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Increased accumulation of heavy metal ions such as Cr6+ and Co2+ due to release from prostheses and metallic implants has been reported. These metal ions have been shown to affect both resting and activated lymphocytes. Natural remedies towards mitigating the cytotoxic effects of metal ions are clearly warranted. Polyphenolic compounds which are part of hydrolysable tannins from natural plant sources are considered effective in cheating heavy metal ions in a biological system. We have isolated and characterized a polyphenolic compound (ellagic acid) from Terminalia arjuna fruits that has been tested for its ability to attenuate the metal ion toxicity in primary human lymphocytes in culture. Cr6+ and Co2+ (100 μM) decreased lymphocyte viability and proliferation and increased apoptosis of resting as well as CD3 and/or CD28-stimulated lymphocytes. Metal ions markedly diminished the cytokine (interleukin-2 and interferon-γ) secretion from activated lymphocytes. Pretreatment with ellagic acid at 25, 50, and 100 μM concentrations effectively improved viability and proliferative responses of both resting and activated lymphocytes, while attenuating the apoptotic index. Ellagic acid also tended to normalize the cytokine secretion from the activated lymphocytes even in the presence of metal ions, suggesting broad effects on the adaptive immune system.

Cobalt (Co) although, an essential element playing a key role in several physiological and biological processes, can transform into a potential toxin when present in higher amounts or in certain chemical forms. The increasing usage of transition metals in industries, agriculture, medicines and technology has led to an alarming rise in cobalt poisoning cases. Exposure to cobalt can cause several health hazards including neurodegenerative disorders like Alzheimer’s disease, Parkinson’s disease, etc. Cobalt may interact with several proteins in the cellular milieu, generating reactive oxygen species (ROS) and thereby triggering apoptosis of the neural cells via DNA damage. The most common method of removal of such metals from the body is by the use of metal chelators. In this study, we report a facile strategy for the clearance of Co (II) from the physiological milieu using citrate functionalized Mn3O4 NPs (C-Mn3O4 NPs). The chelation ability of C-Mn3O4 NPs has been evaluated using steady state and pico-second resolved optical spectroscopy. Our studies reveal that C-Mn3O4 NPs form a stable complex with cobalt ions, thereby reducing the ability of Co2+ to produce reactive oxygen species (ROS) via Fenton like reaction and hence function as a novel nanotherapeutic for the detoxification of cobalt in the human system.

Post-arthroplasty metallosis, which refers to metallic corrosion and deposition of metallic debris in the periprosthetic soft tissues of the body, is an uncommon complication. Systemic cobalt toxicity post-arthroplasty is extremely rare. The few known fatal cases of cobalt toxicity appear to be a result of replacing shattered ceramic heads with metal-on-metal or metal-on-polyethylene implants. Friction between residual shards of ceramic and cobalt-chromium implants allows release of cobalt into the synovial fluid and bloodstream, resulting in elevated whole blood cobalt levels and potential toxicity.This is a single patient chart review of a 60-year-old woman with prior ceramic-on-ceramic right total hip arthroplasty complicated by fractured ceramic components and metallosis of the joint. She underwent synovectomy and revision to a metal-on-polyethylene articulation. Ten months post-revision, she presented to the emergency department (ED) with right hip pain, dyspnea, worsening hearing loss, metallic dysgeusia, and weight loss. Chest CTA revealed bilateral pulmonary emboli (PE), and echocardiogram revealed new cardiomyopathy with global left ventricular hypokinesis with an ejection fraction (EF) of 35-40% inconsistent with heart strain from PE. Whole blood cobalt level obtained two days into her admission was 424.3 mcg/L and 24-h urine cobalt level was 4830.5 mcg/L. Although the patient initially clinically improved with regard to her PE and was discharged to home on hospital day 5, she returned 10 days later with a right hip dislocation and underwent closed reduction of the hip. The patient subsequently decompensated, developing cardiogenic shock, and respiratory failure. She went into pulseless electrical activity (PEA) and expired. Autopsy revealed an extensive metallic effusion surrounding the right hip prosthesis that tested positive for cobalt (41,000 mcg/L). There was also cobalt in the heart muscle tissue (2.5 mcg/g). A whole blood cobalt level obtained two days before she expired was 641.6 mcg/L.This is a case of fatal cobalt-induced cardiomyopathy in a patient whose ceramic components of a total hip arthroplasty fractured causing metallosis with worsening cobalt toxicity. We recommend that when a fractured device is revised with a prosthesis with cobalt-chromium components, whole blood and urine cobalt measurements should be obtained and periodically monitored to evaluate for rising concentrations. Providers should be aware of clinical signs and symptoms of cobalt toxicity in patients who have prostheses with cobalt-chromium components. If suspected, toxicology and orthopedics should be involved for possible chelation and removal of the prosthesis.

