cannot be applied to the ED mode-of-action. Thus, whether for ED low-dose NMDR effects are considered a reproducible scientific fact by European authorities is Gretchen’s question in this politicized field. Recent documents by the SCCS, EFSA and ECHA reviewed herein illustrate the diverging views within European scientific bodies on this issue. Furthermore, ED researchers never replicated findings on low-dose NMDR in blinded inter-laboratory experiments and the CLARITY-BPA core studies could not find evidence for reproducible NMDR for BPA. ECHA proposes a battery of in vitro tests to test all chemicals for ED properties. However, these tests were never validated for relevance and their high positivity rate could lead to increased follow-up animal testing. Based on (i) lack of reproducibility data for low-dose NMDR, (ii) diverging views within European authorities on NMDR and (iii) lack of fully validated in vitro test methods it might be premature to fast-track the wide-ranging changes in the regulatory landscape proposed by the authorities ultimately leading to drastically increased animal testing.

scholarly journals Endocrine disruption of vitamin D activity by perfluoro-octanoic acid (PFOA)

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Andrea Di Nisio ◽  
Maria Santa Rocca ◽  
Luca De Toni ◽  
Iva Sabovic ◽  
Diego Guidolin ◽  
...  
Keyword(s):  
Vitamin D ◽  
Endocrine Disruption ◽  
Bone Development ◽  
Epidemiological Studies ◽  
Consumer Products ◽  
Target Cells ◽  
Surface Plasmon Resonance Analysis ◽  
Cellular Targets ◽  
Toxicological Studies

Abstract Perfluoroalkyl substances (PFAS) are a class of compounds used in industry and consumer products. Perfluorooctanoic acid (PFOA) is the predominant form in human samples and has been shown to induce severe health consequences, such as neonatal mortality, neurotoxicity, and immunotoxicity. Toxicological studies indicate that PFAS accumulate in bone tissues and cause altered bone development. Epidemiological studies have reported an inverse relationship between PFAS and bone health, however the associated mechanisms are still unexplored. Here, we present computational, in silico and in vitro evidence supporting the interference of PFOA on vitamin D (VD). First, PFOA competes with calcitriol on the same binding site of the VD receptor, leading to an alteration of the structural flexibility and a 10% reduction by surface plasmon resonance analysis. Second, this interference leads to an altered response of VD-responsive genes in two cellular targets of this hormone, osteoblasts and epithelial cells of the colorectal tract. Third, mineralization in human osteoblasts is reduced upon coincubation of PFOA with VD. Finally, in a small cohort of young healthy men, PTH levels were higher in the exposed group, but VD levels were comparable. Altogether these results provide the first evidence of endocrine disruption by PFOA on VD pathway by competition on its receptor and subsequent inhibition of VD-responsive genes in target cells.

Receptor and Enzyme Mechanisms as Targets for Endocrine Disruptors

2017 ◽  
Author(s):  
Heather B. Patisaul ◽  
Scott M. Belcher
Keyword(s):  
Nervous System ◽  
Steroid Hormones ◽  
Endocrine Disruptors ◽  
Endocrine Disruption ◽  
Hormone Receptors ◽  
Mammalian Brain ◽  
Mechanistic Studies ◽  
Rapid Signaling ◽  
The Impact ◽  
The Brain

In this chapter, the current understanding of the mechanisms of endocrine disruption on the brain and nervous system are presented. Because the overwhelming majority of mechanistic studies on EDCs have focused on the actions mediated by nuclear hormone receptors, this mechanisms is described in detail. The chapter also discusses the classic transcriptional mechanisms of steroid action and the impact of EDCs on rapid signaling (non-genomic) mechanisms. It presents an overview of the enzymes and pathways involved in the biosynthesis of steroid hormones, which are critical to proper functioning of the HPA and HPG axis, and the neuroactive steroids synthesized and active in the mammalian brain. The potential for EDCs to alter metabolic enzymes, with a focus on possible targets in the metabolic blood-brain barrier, is presented as a potential, though largely unexplored, mode of EDC action in the brain.

