| 1. |
- Anderson, J. K., et al.
(författare)
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Grouping of PFAS for human health risk assessment : Findings from an independent panel of experts
- 2022
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Ingår i: Regulatory toxicology and pharmacology. - : Elsevier. - 0273-2300 .- 1096-0295. ; 134
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Tidskriftsartikel (refereegranskat)abstract
- An expert panel was convened to provide insight and guidance on per- and polyfluoroalkyl substances (PFAS) grouping for the purposes of protecting human health from drinking water exposures, and how risks to PFAS mixtures should be assessed. These questions were addressed through multiple rounds of blind, independent responses to charge questions, and review and comments on co-panelists responses. The experts agreed that the lack of consistent interpretations of human health risk for well-studied PFAS and the lack of information for the vast majority of PFAS present significant challenges for any mixtures risk assessment approach. Most experts agreed that "all PFAS" should not be grouped together, persistence alone is not sufficient for grouping PFAS for the purposes of assessing human health risk, and that the definition of appropriate subgroups can only be defined on a case-by-case manner. Most panelists agreed that it is inappropriate to assume equal toxicity/potency across the diverse class of PFAS. A tiered approach combining multiple lines of evidence was presented as a possible viable means for addressing PFAS that lack analytical and/or toxicological studies. Most PFAS risk assessments will need to employ assumptions that are more likely to overestimate risk than to underestimate risk, given the choice of assumptions regarding dose-response model, uncertainty factors, and exposure information.
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| 2. |
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| 3. |
- Bergman, Åke, et al.
(författare)
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Manufacturing doubt about endocrine disrupter science : A rebuttal of industry-sponsored critical comments on the UNEP/WHO report "State of the Science of Endocrine Disrupting Chemicals 2012"
- 2015
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Ingår i: Regulatory toxicology and pharmacology. - : Academic Press. - 0273-2300 .- 1096-0295. ; 73:3, s. 1007-1017
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Tidskriftsartikel (refereegranskat)abstract
- We present a detailed response to the critique of "State of the Science of Endocrine Disrupting Chemicals 2012" (UNEP/WHO, 2013) by financial stakeholders, authored by Lamb et al. (2014). Lamb et al.'s claim that UNEP/WHO (2013) does not provide a balanced perspective on endocrine disruption is based on incomplete and misleading quoting of the report through omission of qualifying statements and inaccurate description of study objectives, results and conclusions. Lamb et al. define extremely narrow standards for synthesizing evidence which are then used to dismiss the UNEP/WHO 2013 report as flawed. We show that Lamb et al. misuse conceptual frameworks for assessing causality, especially the Bradford-Hill criteria, by ignoring the fundamental problems that exist with inferring causality from empirical observations. We conclude that Lamb et al.'s attempt of deconstructing the UNEP/WHO (2013) report is not particularly erudite and that their critique is not intended to be convincing to the scientific community, but to confuse the scientific data. Consequently, it promotes misinterpretation of the UNEP/WHO (2013) report by non-specialists, bureaucrats, politicians and other decision makers not intimately familiar with the topic of endocrine disruption and therefore susceptible to false generalizations of bias and subjectivity.
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| 4. |
- Beronius, Anna, et al.
(författare)
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Health risk assessment procedures for endocrine disrupting compounds within different regulatory frameworks in the European Union
- 2009
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Ingår i: Regulatory toxicology and pharmacology. - : Elsevier BV. - 0273-2300 .- 1096-0295. ; 55:2, s. 111-122
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Tidskriftsartikel (refereegranskat)abstract
- In this study we have investigated how different regulatory frameworks in Europe cope with identification and risk assessment of endocrine disrupting compounds (EDCs). Four regulatory groups were selected for the investigation: existing industrial chemicals, environmental pollutants in food, pharmaceuticals and plant protection products. The legislation and guidelines for each of these groups were scrutinized and compared in detail. In addition, one recent European risk assessment document each for three identified EDCs, i.e. bisphenol A, dioxins and vinclozolin, were reviewed and compared. We found that the requirements for toxicity testing and availability and scope of risk assessment guidelines varied between the four regulatory frameworks. Also, the general principles regarding the human relevance of the mode of action identified in animal tests differed in the different risk assessments. In conclusion, there is little conformity in the risk assessment processes between these groups of chemicals. Because of the complicated nature of endocrine disruption, test methods, principles and criteria for data interpretation traditionally used might not be directly applicable to EDCs and further development of a transparent and reliable risk assessment process for this type of substances is needed.
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| 5. |
- Ding, Qian, et al.
(författare)
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Occupational exposure limits in Europe and Asia – Continued divergence or global harmonization?
- 2011
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Ingår i: Regulatory toxicology and pharmacology. - : Elsevier. - 0273-2300 .- 1096-0295. ; 61:3, s. 296-309
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Tidskriftsartikel (refereegranskat)abstract
- Occupational exposure limits (OELs) are used as a risk management tool aiming at protecting against negative health effects of occupational exposure to harmful substances. The systems of OEL development have not been standardized and divergent outcomes have been reported. However some harmonization processes have been initiated, primarily in Europe. This study investigates the state of harmonization in a global context. The OEL systems of eight Asian and seventeen European organizations are analyzed with respect to similarities and differences in: (1) the system for determining OELs, (2) the selection of substances, and (3) the levels of the OELs. The majority of the investigated organizations declare themselves to have been influenced by the American Conference of Governmental Industrial Hygienists (ACGIH), and in many cases this can be empirically confirmed. The EU harmonization process is reflected in trends towards convergence within the EU. However, comparisons of Asian and European organizations provide no obvious evidence that OELs are becoming globally harmonized.