Objectives: Based on limited evidence from case reports and small cohort studies of metal-on-metal (MoM) hip implant patients with presumed systemic cobalt (Co) toxicity, and a few animal studies on Co-induced damage to the otovestibular system, it was hypothesised that Co exhibits an ototoxic potential alongside other systemic manifestations. Preliminary investigations from our research group in MoM patients confirmed this assumption for the auditory system, whereas no signs of Co-induced vestibular impairment were detected, and a clear dose-response relationship between the auditory function and the blood Co levels was lacking. Therefore, the current study aimed to extend and validate these findings in a larger sample of MoM patients and control subjects, to explore the potential clinical value of audiovestibular outcome measures in the risk estimation of systemic Co toxicity in this patient population. Design: Fifty patients (32 to 68 years) with a primary unilateral/bilateral MoM hip implant were matched for age, gender, and noise exposure to 50 nonimplanted control subjects. Both groups underwent the same protocol, consisting of an objective auditory [i.e., conventional and high-frequency audiometry, transient-evoked and distortion (TEOAEs and DPOAEs), auditory brainstem responses] and vestibular (i.e., cervical and ocular vestibular evoked myogenic potentials, horizontal and vertical video head impulse tests) test battery, a questionnaire inquiring auditory, balance, and general neurological symptoms, and a blood sample collection to determine the plasma Co concentration. Results: The auditory test battery presented consistently higher audiometric thresholds in the MoM patient group, with group differences ranging from 2.1 to 5.7 dB in the lower frequencies (0.25 to 6.0 kHz) and from 4.6 to 9.3 dB in the high frequencies (8.0 to 14.0 kHz). Group differences at high frequencies were statistically significant (p 0.01). Six patients had elevated Co levels according to our local institutional threshold (>4 or 5 mu g/l for unilateral or bilateral MoM hip implants, resp.), but their audiovestibular outcome measures did not differ significantly from those of the other patients. Conclusions: Corresponding to our preliminary investigations, the results indicate possibly Co-induced (predominantly high-frequency) auditory impairment, probably triggered by toxic damage to the cochlear structures. However, the low mean difference values, the lack of group differences for the patient-reported outcome measures, and the lack of any relationship with the blood Co levels strongly reduce the clinical relevance of these findings. Therefore, the risk of Co-induced ototoxic impairment is considered to be clinically negligible for the majority of MoM hip implant patients, and the use of auditory tests in the risk estimation of systemic Co toxicity should be decided on a case-by-case basis.

Case: We present a case of systemic cobalt toxicity secondary to third-body wear of a cobalt-chromium (CoCr) femoral head following revision of a fractured ceramic bearing. Removal of the CoCr head was followed by resolution of much of the systemic symptoms. Conclusion: This case supports previous reports of cobalt toxicity secondary to catastrophic third-body wear of a CoCr femoral head following a fractured ceramic bearing. It also demonstrates the potential reversibility of many systemic sequelae associated with cobalt toxicity. To our knowledge, this case represents the highest documented blood cobalt level (45,840 nmol/L).

