N-acetylcysteine and ascorbic acid therapy for acute hepatic injury after hexavalent chromium ingestion.

WHAT IS KNOWN AND OBJECTIVE: Hexavalent (VI) chromium is a powerful oxidant that can produce cellular oxidative stress and multi-organ system dysfunction. The role of antioxidants such as N-acetylcysteine (NAC) and ascorbic acid in alleviating organ damage in humans remains unclear. CASE DESCRIPTION: We present a 47-year-old male who ingested 30 mL of plating solution and developed hepatic injury. He was treated with NAC and ascorbic acid with improvement in hepatic function. However, his clinical conditions and jaundice worsened again after discontinuing these therapies. WHAT IS NEW AND CONCLUSION: Our findings suggest a potential role for antioxidant therapy for acute hexavalent chromium poisoning.

[Clinical analysis of 24 cases of occupational chromium rhinopathy].

Occupational chromium rhinopathy is chronic nasal damage caused by chromic anhydride, chromate and dichromate 6-valent chromium compounds. In 2016, 700 people who were exposed to chromium slag in steel plant were checked out. 24 people were found to have nasal injuries. The expert group confirmed 1 case of occupational severe chromium rhinosis and 23 cases of occupational mild chromium rhinosis.There was no significant difference in the incidence, type of work and duration of injury among 24 patients (P>0.05) . Active measures should be taken to prevent chromium rhinopathy and the technological process should be reformed. Occupational health education and occupational health monitoring should be strengthened to avoid exposure of chromium and its compounds through nose and respiratory tract, and to reduce or eliminate the occurrence of chromium rhinosis.

Severe metallosis and elevated chromium in serum following implantation of the joint unloading implant system.

In recent years, the minimally invasive joint-preserving implant system has been developed. The main goal of this device is to unload the medial knee compartment without affecting the lateral compartment. The current authors describe a severe metallosis and elevated chromium in serum following implantation of the joint unloading implant system of a 50-year-old male patient, presented to our hospital 3 years after implantation of a KineSpring System into his left knee due to unicompartmental medial osteoarthritis (OA) in an external hospital. Radiographs showed radiological signs for loosening of the screws in the tibia and a progressive OA on the medial and patellofemoral compartments. Revision surgery with removing of the unloading device was performed at our hospital. The intraoperative situs presented a severe metallosis around the device. Five days after revision surgery, the laboratory parameters revealed an elevated value for chromium in serum, while nickel and cobalt values in serum were normal. Reliable clinical data about the long-term results of the KineSpring System is desperately needed. Further studies are warranted to work out the effects of cobalt and chromium levels and further side effects following the implantation of the extra-articular absorber system.

[Heavy metal poisoning and renal injury in children].

Along with global environmental pollution resulting from economic development, heavy metal poisoning in children has become an increasingly serious health problem in the world. It can lead to renal injury, which tends to be misdiagnosed due to the lack of obvious or specific early clinical manifestations in children. Early prevention, diagnosis and intervention are valuable for the recovery of renal function and children's good health and growth. This paper reviews the mechanism of renal injury caused by heavy metal poisoning in children, as well as the clinical manifestations, diagnosis, and prevention and treatment of renal injury caused by lead, mercury, cadmium, and chromium.

Assessment of the mode of action underlying development of rodent small intestinal tumors following oral exposure to hexavalent chromium and relevance to humans.

Abstract Chronic exposure to high concentrations of hexavalent chromium (Cr(VI)) in drinking water causes intestinal adenomas and carcinomas in mice, but not in rats. Cr(VI) causes damage to intestinal villi and crypt hyperplasia in mice after only one week of exposure. After two years of exposure, intestinal damage and crypt hyperplasia are evident in mice (but not rats), as are intestinal tumors. Although Cr(VI) has genotoxic properties, these findings suggest that intestinal tumors in mice arise as a result of chronic mucosal injury. To better understand the mode of action (MOA) of Cr(VI) in the intestine, a 90-day drinking water study was conducted to collect histological, biochemical, toxicogenomic and pharmacokinetic data in intestinal tissues. Using MOA analyses and human relevance frameworks proposed by national and international regulatory agencies, the weight of evidence supports a cytotoxic MOA with the following key events: (a) absorption of Cr(VI) from the intestinal lumen, (b) toxicity to intestinal villi, (c) crypt regenerative hyperplasia and (d) clonal expansion of mutations within the crypt stem cells, resulting in late onset tumorigenesis. This article summarizes the data supporting each key event in the MOA, as well as data that argue against a mutagenic MOA for Cr(VI)-induced intestinal tumors.

