Toxic Workers

Coping strategy and stress response of European sea bass Dicentrarchus labrax to acute and chronic environmental hypercapnia under hyperoxic conditions

Ozone is a major environmental pollutant inducing severe pulmonary damages. We have compared the effect of ozone on mice subjected to acute (1 ppm, 1 h) and chronic (1.5 ppm, 1 h, twice weekly for 6 weeks) ozone exposure. Our investigations focused on lesions of the lung tissue, inflammation and hyperreactivity using both conventional methods, and a novel digital imaging histological approach based on machine learning programs. Acute exposure caused disruption in the respiratory epithelium with leakage of protein and recruitment of neutrophils in the bronchoalveolar space, leading to lung inflammation and airway hyperresponsiveness to methacholine. All these parameters were also increased upon chronic exposure. Digital imaging analysis allowed to quantify accurately structural changes occurring in the bronchiolar epithelium. Acute exposure mainly induced a significant decrease of epithelium area and thickness in agreement with its desquamation. Chronic exposure caused significant increase of epithelial, bronchial and lumen areas, unlike acute exposure. Morphological changes of epithelial bronchi were accompanied by a significant increase of peribronchial collagen content under both acute and chronic exposure. However, unlike acute exposure, chronic exposure resulted in a significant increase of the area and diameter of airspaces, but a decrease in their number, all of which reflecting the presence of emphysema. In conclusion, the digital imaging approach provides reliable quantitative analysis of pulmonary structural changes which, in combination with functional approaches, allows a comprehensive analysis of the effects of ozone on lung tissue.

Impact of iron exposure on Brazilian coral reefs: Acute vs. chronic stress responses.

Titanium dioxide nanoparticles (TiO2 NPs) have been incorporated into a large range of materials for different usages and they are very likely to come in wastewater and sewage, finally reaching the aquatic ecosystems. Therefore, valuating the impact of TiO2 NPs on aquatic environment is a major concern. The aim of this work was to study the effects of TiO2 NPs on metabolic enzymes activity and haematological indices of the Caspian trout juveniles. After determining 96h-LC50, juveniles have been exposed to 0.1 LC50-96h TiO2 NPs in three replicates for 28 days. The blood samples were collected from fish after acute (24, 48, 72, 96 hours) and sub chronic (7, 14, 21 and 28 days) exposure to the TiO2 NPs. The analysis showed that the red blood cells count (RBC), haemoglobin (Hb), haematocrit (Hct), white blood cells count (WBC) and lymphocytes have been increased after acute and sub chronic exposure to TiO2 NPs. Levels of neutrophils and monocytes were increased mostly in acute treatments. Mean Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin (MCH) and Mean Corpuscular Hemoglobin Concentration (MCHC) showed no significant differences. According to analysis of metabolic enzymes activities, levels of Alkaline Phosphatase (ALP) and Aspartate Amino Transferase (AST) after acute and sub chronic exposure as compared to control group were increased/decreased, respectively. Alanine Aminotransferase (ALT) levels showed significant decrease (p<0.05) after 28 days. Lactate Dehydrogenase (LDH) enzyme level increased mostly after acute exposure. The obtained results indicated that the presence of very low amount of TiO2 NPs could affect most haematological and metabolic enzymes of Caspian trout juvenile.

BackgroundIn a previous study, we showed that individuals who had participated in oil clean-up tasks after the wreckage of the Prestige presented an increase of structural chromosomal alterations two years after the acute exposure had occurred. Other studies have also reported the presence of DNA damage during acute oil exposure, but little is known about the long term persistence of chromosomal alterations, which can be considered as a marker of cancer risk. ObjectivesWe analyzed whether the breakpoints involved in chromosomal damage can help to assess the risk of cancer as well as to investigate their possible association with DNA repair efficiency. MethodsCytogenetic analyses were carried out on the same individuals of our previous study and DNA repair errors were assessed in cultures with aphidicolin. ResultsThree chromosomal bands, 2q21, 3q27 and 5q31, were most affected by acute oil exposure. The dysfunction in DNA repair mechanisms, expressed as chromosomal damage, was significantly higher in exposed-oil participants than in those not exposed (p= 0.016). ConclusionThe present study shows that breaks in 2q21, 3q27 and 5q31 chromosomal bands, which are commonly involved in hematological cancer, could be considered useful genotoxic oil biomarkers. Moreover, breakages in these bands could induce chromosomal instability, which can explain the increased risk of cancer (leukemia and lymphomas) reported in chronically benzene-exposed individuals. In addition, it has been determined that the individuals who participated in clean-up of the oil spill presented an alteration of their DNA repair mechanisms two years after exposure.