The purpose of this study was to investigate the sublethal Co toxicity on rainbow trout (Oncorhynchus mykiss). Trout were exposed to Co and selected parameters were evaluated at intervals of 1, 15 and 30 days. Fish exposed to higher levels of Co grew slower than fish exposed to lower levels of Co. Weight gain, specific growth rate (SGR) decreased linearly with the increase of cobalt in the water. The body condition factor (CF) of fish reared in water with low cobalt concentration decreased substantially but this decrease was not significant for fish exposed to higher cobalt concentration. The values of the feed conversion ratio (FCR) increased in fish exposed to higher levels of Co. Co significantly changed the activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and decreased at day 30, and in both cases this decrease was more remarkable at day 15 so that the level of AST and ALT reached the control value at day 30. The alkaline phosphatase (ALP) level also showed a remarkable 15-day decline. There was a significant increase in glucose (G) concentration in both Co-exposed groups on day 15. However, serum cholesterol (Chl) was significantly reduced on day 15 and increased on day 30; there were no significant differences in both exposed Co-groups. The triglyceride (TG) level also decreased substantially. There was no regular pattern of total protein (TP) in the serum, so that no significant differences were found in the level of TP between low and high-exposed fish. In summary, this study suggests that exposure of essential trace elements such as cobalt may change growth and biochemical parameters, and that measurement of these parameters may be used in toxicological studies to determine the general health status of fish.

Cobalt (Co) and its compounds are widely distributed in nature and are part of numerous anthropogenic activities. Although cobalt has a biologically necessary role as metal constituent of vitamin B-12, excessive exposure has been shown to induce various adverse health effects. This review provides an extended overview of the possible Co sources and related intake routes, the detection and quantification methods for Co intake and the interpretation thereof, and the reported health effects. The Co sources were allocated to four exposure settings: occupational, environmental, dietary and medical exposure. Oral intake of Co supplements and internal exposure through metal-on-metal (MoM) hip implants deliver the highest systemic Co concentrations. The systemic health effects are characterized by a complex clinical syndrome, mainly including neurological (e.g. hearing and visual impairment), cardiovascular and endocrine deficits. Recently, a biokinetic model has been proposed to characterize the dose-response relationship and effects of chronic exposure. According to the model, health effects are unlikely to occur at blood Co concentrations under 300 [mu g/1(100 mu g/1 respecting a safety factor of 3) in healthy individuals, hematological and endocrine dysfunctions are the primary health endpoints, and chronic exposure to acceptable doses is not expected to pose considerable health hazards. However, toxic reactions at lower doses have been described in several cases of malfunctioning MoM hip implants, which may be explained by certain underlying pathologies that increase the individual susceptibility for Co-induced systemic toxicity. This may be associated with a decrease in Co bound to serum proteins and an increase in free ionic Co2+. As the latter is believed to be the primary toxic form, monitoring of the free fraction of Co2+ might be advisable for future risk assessment. Furthermore, future research should focus on longitudinal studies in the clinical setting of MoM hip implant patients to further elucidate the dose-response discrepancies.

Cobalt toxicity is a well-documented complication of total hip arthroplasty (THA) when cobalt-chrome implants are utilized. A recent area of attention is “cobaltism, ” which results from cobalt exposure from cobalt-containing orthopedic implants, chemistry kits, weather indicators, antiquated anemia therapies, cement, fly ash, dyes, mineral wool, asbestos, molds for ceramic tiles, mining, porcelain paint, orthopedic implants, and dental hardware. Like other transition metals, cobalt is a multiorgan toxin. Organ systems affected by acute cobalt poisoning include endocrine, gastrointestinal, central and peripheral nervous system, hematologic, cardiovascular, and metabolic. Chronic inhalational exposures affect the pulmonary system and dermatologic system.

This experiment was undertaken to study the toxic effects of cobalt chloride in rats. Sixty-five rats weighing 207 ± 7 g were used. Cobalt chloride was administrated orally in low and high doses for 90 d. The aim of study was to evaluate the effects of cobalt on blood (RBC, WBC, Hb, PLT and HCT) and to investigate the abilities of deferasirox (DFX) and desferrioxamine (DFO) as chelators in removing cobalt from the blood. Cobalt and iron concentrations were determined by flame atomic absorption spectrometer (FAAS). Results show that both of chelators are able to remove cobalt but DFX was more effective, whereas the combined therapy is more efficient.