Toxicological Studies of a Representative Xerox Reprographic Toner

1999 ◽  
Vol 18 (1) ◽  
pp. 23-34 ◽  
Author(s):  
George H. Y. Lin ◽  
Joseph C. Wilson
Keyword(s):  
Safety Concern ◽  
Safety Issue ◽  
Chinese Hamster ◽  
Health And Safety ◽  
Consumer Products ◽  
Worst Case ◽  
Inhalation Study ◽  
Charge Control ◽  
Toxicological Studies

Typical Xerox reprographic toners consist of a thermoplastic polymer as the major component, a colorant (carbon black or color pigment), and low quantities of additives such as charge control and/or lubricating agents. Another type of Xerox toner contains iron oxides and a polymer as the major components. Among all toners marketed by Xerox Corporation, the original 1075 toner (being discontinued and reformulated) was a major safety concern, because it contained approximately 2% cetylpyridinium chloride (CPC) as a charge control agent. CPC by itself is very toxic and causes severe irritation to the eye and skin. Although CPC has been used in very low concentrations in consumer products such as mouthwash, it was unknown whether a 50-fold dilution of CPC in the toner formulation would represent any safety issue. Therefore, a series of toxicological testing on the original 1075 toner was conducted. The test results indicate that the original Xerox 1075 toner was practically nontoxic following acute oral, dermal, and inhalation exposures; nonirritating to the eye; nonir-ritating/nonsensitizing to the skin; nonmutagenic in a battery of short-term assays (Ames Salmnonella/microsome assay, mouse lym-phoma assay, in vitro sister chromatid exchange assay in Chinese hamster ovarian cells, and in vitro BALB/3T3 cell transformation assay); and nonteratogenic in rats when inhaling the toner dust up to 1.2 g/m3. In addition, no mutagenic responses were observed from testing the urine or feces (by Ames test) and bone marrow (by examining micronucleus formation) of rats exposed to the toner dust at 1.3 g/m3 at the end of a subchronic inhalation study. Because all Xerox toners are alike, the toxicology of the original Xerox 1075 toner was considered a “worst-case” situation, relative to health and safety. However, it did not appear to represent any health and safety issue. The results of this study, together with the fact that no evidence of carcinogenicity was found in the Xerox chronic inhalation study on toner, indicate that Xerox toners are not safety hazards, with respect to the end points indicated in this report.

Platelet Aggregation Induced in Vitro by Therapeutic Ultrasound

1977 ◽  
Vol 38 (03) ◽  
pp. 0640-0651 ◽  
Author(s):  
B. V Chater ◽  
A. R Williams
Keyword(s):  
Platelet Aggregation ◽  
Direct Action ◽  
Adenosine Diphosphate ◽  
Ultrasonic Cavitation ◽  
Related Phenomenon ◽  
Release Reaction ◽  
Physical Conditions ◽  
Platelet Aggregates ◽  
Active Substances

SummaryPlatelets were found to aggregate spontaneously when exposed to ultrasound generated by a commercial therapeutic device. At a given frequency, aggregation was found to be a dose-related phenomenon, increasing intensities of ultrasound inducing more extensive and more rapid aggregation. At any single intensity, the extent aggregation was increased as the frequency of the applied ultrasound was decreased (from 3.0 to 0.75 MHz).Ultrasound-induced platelet aggregation was found to be related to overall platelet sensitivity to adenosine diphosphate. More sensitive platelets were found to aggregate spontaneously at lower intensities of sound, and also the maximum extent of aggregation was found to be greater. Examination of ultrasound-induced platelet aggregates by electron microscopy demonstrated that the platelets had undergone the release reaction.The observation that haemoglobin was released from erythrocytes in whole blood irradiated under identical physical conditions suggests that the platelets are being distrupted by ultrasonic cavitation (violent gas/bubble oscillation).It is postulated that overall platelet aggregation is the result of two distinct effects. Firstly, the direct action of ultrasonic cavitation disrupts a small proportion of the platelet population, resulting in the liberation of active substances. These substances produce aggregation, both directly and indirectly by inducing the physiological release reaction in adjacent undamaged platelets.

Structure-Based Virtual Screening of Perfluoroalkyl and Polyfluoroalkyl Substances (PFASs) as Endocrine Disruptors of Androgen Receptor Activity Using Molecular Docking and Machine Learning

2020 ◽  
Author(s):  
Azhagiya Singam Ettayapuram Ramaprasad ◽  
Phum Tachachartvanich ◽  
Denis Fourches ◽  
Anatoly Soshilov ◽  
Jennifer C.Y. Hsieh ◽  
...  
Keyword(s):  
Machine Learning ◽  
Molecular Docking ◽  
Androgen Receptor ◽  
Endocrine Disruptors ◽  
Hormone Receptors ◽  
Steroid Hormone Receptors ◽  
Machine Learning Techniques ◽  
Support Vector ◽  
Polyfluoroalkyl Substances ◽  
Perfluoroalkyl And Polyfluoroalkyl Substances

Perfluoroalkyl and Polyfluoroalkyl Substances (PFASs) pose a substantial threat as endocrine disruptors, and thus early identification of those that may interact with steroid hormone receptors, such as the androgen receptor (AR), is critical. In this study we screened 5,206 PFASs from the CompTox database against the different binding sites on the AR using both molecular docking and machine learning techniques. We developed support vector machine models trained on Tox21 data to classify the active and inactive PFASs for AR using different chemical fingerprints as features. The maximum accuracy was 95.01% and Matthew’s correlation coefficient (MCC) was 0.76 respectively, based on MACCS fingerprints (MACCSFP). The combination of docking-based screening and machine learning models identified 29 PFASs that have strong potential for activity against the AR and should be considered priority chemicals for biological toxicity testing.