Associations of chronic and acute ambient heat exposure with sex hormones: A longitudinal study in women receiving assisted reproductive technology.

What is the central question of this study? Endothelium-dependent flow-mediated dilatation (FMD) is impaired during acute (60min) exposure to moderate hypoxia. We examined whether FMD is impaired to the same degree during exposure to milder hypoxia. Additionally, we assessed whether smooth muscle vasodilatory capacity [glyceryl trinitrate (GTN)-induced dilatation] is impaired during acute hypoxic exposure. What is the main finding and its importance? A graded impairment in FMD and GTN-induced dilatation was evident during acute (≤60min) exposure to mild and moderate hypoxia. This study is the first to document these graded impairments, and provides rationale to examine the relationship between graded increases in sympathetic nerve activity with hypoxia on FMD and GTN-induced dilatation. Endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent dilatation [induced with glyceryl trinitrate (GTN)] are impaired at high altitude (5050m), and FMD is impaired after acute exposure (<60min) to normobaric hypoxia equivalent to ∼5050m (inspired oxygen fraction∼0.11). Whether GTN-induced dilatation is impaired acutely and whether FMD is impaired during milder hypoxia are unknown. Therefore, we assessed brachial FMD at baseline and after 30min of mild (end-tidal PO2 74±2mmHg) and moderate (end-tidal PO2 50±3mmHg) normobaric hypoxia (n=12) or normoxia (time-control trial; n=10). We also assessed GTN-induced dilatation after the hypoxic FMD tests and in normoxia on a separate control day (n=8). Compared with the normoxic baseline, reductions during mild and moderate hypoxic exposure were evident in FMD (mild versus moderate, -1.2±1.1 versus -3.1±1.7%; P=0.01) and GTN-induced dilatation (-2.1±1.0 versus -4.2±2.0%; P=0.01); the declines in FMD and GTN-induced dilatation were greater during moderate hypoxia (P<0.01). When allometrically corrected for baseline diameter and FMD shear rate under the curve, FMD was attenuated in both conditions (mild versus moderate, 0.6±0.9 versus 0.8±0.7%; P≤0.01). After 30min of normoxic time control, FMD was reduced (-0.6±0.3%; P=0.02). In summary, there was a graded impairment in FMD during mild and moderate hypoxic exposure, which appears to be influenced by shear patterns and incremental decline in smooth muscle vasodilator capacity (impaired GTN-induced dilatation). Our findings from the normoxic control study suggest the decline in FMD in acute hypoxia also appears to be influenced by 30min of supine rest/inactivity.

Methamphetamine and cocaine are among the most commonly abused psychostimulants. Repeated injections of psychostimulants produce behavioral sensitization or augmented locomotion in rats. Behavioral sensitization to methamphetamine and cocaine is long lasting and persists after cessation of drug treatment. Because dopamine and glutamate are major neurotransmitters of the neostriatum, we evaluated the profile of cocaine- or methamphetamine-evoked dopamine and glutamate overflow in the caudate putamen, nucleus accumbens, ventral tegmental area, and substantia nigra compacta of the rat brain. We also compared acute exposure to these drugs with chronic treatment and early withdrawal. Acute injection of methamphetamine (1 mg/kg of body weight) or cocaine (10 mg/kg) resulted in elevated levels of extracellular dopamine in all brain regions measured, although the magnitude of increase varied between brain regions. Overall, methamphetamine caused more dopamine to accumulate in the extracellular space than did cocaine when administered to animals during early withdrawal (7 days of daily injections and challenge on day 11). For example, a challenge injection of methamphetamine produced a greater elevation of extracellular dopamine in the caudate putamen when compared to acute (naïve) exposure. By contrast, a challenge injection of cocaine resulted in dopamine levels in the caudate putamen that were lower than those observed for acute exposure. In the ventral tegmental area and the substantia nigra compacta, a challenge injection of methamphetamine or cocaine resulted in extracellular dopamine levels that were lower than those for acute exposure. Thus, it appears that behavioral sensitization to cocaine can be sustained during early withdrawal in the absence of augmented drug-evoked dopamine overflow. Acute injection of methamphetamine or cocaine did not change extracellular levels of glutamate in the neostriatum. Cocaine challenge (early withdrawal) increased glutamate overflow in the caudate putamen and the nucleus accumbens. In contrast, methamphetamine challenge increased glutamate overflow in the caudate putamen, but it decreased glutamate in the nucleus accumbens. In the ventral tegmental area and the substantia nigra compacta, acute methamphetamine exposure decreased glutamate overflow, but acute cocaine exposure increased it. Although amphetamines and cocaine induce similar behavioral responses, the results presented here demonstrate that at the neurochemical level (neurotransmitter release) they sometimes evoke opposite effects depending on the brain region studied and the duration of drug treatment. Moreover, the sensitized augmentation of locomotor activity observed by us and others in response to a challenge injection of cocaine is not dependent on elevation of the extracellular concentration of dopamine in the neostriatum. We are currently investigating the hypothesis that cocaine activates peptidergic systems of the neostriatum and that these systems modulate the synaptic release of dopamine in response to psychostimulants.

