Cardiac function may be compromised in patients with elevated blood cobalt levels secondary to metal-on-metal hip implants.

Aims: Elevated blood cobalt levels secondary to metal-on-metal (MoM) hip arthroplasties are a suggested risk factor for developing cardiovascular complications including cardiomyopathy. Clinical studies assessing patients with MoM hips using left ventricular ejection fraction (LVEF) have found conflicting evidence of cobalt-induced cardiomyopathy. Global longitudinal strain (GLS) is an echocardiography measurement known to be more sensitive than LVEF when diagnosing early cardiomyopathies. The extent of cardiovascular injury, as measured by GLS, in patients with elevated blood cobalt levels has not previously been examined. Methods: A total of 16 patients with documented blood cobalt ion levels above 13 µg/l (13 ppb, 221 nmol/l) were identified from a regional arthroplasty database. They were matched with eight patients awaiting hip arthroplasty. All patients underwent echocardiography, including GLS, investigating potential signs of cardiomyopathy. Results: Patients with MoM hip arthroplasties had a mean blood cobalt level of 29 µg/l (495 nmol/l) compared to 0.01 µg/l (0.2 nmol/l) in the control group. GLS readings were available for seven of the MoM cohort, and were significantly lower when compared with controls (-15.5% vs -18% (MoM vs control); p = 0.025)). Pearson correlation demonstrated that GLS significantly correlated with blood cobalt level (r = 0.8521; p < 0.001). However, there were no differences or correlations for other echocardiography measurements, including LVEF (64.3% vs 63.7% (MoM vs control); p = 0.845). Conclusion: This study supports the hypothesis that patients with elevated blood cobalt levels above 13 µg/l in the presence of a MoM hip implant may have impaired cardiac function compared to a control group of patients awaiting hip arthroplasty. It is the first study to use the more sensitive parameter of GLS to assess for any cardiac contractile dysfunction in patients with a MoM hip implant and a normal LVEF. Larger studies should be performed to determine the potential of GLS as a predictor of cardiac complications in patients with MoM arthroplasties.

Is there still an indication for the Birmingham Hip Resurfacing in femoral head osteonecrosis?

PURPOSE: Osteonecrosis of the femoral head (ONFH) is a progressive hip disease. Hip resurfacing arthroplasty (HRA) is a preferred surgical procedure among hip arthroplasty performed in young patients. The aim of this study is to show the long-term clinical and radiological results of HRA procedures performed for patients suffering from ONFH. METHODS: Forty-five patients who underwent hip resurfacing with the diagnosis of femoral head osteonecrosis were included in the study. The Harris Hip Score (HHS) was used for clinical scoring of the patients. The blood chromium, cobalt, white blood cell (WBC) count, and CRP levels of patients were checked. Ultrasonography (USG) was performed for all patients at mid-term control checked for pseudo-tumours. For the radiological evaluation, acetabular inclination, stem shaft angle, prothesis-to-neck ratio, osteolysis zones, and heterotopic ossification were used. RESULTS: The mean age of the patients was 46.6 ± 9.3 years, and the mean follow-up period was 11.83 ± 2.9 years. The mean HHS was 90.3 ± 12.8 for final follow-up. The mean WBC value was 8.2 109/L, mean CRP value was 6.3 mg/L, mean chromium value was 4.9 µg/L, and mean cobalt value was 1.8 µg/L. Inclination changing 0.2°(p = 0.788), stem shaft angle changing 0.7°(p = 0.424), and neck-to-prosthesis ratio changing 0.01°(p = 0.075). No pseudo-tumours were detected in any patients in USG examination. CONCLUSION: HRA provides long-term implant survival and excellent clinical outcomes for end-stage ONFH patients with low complication rates.

The association of cobalturia with cobaltism symptoms a prospective blinded study of 229 post-arthroplasty patients.

