Critical Reviews in Toxicology最新文献

Historically, benzene has been widely used in a large variety of applications. Occupational exposure limits (OELs) were set for benzene as it was found to be acutely toxic, causing central nervous system depression at high exposures. OELs were lowered when it was discovered that chronic exposure to benzene could cause haematotoxicity. After confirmation that benzene is a human carcinogen causing acute myeloid leukaemia and possibly other blood malignancies, OEL were further lowered. The industrial application of benzene as solvent is almost completely discontinued but it is still used as feedstock for the production of other materials, such as styrene. Occupational exposure to benzene may also occur since it is present in crude oil, natural gas condensate and a variety of petroleum products and because benzene can be formed in combustion of organic material. In the past few years, lower OELs for benzene in the range of 0.05-0.25 ppm have been proposed or were already established to protect workers from benzene-induced cancer. The skin is an important potential route of exposure and relatively more important at lower OELs. Consequently, human biomonitoring - which integrates all exposure routes - is routinely applied to control overall exposure to benzene. Several potential biomarkers have been proposed and investigated. For compliance check of the current low OELs, urinary S-phenylmercapturic acid (S-PMA), urinary benzene and blood benzene are feasible biomarkers. S-PMA appears to be the most promising biomarker but proper validation of biomarker levels corresponding to airborne benzene concentrations below 0.25 ppm are needed.

Existing literature suggests an association between chronic cadmium (Cd) exposure and the induction of DNA damage and genotoxicity. However, observations from individual studies are inconsistent and conflicting. Therefore current systematic review aimed to pool evidence from existing literature to synthesize quantitative and qualitative corroboration on the association between markers of genotoxicity and occupational Cd exposed population. Studies that evaluated markers of DNA damage among occupationally Cd-exposed and unexposed workers were selected after a systematic literature search. The DNA damage markers included were chromosomal aberrations (chromosomal, chromatid, sister chromatid exchange), Micronucleus (MN) frequency in mono and binucleated cells (MN with condensed chromatin, lobed nucleus, nuclear buds, mitotic index, nucleoplasmatic bridges, pyknosis, and karyorrhexis), comet assay (tail intensity, tail length, tail moment, and olive tail moment), and oxidative DNA damage (8-hydroxy-deoxyguanosine). Mean differences or standardized mean differences were pooled using a random-effects model. The Cochran-Q test and I² statistic were used to monitor heterogeneity among included studies. Twenty-nine studies with 3080 occupationally Cd-exposed and 1807 unexposed workers were included in the review. Cd among the exposed group was higher in blood [4.77 μg/L (-4.94-14.48)] and urine samples [standardized mean difference 0.47 (0.10-0.85)] than in the exposed group. The Cd exposure is positively associated with higher levels of DNA damage characterized by increased frequency of MN [7.35 (-0.32-15.02)], sister chromatid exchange [20.30 (4.34-36.26)], chromosomal aberrations, and oxidative DNA damage (comet assay and 8OHdG [0.41 (0.20-0.63)]) compared to the unexposed. However, with considerable between-study heterogeneity. Chronic Cd exposure is associated with augmented DNA damage. However, more extensive longitudinal studies with adequate sample sizes are necessary to assist the current observations and promote comprehension of the Cd's role in inducing DNA damage.Prospero Registration ID: CRD42022348874.

Extracellular vesicles (EVs) derived from parental cells could communicate with neighboring or distant recipient cells. The components in EVs, especially non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, could regulate the functions of the recipient cells. Meanwhile, EVs could also be used as valuable biomarkers and drug delivery carriers. Moreover, environmental toxicants may alter EVs components and regulate EVs-mediated pathogenesis of various diseases. In this review, we mainly summarized the roles of EV-derived non-coding RNAs in the regulation of cell dysfunctions in various adverse pregnancy outcomes, such as preeclampsia (PE), gestational diabetes mellitus (GDM), and miscarriage. Moreover, the effects of environmental toxicants on the components and functions of EVs, as well as on their regulatory roles in these diseases, were also discussed.

Treatment of food-producing animals with veterinary medicinal products (VMPs) can result in residues in foodstuffs (e.g. eggs, meat, milk, or honey) representing a potential consumer health risk. To ensure consumer safety, worldwide regulatory concepts for setting safe limits for residues of VMPs e.g. as tolerances (US) or maximum residue limits (MRLs, EU) are used. Based on these limits so-called withdrawal periods (WP) are determined. A WP represents the minimum period of time required between the last administration of the VMP and the marketing of foodstuff. Usually, WPs are estimated using regression analysis based on residue studies. With high statistical confidence (usually 95% in the EU and 99% in the US) the residues in almost all treated animals (usually 95%) have to be below MRL when edible produce is harvested. Here, uncertainties from both sampling and biological variability are taken into account but uncertainties of measurement associated with the analytical test methods are not systematically considered. This paper describes a simulation experiment to investigate the extent to which relevant sources of measurement uncertainty (accuracy and precision) can impact the length of WPs. A set of real residue depletion data was artificially 'contaminated' with measurement uncertainty related to permitted ranges for accuracy and precision. The results show that both accuracy and precision had a noticeable effect on the overall WP. Due consideration of sources of measurement uncertainty may improve the robustness, quality and reliability of calculations upon which regulatory decisions on consumer safety of residues are based.

Historically, hydrogen sulfide (H₂S) poisoning has extremely high and irreparable mortality. Currently, the identification of H₂S poisoning needs to combine with the case scene analysis in forensic medicine. The anatomy of the deceased seldom had obvious features. There are also a few reports about H₂S poisoning in detail. As a result, we give a comprehensive analysis of the related knowledge on the forensic aspect of H₂S poisoning. Furthermore, we provide the analytical methods of H₂S and its metabolite-which may assist in H₂S poisoning identification.

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.