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Bibliography Tag: risk assessment

Apel et al., 2020

Apel, P., Rousselle, C., Lange, R., Sissoko, F., Kolossa-Gehring, M., & Ougier, E.; “Human biomonitoring initiative (HBM4EU) – Strategy to derive human biomonitoring guidance values (HBM-GVs) for health risk assessment;” International Journal of Hygiene and Environmental Health, 2020, 230, 113622; DOI: 10.1016/j.ijheh.2020.113622.


The European Joint Program “HBM4EU” is a joint effort of 30 countries and the European Environment Agency, co-funded under the European Commission’s Horizon 2020 program, for advancing and implementing human biomonitoring (HBM) on a European scale and for providing scientific evidence for chemical policy making. One important outcome will be a Europe-wide improvement and harmonization of health risk assessment following the coordinated derivation or update of health-related guidance values referring to the internal body burden. These guidance values – named HBM guidance values or HBM-GVs – can directly be compared with HBM data. They are derived within HBM4EU for priority substances identified by the HBM4EU chemicals prioritization strategy based on existing needs to answer policy relevant questions as raised by national and EU policy makers. HBM-GVs refer to both the general population and occupationally exposed adults. Reports including the detailed reasoning for the values’ proposals are subjected to a consultation process within all partner countries of the consortium to reach a broad scientific consensus on the derivation approach and on the derived values. The final HBM-GVs should be applied first within the HBM4EU project, but may also be useful for regulators and risk assessors outside this project. The subsequent adoption of derived HBM-GVs at EU-level needs to be discussed and decided within the responsible EU bodies. Nevertheless, the establishment of HBM-GVs as part of HBM4EU is already a step forward in strengthening HBM-based policy efforts for public and occupational health. The strategy for deriving HBM-GVs which is based on already existing approaches from the German HBM Commission, the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) as well as from the US-based scientific consultant Summit Toxicology, the allocation of a level of confidence to the derived values, and the consultation process within the project are comprehensively described to enlighten the work accomplished under the HBM4EU initiative. FULL TEXT

Alberto et al., 2016

Alberto, D., Serra, A. A., Sulmon, C., Gouesbet, G., & Couee, I.; “Herbicide-related signaling in plants reveals novel insights for herbicide use strategies, environmental risk assessment and global change assessment challenges;” Science of The Total Environment, 2016, 569-570, 1618-1628; DOI: 10.1016/j.scitotenv.2016.06.064.


Herbicide impact is usually assessed as the result of a unilinear mode of action on a specific biochemical target with a typical dose-response dynamics. Recent developments in plant molecular signaling and crosstalk between nutritional, hormonal and environmental stress cues are however revealing a more complex picture of inclusive toxicity. Herbicides induce large-scale metabolic and gene-expression effects that go far beyond the expected consequences of unilinear herbicide-target-damage mechanisms. Moreover, groundbreaking studies have revealed that herbicide action and responses strongly interact with hormone signaling pathways, with numerous regulatory protein-kinases and -phosphatases, with metabolic and circadian clock regulators and with oxidative stress signaling pathways. These interactions are likely to result in mechanisms of adjustment that can determine the level of sensitivity or tolerance to a given herbicide or to a mixture of herbicides depending on the environmental and developmental status of the plant. Such regulations can be described as rheostatic and their importance is discussed in relation with herbicide use strategies, environmental risk assessment and global change assessment challenges. FULL TEXT

Connolly et al., 2020

Connolly, A., Coggins, M. A., & Koch, H. M.; “Human Biomonitoring of Glyphosate Exposures: State-of-the-Art and Future Research Challenges;” Toxics, 2020, 8(3); DOI: 10.3390/toxics8030060.