INTRODUCTION: Cobalt is a mitochondrial toxin, clinical cobaltism manifests with constitutional, neurologic, and cardiovascular symptomatology. Cobalt's severe toxidrome is known through case reports from extreme wear or corrosion of cobalt-chromium arthroplasty components. However, the spectrum and epidemiology of orthopedic-implant cobaltism and its relationship to duration and degree of cobalt exposure are not well defined. METHODS: The relationship of urine-cobalt concentration and duration of exposure to cobalt-chromium joint implants and cobaltism symptomatology were prospectively studied in 229 patients. Subjects received a Cobaltism-Symptom-Inventory-Score (CSIS) based on a protocolized interview and examination followed by a spot urine-cobalt measurement. RESULTS: 129 (56%) subjects were cobalturic (urine-cobalt ≥1.0 ppb). 122 (53%) subjects had a CSIS of >2, this status significantly associates with cobalturia. Median [IQR] urine-cobalt in the subjects with a CSIS >2 was 4.1[1.1-17.0] ppb compared to 0.5[0.5-1.4] ppb in subjects with CSIS ≤ 2. Cobalturia has a sensitivity of 0.69, a specificity of 0.77, and a positive predictive value of 0.74 for a CSIS of >2. The product of years-exposed to a cobalt-chromium implant and urine-cobalt by quartiles significantly positively associates with the Cobaltism-Symptom-Inventory-Score. CONCLUSION: A urine-cobalt of ≥1 ppb likely indicates adverse systemic exposure to orthopedic-implant generated cobalt. Cobaltism severity as quantified by the CSIS significantly correlates with the product of spot urine-cobalt concentration and years-exposed to a cobalt-chromium orthopedic-implant indicating a dose-response relationship. Medical provider and public awareness of orthopedic-implant cobaltism is vital because tens-of-millions are at-risk and early cobaltism is reversible. Further use of cobalt-chromium orthopedic-implants should be questioned given cobaltism becomes clinically apparent at a spot urine-cobalt of 1 ppb or greater. Monitoring of patients with high-risk cobalt-chromium orthopedic-implants appears to be indicated.

A Comparison of Clinical Outcomes After Total Knee Arthroplasty in Patients With Preoperative Nickel Allergy Receiving Cobalt Chromium or Nickel-Free Implant.

BACKGROUND: The role of metal hypersensitivity reactions in total knee arthroplasty (TKA) failure is debated. There is no consensus on whether use of a more expensive nickel-free implant is indicated for patients who have preoperative nickel allergy. The purpose of this study was to examine the outcome of patients who have preoperative nickel allergy receiving nickel-free or cobalt chromium (CoCr) implants. METHODS: This was a retrospective review of 17,798 patients who underwent 20,324 unilateral primary TKAs between 2016 and 2020. Presence of preoperative nickel allergy was determined (n = 282). Patients were divided into 2 cohorts: those receiving (1) nickel-free or (2) CoCr implants. Clinical outcome scores and revision rates were assessed. RESULTS: 243 received a nickel-free implant and 39 received a CoCr implant. There was no significant difference in revision rate between the cohorts. Survivorship free of revision was 94% in the CoCr implant cohort and 98% in the nickel-free implant cohort (P = .9). When comparing clinical outcome scores between cohorts, there was no difference in preoperative, 6-week or 1-year Knee Osteoarthritis Outcome Score Joint Replacement, Visual Analog Scale (VAS), Lower Extremity Activity Scale, Patient-Reported Outcomes Measurement Information System (PROMIS), and Veterans RAND 12-item scores between cohorts. CONCLUSION: In this retrospective cohort study, there was no difference in revision rates or clinical outcomes in patients who had a nickel allergy undergoing primary TKA with CoCr or nickel-free implants. Further studies are needed to determine if nickel allergy is an independent risk factor for worse TKA outcomes in general.

Analysis of Hexavalent Chromium in Cement Samples From Countries Within and Outside the EU: A Study From the International Contact Dermatitis Research Group.

