Critical Reviews in Toxicology最新文献

Long-term inhalation exposure to manganese (Mn) metal or its inorganic compounds can result in manganism or subclinical neurofunctional deficits. Studies have described affected workers in Mn dioxide mining, Mn-containing ore crushing and milling facilities, manufacturing of dry-cell batteries, Mn steel and alloy production plants, and in welders. The objective of this study was to critically review existing evidence on the reliability of potential biomarkers of Mn exposure, specifically the relationship between inhalation exposure to Mn particulates in different occupational settings and Mn concentrations in blood and other biological fluids and tissues, with a particular focus on whole blood as a potentially useful medium for measuring internal tissue dose. We also examined available evidence on the relationship between Mn levels in blood and adverse clinical and subclinical neurotoxic outcomes. Three bibliographic databases were searched for relevant studies and identified references were screened by two independent reviewers. Of the 6338 unique references identified, 76 articles were retained for data abstraction. Findings indicate that the relationships between Mn in blood and both external Mn exposure indices and neurofunctional impairments are limited and inconsistent. Different sources of exposure to Mn compounds, heterogeneity in the methodological approaches, and inadequate reporting of essential information limited direct comparison of the reported findings. Among the Mn-exposure biomarkers considered in this review - including biomarkers in blood, plasma, serum, erythrocytes, urine, bone, toenails, fingernails, hair, saliva - biomarkers in whole blood may provide to be most useful in Mn biomonitoring and risk assessment.

Adverse pregnancy outcomes, such as preeclampsia, gestational diabetes mellitus, fetal growth restriction, and recurrent miscarriage, occur frequently in pregnant women and might further induce morbidity and mortality for both mother and fetus. Increasing studies have shown that dysfunctions of human trophoblast are related to these adverse pregnancy outcomes. Recent studies also showed that environmental toxicants could induce trophoblast dysfunctions. Moreover, non-coding RNAs (ncRNAs) have been reported to play important regulatory roles in various cellular processes. However, the roles of ncRNAs in the regulation of trophoblast dysfunctions and the occurrence of adverse pregnancy outcomes still need to be further investigated, especially with exposure to environmental toxicants. In this review, we analyzed the regulatory mechanisms of ncRNAs and m6A methylation modification in the dysfunctions of trophoblast cells and the occurrence of adverse pregnancy outcomes and also summarized the harmful effects of environmental toxicants. In addition to DNA replication, mRNA transcription, and protein translation, ncRNAs and m6A modification might be considered as the fourth and fifth elements that regulate the genetic central dogma, respectively. Environmental toxicants might also affect these processes. In this review, we expect to provide a deeper scientific understanding of the occurrence of adverse pregnancy outcomes and to discover potential biomarkers for the diagnosis and treatment of these outcomes.

North African countries; Algeria, Egypt, Libya, Morocco and Tunisia suffer from mycotoxin contamination. Various studies have indicated the presence of mycotoxins in raw milk and cereals (i.e. wheat, barley, maize and cereal-based products). Aflatoxins (AFs), Aflatoxin M1 (AFM1), Ochratoxin A (OTA), Fumonisin (FB1) and Zearalenone (ZEN)-mycotoxin are the most detected due to climatic change in the region. In this review, we will present the kind of foods and feeds cereals and milk based products contaminated and the level of their contaminated mycotoxin. On the other hand, researchers try to find biologic methods to remove/mitigate mycotoxins in food and feed using bio-products. But the research works concerning legislations and mycotoxin risk assessment still rare. Therefore, it appears necessary to make review on the current status of mycotoxins in North African countries in order to explore data related to contamination of basic food in this region and to highlight the problem to the policy-makers to establish a serious legislation on this matter. On the other hand, to give more information to the worldwide readers about the impact of climate change on the food and feed pollution on mycotoxins in the Mediterranean Sea region.

