Critical Reviews in Toxicology最新文献

Herbal medicines (HMs) have long been considered safe and effective without serious toxic and side effects. With the continuous use of HMs, more and more attention has been paid to adverse reactions and toxic events, especially the nephrotoxicity caused by natural compounds in HMs. The composition of HMs is complex and various, especially the mechanism of toxic components has been a difficult and hot topic. This review comprehensively summarizes the kidney toxicity characterization and mechanism of nephrotoxic natural compounds (organic acids, alkaloids, glycosides, terpenoids, phenylpropanoids, flavonoids, anthraquinones, cytotoxic proteins, and minerals) from different sources. Recommendations for the prevention and treatment of HMs-induced kidney injury were provided. In vitro and in vivo models for evaluating nephrotoxicity and the latest biomarkers are also included in this investigation. More broadly, this review may provide theoretical basis for safety evaluation and further comprehensive development and utilization of HMs in the future.

Alpha-diketones, notably diacetyl, have been used as flavoring agents. When airborne in occupational settings, exposures to diacetyl have been associated with serious respiratory disease. Other α-diketones, such as 2,3-pentanedione, and analogues such as acetoin (a reduced form of diacetyl), require evaluation, particularly, in light of recently available toxicological studies. The current work reviewed mechanistic, metabolic, and toxicology data available for α-diketones. Data were most available for diacetyl and 2,3-pentanedione, and a comparative assessment of their pulmonary effects was performed, and an occupational exposure limit (OEL) was proposed for 2,3-pentanedione. Previous OELs were reviewed and an updated literature search was performed. Respiratory system histopathology data from 3-month toxicology studies were evaluated with benchmark dose (BMD) modelling of sensitive endpoints. This demonstrated comparable responses at concentrations up to 100 ppm, with no consistent overall pattern of greater sensitivity to either diacetyl or 2,3-pentanedione. In contrast, based on draft raw data, no adverse respiratory effects were observed in comparable 3-month toxicology studies that evaluated exposure to acetoin at up to 800 ppm (highest tested concentration), indicating that acetoin does not present the same inhalation hazard as diacetyl or 2,3-pentanedione. To derive an OEL for 2,3-pentanedione, BMD modelling was conducted for the most sensitive endpoint from 90-day inhalation toxicity studies, namely, hyperplasia of nasal respiratory epithelium. On the basis of this modelling, an 8-hour time-weighted average OEL of 0.07 ppm is proposed to be protective against respiratory effects that may be associated with chronic workplace exposure to 2,3-pentanedione.

Tefluthrin is a Type I pyrethroid insecticide widely used all over the world. Residues of tefluthrin in various agricultural and animal-derived products may be related to potential human health risks. Tefluthrin metabolism in mammals involves hydrolysis of the ester bond to form cyclopropane acid and 4-methylbenzyl alcohol moieties, followed by oxidation. In this review manuscript, we provide crucial information regarding the toxicity of pyrethroids and propose natural antioxidants for amelioration poisoning in humans and animals. We call for the rational use of tefluthrin as an agrochemical product and for greater attention to the residual toxicity caused by tefluthrin in primary and succeeding crops. This greater attention is required given the global use of tefluthrin.

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.