An incident study about acute and chronic human exposure to uranium by high-resolution inductively coupled plasma mass spectrometry (HR-ICPMS)

Assessment of the impact of radiation exposure on human lifetime is an actual problem in radiation medicine. The aim of the study was to assess lifetime in Mayak PA workers who had developed acute radiation syndrome following accidental acute high-dose external exposure and in those individuals who had taken part in nuclear accidents but had not developed the syndrome. Study analyses considered 58 deceased Mayak PA workers (50 males and 8 females) and were performed using STATISTICA 10 software. Five indicators of lifetime were studied: static – before and after acute exposure, total lifetime, as well as potential – potential years of life lost and the proportion of people who lived less than 35 years. The study demonstrated significant decrease in static indicators excluding lifetime before acute exposure and increase in potential indicators of lifetime in workers with severe and especially with extreme acute radiation syndrome compared to workers with moderate and modest acute radiation syndrome and to workers free of the syndrome. The reason for the decrease of lifetime in workers with extreme acute radiation syndrome was extremely severe course of the disease. Decrease of lifetime in cases with severe level of the syndrome was mainly due to early death from malignancies. A significant linear regression association with natural logarithm of acute radiation dose in Gy was observed for lifetime indicators. At 1 logarithm of the radiation dose, the lifetime after acute exposure was reduced by 8.3 years, total lifetime by 8.8 years, and potential years of life lost increased by 8.4 years. The relative risk of the increase of the proportion of workers with less than 35 years of life was considerably higher in workers with extreme and severe acute radiation syndrome and in workers with acute radiation doses above 10 Gy compared to other groups of workers: 26.8 and 18.8 (95% CI: 3.8–191.1 and 2.7–129.8; p&lt;0.001), respectively. Thus, for the first time, a reduction in lifetime after acute radiation syndrome was found among Mayak PA workers.

2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most widely used herbicides in the world, but its mutagenic and carcinogenic potential is still controversial. We simulated environmental exposure to 2,4-D, with the objective of evaluating the genotoxic effect of acute and chronic exposure to 2,4-D in rodents. We also evaluated the performance of machine learning algorithms in detecting differences in exposure groups through recognition performed from genotoxic characteristics. In the acute phase, 88 Swiss mice were used, distributed in five groups and exposed to nebulizations at different time intervals (24, 48, 72 and 192 hr). In the chronic phase, 88 Wistar rats were used, distributed in two groups (inhaled and oral) and exposed for six months. Femoral bone marrow cells were collected for a micronucleus test and comet assay. Data were evaluated by pattern recognition algorithms. In acute exposure, medium and high concentrations induced DNA damage in the comet assay, but these concentrations did not increase micronucleated cells. In the chronic exposure, there was an increase in micronuclei and DNA damage in the comet assay in all exposed groups regardless of the exposure route. The data showed a robust pattern of distinction between exposed and nonexposed groups to 2,4-D. Our data showed that both acute inhalation exposure and chronic oral and inhalation exposure to 2,4-D can cause genotoxic effects regardless of concentration. Machine learning showed a clear distinction between the control groups and those exposed to 2,4-D, and the effects of exposure are not concentration-dependent.

Genotoxic, metabolic, and biological responses of Chironomus sancticaroli Strixino & Strixino, 1981 (Diptera: Chironomidae) after exposure to BBP.

Nickel (Ni) is a widespread metal that occurs in food and drinking water from both natural and anthropogenic sources. Oral exposure to Ni can induce a variety of adverse effects; the European Food Safety Authority established a tolerable daily intake (TDI) of 13μg/kg bw and a lowest-observed-adverse-effect level (LOAEL) of 4.3μg/kg bw to assess the risk of allergic reactions upon acute exposure. This study, the first conducted in Armenia, aimed to assess the dietary exposure of the adult Yerevan population (1272 subjects of both sexes) to Ni in a total diet study (TDS). Detection of Ni was carried out using atomic absorption spectrometry. To determine food consumption values, a 24-h recall survey was used. Following the K-means clustering test, two clusters were determined for food product intake. For the risk characterization of acute oral exposure, the margin of exposure (MOE) was calculated using both deterministic and probabilistic (Monte Carlo method) approaches. The average total exposure was 4.396μg/kg bw, with limited influence by age and gender. The main contributors were "fruits and vegetables" followed by "bread and flour-based products": the total intake would be 5.11μg/kg bw for a woman with high consumption of fruits and vegetables. Hence, the estimated chronic dietary exposure was below the TDI, irrespective of age and gender groups, and including high consumers. However, acute oral exposure estimates led to MOE values of less than 30 for most food products, indicating potential health concerns for Ni-sensitized individuals. The Monte Carlo approach indicated that the probability of occurrence of MOE lower than 30 was very high in the case of beef/veal, pork and chicken meat, eggs, and fish, alongside vegetable sources such as buckwheat, tomato, watermelon/melon, and potatoes. The findings prompt an investigation of Ni sources in the target foods in the Caucasus area.