Cobalt naturally occurs in air, rocks, soils, and water, and it has diverse industrial and biomedical applications. It is an essential trace metal and cofactor for vitamin B12 (cyanocobalamin) but can be toxic after a minimal increase in concentration. Inhalation and dietary ingestion are the main external sources of cobalt exposure; however, internal exposure from cobalt hip or oral implants and the use of nanoparticles are on the rise. Cobalt is absorbed through the gastrointestinal tract and accumulated in the liver, kidney, pancreas, heart, skeleton, and skeletal muscle. The deficiency in humans with balanced diet has never been reported. It is excreted through kidney, and excretion efficiency decreases with time and elevated dose. Chronic increases of cobalt in serum may result in long-term adverse biological effects such as immune modulation, oxidative DNA damage, and maybe carcinogenesis. Serum cobalt concentrations higher than 300 µg/L are associated with neurological, cardiac, hematological, and endocrine toxicity. The higher level of cobalt in the tissue competes with calcium uptake and influences other signaling involving hypoxic response, oxidative stress, and energy metabolism. Possible abuse of cobalt supplements by athletes as an alternative to Epo doping for enhancing aerobic performance is a deep concern. Food and Drug Administration (FDA) has not established any guidance, however, the European Food Safety Authority (EFSA) has suggested a dose of 600 µg/day.

As adverse events related to metal on metal hip arthroplasty have been better understood, there has been increased interest in toxicity related to the high circulating levels of cobalt ions. However, distinguishing true toxicity from benign elevations in cobalt levels can be challenging. The purpose of this review is to examine the use of cobalt alloys in total hip arthroplasty, to review the methods of measuring circulating cobalt levels, to define a level of cobalt which is considered pathological and to review the pathophysiology, risk factors and treatment of cobalt toxicity. To the best of our knowledge, there are 18 published cases where cobalt metal ion toxicity has been attributed to the use of cobalt-chromium alloys in hip arthroplasty. Of these cases, the great majority reported systemic toxic reactions at serum cobalt levels more than 100 μg/L. This review highlights some of the clinical features of cobalt toxicity, with the goal that early awareness may decrease the risk factors for the development of cobalt toxicity and/or reduce its severity. Take home message: Severe adverse events can arise from the release of cobalt from metal-on-metal arthroplasties, and as such, orthopaedic surgeons should not only be aware of the presenting problems, but also have the knowledge to treat appropriately. Cite this article: Bone Joint J 2016;98-B:14–20.

Recently, the use of metal-on-metal articulations in total hip arthroplasty (THA) has led to an increase in adverse events owing to local soft-tissue reactions from metal ions and wear debris. While the majority of these implants perform well, it has been increasingly recognised that a small proportion of patients may develop complications secondary to systemic cobalt toxicity when these implants fail. However, distinguishing true toxicity from benign elevations in cobalt ion levels can be challenging.The purpose of this two part series is to review the use of cobalt alloys in THA and to highlight the following related topics of interest: mechanisms of cobalt ion release and their measurement, definitions of pathological cobalt ion levels, and the pathophysiology, risk factors and treatment of cobalt toxicity. Historically, these metal-on-metal arthroplasties are composed of a chromium-cobalt articulation.The release of cobalt is due to the mechanical and oxidative stresses placed on the prosthetic joint. It exerts its pathological effects through direct cellular toxicity.This manuscript will highlight the pathophysiology of cobalt toxicity in patients with metal-on-metal hip arthroplasties.Take home message: Patients with new or evolving hip symptoms with a prior history of THA warrant orthopaedic surgical evaluation. Increased awareness of the range of systemic symptoms associated with cobalt toxicity, coupled with prompt orthopaedic intervention, may forestall the development of further complications.Cite this article: Bone Joint J 2016;98-B:6–13.

Introduction Metal toxicity from metal-on-metal hip replacements is now well documented and several large series have reported local reactions. Although less common, there are reports of similar reactions from failed ceramic liners. Systemic effects documented in literature have been grouped into cardiac, neuro-ocular and thyroid signs. Methods and results We report a case of a patient who had revision for fractured ceramic liner to metal on polyethylene. Third body effect of the ceramic particles led to wear through of the poly liner and the head directly articulating with metal shell. He developed cardiac and neurological features of cobalt toxicity in addition to extensive soft tissue destruction. Revision of the bearing surfaces and synovectomy led to clinical improvement and fall in metal ion levels. Conclusions We recommend 2-stage revision in such situations and close monitoring of all these patients.