Glyphosate continues to attract controversial debate following the International Agency for Research on Cancer carcinogenicity classification in 2015. Despite its ubiquitous presence in our environment, there remains a dearth of data on human exposure to both glyphosate and its main biodegradation product aminomethylphosphonic (AMPA). Herein, we reviewed and compared results from 21 studies that use human biomonitoring (HBM) to measure urinary glyphosate and AMPA. Elucidation of the level and range of exposure was complicated by differences in sampling strategy, analytical methods, and data presentation. Exposure data is required to enable a more robust regulatory risk assessment, and these studies included higher occupational exposures, environmental exposures, and vulnerable groups such as children. There was also considerable uncertainty regarding the absorption and excretion pattern of glyphosate and AMPA in humans. This information is required to back-calculate exposure doses from urinary levels and thus, compared with health-based guidance values. Back-calculations based on animal-derived excretion rates suggested that there were no health concerns in relation to glyphosate exposure (when compared with EFSA acceptable daily intake (ADI)). However, recent human metabolism data has reported as low as a 1% urinary excretion rate of glyphosate. Human exposures extrapolated from urinary glyphosate concentrations found that upper-bound levels may be much closer to the ADI than previously reported. FULL TEXT

Gray et al., 2000

Gray, George M., Goldstein, Bernard D., Bailar, John, Davis, Devra Lee, Delzell, Elizabeth, Dost, Frank, Greenberg, Raymond S., Hatch, Maureen, Hodgson, Ernest, Ibrahim, Michel A., Lamb, James, Lavy, Terry, Mandel, Jack, Monson, Richard, Robson, Mark, Shore, Roy, & Graham, John D.; “The Federal Government’s Agricultural Health Study: A Critical Review with Suggested Improvements;” Human and Ecological Risk Assessment: An International Journal, 2000, 6(1), 47-71; DOI: 10.1080/10807030091124446.


The Agricultural Health Study (AHS) has approximately 90,000 pesticide applicators and their spouses enrolled in a number of studies to determine whether exposures to specific pesticides are associated with various cancers and other adverse health outcomes. Although the AHS was intended to be an integrated program of studies, some significant difficulties have emerged. In this report, we examine the design of the AHS, identify important program strengths and flaws, suggest various improvements in the program, and recommend ancillary studies that could be undertaken to strengthen the AHS.

Overall, the AHS is collecting a large amount of information on potential determinants of health status among farmers and farm families. A promising feature of the AHS is the prospective cohort study of cancers among farmers in which the research design determines exposures prior to the diagnosis of disease. More effort needs to be devoted to reducing selection bias and information bias. Success of the cohort study will depend in part on follow-up surveys of the cohort to determine how exposures and disease states change as the cohort ages. The cross-sectional and case-control studies planned in the AHS are less promising because they will be subject to some of the same criticisms, such as potentially biased and imprecise exposure assessment, that have characterized the existing literature in this field.

Important limitations of the AHS include low and variable rates of subject response to administered surveys, concerns about the validity of some self-reported non-cancer health outcomes, limited understanding of the reliability and validity of self-reporting of chemical use, an insufficient program of biological monitoring to validate the exposure surrogates employed in the AHS questionnaires, possible confounding by unmeasured, nonchemical risk factors for disease, and the absence of detailed plans for data analysis and interpretation that include explicit, a priori hypotheses. Although the AHS is already well underway, most of these limitations can be addressed by the investigators if adequate resources are made available. If these limitations are not addressed, the large amounts of data generated in the AHS will be difficult to interpret. If the exposure and health data can be validated, the scientific value of the AHS should be substantial and enduring.

A variety of research recommendations are made to strengthen the AHS. They include reliability and validity studies of farmer reporting of chemical use, biological monitoring studies of farmers and members of farm families, and validity studies of positive and negative self-reports of disease status. Both industry and government should consider expanded research programs to strengthen the AHS.


Hernandez et al, 2013

Hernandez, A. F., Parron, T., Tsatsakis, A. M., Requena, M., Alarcon, R., & Lopez-Guarnido, O.; “Toxic effects of pesticide mixtures at a molecular level: their relevance to human health;” Toxicology, 2013, 307, 136-145; DOI: 10.1016/j.tox.2012.06.009.


