Relevance and reliability of experimental data in human health risk assessment of pesticides

Kaltenhäuser, Johanna; Kneuer, Carsten; Marx‐Stoelting, Philip; Niemann, Lars; Schubert, J.; Stein, Bernd; Solecki, Roland

doi:10.1016/j.yrtph.2017.06.010

Cited by 38 publications

(27 citation statements)

References 25 publications

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“…However, many of these studies are never published in the peer-reviewed literature since they contain proprietary information that is subject to confidentiality. For this reason, data from peer-reviewed scientific publications, in addition to mandatory regulatory toxicology studies, constitute an important part of the database used for the risk assessment of chemicals previously approved and marketed, but more often than not, such information is not available for newly developed chemicals (Kaltenhäuser et al 2017). Regulatory studies typically expose genetically homogenous, inbred strains of experimental animals to a range of (usually high) doses of a chemical under-defined and controlled conditions to establish at which dose level chemicals elicit clear toxic effects or even death (NRC 2007).…”

Section: The Role and Critical Assessment Of The Reliability And Relementioning

confidence: 99%

“…Their contribution to the overall weight of evidence is influenced by the test organism, study design, statistical methods, documentation, and reporting of methods and results. Criteria for relevance and reliability of toxicological data need to be considered when this type of information is used for regulatory purposes (Roth and Ciffroy 2016;Kaltenhäuser et al 2017).…”

Section: The Role and Critical Assessment Of The Reliability And Relementioning

confidence: 99%

“…However, adherence to GLP does not guarantee methodological quality or error-free experimentation and data analysis, nor does it ensure that the study is actually relevant for human health risk assessment. Furthermore, the lack of adherence of published toxicological studies to OECD-TGs does not mean that these studies are not of high quality (Kaltenhäuser et al 2017).…”

Section: The Role and Critical Assessment Of The Reliability And Relementioning

confidence: 99%

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Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures

et al. 2019

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Humans are exposed to multiple chemicals on a daily basis instead of to just a single chemical, yet the majority of existing toxicity data comes from single-chemical exposure. Multiple factors must be considered such as the route, concentration, duration, and the timing of exposure when determining toxicity to the organism. The need for adequate model systems (in vivo, in vitro, in silico and mathematical) is paramount for better understanding of chemical mixture toxicity. Currently, shortcomings plague each model system as investigators struggle to find the appropriate balance of rigor, reproducibility and appropriateness in mixture toxicity studies. Significant questions exist when comparing single-to mixture-chemical toxicity concerning additivity, synergism, potentiation, or antagonism. Dose/concentration relevance is a major consideration and should be subthreshold for better accuracy in toxicity assessment. Previous work was limited by the technology and methodology of the time, but recent advances have resulted in significant progress in the study of mixture toxicology. Novel technologies have added insight to data obtained from in vivo studies for predictive toxicity testing. These include new in vitro models: omics-related tools, organs-on-a-chip and 3D cell culture, and in silico methods. Taken together, all these modern methodologies improve the understanding of the multiple toxicity pathways associated with adverse outcomes (e.g., adverse outcome pathways), thus allowing investigators to better predict risks linked to exposure to chemical mixtures. As technology and knowledge advance, our ability to harness and integrate separate streams of evidence regarding outcomes associated with chemical mixture exposure improves. As many national and international organizations are currently stressing, studies on chemical mixture toxicity are of primary importance.

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Section: The Role and Critical Assessment Of The Reliability And Relementioning

confidence: 99%

Section: The Role and Critical Assessment Of The Reliability And Relementioning

confidence: 99%

Section: The Role and Critical Assessment Of The Reliability And Relementioning

confidence: 99%

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Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures

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“…Thus, data from peer‐reviewed scientific literature should be taken into account for regulatory risk assessment of pesticide active substances, provide they are of sufficient quality after being assessed for methodological reliability. Their contribution to the overall WoE is influenced by factors including test organism, study design and statistical methods, as well as test item identification, documentation and reporting of results (Kaltenhäuser et al., ).…”

Section: Integrating the Diverse Streams Of Evidence: Human (Epidemiomentioning

confidence: 99%

Scientific Opinion of the PPR Panel on the follow‐up of the findings of the External Scientific Report ‘Literature review of epidemiological studies linking exposure to pesticides and health effects’