Outline of occupational chromium poisoning in China.

The present study analyzed the feature of occupational chromium poisoning in China since the 1980s. The collected data were acquired from 18 previous surveys of chromium poisoning in 14 cities of China. The method of risk assessment was applied to calculate the relative risk and 95% CI, p < 0.05 was considered as a significant risk. The results showed that nasal disease was the most common sign of occupational chromium poisoning, and the prevalence rate of nasal disease was 17.83% in total population of 6,998. Further, the risk analysis showed that occupational chromium poisoning led to an increased risk of lung or liver cancer in male workers due to the definite carcinogenicity of hexavalent chromium. Significantly, an increased risk of spontaneous or threatened abortion was also found in female workers. In conclusion, these studies suggest that early detection of impaired reproductive function or impaired lung or liver function in female or male workers is essential for controlling occupational chromium poisoning in China.

Blood chromium levels of children working in gem-polishing industries in India.

The gem-polishing industry in Jaipur, India employs a substantial proportion of children. The process of polishing may result in exposure to chromium in working children. Thus, this study aims to find out the levels of chromium in these working children and the associated factors. Blood samples were analysed for chromium using atomic absorption spectrophotometer. The mean blood chromium levels were 2.51 ± 1.11 mg/100 ml and 2.33 ± 1.10 mg/100 ml in working and school children, respectively, which is well within the permissible levels. However, the practice of employing children should be totally curbed.

Effect of nickel and chromium exposure on buccal cells of electroplaters.

The electroplating industry commonly involves the use of nickel and chromium. An assessment of the genotoxic effects of these metals can be carried out by micronucleus (MN) test in buccal cells. Other nuclear anomalies (NA) observed in buccal cells viz., karyorrhexis, pyknosis and karyolysis are also the indicators of genotoxicity. The current study aims at determining the extent of genotoxic damage in relation to the duration of exposure to nickel and hexavalent chromium via micronuclei induction and other nuclear anomalies. The present investigation included 150 subjects of which 50 individuals with no history of nickel/chromium exposure (Group I) were taken as control, 50 electroplaters exposed to nickel and hexavalent chromium for duration of less than 10 years (Group II) and 50 electroplaters exposed for ≥10 years (Group III) were included. Slides of buccal cells were prepared and the frequency of MN (‰) and NA (‰) were calculated. ANOVA was applied to test significance. Results were considered significant at p < 0.05 and p < 0.001. Group III showed the highest MN frequency (1.08 ± 0.54‰, p < 0.05), karyorrhexis (20.75 ± 6.29, p < 0.05), karyolysis (3.50 ± 1.91, p < 0.001), binucleate (4.75 ± 2.75, p < 0.05) and enucleated cells (5.75 ± 1.70, p < 0.05). Significant increase in frequencies between Group II and III was found as duration of exposure increased. Plasma nickel and chromium levels were also determined which showed a positive correlation with frequency MN and other nuclear abnormalities (p < 0.01).

[Worldwide cancer mortality among chromium platers].

The elevated risk of lung cancer among chromate-producing workers has been confirmed by many epidemiological studies. Although chromium has been most used in the chromium plating industry and many platers are employed in small-scale factories, cancer studies have been documented in only a few investigations. We have conducted several prospective cohort studies in Japanese chromium platers and recently extended them through 2003. We additionally surveyed epidemiological studies among chromium platers carried out in other parts of the world. Occupational chromium exposure through chromium plating work may be a risk factor for mortality not only from lung cancer but also malignant lymphoma and brain tumor. The age at first exposure to chromium may be a more important factor than the duration of exposure for an increased risk of lung cancer and malignant lymphoma.

Aging erythrocyte membranes as biomimetic nanometer carriers of liver-targeting chromium poisoning treatment.