This review investigated which patterns of thyroid- and brain-related effects are seen in rats upon gestational/lactational exposure to 14 substances causing thyroid hormone imbalance by four different modes-of-action (inhibition of thyroid peroxidase, sodium-iodide symporter and deiodinase activities, enhancement of thyroid hormone clearance) or to dietary iodine deficiency. Brain-related parameters included motor activity, cognitive function, acoustic startle response, hearing function, periventricular heterotopia, electrophysiology and brain gene expression. Specific modes-of-action were not related to specific patterns of brain-related effects. Based upon the rat data reviewed, maternal serum thyroid hormone levels do not show a causal relationship with statistically significant neurodevelopmental effects. Offspring serum thyroxine together with offspring serum triiodothyronine and thyroid stimulating hormone appear relevant to predict the likelihood for neurodevelopmental effects. Based upon the collated database, thresholds of ≥60%/≥50% offspring serum thyroxine reduction and ≥20% and statistically significant offspring serum triiodothyronine reduction indicate an increased likelihood for statistically significant neurodevelopmental effects; accuracies: 83% and 67% when excluding electrophysiology (and gene expression). Measurements of brain thyroid hormone levels are likely relevant, too. The extent of substance-mediated thyroid hormone imbalance appears more important than substance mode-of-action to predict neurodevelopmental impairment in rats. Pertinent research needs were identified, e.g. to determine whether the phenomenological offspring thyroid hormone thresholds are relevant for regulatory toxicity testing. The insight from this review shall be used to suggest a tiered testing strategy to determine whether gestational/lactational substance exposure may elicit thyroid hormone imbalance and potentially also neurodevelopmental effects.

Hunters Point Naval Shipyard in San Francisco, California was deemed a Superfund site by the USEPA in 1989 due to chemical and radiological contamination resulting from U.S. Navy operations from 1939 to 1974. During characterization and remediation efforts, over 50,000 radiological soil samples and 19,000 air samples were collected. This risk assessment, conducted in accordance with federal guidelines, represents the first comprehensive evaluation of past, present, and future health risks associated with radionuclides present at the site. The assessment indicated that before site remediation, most radionuclide soil concentrations were at or near local background concentrations. Had such low remedial goals not been established, significant remediation of surface soils would not have been necessary to protect human health. The pre-remediation lifetime incremental cancer morbidity risks for on-site workers and theoretical on-site residents due to radionuclide contamination were found to be 1.3 × 10^-6 and 3.2 × 10^-6, respectively. The post-remediation risks to future on-site residents were found to be 6.3 × 10^-8 (without durable cover) and 3.7 × 10^-8 (with durable cover), while post-remediation risks to on-site workers were found to be 2.6 × 10^-8 (without durable cover) and 1.6 × 10^-8 (with durable cover). Risk estimates for all scenarios were found to be significantly below the acceptable risk of 3 × 10^-4 approved by regulatory agencies. Upwind and downwind air samples collected during remediation indicate that remediation activities never posed a measurable risk to off-site residents. This risk assessment emphasizes the importance of establishing clear and scientifically rigorous soil remedial goals at sites as well as understanding local radionuclide background concentrations.

The direct peptide reactivity assay (DPRA) is an OECD test guideline method that aims to determine if a chemical is reactive enough to be a skin sensitiser. It involves incubation of the test chemical at 5 mMolar concentration for 24 h with a cysteine-based peptide at 0.5 mMolar concentration and measurement of the percentage depletion (DP) of the peptide. The kinetic direct peptide reactivity assay (kDPRA) is derived from the DPRA and involves incubating the peptide with the test chemical at a range of concentrations and incubation times to produce a data matrix of DP values, which is analysed to give a reactivity parameter logk_max that assigns chemicals to the 1A potency class (high potency) if logk_max reaches the threshold value of -2. Here the DPRA, with a threshold of 47% DP, is compared against the kDPRA for their abilities to distinguish between the 1A and non-1A potency classes. It is found that they perform very similarly against a dataset of 157 chemicals with known potency, with only marginal differences in predictive performance. The thresholds of -2.0 (kDPRA) and 47% DP (DPRA) to distinguish 1A sensitisers are not scientific absolutes but the best compromises for a heterogenous set of data containing classes of chemicals for which different thresholds would be applicable. It is concluded that although the kDPRA represents a major advance towards predicting skin sensitisation potency on a continuous basis without animal testing, it offers no significant advantage over the DPRA for the purpose of 1A classification.