Investigating Non-Therapeutic Pharmaceutical Substances for Improving In-Vitro Efficacy of Clindamycin Phosphate Against MRSA and Staphylococcus Epidermidis

2020 ◽  
Vol 18 (2) ◽  
pp. 63-72
Author(s):  
Mohd Aftab Alam ◽  
Fahad I. Al-Jenoobi ◽  
Khaled A. Alzahrani ◽  
Mohammad H. Al-Agamy ◽  
Abdullah M. Al-Mohizea
Keyword(s):  
Fusidic Acid ◽  
Staphylococcus Epidermidis ◽  
Sorbic Acid ◽  
Tween 80 ◽  
Lauryl Sulfate ◽  
Individual Substance ◽  
Dependent Effect ◽  
Pharmaceutical Excipients ◽  
Active Substances

The aim of present study was to investigate the effect of pharmaceutical excipients and other active substances on antimicrobial efficacy of standard antibiotic against resistant and susceptible microorganisms. Pharmaceutical excipients (sodium lauryl sulfate [SLS], Tween-80, citric acid, NaOH, NaCl) and active substances (fusidic acid, sorbic acid) were investigated to check in-vitro efficacy and their effect on the efficacy of standard antibiotic. Clindamycin was selected as standard antibiotic. Clindamycin was found to be ineffective against methicillin-resistant Staphylococcus aureus (MRSA). Fusidic acid and SLS showed concentration dependent effect against MRSA. Other tested substances were also ineffective against MRSA, and also failed to improve the susceptibility of MRSA towards clindamycin. The clindamycin + fusidic acid (0.05 µg, 0.1 µg), and clindamycin + SLS (0.5 mg, 1 mg) showed concentration dependent effect on Staphylococcus epidermidis (S. epidermidis). Clindamycin combinations with fusidic acid or SLS showed better inhibition of S. epidermidis, than individual substance. At lower concentration of clindamycin (2 µg), the sorbic acid (25 µg) improves its effectiveness. SLS (0.5 mg, 1 mg) and clindamycin (4 µg, 10 µg) showed almost equal zone of inhibition against S. epidermidis, respectively. Present findings showed that certain pharmaceutical excipients (e.g. SLS) are effective against resistant and susceptible microbes, and suggested that more excipients should be screened for their antimicrobial potential and their ability to improve the efficacy of standard antibiotics.

Uncertainties Associated with Assessing the Risk of an Endocrine Active Substance in the Canadian Environment

2001 ◽  
Vol 36 (2) ◽  
pp. 319-330 ◽  
Author(s):  
Mark Servos ◽  
Don Bennie ◽  
Kent Burnison ◽  
Philippa Cureton ◽  
Nicol Davidson ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Endocrine Disruption ◽  
Endocrine System ◽  
Problem Formulation ◽  
Normal Function ◽  
Weight Of Evidence ◽  
Biological Responses ◽  
Low Concentrations ◽  
Multigenerational Effects

Abstract A number of biological responses and multigenerational effects, mediated through the disruption of endocrine systems, have been observed in biota exposed to relatively low concentrations of environmental contaminants. These types of responses need to be considered within a weight of evidence approach in our risk assessment and risk management frameworks. However, including endocrine responses in an environmental risk assessment introduces a number of uncertainties that must be considered. A risk assessment of nonylphenol and nonylphenol polyethoxylates (NP/NPE) is used as a case study to demonstrate the sources and magnitude of some of the uncertainties associated with using endocrine disruption as an assessment endpoint. Even with this relatively well studied group of substances, there are substantial knowledge gaps which contribute to the overall uncertainties, limiting the interpretation within the risk assessment. The uncertainty of extrapolating from in vitro or biochemical responses to higher levels of organization or across species is not well understood. The endocrine system is very complex and chemicals can interact or interfere with the normal function of endocrine systems in a number of ways (e.g., receptors, hormones) which may or may not result in an adverse responses in the whole organism. Using endocrine responses can lead to different conclusions than traditional endpoints due to a variety of factors, such as differences in relative potencies of chemicals for specific endpoints (e.g., receptor binding versus chronic toxicity). The uncertainties can also be considerably larger and the desirability of using endocrine endpoints should be carefully evaluated. Endocrine disruption is a mode of action and not a functional endpoint and this needs to be considered carefully in the problem formulation stage and the interpretation of the weight of evidence.

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