We wish to thank Drs Bushfield and Day for their interest in our recent publication on early acclimatization, in which we used this group's metrics for calculating renal reactivity (RR) (Zouboules et al., 2018). That the derivation of base excess used by us was not developed to assess early acclimatization responses. The use of assumed normative values was potentially misleading, particularly when researchers have each participant's actual measured values available. For the base excess issue (a), we would like to note that Zubieta-Calleja and coworkers state that in acclimatized residents, a hypocapnic P aC O 2 ${P_{{\mathrm{aC}}{{\mathrm{O}}_2}}}$ at the altitude of La Paz, Bolivia, (3500 m) does not exist, rather a normocapnic P aC O 2 ${P_{{\mathrm{aC}}{{\mathrm{O}}_2}}}$ for a corrected altitude (Zubieta-Calleja et al., 2011). To observe how fast base excess reacts and then approaches zero in our experiment we used their altitude-corrected formula. We should have stated in context in the Methods section that we calculated base excess in this manner also for this purpose. Bushfield and Day rightly criticize this deficit, since we failed to mention this. Regarding the issue that the normative values were potentially misleading (b), we would like to point out that directly measured values are on display in Table 1 ( P aC O 2 ${P_{{\mathrm{aC}}{{\mathrm{O}}_2}}}$ ) and Figure 2 (Skalla et al., 2025): in Figure 2 measured and calculated values are given in four panels. In this way, HCO3−(a), pHa, as well as calculated renal reactivity and base excess are presented in parallel. We feel that we have committed neither any ‘normalizing away’ nor ‘obscuring’ of direction and magnitude of any response. The presentation, however, might have been clearer. The search for acute-exposure (<1 week) and acclimatized values of HCO3−(a) and P aC O 2 ${P_{{\mathrm{aC}}{{\mathrm{O}}_2}}}$ guides us to the excellent review of Ramirez-Sandoval et al. (2016). Here, calculated and some measured HCO3−(a) and P aC O 2 ${P_{{\mathrm{aC}}{{\mathrm{O}}_2}}}$ values are reported with some limitations; however, the altitude of our experiment (3100 m) should result in a derived HCO3−(a) of 21.7 mEq/L (acute exposure, <1 week) and 18.3 mEq/L in acclimatized individuals. One notable limitation is the assumption of a pHa of 7.4 in most calculations (Ramirez-Sandoval et al., 2016). Considering available data, it seems reasonable to assume acclimatization to 3100 m when HCO3−(a) reaches the approximate threshold of 18.3 mEq/L and, similarly, altitude-corrected base excess reaches zero. Based on the contribution of Bushfield and Day we now regret that we failed to present this information in the original submission. Similar to the approach of base excess converging toward zero, one could describe the trajectory of calculated HCO3−(a) from lowland values of 24.5 mEq/L to the acclimatized value at an altitude of 21.7 (acute exposure) and 21.3 mEq/L (chronic exposure) as described in the work of Ramirez-Sandoval et al. (2016). The lack of direct measurements commands further studies of HCO3−(a), pHa and P aC O 2 ${P_{{\mathrm{aC}}{{\mathrm{O}}_2}}}$ after acute or chronic exposure to altitude in healthy individuals. Missing correction for altitude may also have medical implications: Negrete-Pedraza and coworkers reported that in Mexico City (2250 m) children were falsely assumed to suffer from renal tubular acidosis on the basis of a defect of the chloride–HCO3− anion exchanger in the renal tubules (Negrete-Pedraza et al., 2024). The children showed HCO3− values below normal (i.e. below lowland values) and many were thought to suffer from an acid–base disorder such as renal tubular acidosis. This may be of interest since salt retention might have implications with oedema formation. There is work left to do. In conclusion, we would like to thank Drs Bushfield and Day for their valuable comments and the editor for the opportunity to clarify and to add information to our work. All authors have read and approved the final version of this manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed. None declared. None.

UV and hydrogen peroxide treatment restores changes in innate immunity caused by exposure of fish to reuse water