Chlorpyrifos (CP) is one of the most popular organophosphorus pesticides that is commonly used in agricultural and nonagricultural environments to combat pests. However, several concerns regarding contamination due to the unmitigated use of chlorpyrifos have come up over recent years. This has popularized research on various techniques for chlorpyrifos detection. Since conventional methods do not enable smooth detection, the recent trends of chlorpyrifos detection have shifted toward electrochemical and optical sensing techniques that offer higher sensitivity and selectivity. The objective of this review is to provide a brief overview of some of the important and innovative contributions in the field of electrochemical and optical sensing of chlorpyrifos with a primary focus on the comparative advantages and shortcomings of these techniques. This review paper will help to offer better perspectives for research in organophosphorus pesticide detection in the future.

Fluoride, one of the global groundwater contaminants, is ubiquitous in our day-to-day life from various natural and anthropogenic sources. Numerous in vitro, in vivo, and epidemiological studies are conducted to understand the effect of fluoride on biological systems. A low concentration of fluoride is reported to increase oral health, whereas chronic exposure to higher concentrations causes fluoride toxicity (fluorosis). It includes dental fluorosis, skeletal fluorosis, and fluoride toxicity in soft tissues. The mechanism of fluoride toxicity has been reviewed extensively. However, epigenetic regulation in fluoride toxicity has not been reviewed. This systematic review summarizes the current knowledge regarding fluoride-induced epigenetic toxicity in the in vitro, in vivo, and epidemiological studies in mammalian systems. We examined four databases for the association between epigenetics and fluoride exposure. Out of 932 articles (as of 31 March 2022), 39 met our inclusion criteria. Most of the studies focused on different genes, and overall, preliminary evidence for epigenetic regulation of fluoride toxicity was identified. We further highlight the need for epigenome studies rather than candidate genes and provide recommendations for future research. Our results indicate a correlation between fluoride exposure and epigenetic processes. Further studies are warranted to elucidate and confirm the mechanism of epigenetic alterations mediated fluoride toxicity.

Aluminum (Al) salts are commonly used as adjuvants in human and veterinary vaccines for almost a century. Despite this long history of use and the very large number of exposed individuals, data in the literature concerning the fate of these molecules after injection and their potential effects on the nervous system is limited. In the context of (i) an increase of exposure to Al salts through vaccination; (ii) the absence of safety values determined by health regulators; (iii) the lack of robustness of the studies used as references to officially claim Al adjuvant innocuity; (iv) the publication of several animal studies investigating Al salts clearance/biopersistence and neurotoxicity; we have examined in this review all published studies performed on animals and assessing Al adjuvants kinetics, biodistribution, and neuromodulation since the first work of A. Glenny in the 1920s. The diversity of methodological approaches, results, and potential weaknesses of the 31 collected studies are exposed. A large range of protocols has been used, including a variety of exposure schedule and analyses methods, making comparisons between studies uneasy. Nevertheless, published data highlight that when biopersistence, translocation, or neuromodulation were assessed, they were documented whatever the different in vivo models and methods used. Moreover, the studies pointed out the crucial importance of the different Al adjuvant physicochemical properties and host genetic background on their kinetics, biodistribution, and neuromodulatory effects. Regarding the state of the art on this key public health topic, further studies are clearly needed to determine the exact safety level of Al salts.

Bisphenol A (BPA) is a ubiquitous chemical compound constantly being released into the environment, making it one of the most persistent endocrine-disrupting chemical (EDC) in nature. This EDC has already been associated with developing various pathologies, such as diabetes, obesity, and cardiovascular, renal, and behavioral complications, among others. Therefore, over the years, BPA has been replaced, gradually, by its analog compounds. However, these compounds are structurally similar to BPA, so, in recent years, questions have been raised concerning their safety for human health. Numerous investigations have been performed to determine the effects BPA substitutes may cause, particularly during pregnancy and prenatal life. On the other hand, studies investigating the association of these compounds with the development of cardiovascular diseases (CVD) have been developed. In this sense, this review summarizes the existing literature on the transgenerational transfer of BPA substitutes and the consequent effects on maternal and offspring health following prenatal exposure. In addition, these compounds' effects on the cardiovascular system and the susceptibility to develop CVD will be presented. Therefore, this review aims to highlight the need to investigate further the safety and benefits, or hazards, associated with replacing BPA with its analogs.