Symptomatic cobalt toxicity from a failed total hip replacement is a rare, but devastating complication. Potential clinical findings include cardiomyopathy, hypothyroidism, skin rash, visual and hearing impairment, polycythaemia, weakness, fatigue, cognitive impairment, and neuropathy. The case is presented of a 74 year-old man in whom, after a ceramic–ceramic replacement and two episodes of prosthetic dislocation, it was decided to replace it with a polyethylene–metal total hip arthroplasty (THA). At 6 months after the revision he developed symptoms of cobalt toxicity, confirmed by analytical determination (serum cobalt level = 651.2 μg/L). After removal of the prosthesis, the levels of chromium and cobalt in blood and urine returned to normal, with the patient currently being asymptomatic. It is recommended to use a new ceramic on ceramic bearing at revision, in order to minimise the risk of wear-related cobalt toxicity following breakage of ceramic components.

Background Cobalt is an important metal cofactor of many living cells. However, excessive cobalt is toxic and can cause cell death and even several diseases in humans. Saccharomyces cerevisiae is a useful tool for studying metal homeostasis and many of the genes and pathways are highly conserved in higher eukaryotes including humans. Methods The intracellular cobalt and reactive oxygen species (ROS) levels were measured by an atomic absorption spectrometer and DHE staining method, respectively. The expression of genes involved in scavenging oxidative stress was tested by qPCR method, while the expression of UPRE-lacZ report gene was analyzed via β-galactosidase activity assay. Results Using a genome-scale genetic screen, 153 cobalt-sensitive and 37 cobalt-tolerant gene deletion mutants were identified from Saccharomyces cerevisiae. We showed that 101 of the cobalt-sensitive mutants accumulated higher intracellular cobalt compared to wild-type. The intracellular ROS levels in 112 of the mutants were induced by cobalt, which might be caused by the decreased expression of genes involved in scavenging oxidative stress in response to cobalt. Moreover, more than one-third of the cobalt-sensitive mutants were also sensitive to tunicamycin, and cobalt stress might induce the unfolded protein response (UPR) through serine/threonine kinase and endoribonuclease Ire1. Conclusions This study reinforced the fact that cobalt toxicity might be due to the high intracellular cobalt and ROS levels, and the endoplasmic reticulum stress responses induced by cobalt. General significance Elucidating the toxicity mechanisms of cobalt stress response will help reveal new routes for the treatment of the diseases induced by cobalt.

BACKGROUND Prosthetic hip–associated cobalt toxicity (PHACT) is an uncommon, but potentially devastating, complication for patients with metal-on-metal hip implants (MoMs). Clinical management of PHACT is poorly defined, with primary intervention being MoM explant followed by chelation therapy. Therapeutic plasma exchange (TPE) in cobalt toxicity has not been previously described. Given that cobalt is predominantly albumin bound, it should theoretically be removed by TPE. Here we report a case of PHACT and our experience using TPE to lower plasma cobalt levels. CASE REPORT A 61-year-old woman developed deafness, blindness, ambulatory dysfunction, and endocrinopathies after MoM implant. Cobalt levels on admission were greater than 1500 µg/L. In an attempt to rapidly lower cobalt levels before MoM explant, hemodialysis and TPE were performed. Hemodialysis removed negligible amounts of cobalt. One session of TPE temporarily removed approximately two-thirds of measurable cobalt, but levels rebounded to pre-TPE values after 8 hours. It was only after MoM removal that cobalt levels plateaued below 300 µg/L and clinical symptoms improved. DISCUSSION TPE removed cobalt from a PHACT patient, but a durable decrease in cobalt was only achieved after MoM explant. These findings are comparable to reports where chelation was employed in PHACT patients before MoM explant. The observed rebound phenomenon is likely from rapid equilibration between the immense extravascular tissue source (the MoM) and the intravascular compartment. CONCLUSION TPE may serve as adjunctive therapy for PHACT patients whose cobalt levels remain high after explant, especially in patients with renal failure, in whom chelation is contraindicated.