Pesticides almost always occur in mixtures with other ones. The toxicological effects of low-dose pesticide mixtures on the human health are largely unknown, although there are growing concerns about their safety. The combined toxicological effects of two or more components of a pesticide mixture can take one of three forms: independent, dose addition or interaction. Not all mixtures of pesticides with similar chemical structures produce additive effects; thus, if they act on multiple sites their mixtures may produce different toxic effects. The additive approach also fails when evaluating mixtures that involve a secondary chemical that changes the toxicokinetics of the pesticide as a result of its increased activation or decreased detoxification, which is followed by an enhanced or reduced toxicity, respectively. This review addresses a number of toxicological interactions of pesticide mixtures at a molecular level. Examples of such interactions include the postulated mechanisms for the potentiation of pyrethroid, carbaryl and triazine herbicides toxicity by organophosphates; how the toxicity of some organophosphates can be potentiated by other organophosphates or by previous exposure to organochlorines; the synergism between pyrethroid and carbamate compounds and the antagonism between triazine herbicides and prochloraz. Particular interactions are also addressed, such as those of pesticides acting as endocrine disruptors, the cumulative toxicity of organophosphates and organochlorines resulting in estrogenic effects and the promotion of organophosphate-induced delayed polyneuropathy. FULL TEXT

Backhaus and Faust, 2012

Backhaus, T., & Faust, M.; “Predictive environmental risk assessment of chemical mixtures: a conceptual framework;” Environmental Science & Technology, 2012, 46(5), 2564-2573; DOI: 10.1021/es2034125.


Environmental risks of chemicals are still often assessed substance-by-substance, neglecting mixture effects. This may result in risk underestimations, as the typical exposure is toward multicomponent chemical “cocktails”. We use the two well established mixture toxicity concepts (Concentration Addition (CA) and Independent Action (IA)) for providing a tiered outline for environmental hazard and risk assessments of mixtures, focusing on general industrial chemicals and assuming that the “base set” of data (EC50s for algae, crustaceans, fish) is available. As mixture toxicities higher than predicted by CA are rare findings, we suggest applying CA as a precautious first tier, irrespective of the modes/mechanisms of action of the mixture components. In particular, we prove that summing up PEC/PNEC ratios might serve as a justifiable CA-approximation, in order to estimate in a first tier assessment whether there is a potential risk for an exposed ecosystem if only base-set data are available. This makes optimum use of existing single substance assessments as more demanding mixture investigations are requested only if there are first indications of an environmental risk. Finally we suggest to call for mode-of-action driven analyses only if error estimations indicate the possibility for substantial differences between CA- and IA-based assessments. FULL TEXT

Boobis et al., 2008

Boobis, A. R., Ossendorp, B. C., Banasiak, U., Hamey, P. Y., Sebestyen, I., & Moretto, A.; “Cumulative risk assessment of pesticide residues in food;” Toxicology Letters, 2008, 180(2), 137-150; DOI: 10.1016/j.toxlet.2008.06.004.