Background: Allergic contact dermatitis (ACD) caused by hexavalent chromium (Cr(VI)) is often severe and difficult to treat. The content of Cr(VI) in cement can be reduced by, for example, addition of iron(II) sulfate. Since 2005 the content of Cr(VI) in cement is regulated in the EU Directive 2003/53/EC and must not exceed 2 ppm. Since this regulation came into force, ACD caused by cement has markedly been reduced. Objective: To investigate Cr(VI) and total chromium content in samples of cement from countries within and outside the EU. Methods: The members of the International Contact Dermatitis Research Group (ICDRG) were invited to participate in the study with the aim to collect cement samples from geographically different areas. The content of Cr(VI) in the samples was estimated by the diphenyl carbazide spot test, atomic absorption spectroscopy was used to assess the total chromium content. Results: Forty-five cement samples were analyzed, containing amounts of Cr(VI) from <0.1 to >70 ppm. Twenty-one samples contained >2 ppm Cr(VI), 24 contained less. Four of 17 samples from within the EU contained >2 ppm Cr(VI), that is, higher amounts than stipulated in the EU directive, as compared with 17 samples from countries outside the EU. Conclusion: In countries outside the EU, significantly more cement samples contained >2 ppm Cr(VI).

Copper modified cobalt-chromium particles for attenuating wear particle induced-inflammation and osteoclastogenesis.

The nature of aseptic prosthetic loosening mainly relates to the wear particles that induce inflammation and subsequent osteoclastogenesis. The ideal approach to impede wear particle-induced osteolysis should minimize inflammation and osteoclastogenesis. In this work, Co29Cr9W3Cu particles were used as a research model for the first time to explore the response of Co29Cr9W3Cu particles to inflammatory response and osteoclast activation in vitro and in vivo by using Co29Cr9W particles as the control group. In vitro studies showed that the Co29Cr9W3Cu particles could promote the generation of M2-phenotype macrophages and increase the expression level of anti-inflammatory factor IL-10, while inhibiting the formation of M1-phenotype macrophages and down-regulating the expression of inflammatory factors TNF-α, IL-6 and IL-1ß; More importantly, the Co29Cr9W3Cu particles reduced the expression of NF-κB and downstream osteoclast related-specific transcription marker genes, such as TRAP, NFATc1, and Cath-K; In vivo results indicated that the Co29Cr9W3Cu particles exposed to murine calvarial contributed to decreasing the amount of osteoclast and osteolysis area. These findings collectively demonstrated that Cu-bearing cobalt-chromium alloy may potentially delay the development of aseptic prosthetic loosening induced by wear particles, which is expected to provide evidence of Co29Cr9W3Cu alloy as an alternative material of joint implants with anti-wear associated osteolysis.

Characterization of ion release from a novel biomaterial, Molybdenum-47.5Rhenium, in physiologic environments.

BACKGROUND CONTEXT: Metals from spinal implants are released into surrounding tissues by various mechanisms. Metal ion release has been associated with clinical implant failure, osteolysis, and remote site accumulation with adverse events. Significant corrosion and associated metal ion release has been described with currently used spinal implant alloys. A novel metal alloy, Molybdenum-47.5Rhenium alloy (MoRe®), was approved for use in medical implants in 2019 by the FDA. PURPOSE: To evaluate the metal ion release profile of MoRe alloy after immersion in both a stable physiologic, as well as in an inflammatory environment. STUDY DESIGN: In vitro study. METHODS: The ion release profile of the MoRe alloy was comprehensively evaluated in-vitro after prolonged immersion in physiologic and inflammatory environments. Ion concentration analyses were then conducted using inductively coupled plasma-mass spectrometry (ICP-MS) methods. Comparative testing of titanium (Ti-6Al-4V) and cobalt chromium (Co-28Cr-6Mo) was also performed. RESULTS: Under baseline physiologic conditions, the MoRe alloy demonstrates very low molybdenum and rhenium ion release rates throughout the 30-day test period. During the first time interval (day 0-1), low levels of molybdenum and rhenium ions are detected (<0.3 µg/cm2 day) followed by a rapid reduction in the ion release rates to <0.05 µg/cm2 day during the second time interval (days 1-3) followed by a further reduction to very low steady-state rates <0.01 µg/cm2 day during the third time interval (days 3-7), which were maintained through 30 days. In the inflammatory condition (H2O2 solution), there was a transient increase in the release of molybdenum and rhenium ions, followed by a return to baseline ion release rates (days 2-4), with a further reduction to low steady-state rates of ∼0.01 µg/cm2 day (days 4-8). The measured molybdenum and rhenium ion release rates in both steady state (<0.01 µg/cm2 day), and inflammatory environments (0.01 µg/cm2 day) were far below the established FDA-permitted daily exposure (PDE) of 1,900 µg/cm2 day for molybdenum and 4,400 µg/cm2 day for rhenium. In contrast, titanium and cobalt chromium approached or exceeded their established PDE values in an inflammatory environment. CONCLUSIONS: The novel biomaterial MoRe demonstrated a lower metal ion release profile in both a physiologic and inflammatory environment and was well below the established PDE.  Comparative testing of the cobalt-chromium and titanium alloys found higher levels of ion release in the inflammatory environment that exceeded the PDE for cobalt and vanadium.