We report two Australian patients with possible cobalt toxicity related to metal-on-metal total hip replacements. Both patients were treated for osteoarthritis with a DePuy ASR (articular surface replacement) XL Acetabular Hip System prosthesis, which contains cobalt and chromium, and which has recently been recalled from the market.

Cobalt (Co) commonly co-exists with copper (Cu) in natural soils, but the information about their combined effects on plants is poorly available. In this study, we hydroponically investigated the combined effects of Co and Cu on two barley genotypes differing in Co toxicity tolerance to reveal the interaction pattern of these two metals. The results showed that single treatment of Co or Cu at the dose of 100 μM led to a significant decrease of growth and photosynthetic rate, and a significant increase of lipid peroxidation, ROS radicals as well as anti-oxidative enzyme (SOD, CAT and GR) activities and glutathione content, with the extent of effect being less in Yan66 than Ea52. The combined treatment of Co and Cu alleviated the toxicity of both metals in comparison with each metal treatment alone, as reflected by improved growth and photosynthesis, and much slight oxidative stress. The alleviation of metal toxicity upon combined treatment is mainly attributed to a drastic reduction of Co uptake and its translocation from roots to shoots. It may be suggested that interaction of Co and Cu on their uptake and movement in plants is antagonistic.

Svrha istraživanja je bila ispitati subletalnu toksičnost kobalta (Co) kod kalifornijske pastrve (Oncorhynchus mykiss). Ribe su bile izložene Co i odabrani pokazatelji su procijenjeni u intervalima od 1, 15 i 30 dana. Pastrve izložene višim razinama Co imale su sporiji rast od riba izloženih nižim razinama Co. Prirast mase (WG) i specifična stopa rasta (SGR) linearno se smanjivala s porastom kobalta u vodi. Kondicijski faktor riba izloženoj nižoj koncentraciji Co bio je značajno smanjen. Vrijednostikonverzije hrane (FCR) su se povećale kod riba izloženoj višim koncentracijama kobalta. Co je značajno promijenio aktivnost enzima AST i ALT te se smanjio tijekom 30 dana. Razina alkalne fosfataze (ALP) također je pokazala značajan pad ali već tijekom 15 dana. Došlo je i do značajnog povećanja koncentracije glukoze (G) u obje skupine izložene Co 15.ti dan. Međutim, kolesterol u serumu (Chl) je bio značajno smanjen 15.og dana, a povećao se tijekom30 dana istraživanja. Razina triglicerida (TG) također se značajno smanjila a značajne razlike u razini ukupnih proteina (TP) nisu utvrđene između riba izložene niskoj i visokoj koncentraciji Co. Istraživanjem se utvrdilo da izlaganje esencijalnim elemenatima u tragovima kao što je kobalt može utjecati na rast i biokemijske parametre pastrve. Mjerenje navedenih pokazatelja u istraživanju semože upotrijebiti u toksikološkim analizama za utvrđivanje općeg zdravstvenog stanja ribe., The purpose of this study was to investigate the sublethal Co toxicity on rainbow trout (Oncorhynchus mykiss). Trout were exposed to Co and selected parameters were evaluated at intervals of 1, 15 and 30 days. Fish exposed to higher levels of Co grew slower than fish exposed to lower levels of Co. Weight gain, specific growth rate (SGR) decreased linearlywith the increase of cobalt in the water. The body condition factor (CF) of fish reared in water with low cobalt concentration decreased substantially but this decrease was not significant for fish exposed to higher cobaltconcentration. The values of the feed conversion ratio (FCR) increased in fish exposed to higher levels of Co. Co significantly changed the activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and decreased at day 30, and in both cases this decrease was more remarkable at day 15 so that the level of AST and ALT reached the control value at day 30. The alkaline phosphatase (ALP) level also showed a remarkable 15-day decline. There was a significant increase in glucose (G) concentration in both Co-exposed groups on day 15. However, serum cholesterol (Chl) was significantly reduced on day 15 and increased on day 30; there were no significant differences in both exposed Co-groups. The triglyceride (TG) level also decreased substantially. There was no regular pattern of total protein (TP) in the serum, so that no significant differences were found in the level of TP between low and high-exposed fish. In summary, this study suggests that exposure of essential trace elements such as cobalt may change growth and biochemical parameters, and that measurement of these parameters may be used in toxicological studies to determine the general health status of fish.