Residues¹,

Ockleford²,

Adriaanse³

et al. 2017

EFS2

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In 2013, EFSA published a comprehensive systematic review of epidemiological studies published from 2006 to 2012 investigating the association between pesticide exposure and many health outcomes. Despite the considerable amount of epidemiological information available, the quality of much of this evidence was rather low and many limitations likely affect the results so firm conclusions cannot be drawn. Studies that do not meet the 'recognised standards' mentioned in the Regulation (EU) No 1107/2009 are thus not suited for risk assessment. In this Scientific Opinion, the EFSA Panel on Plant Protection Products and their residues (PPR Panel) was requested to assess the methodological limitations of pesticide epidemiology studies and found that poor exposure characterisation primarily defined the major limitation. Frequent use of case-control studies as opposed to prospective studies was considered another limitation. Inadequate definition or deficiencies in health outcomes need to be avoided and reporting of findings could be improved in some cases. The PPR Panel proposed recommendations on how to improve the quality and reliability of pesticide epidemiology studies to overcome these limitations and to facilitate an appropriate use for risk assessment. The Panel recommended the conduct of systematic reviews and meta-analysis, where appropriate, of pesticide observational studies as useful methodology to understand the potential hazards of pesticides, exposure scenarios and methods for assessing exposure, exposure-response characterisation and risk characterisation. Finally, the PPR Panel proposed a methodological approach to integrate and weight multiple lines of evidence, including epidemiological data, for pesticide risk assessment. Biological plausibility can contribute to establishing causation.

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“…Furthermore, peer-reviewed literature also tends to be biased 569 towards the better-known substances, and switching the academic attention to the next group of 570 'emerging' substances tends to have a lengthy lag period (Bao et al, 2015;Li et al, 2018). Despite 571 these challenges, peer-reviewed literature deserves to be given proper consideration in hazard 572 assessment and prioritization studies (Kaltenhäuser et al, 2017;Myers et al, 2010). Increasingly, this 573 is being done using a systematic review methodology, originally developed in the medical field, and 574 now being gradually implemented for toxicological assessments as well (Birnbaum et With regard to the generation of new data on the health hazards of plastic packaging-associated 587 chemicals, the focus of toxicity testing may need to shift from assessing individual substances 588 towards looking at the mixtures of chemicals present in a finished packaging article .…”

Section: Challenges and Information Requirements 509mentioning

confidence: 99%

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Supplemental Information 1: SF1 Categories Estracted From CPCat

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23Global plastics production has reached 380 million metric tons in 2015, with around 40% used for 24 packaging. Plastic packaging is diverse and made of multiple polymers and numerous additives, along 25 with other components, such as adhesives or coatings. Further, packaging can contain residues from 26 substances used during manufacturing, such as solvents, along with non-intentionally added 27 substances (NIAS), such as impurities, oligomers, or degradation products. To characterize risks from 28 chemicals potentially released during manufacturing, use, disposal, and/or recycling of packaging, 29 comprehensive information on all chemicals involved is needed. Here, we present a database of 30 Chemicals associated with Plastic Packaging (CPPdb), which includes chemicals used during 31 manufacturing and/or present in final packaging articles. The CPPdb lists 906 chemicals likely 32 associated with plastic packaging and 3377 substances that are possibly associated. Of the 906 33 chemicals likely associated with plastic packaging, 63 rank highest for human health hazards and 68 34 for environmental hazards according to the harmonized hazard classifications assigned by the 35 European Chemicals Agency within the Classification, Labeling and Packaging (CLP) regulation 36 implementing the United Nations' Globally Harmonized System (GHS). Further, 7 of the 906 37 substances are classified in the European Union as persistent, bioaccumulative, and toxic (PBT), or 38 very persistent, very bioaccumulative (vPvB), and 15 as endocrine disrupting chemicals (EDC). Thirty-39 four of the 906 chemicals are also recognized as EDC or potential EDC in the recent EDC report by the 40 United Nations Environment Programme. The identified hazardous chemicals are used in plastics as 41 monomers, intermediates, solvents, surfactants, plasticizers, stabilizers, biocides, flame retardants, 42 accelerators, and colorants, among other functions. Our work was challenged by a lack of 43 transparency and incompleteness of publicly available information on both the use and toxicity of 44 numerous substances. The most hazardous chemicals identified here should be assessed in detail as 45 potential candidates for substitution. 46 47

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Relevance and reliability of experimental data in human health risk assessment of pesticides

Cited by 38 publications

References 25 publications

Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures

Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures

Scientific Opinion of the PPR Panel on the follow‐up of the findings of the External Scientific Report ‘Literature review of epidemiological studies linking exposure to pesticides and health effects’

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