Contact allergy to metals in metalworkers: A systematic review and meta-analysis.

Occupational hand eczema is frequent in metalworkers. The contribution of metal allergies is poorly elucidated even though such exposures are common at the workplace. To estimate the prevalence of metal allergy to cobalt (Co), chromium (Cr) and nickel (Ni) in metalworkers and compare these to estimates from the European Surveillance System on Contact Allergies (ESSCA). Two authors independently searched PubMed for studies reporting on the prevalence of metal allergy in metalworkers. Proportion meta-analyses were performed to calculate the pooled proportions of metal allergy in metalworkers. In total, 29 studies (22 from Europe) were included yielding 5691 subjects for quantitative analysis. The pooled proportion (95% confidence interval) of Co, Cr and Ni in European metalworkers with dermatitis referred to patch test clinics was 8.2% (5.3%-11.7%), 8.0% (5.1%-11.4%), and 11.0% (7.3%-15.4%), respectively. The corresponding estimates for unselected metalworkers from workplace studies were 4.9% (2.4%-8.1%), 5.2% (1.0%-12.6%), and 7.6% (3.8%-12.6%), respectively. In comparison, the prevalence of metal allergy in 13 382 consecutive European males with dermatitis was 3.9% (3.6%-4.2%), 4.4% (4.1%-4.8%) and 6.7% (6.3%-7.0%) for Co, Cr and Ni, respectively. Data on sex, age, body piercings and atopic dermatitis in metalworkers with metal allergy was mostly lacking. Metal allergy to all three metals was significantly more common in European metalworkers with dermatitis attending patch test clinics as compared to ESSCA data, indicating a relationship to occupational exposures, however, confounders could not be accounted for.

Chromium as a Risk Factor for Breast Cancer: A Meta-Analysis.

BACKGROUND: Chromium (Cr) is a transition metal, natural element. Chromium is the 21st most abundant element in Earth's crust. Cr is found in soil, rocks and living organisms. It may have various oxidation states, from -2 to +6, but most of these states are too unstable to exist in any significant quantities. The purpose of this review and meta-analysis is to critically assess the scientific evidence on the carcinogenic effects of chromium (Cr) and to determine whether there is currently sufficient evidence to suggest that that there is a link between chromium levels in hair and blood serum and breast cancer in women. MATERIAL AND METHODS: Research on the relationship between heavy metal chromium and the risk of developing breast cancer has been searched in PubMed, EMBASE, Web of Science, Scopus among papers published between January 2000 and September 2020. The search used the following terms (MeSH): breast cancer, women, trace elements, metals, chromium, chemically-induced, hair, serum using additional terms. RESULTS: In the second group of comparisons of women from "ecologically clean" districts of Aktobe Region, there were significantly lower indicators of the microelements in tumor tissue. The amount of Fe ranges from 38.46 to 65.39 ug/g (average 49.56±5.81 ug/g), Cu from 2.8 to 6.69 ug/g (average 5.06±1.01 ug/g), Zn from 1.89 to 5.38 ug/g (average 3.88±0.89 ug/g), Cr from zero to 6,1 ug/g (average 2.13±1.29 ug/g), Ni from 0.11 to 0.42 ug/g (average 0.28±0.067 ug/g) и Pb from zero to 0.19 ug/g (average 0.098±0.06 ug/g). CONCLUSION: The article established that women who live or work in ecologically polluted areas or have problems with micronutrient exchange need in-depth screening and more frequent screening for early detection of pre- and breast cancer.