Cobalt is a widely used in the industrial production of hard metals. Cobalt ingestion has been reported to cause widespread systemic toxicity, but its effects on vision have been sparsely reported. The authors report the case of a patient who ingested cattle magnets, which remained in his stomach for an unknown duration of time. These magnets largely consist of cobalt that gradually leached into his blood stream, resulting in protean systemic manifestations, which included optic atrophy.

Prosthetic hip-associated cobalt toxicity (PHACT) is gaining recognition due to the use of metal-on-metal total hip replacements. Identifying true toxicity from merely elevated cobalt levels can be extremely difficult due to the lack of available data. An extensive review of the medical literature was undertaken to characterize cobalt toxicity from prosthetic hips. As an objective approach to making the diagnosis of PHACT, we suggest the following criteria: (1) elevated serum or whole blood cobalt levels due to a prosthetic hip, (2) at least two test-confirmed findings consistent with cobalt toxicity, and (3) exclusion of other etiologies. Adhering to objective diagnostic data for PHACT is a realistic and prudent method by which to eliminate the subjectivity of vague or difficult to identify complaints. These diagnostic criteria are not meant to evaluate prosthetic hardware failure, but as a means to identify systemic cobalt toxicity. Finally, assessment of cobalt toxicity from prosthetic hips should be done in conjunction with a medical toxicologist.

This case illustrates the potential for systemic cobalt toxicity in non-metal-on-metal bearings and its potentially devastating consequences. We present a 71-year-old male with grinding sensations in his right hip following ceramic-on-ceramic total hip arthroplasty (THA). After diagnosing a fractured ceramic liner, the hip prosthesis was revised into a metal-on-polyethylene bearing. At one year postoperatively, X-rays and MARS-MRI showed a fixed reversed hybrid THA, with periarticular densities, flattening of the femoral head component, and a pattern of periarticular metal wear debris and pseudotumor formation. Before revision could take place, the patient was admitted with the clinical picture of systemic cobalt toxicity, supported by excessively high serum cobalt and chromium levels, and ultimately died. At autopsy dilated cardiomyopathy as cause of death was hypothesized. A third body wear reaction between ceramic remnants and the metal femoral head very likely led to excessive metal wear, which contributed systemic cobalt toxicity leading to neurotoxicity and heart failure. This case emphasizes that fractured ceramic-on-ceramic bearings should be revised to ceramic-on-ceramic or ceramic-on-polyethylene bearings, but not to metal-on-polyethylene bearings. We aim to increase awareness among orthopedic surgeons for clinical clues for systemic cobalt intoxication, even when there is no metal-on-metal bearing surface.

Symptomatic cobalt toxicity from a failed total hip replacement is a rare, but devastating complication. Potential clinical findings include cardiomyopathy, hypothyroidism, skin rash, visual and hearing impairment, polycythaemia, weakness, fatigue, cognitive impairment, and neuropathy. The case is presented of a 74year-old man in whom, after a ceramic-ceramic replacement and two episodes of prosthetic dislocation, it was decided to replace it with a polyethylene-metal total hip arthroplasty (THA). At 6months after the revision he developed symptoms of cobalt toxicity, confirmed by analytical determination (serum cobalt level=651.2mug/L). After removal of the prosthesis, the levels of chromium and cobalt in blood and urine returned to normal, with the patient currently being asymptomatic. It is recommended to use a new ceramic on ceramic bearing at revision, in order to minimise the risk of wear-related cobalt toxicity following breakage of ceramic components.

Heavy metals pollution of soils become the most serious environmental problem resulted in decreased soil fertility and crop yield losses. Cobalt (Co), as a beneficial element, can be a contaminant in soils due to agricultural additives or metal refineries, it causes irreversible damage to several physiological and metabolic constituents at higher concentrations. In this investigation we study the effects of different Co concentrations (0, 50,150, 250, 350 µM as CoCl2) on growth and physiological processes in wheat (Triticum aestivum) plants and discuss the role of spraying with salicylic acid (0.5 mM) for ameliorating effect of cobalt toxicity in wheat leaves. Cobalt causing a significant reduction in fresh and dry biomass, shoot height, water content and total photosynthetic pigments. This was accompanied with accumulation of H2O2 and MDA contents and induction of some antioxidant enzymes activities. There was an increase in SOD activity with increasing Co concentration then decline, a significant increase in APX and PPO activities while CAT was significantly declined. Spraying wheat seedlings with salicylic acid can be recognized to significantly increase in all tested growth parameters and that was attributed to decrease, to some extent, the accumulation of H2O2 and MDA and improve the activity of antioxidant enzymes.