Chromium poisoning has become one of the most common heavy metal poisoning occupational diseases with high morbidity and mortality. However, most antidotes detoxify the whole body and are highly toxic. To achieve hepato-targeted chromium poisoning detoxification, a novel hepato-targeted strategy was developed using aging erythrocyte membranes (AEMs) as biomimetic material coated with a dimercaptosuccinic acid (DMSA) nanostructured lipid carrier to construct a biomimetic nano-drug delivery system. The particle size, potential, drug loading, encapsulation rate, in vitro release, and stability of the nanoparticles (NPs) were characterized. Confocal microscopy and flow cytometry showed that the prepared NPs could be phagocytized by RAW264.7 macrophage cells. The efficacy of AEM-DMSA-NPs for targeted liver detoxification was evaluated by in vitro MTT analysis and an in vivo model of chromium poisoning. The results showed that the NPs could safely and efficiently achieve targeted liver chromium poisoning detoxification. All the results indicated that the biomimetic nano-drug delivery system mediated by aging erythrocyte membranes and containing DMSA nanoparticles could be used as a novel therapeutic drug delivery system potentially targeting liver detoxification.

"Nearly a stairway to heaven"--severe dichromate intoxication in a young man.

A 22-year-old man presented with dichromate intoxication in a suicidal attempt. He exhibited signs of liver and renal toxicity and very high serum chromium levels. Since it has been reported in the literature that hemodialysis and hemoperfusion are not sufficient to remove chromium, we tried plasmapheresis considering the fact that chromium salts bind to protein. Five plasmapheresis treatment sessions significantly lowered his serum and urinary chromium concentrations. The patient survived without organ damage despite ingestion of a lethal dichromate dose and high serum chromium concentration. Thus, plasmapheresis should be considered as a potential therapeutic option to reduce chromium concentrations.

Effect of chromium on the level of IL-12 and IFN-gamma in occupationally exposed workers.

Chromium may affect humoral and cellular immunity, acting on T lymphocytes as well as on granulocytes and monocytes cells. Cytokines play an important role in the immune balance. In this study, the level of IL-12 and IFN-gamma were evaluated in the sera and PHA/LPS stimulated culture supernatant of human PBMCs of healthy volunteers and occupationally exposed chromium workers. All the workers were highly exposed to chromium having mean of 104.65+/-77.21 microg/dL (range 23.7-316.8 microg/dL). A suspension of exposed and unexposed human PBMC (0.5x10(6) cells/ml) prepared and cultured in RPMI-1640 supplemented with 10% FCS for 18 h in the presence or absence of LPS (10 ng/ml) which used for stimulation of IL-12 and IFN-gamma. The level of IL-12 and IFN-gamma were evaluated in the sera samples as well as LPS stimulated and unstimulated culture supernatant of h-PBMCs of chromium exposed workers. In these chromium exposed workers the level of IL-12 was 433.66+/-197.49 pg/ml and 983.45+/-330.99 pg/ml in LPS stimulated culture supernatant of normal individuals and highly chromium exposed workers, which was significant (P<0.05). Although the level of IL-12 was (78.61+/-61.03 pg/ml to 146.52+/-46.37 pg/ml) elevated in unstimulated culture supernatant of h-PBMCs of chromium exposed individuals as compared to control, but it was not significant. This observation also suggests that a significant increase in IFN-gamma production in LPS stimulated and unstimulated culture supernatant of h-PBMCs of chromium exposed workers as compared to control. However, IFN-gamma level have a significant positive correlation between blood chromium level (r=0.833, t=6.3872, P 0.05) and exposure time (in years) (r=0.8916, t=8.3540, P 0.05) of the occupationally exposed workers.

Acute severe chromium poisoning after dermal exposure to hexavalent chromium.

Severe acute chromium poisoning related to dermal involvement has rarely been reported in the literature. We report a case of acute severe chromium poisoning through skin exposure as a result of a chemical burn of 15% of the body surface area and multiple organ failure after short-term exposure. Medical interventions, including mechanical ventilation, continuous venovenous hemofiltration, and plasmapheresis were performed. In addition, a chelating agent, dimercaptopropane sulfonic acid, was infused intravenously, combined with intravenous N-acetylcysteine and ascorbic acid as adjuvant therapy. The patient was discharged on day 33 without long-term sequelae. The consequence of transdermal exposure of hexavalent chromium should not be overlooked.