Transgenerational effects of zinc, selenium and chromium supplementation on glucose homeostasis in female offspring of gestational diabetes rats.

Clinical studies have demonstrated that maternal gestational diabetes mellitus (GDM) increases the offspring's risk of developing glucose intolerance. Our previous study reported that co-supplementation with zinc, selenium, and chromium improved insulin resistance in diet-induced GDM rats. Here, Transgenerational effects of supplementation with zinc (10 mg/kg.bw), selenium (20 µg/kg.bw), and chromium (20 µg/kg.bw) in F1 female offspring of both zinc, selenium and chromium (ZnSeCr)-treated, and untreated GDM rats daily by gavage from weaning to the postpartum were investigated in the present study. Glucose homeostasis in the F1 female offspring of GDM at different stages were evaluated. Maternal GDM did increase the birth mass of newborn F1 female offspring, as well as the serum glucose and insulin levels. Zinc, selenium and chromium supplementation attenuated the GDM-induced mass gain, increased serum glucose and insulin levels in the female neonates. The high fat and sucrose (HFS) diet-fed GDM-F1 offspring developed GDM, with glucose intolerance, hyperglycemia and insulin resistance during pregnancy. Moreover, endoplasmic reticulum (ER) stress-related protein levels were increased and the activation of insulin signaling pathways were reduced in the liver of HFS-fed GDM-F1 offspring. Whereas glucose homeostasis in parallel with insulin sensitivity was normalized in the female offspring of GDM by supplementation both F0 dams and F1 offspring with zinc, selenium and chromium, not in those either F0 or F1 elements supplemented offspring. Therefore, we speculate that zinc, selenium and chromium supplementation may have a potential beneficial transgenerational effect on the glucose homeostasis in the female offspring of GDM.

Blood cobalt ion level in patients with different sizes of cobalt/chrome femoral head with the Accolade TMZF stem.

BACKGROUND: Corrosion of stem-cobalt/chromium (Co/Cr) head interface and subsequent systemic Co ion complication have been a clinical concern after total hip arthroplasty (THA). The aim of this study is to investigate correlation between type of femoral head and blood Co ion level. METHODS: One hundred four patients with THA using accolade TMZF and Co/Cr femoral head (32-mm; 55 cases, 36-mm; 20 cases, dual mobility system (DM) with 22.2 or 28-mm inner head; 29 cases) participated in this study, and blood Co ion concentration test was performed in patients a minimum of four years after THA. RESULTS: DM group was significantly older than 32-mm and 36-mm group (DM: 73.9 ± 4.6, 32-mm: 63.3 ± 8.5, 36-mm: 66.8 ± 10.5). The median (interquartile range) blood Co concentration of each group was 32-mm group 0.26 µg/L (0.69), 36-mm group; 0.21 µg/L (0.30); and DM group 0.21 µg/L (0.13). There was a significant difference of Co concentration between DM and 32-mm group (p = 0.023). Abnormal values of the blood Co concentration (> 1 µg/L) were observed in the 32-mm group; 12 cases (21.8%), 36-mm group; 2 cases (10.0%); and DM group; 0 case (0%) (p = 0.018). CONCLUSIONS: Co blood concentration differed among the different sizes of Co/Cr femoral head. THA using DM is a safe option with low risk of complication from cobalt ion if it is used for elderly patients.

Parental occupational exposure to combustion products, metals, silica and asbestos and risk of childhood leukaemia: Findings from the Childhood Cancer and Leukaemia International Consortium (CLIC).