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| 6. |
- Fick, Jerker, et al.
(författare)
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Predicted critical environmental concentrations for 500 pharmaceuticals
- 2010
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Ingår i: Regulatory toxicology and pharmacology. - : Elsevier. - 0273-2300 .- 1096-0295. ; 58:3, s. 516-23
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Tidskriftsartikel (refereegranskat)abstract
- A growing number of pharmaceuticals are found in surface waters worldwide, raising concerns about their effects on aquatic organisms and it is a major challenge to develop a rational strategy for prioritizing drugs on which to focus the most extensive environmental research efforts. However, in contrast to most other chemicals, very good understanding of the human potency of pharmaceuticals has been obtained through efficacy and safety testing. Assuming that a drug acts primarily through the same target(s) also in a non-target species, it would be possible to predict the likelihood for pharmacological interactions in wildlife. Among aquatic organisms, fish most often share drug targets with humans. In this study, we have calculated the predicted critical environmental concentration (CECs), i.e. the surface water concentration expected to cause a pharmacological effect in fish, for 500 pharmaceuticals, assuming equivalent pharmacological activity. The CECs are based on literature data on human potencies together with a predicted bioconcentration factor in fish for each drug based on lipophilicity. We propose that CECs could be used as preliminary indicators of specific drugs' potential to cause adverse pharmacological effects at specific water concentrations, used when selecting pharmaceuticals to include in screening campaigns and for assessing relevant detection limits.
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| 7. |
- Fu, Xin, et al.
(författare)
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Acute, subacute toxicity and genotoxic effect of Bio-Quinone (R) Q10 in mice and rats
- 2009
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Ingår i: Regulatory toxicology and pharmacology. - : Elsevier BV. - 0273-2300 .- 1096-0295. ; 53:1, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, the acute, subacute and genetic toxicity of Coenzyme Q10 (CoQ10) in the form of Bio-Quinone (R) (Pharma Nord, Denmark) was assessed. LD50 of CoQ10 by oral treatment was greater than 20 g/kg body weight in both female and male mice. Genotoxicity was assessed in mice by Ames test in Salmonella typhimurium strains TA97, TA98, TA100 and TA102, by bone marrow micronucleus test and sperm abnormality. Thirty-day subacute toxicity was conducted with oral daily dose at 0, 0.56, 1.13 and 2.25 g/kg body weight in rats. No significant changes in body weight, food intake, behavior, mortality, hematology, blood biochemistry, vital organ weight, sperm abnormality, mutagenicity and micro-nucleus formation were observed and no clinical signs or adverse effects were detected by administration of CoQ10. These results support the safety of CoQ10 for oral consumption.
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| 8. |
- Halamoda-Kenzaoui, Blanka, et al.
(författare)
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Bridging communities in the field of nanomedicine
- 2019
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Ingår i: Regulatory toxicology and pharmacology. - : Elsevier BV. - 0273-2300 .- 1096-0295. ; 106, s. 187-196
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Tidskriftsartikel (refereegranskat)abstract
- An early dialogue between nanomedicine developers and regulatory authorities are of utmost importance to anticipate quality and safety requirements for these innovative health products. In order to stimulate interactions between the various communities involved in a translation of nanomedicines to clinical applications, the European Commission's Joint Research Centre hosted a workshop titled "Bridging communities in the field of Nanomedicine" in Ispra/Italy on the 27th -28th September 2017. Experts from regulatory bodies, research institutions and industry came together to discuss the next generation of nanomedicines and their needs to obtain regulatory approval. The workshop participants came up with recommendations highlighting methodological gaps that should be addressed in ongoing projects addressing the regulatory science of nanomedicines. In addition, individual opinions of experts relevant to progress of the regulatory science in the field of nanomedicine were summarised in the format of a survey.
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| 9. |
- Hansson, Sven Ove, et al.
(författare)
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The substitution principle
- 2011
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Ingår i: Regulatory toxicology and pharmacology. - : Elsevier BV. - 0273-2300 .- 1096-0295. ; 59:3, s. 454-460
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Tidskriftsartikel (refereegranskat)abstract
- According to the substitution principle, hazardous chemicals should be replaced by less hazardous alternatives. In this paper, the major issues concerning the more precise definition of the principle are analyzed, and a general purpose definition is proposed. It is claimed that the priority between reducing hazard, functionality and economical considerations in the application of the substitution principle is a matter for adjustment in each particular case that cannot be settled beforehand. None of these objectives can have absolute priority over the others, but the substitution principle is aimed at increasing the priority given to the reduction of hazards to human health and the environment. Major methods to promote and implement the principle are summarized, current legislative approaches are discussed, and proposals for efficient implementation are made. It is emphasized that the primary responsibility for avoiding hazardous substances and processes rests with industry.
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| 10. |
- Hansson, Sven Ove, et al.
(författare)
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Towards, a theory of tiered testing
- 2007
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Ingår i: Regulatory toxicology and pharmacology. - : Elsevier BV. - 0273-2300 .- 1096-0295. ; 48:1, s. 35-44
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Tidskriftsartikel (refereegranskat)abstract
- Tiered testing is an essential part of any resource-efficient strategy for the toxicity testing of a large number of chemicals, which is required for instance in the risk management of general (industrial) chemicals, In spite of this, no general theory seems to be available for the combination of single tests into efficient tiered testing systems. A first outline of such a theory is developed. It is argued that chemical, toxicological, and decision-theoretical knowledge should be combined in the construction of such a theory. A decision-theoretical approach for the optimization of test systems is introduced. It is based on expected utility maximization with simplified assumptions covering factual and value-related information that is usually missing in the development of test systems.
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