Cellular responses in the cyprinid Leuciscus cephalus from a contaminated freshwater ecosystem.

The response of wild chubs (Leuciscus cephalus) to chemical pollution was assessed in a metal contaminated river (Cecina River, Italy) through a wide battery of biomarkers which included: Comet assay detecting DNA strand breaks; diffusion assay for apoptosis induction; micronucleus test assessing chromosomal alterations; ethoxyresorufin O-deethylase (EROD) activity for the induction of cytochrome P 4501A; acetylcholinesterase (AChE) activity responsive to pesticide exposure; vitellogenin gene expression in males revealing estrogenic effects. Bioaccumulation of mercury, chromium and polycyclic aromatic hydrocarbons (PAHs) was also determined. Levels of mercury and PAHs were higher in tissues of chubs sampled from the most downstream station, reflecting an anthropogenic pollution of industrial origin. Otherwise, accumulation of Cr was quite similar in fish along the entire course of Cecina River confirming a natural origin due to local geochemical features. Biomarker responses revealed a significant increase of apoptotic cells, DNA stand breaks and micronucleus frequency in chubs from the more impacted sites. A slight EROD induction and AChE inhibition were only seen at the most downstream station demonstrating a limited impact due to PAHs and pesticides. On the other hand, the induction of vitellogenin gene in male chubs was measured in all the sites, suggesting a diffuse estrogenic effect. This study confirmed the utility of large batteries of biomarkers in biomonitoring studies and the suitability of wild chub as bioindicator organism for river basins.

Suppression of IL-6 level in human peripheral blood mononuclear cells stimulated with PHA/LPS after occupational exposure to chromium.

The toxic metals alter the immune response of animals as well as humans. In addition to the well documented and numerous toxic effect of chromium on various target organs, number of studies shown that acute and chronic exposure to inorganic chromium may result in impairment of immune functions in the experimental systems. Immunosuppression appears to be more subtle effect of exposure to heavy metals. Therefore, we have taken two different groups of chromium exposed individuals. These were leather tanning workers and chromeplaters. These groups of individuals were regularly exposed to chromium. All the leather tanning workers were highly exposed to chromium having a mean of 96.60+/-113.95 mg/dl (range 12.4-417.21 mg/dl). A suspension of exposed and unexposed human PBMC (0.5x10(6) cells/ml) prepared and cultured in RPMI-1640 supplemented with 10% FCS for 18 h in the presence or absence of PHA (5 microg/ml) and LPS (10 ng/ml) which used for stimulation of IL-2, IL-4, TNF-alpha, IL-10 and IL-6, respectively. The levels of Th1/Th2 cytokine: IL-2, IL-4, TNF-alpha, IL-10 and IL-6 were evaluated in the sera and PHA/LPS stimulated culture supernatant of human PBMCs of chromium exposed workers. In these workers the level of IL-6 was 543.95+/-123.75 pg/ml and 388.40+/-61.24 pg/ml in PHA/LPS stimulated culture supernatant of normal individuals and highly chromium exposed workers, which was significant (P<0.05). This observation suggests that IL-6 levels were suppressed in chromium exposed groups as compared to unexposed healthy volunteers. Although the level of IL-2 in PHA stimulated culture supernatant of PBMCs was suppressed in chromium exposed individuals but it was not significant, IL-4 and IL-10 could not be detected. However, there was no difference in TNF-alpha levels in sera samples as well as unstimulated culture supernatant of h-PBMCs of chromium exposed individuals as compared to control.

Transcriptome analysis reveals the molecular mechanism of hepatic metabolism disorder caused by chromium poisoning in chickens.