Parental occupational exposures around conception (father) or during pregnancy (mother) have been hypothesized as potential predisposing factors for childhood leukaemia. We investigated parental exposure to several known occupational carcinogens and childhood leukaemia risk. We conducted a pooled analysis using case-control data from four European countries (3362 childhood leukemia cases and 6268 controls). Parental occupational exposures to polycyclic aromatic hydrocarbons (PAH), diesel engine exhaust (DEE), chromium, nickel, crystalline silica, and asbestos were assessed by a general population job-exposure matrix. We estimated odd ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models for all childhood leukaemia combined, by leukaemia type (ALL and AML) and by ALL subtype (B-lineage and T-lineage). We found an association between high paternal occupational exposure to crystalline silica and childhood ALL (OR 2.20, CI 1.60-3.01) with increasing trend from no exposure to high exposure (P = <0.001), and also for AML (OR 2.03, CI 1.04-3.97; P for trend = 0.008). ORs were similar for B- and T-lineage ALL. For ALL, ORs were also slightly elevated with wide confidence intervals for high paternal occupational exposure to chromium (OR 1.23, CI 0.77-1.96), and DEE (OR 1.21, CI 0.82-1.77). No associations were observed for paternal exposures to nickel, PAH and asbestos. For maternal occupational exposure we found several slightly elevated odds ratios but mostly with very wide confidence intervals due to low numbers of exposed mothers. This is a first study suggesting an association between fathers' occupational exposure to crystalline silica and an increased risk of childhood leukaemia in their offspring. As this association was driven by certain occupations (field crop farmers and miners) where other potentially relevant exposures like pesticides and radon may also occur, more research is needed to confirm our findings of an association with crystalline silica, and if so, mechanistic studies to understand the pathways.

Trivalent chromium supplementation ameliorates adjuvant induced rheumatoid arthritis through up-regulation of FOXP3 and decrease in synovial Cathepsin G expression.

BACKGROUND: Rheumatoid arthritis (RA) is a known debilitating autoimmune disease. Immune-suppressants that are used for disease treatment have serious side effects, therefore, trivalent chromium (Cr (III)); which has shown evidence of its influences on some inflammatory pathways and cytokines; was used in this study for the first time to be assessed for its therapeutic effect in RA rat model and was compared to prednisolone in a trial to find a treatment with lesser side effects. METHODS: Adult male albino rats were randomly divided into four groups: normal, untreated RA, prednisolone treated RA (1.25 mg/kg/day) and Cr (III) treated RA groups (80 µg/kg/day), induction of RA was done by subcutaneous complete Freund adjuvant injection. Study duration was 4 weeks throughout which arthritis scoring and weight measurement were pursued. Histopathological examination and immunohistochemical FOXP3 assessment were done for joint biopsies. Serum inflammatory markers (interleukin 17, interleukin 10, CRP) and synovial erosive arthritis marker (Cathepsin G) were measured. HDL and non-HDL cholesterol were estimated as well. RESULTS: Cr (III) treatment showed marked clinical and histopathological improvement, also astonishing anti-inflammatory effects (increase in FOXP3 expression and interleukin 10, with decrease in interleukin 17, CRP and synovial Cathepsin G) to the extent that Cr (III) effects on inflammation abolishment were comparable to that of prednisolone and even better at some aspects. Moreover, Cr (III) was protective from side effects, i.e., weight gain and dyslipidemia that were seen with prednisolone treatment. CONCLUSIONS: Cr (III) is promising in treating RA and it lacks some side effects of accustomed immune-modulatory agents including prednisolone. Further experimental studies and clinical trials should be held to see the efficacy of Cr (III) in different doses and to assess its long term side effects when used for rheumatoid arthritis and other autoimmune diseases treatment.

Contact sensitization to iron: A potentially underestimated metal allergen and elicitor of complications in patients with metal implants.