Cobalt metallosis after revision metal-on-polyethylene total hip arthroplasty for catastrophic failure of ceramic components is uncommon but a potentially devastating complication. Common findings associated with heavy metal toxicity include cardiomyopathy, hypothyroidism, skin rashes, visual disturbances, hearing changes, polycythemia, weakness, fatigue, cognitive deterioration, and neuropathy. We report a case of a 57-year-old woman who presented with complaints of progressively worsening hip pain, fatigue, memory loss, lower extremity sensory loss, persistent tachycardia, and ocular changes 5 years after synovectomy and revision of a failed ceramic-on-ceramic total hip arthroplasty to metal-on-polyethylene components. A cobalt level of 788.1 ppb and chromium level of 140 ppb were found on presentation and subsequently decreased to 468.8 ppb and 105.9 ppb, respectively, 2 weeks after revision to a ceramic-on-polyethylene total hip arthroplasty. Improvement of symptoms accompanied this decrease in cobalt and chromium levels. Revision of failed ceramic arthroplasties with later-generation ceramics to avoid this potential complication is recommended.

Cobalt (Co) contamination in soils is becoming a severe issue in environment safety and crop production. Calcium (Ca), as a macro-nutrient element, shows the antagonism with many divalent heavy metals and the capacity of alleviating oxidative stress in plants. In this study, the protective role of Ca in alleviating Co stress was hydroponically investigated using two barley genotypes differing in Co toxicity tolerance. Barley seedlings exposed to 100µM Co showed the significant reduction in growth and photosynthetic rate, and the dramatic increase in the contents of reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH) and oxidized glutathione (GSSG), and the activities of anti-oxidative enzymes, with Ea52 (Co-sensitive) being much more affected than Yan66 (Co-tolerant). Addition of Ca in growth medium alleviated Co toxicity by reducing Co uptake and enhancing the antioxidant capacity. The effect of Ca in alleviating Co toxicity was much greater in Yan66 than in Ea52. The results indicate that the alleviation of Co toxicity in barley plants by Ca is attributed to the reduced Co uptake and enhanced antioxidant capacity.

A 39-year-old female with elevated serum cobalt levels from her bilateral hip prostheses presented with a 3-week history of blurred vision in her left eye. Optical coherence tomography revealed patchy degeneration of the photoreceptor-retinal pigment epithelium (RPE) complex. The lesions were hypofluorescent on indocyanine green angiography. We postulate that this is a case of implant-related chorio-retinal cobalt toxicity.

The influence of cobalt speciation on the toxicity of cobalt to methylotrophic methanogenesis in anaerobic granular sludge was investigated. The cobalt speciation was studied with three different media that contained varying concentrations of complexing ligands [carbonates, phosphates and ethylenediaminetetraacetic acid (EDTA)]. Three fractions (nominal added, dissolved and free) of cobalt were determined in the liquid media and were correlated with data from batch toxicity experiments. The average concentration of cobalt that was required for 50% inhibition of methanogenic activity (IC50) for free Co2+ in the three sets of measurements was 13 micromol/L with a standard deviation of 22% and a similarity of 72% between the data obtained in the three different media for the range of cobalt concentrations investigated. The standard deviation of the IC50 for the other two fractions was much higher, i.e. 85 and 144% for the added cobalt and dissolved cobalt, respectively, and the similarity was almost 0% for both fractions. Complexation (and precipitation) with EDTA, phosphates and carbonates was shown to decrease the toxicity of cobalt on methylotrophic methanogenesis. The free cobalt concentration is proposed to be the key parameter to correlate with cobalt toxicity. Thus, the toxicity of cobalt to granular sludge can be estimated based on the equilibrium-free cobalt concentration.