There is increasing need to address the potential risks of combined exposures to multiple residues from pesticides in the diet. The available evidence suggests that the main concern is from dose addition of those compounds that act by the same mode of action. The possibility of synergy needs to be addressed on a case-by-case basis, where there is a biologically plausible hypothesis that it may occur at the levels of residues occurring in the diet. Cumulative risk assessment is a resource-intense activity and hence a tiered approach to both toxicological evaluation and intake estimation is recommended, and the European Food Safety Authority (EFSA) has recently published such a proposal. Where assessments have already been undertaken by some other authority, full advantage should be taken of these, subject of course to considerations of quality and relevance. Inclusion of compounds in a cumulative assessment group (CAG) should be based on defined criteria, which allow for refinement in a tiered approach. These criteria should include chemical structure, mechanism of pesticidal action, target organ and toxic mode of action. A number of methods are available for cumulating toxicity. These are all inter-related, but some are mathematically more complex than others. The most useful methods, in increasing levels of complexity and refinement, are the hazard index, the reference point index, the Relative Potency Factor method and physiologically based toxicokinetic modelling, although this last method would only be considered should a highly refined assessment be necessary. Four possible exposure scenarios are of relevance for cumulative risk assessment, acute and chronic exposure in the context of maximum residue level (MRL)-setting, and in relation to exposures from the actual use patterns, respectively. Each can be addressed either deterministically or probabilistically. Strategies for dealing with residues below the limit of detection, limit of quantification or limit of reporting need to be agreed. A number of probabilistic models are available, but some of there are geographically constrained due to the underlying datasets used in their construction. Guidance on probabilistic modelling needs to be finalised. Cumulative risk assessments have been performed in a number of countries, on organophosphate insecticides alone (USA) or together with carbamates (UK, DK, NL), triazines, chloroacetanilides, carbamates alone (USA), and all pesticides (DE). All identifiable assumptions and uncertainties should be tabulated and evaluated, at least qualitatively. Those likely to have a major impact on the outcome of the assessment should be examined quantitatively. In cumulative risk assessment, it is necessary, as in other risk assessments, for risk managers to consider what level of risk would be considered “acceptable”, for example what percentile of the population should be below the reference value. Criteria for prioritising CAGs for cumulative risk assessment include frequency of detection in monitoring programmes, high usage, high exposure relative to the reference value, large number of compounds (e.g. five or more) in a group. FULL TEXT

Vineis, 2019

Vineis, P.; “Public Health and Independent Risk Assessment;” American Journal of Public Health, 2019, 109(7), 978-980; DOI: 10.2105/AJPH.2019.305142.


Morabia, 2019

Morabia, A.; “Fighting Independent Risk Assessment of Talc and Glyphosate: Whose Benefit Is It Anyway?;” American Journal of Public Health, 2019, 109(7), 955-956; DOI: 10.2105/AJPH.2019.305144.


Schaden et al., 2020

Schaden, Helmut Burtscher, Clausing, Peter, & Van Scharen, Hans. “Factsheet: Dangerous Confidence in ‘Good Laboratory Practices,'” February 11, 2020, Corporate Europe Observatory and PAN Germany.


Our authorisation system for chemicals is based on the principle that manufacturers must prove, by means of scientifc studies, that their products do not pose unacceptable risks to public health and the environment. It is therefore also the responsibility of manufacturers to commission certifed contract laboratories to carry out the toxicological studies necessary for the approval procedure. As a guarantee against manipulation and falsifcation of these “regulatory” studies, regulatory authorities worldwide rely on the certifed standard of “Good Laboratory Practice” (GLP). This standard provides for strict documentation requirements and regular internal and external controls. However, the current fraud scandal involving a German contract laboratory certifed according to GLP, shows that this trust is unlikely to be justifed. According to reports, GLP studies have been manipulated and falsifed there since 2005.

  • Recent research now shows that LPT has also produced studies that were part of the study package for the EU-wide approval of glyphosate in December 2017: One in seven studies in this package, which was the basis to grant re-approval for glyphosate, came from LPT. These fndings are worrying in two ways: – On the one hand, there is the fundamental question of whether the risk assessments for medicines, pesticides and chemicals based on LPT studies can be trusted.
  •  Even more worrying is the general realisation that laboratories, despite the supposedly “tamper-proof” GLP standard, are apparently able to falsify studies over years and decades without being noticed by the control authorities.

The classifcation of glyphosate as “non-carcinogenic” and “not genotoxic“o is based, among other things, on the European authorities’ full confdence in the GLP system. In the EU assessment proces GLP studies were automatically classifed as reliable; This in stark contrast with the numerous “non-GLP studies” from university research, peer reviewed and published, most of which reported evidence of a genotoxic effect and an increased risk of lymphatic cancer in users of glyphosate, were disqualifed by the authorities as “unreliable“.

The LPT counterfeiting scandal reveals the failure of a regulatory system, that places the commissioning and preparation of studies in the hands of industry. At the same time, it confrms the urgency of a fundamental reform of this system for identifying the risks of chemicals, as called for by the European coalition “Citizens for Science in Pesticide Regulation” in October 2018. FULL TEXT

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