BACKGROUND: Little is known about sensitization to iron (Fe) in private, occupational, and medical settings, particulary implantology. OBJECTIVES: To investigate sensitization to metals, particularly to Fe, both in pre-implant individuals with presumed metal allergy and in patients with suspected metal implant allergy. To further characterize Fe-sensitized individuals. METHODS: Analysis of patch test reactions to an Fe (II) sulfate-containing metal series in 183 consecutive patients (41 pre-implant, 142 metal implant bearers). Test readings were on day (D)2, D3, and D6. Evaluation of questionnaire-aided history of metal reactivity patterns and demographics of Fe reactors. RESULTS: Metal reactivity in pre-implant/implant/total group was: to nickel 39%/30%/32%; to cobalt 17%/15%/15%; and to chromium 7%/13%/11%. Co-sensitizations cobalt/nickel (19/58) and cobalt/chromium (11/21) were significant at P < .001; co-sensitizations Fe/nickel (4/10) and chromium/knee arthroplasty (11/73) at P = .03. Ten of 183 (5.5%) reacted to Fe (2 of 41 pre-implant patients, 8 of 142 implant bearers), with 10 reacting only on D6. Fe reactivity was highest in complicated knee arthroplasty (7/73). Further peculiarities of Fe reactors included frequent isolated Fe reactivity (6/10), occupational metal exposure (7/10), previous (par)enteral Fe substitution (6/10). CONCLUSIONS: The 5.5% prevalence of Fe reactions suggests a potentially underestimated role of this metal allergen in general and in implant bearers. The latter also shows a distinct metal sensitization pattern.

Assessment of intestinal injury of hexavalent chromium using a modified in vitro gastrointestinal digestion model.

Intestinal injury assessment of hexavalent chromium (Cr-VI) in humans is crucial for quantifying assessment of adverse health risk posed by the intake of Cr (VI)-contaminated water. To overcome the deficiency in simulating human gastric reduction and intestinal absorption, we modified the constituents of simulated gastric fluid in in vitro digestion method by adding reductants glutathione (18 µM) and ascorbic acid (180 µM), which incorporated with human intestinal epithelial model to construct an in vitro gastrointestinal digestion (IVGD) model for intestinal injury assessment. Cr-VI bioaccessibility results from IVGD model showed that weak gastric acidity significantly increased the intestinal accessible Cr-VI dose by 22.41-38.43 folds. The time-course intestinal absorption indicated prolongation of intestinal exposure destroyed the intestinal epithelium, and 24 h after Cr-VI treatment was a good time point to perform intestinal absorption and toxicity assessment. A series of cell-based bioassays provided initial warning of adverse effect, suggesting that epithelial integrity exhibited greatest sensitivity to Cr-VI exposure and might be used as a sensitive marker for the toxicity assessment of oral exposure to Cr-VI. Notably, this study provides a feasible strategy for delineation of Cr-VI biotransformation and intestinal injury following ingestion exposure, which contributes to address the toxicity data gap of low-dose exposure in humans and puts forward a reference for intestinal toxicity assessment of other chemicals.

Occupational exposure to hexavalent chromium. Part II. Hazard assessment of carcinogenic effects.

Hexavalent chromium (Cr(VI)) compounds have been studied extensively and several agencies have described their toxicological profile. In the past, personnel of the Dutch Ministry of Defence may have been exposed to Cr(VI) during maintenance activities on NATO equipment. To investigate if this exposure may have caused irreversible adverse health effects, the Dutch National Institute for Public Health and the Environment (RIVM) summarized all available knowledge from previous evaluations. This information was complemented with a scoping review to retrieve new scientific literature. All scientific evidence was evaluated in workshops with external experts to come to an overview of irreversible adverse health effects that could be caused by occupational exposure to Cr(VI) compounds. This review provides the hazard assessment for occupational exposure to Cr(VI) and carcinogenic effects by integrating and weighting evidence provided by international agencies complemented with newly published studies. It was concluded that occupational exposure to Cr(VI) can cause lung cancer, nose and nasal sinus cancer in humans. Cr(VI) is suspected to cause stomach cancer and laryngeal cancer in humans. It is currently insufficiently clear if Cr(VI) can cause cancer of the small intestine, oral cavity, pancreas, prostate or bladder in humans.

Occupational exposure to hexavalent chromium. Part I. Hazard assessment of non-cancer health effects.