Chromium (Cr) is one of the most important environmental pollutants which are released into the environment due to their wide usage in numerous industries. The excess of Cr (VI) can induce hepatotoxicity, while the molecular mechanism that is involved in Cr (VI)-induced hepatotoxicity is unclear. We demonstrated the induction of chromium poisoning model in chickens to identify the differentially expressed genes (DEGs), and their functions were analyzed under different physiological and pathological conditions. Histopathological examination and transcriptome data for chromium-poisoned livers and control livers were annotated with Illumina® HiSeq 2000. The histopathological examination in chromium poisoning groups showed diapedesis, hemolysis, degeneration, nucleus pycnosis, and central phlebectasia in the liver. A total of 334 genes were upregulated and 509 genes were downregulated. The most strongly upregulated genes were HKDC1, DDX4, ACACA, FDFT1, CYYR1, PPP1R3C, and SLC16A14, while the most downregulated genes were MYBPC3, CCKAR, PCK1, and CPT1A. A Gene Ontology (GO) term with the highest enrichment of DEGs is small molecule metabolic process. In cell component domain, the term with the highest enrichment is extracellular matrix. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that glucose metabolism, lipid metabolism, and protein metabolism were the most important metabolic pathways in the liver. The current study first time provides important clues and evidence for identifying the differentially expressed genes in livers due to Cr (VI)-induced liver injury in chickens.

Application of ICP-MS and HPLC-ICP-MS for diagnosis and therapy of a severe intoxication with hexavalent chromium and inorganic arsenic.

ICP-MS and HPLC-ICP-MS were applied for diagnosis and therapeutic monitoring in a severe intoxication with a liquid containing hexavalent chromium (Cr(VI)) and inorganic arsenic (iAs). In this rare case a liver transplantation of was considered as the only chance of survival. We developed and applied methods for the determination of Cr(VI) in erythrocytes and total chromium (Cr) and arsenic (As) in blood, plasma, urine and liver tissue by ICP-MS. Exposure to iAs was diagnosed by determination of iAs species and their metabolites in urine by anion exchange HPLC-ICP-MS. Three days after ingestion of the liquid the total Cr concentrations were 2180 and 1070µg/L in whole blood and plasma, respectively, and 4540µg/L Cr(VI) in erythrocytes. The arsenic concentration in blood was 206µg/L. The urinary As species concentrations were <0.5, 109, 115, 154 and 126µg/L for arsenobetaine, As(III), As(V), methylarsonate (V) and dimethylarsinate (V), respectively. Total Cr and As concentrations in the explanted liver were 11.7 and 0.9mg/kg, respectively. Further analytical results of this case study are tabulated and provide valuable data for physicians and toxicologists.

Metal-on-Metal Hip Joint Prostheses: a Retrospective Case Series Investigating the Association of Systemic Toxicity with Serum Cobalt and Chromium Concentrations.

INTRODUCTION: There have been concerns about prosthesis failure and the potential for systemic toxicity due to release of cobalt and chromium from metal-on-metal hip joint prostheses (MoM-HP). There is conflicting evidence on whether there is a correlation between higher cobalt and chromium concentrations and systemic toxicity. METHODS: We undertook a retrospective review of consecutive patients with MoM-HP referred for outpatient review in toxicology clinics in London, UK, and in the USA recorded in the Toxicology Investigators Consortium (ToxIC) Registry from June 2011 to June 2015. RESULTS: Thirty-one cases were identified; the median (IQR) serum cobalt concentration was 10.0 (3.8-32.8) mcg/L, and the median (IQR) serum chromium concentration was 6.9 (3.7-18.7) mcg/L. Twenty-three (74.2%) had symptoms, most commonly lethargy, hearing loss, and tinnitus. The odds ratios of symptomatic/asymptomatic patients for metal ion concentrations above/below 7 mcg/L were 1.87 (95% CI 0.37-9.57, p = 0.45) and 0.60 (95% CI 0.10-3.50, p = 0.57) for cobalt and chromium, respectively. Two (6.5%) patients with systemic cobalt toxicity had median (IQR) serum cobalt concentrations significantly higher than those without systemic features (630.4 [397.6-863.2] mcg/L versus 9.8 [2.9-16.4] mcg/L; p = 0.017). However, overall, there were no differences between cobalt (p = 0.38) or chromium (p = 0.92) concentrations between symptomatic and asymptomatic patients and no clinical features or investigation results correlated with cobalt or chromium concentration. CONCLUSION: Two (6.5%) of 31 individuals referred for assessment of MoM-HP were diagnosed with systemic cobalt toxicity. However, despite a high prevalence of reported symptoms, neither symptoms nor investigation results correlated with serum cobalt or chromium concentrations.