Hexavalent chromium (Cr(VI)) compounds have been studied extensively and several agencies have described their toxicological profile. In the past, personnel of the Dutch Ministry of Defence may have been exposed to Cr(VI) during maintenance activities. To investigate if this exposure may have caused irreversible adverse health effects, the Dutch National Institute for Public Health and the Environment (RIVM) summarized all available knowledge from previous evaluations. This information was complemented with a scoping review to retrieve new scientific literature. All scientific evidence was evaluated in workshops with external experts to come to an overview of irreversible adverse health effects that could be caused by occupational exposure to Cr(VI) compounds. This review focuses on non-cancer health effects. It was concluded that occupational exposure to Cr(VI) can cause perforation of the nasal septum by chromium ulcers, chronic lung diseases, including asthma, rhinitis, pulmonary fibrosis and COPD, skin ulcers and allergic contact dermatitis in humans. It is currently insufficiently clear if Cr(VI) can cause irreversible diseases due to disturbances of the immune system (other than allergic contact eczema, allergic asthma and rhinitis and chronic lung diseases) or adverse effects on fertility or prenatal development in humans.

Hexavalent chromium disrupts chromatin architecture.

Accessibility of DNA elements and the orchestration of spatiotemporal chromatin-chromatin interactions are critical mechanisms in the regulation of gene transcription. Thus, in an ever-changing milieu, cells mount an adaptive response to environmental stimuli by modulating gene expression that is orchestrated by coordinated changes in chromatin architecture. Correspondingly, agents that alter chromatin structure directly impact transcriptional programs in cells. Heavy metals, including hexavalent chromium (Cr(VI)), are of special interest because of their ability to interact directly with cellular protein, DNA and other macromolecules, resulting in general damage or altered function. In this review we highlight the chromium-mediated mechanisms that promote disruption of chromatin architecture and how these processes are integral to its carcinogenic properties. Emerging evidence shows that Cr(VI) targets nucleosomal architecture in euchromatin, particularly in genomic locations flanking binding sites of the essential transcription factors CTCF and AP1. Ultimately, these changes contribute to an altered chromatin state in critical gene regulatory regions, which disrupts gene transcription in functionally relevant biological processes.

Comparison of the long-term cause of failure and survivorship of four hundred and twenty seven metal-on-metal hip arthroplasties: resurfacing versus large head total hip arthroplasty.

INTRODUCTION: Comparison of mid- to long-term cause of failure and survivorship of metal-on-metal (MoM) resurfacing hip arthroplasty (RHA) and large head total hip arthroplasty (THA) remains sparse. This study aimed to identify and compare the cause of failure and survivorship of MoM RHA and THA at a minimum ten year follow-up. METHODS: Four hundred twenty-seven MoM hip arthroplasties (286 THA and 141 RHA) were retrospectively analyzed at a mean follow-up of 13 ± three years. Causes of failure were reported as MoM specific (i.e., adverse reaction to metal debris (ARMD) and painful hip with ion elevation) or MoM non-specific (i.e., fracture, infection, and dislocation). Chromium (Cr) and cobalt (Co) ion levels and Co/Cr ratio were compared. Survivorship was compared according to the cause of failure with revision as the endpoint. RESULTS: The rate of ARMD was significantly higher in THA (OR = 2.9 [95%-CI: 1-7]; p = 0.02). No significant difference was detected in failure rate due to other causes between the two groups (p = 0.2-0.9). Ion levels and Co/Cr ratio were both significantly higher in THA (p < 0.01). Survivorship was significantly lower in THA compared to RHA at ten years [89% (95%-CI: 85%-91%) vs 96% (95%-CI: 91%-98%); p = 0.01] and 15 years [73% (95%-CI: 67%-78%) vs 83% (95%-CI: 73%-90%); p = 0.01]. CONCLUSION: RHA survivorship was significantly higher at any time point. Failure rate due to ARMD was significantly higher in THA while no significant difference in other causes of failure was observed between the two groups. This result emphasizes the role of fretting corrosion at the head-neck junction (i.e., trunnionosis) with significantly higher ion levels and Co/Cr ratio dissociation in THA.