Cobalt-Chromium Toxicity Resource Center

Metal Toxicity Expert


Metal Toxicology Expert Part 1: Background and Expertise of Toxicology

Metal Toxicity Expert Dr. Michael McCabe started his education in Toxicology as an undergraduate Biology major. After graduating, he furthered his education at Albany Medical College in the Microbiology and Immunology Department where he received his doctorate. At this time, his thesis highlighted the effects of heavy metals, such as lead and mercury, on the immune system and the immune response. In graduate school he studied immunology and immune mechanisms. This led him to the field of Immunotoxicology, using metals as tools to initiate an immune response. He studied this from the perspective of the immune system as well as the relevance of toxicology issues. Following graduate school, he went to Sweden where he studied at the Karolinska Institute, a medical university in Solana within Stockholm. At the Karolinska Institute, he studied cell death including apoptotic and necrotic signaling pathways. After completing his post doctoral period in two years, he came back to the United States to begin his career in Academia. First, he began at Wayne State University in Detroit, Michigan, and then the University of Rochester’s Department of Environmental Medicine. The basis of his research primarily focuses on the mechanisms of metal induced changes in the immune system in relation to immune mediated diseases.

Metal Toxicology Expert Part 2: What are the effects when metal debris is released from a prosthetic hip?

The effects of metal debris released from prosthetic hips include component loosening, component malalignment, infection, bone fractures, dislocation, metal sensitivity, and significant pain. Other issues include soft tissue destruction which may compromise revisions and revision surgery. In mal alignment, particular surfaces are grinding improperly which causes metal fragments and ions to release and enter into surrounding tissues and joint spaces. This wear debris may also contribute to irritation and inflammation in adjacent tissues and systemically throughout the body.

Metal Toxicology Expert Part 3: Effects of elevated cobalt and chromium

There are relevant, and reliable, studies that indicate the normal blood levels for both cobalt and chromium are below a microgram per liter of blood. This is below a part per billion. Some studies indicate a normal range of 0.1 to 0.3 micrograms per liter. Normal is defined as the level in the human population that is not exposed to cobalt or chromium through occupational industrial sources. Similarly, the normal population with respect to blood cobalt and chromium levels does not include individuals who have a metal alloy containing prosthesis. The definition of normal blood levels is complicated by the fact that the normal concentrations of cobalt and chromium in blood are at or near the limit of detection for these two ions. This is further complicated by a lack of standardization and specimen collection in laboratory and analytical procedures. Practically speaking, and to provide some semblance of scientific consensus, normal levels of cobalt and chromium in blood are often reported by testing laboratories to be in the 0.1 to 2 microgram per liter range. This is considered an order of magnitude range between the 0.1 to 2 microgram per liter as a working definition of normal cobalt and chromium blood levels. The terms “microgram per liter” and “parts per billion” are equivalent, and may be used interchangeably. For instance, 1 microgram per liter is the same as one part per billion, or 5 micrograms per liter is equivalent to 5 parts per billion.

Metal Toxicology Expert Part 4: Testing blood for cobalt and chromium

One should be aware of the issues stemming from collected blood samples for trace metal analysis as well as analyzing those samples and specimens for trace metal analysis back in the laboratory. It is called trace metal analysis, and the emphasis is on the word trace. This means that they are at low levels often times at the limit of detection in the normal population. Therefore, the collection of that specimen is highly susceptible to environmental contamination. There are appropriate procedures that need to be followed in order to ensure that in the process of collecting the sample, whether via blood, serum or urine sample, that the sample itself is not contaminated with trace elements in the environment, or trace elements that are often times present in the blood collection tubes that are used. The solution is to employ a standardized protocol for the individual who is collecting the blood and be aware of what the sample is going to be used for, which is trace metal analysis. Regular blood collecting tubes are grossly contaminated with trace metals including cobalt and chromium. The stoppers on the collecting tubes contain pigments of both cobalt and chromium. There are trace metal free tubes to which the blood sample needs to be collected. There are also steps and procedures which the phlebotomist, person who draws the blood, should follow when collecting a sample of a patient with the intent to analyze levels of cobalt and chromium. The integrity of these procedures needs to be upheld at the lab where the blood is tested. The testing needs to be done in a lab that is certified and has standardized protocols to measure the low levels of these ions. For instance, one standard protocol is to draw two tubes of blood of which the first is disregarded. Only the second tube is analyzed because the stainless steel needle that is used to draw blood can have metal contamination. The reasoning is that if you draw the first vial of blood you are flushing out the contaminants of the needle and the second vial won’t be contaminated by what is carried over by the needle. If you are getting your blood drawn for metal analysis, I would ask the phlebotomist if they are aware of the standardized protocols and standard practice to collect that sample in order to prevent environmental contaminants.

Metal Metal Toxicology Expert Part 5: What studies should have been conducted regarding cobalt exposure?

Cobalt exposure can occur from various settings such as work, industrial or manufacturing environments. However, it is important to differentiate the source of exposure from cobalt. Inhalation differs from an internal source of exposure from metal prosthesis, such as an implanted Metal on metal (MOM) hip prosthesis. Workers who come into contact with cobalt-containing powders via the inhalation develop respiratory problems such as occupational asthma or pulmonary fibrosis. These issues stem from inhaling increased levels of cobalt that are a hazard of their work environment. Increased levels of cobalt then trigger an immune response via an inflammatory process which then results in the respiratory issues. In addition to respiratory ailments, exposure to high levels of cobalt can cause dermatologic reactions including, but not limited to, contact dermatitis and rashes of the skin. The issues from contact with cobalt minerals provide a useful insight into the immunological response within the body from cobalt containing MOM prostheses. These issues also created guidelines stating what environmental levels of cobalt are safe in comparison to the biologically-occurring, blood and urinary levels, of cobalt. The allowable biological levels of cobalt within the blood and urine are defined as five parts per billion, or five micrograms per liter. This demonstrates the normal levels of cobalt in the body, and informs us that per occupational regulatory standards anything above five parts per billion is considered abnormal. However, patients with cobalt containing MOM prostheses are not subject to these standards. Patients with MOM prostheses do not fall under any permissible regulations thus far. There are currently no guidelines indicating safe cobalt ion levels for patients with these prostheses. This places treating surgeons in a precarious position because there are no defined standards for evaluating metal ion levels in patients with poorly performed MOM hip replacements. In regard to hip revisions, long term health consequences are determined on an individual case by case basis. The extent of implant wear is established using systemic metal ion monitoring with blood and urine tests.

Metal Toxicology Expert Part 6: What are the effects of elevated blood cobalt levels?

Occupational exposure of elevated cobalt levels results in respiratory problems like occupational asthma or pulmonary fibrosis. Compromised lung function is a consequence of increased cobalt inhalation. This type of exposure informs us of the consequences and biological response of various cobalt and chromium exposures. Stimulation of both an inflammatory and immune response occurs with increased levels cobalt and chromium regardless of the method of exposure. Contact dermatitis, a skin rash, is an example of an inflammatory response and immunological stimuli from dermal exposure. Many lung problems occur from cobalt inhalation which stimulates immunological mechanisms in the lung. Similarly, there is an analogous immune reaction from exposure to cobalt and chromium from Metal on metal (MOM) hip prostheses within the body. The manifestation of cobalt toxicity, cobaltism, can result in cardiomyopathy. Cardiomyopathy is a heart defect caused by swelling of the heart tissues. Studies done in Canada indicated that people who consumed cobalt-containing beer (cobalt is used as an anti-foaming agent), developed heart problems. Therefore, these patients exposed to high levels of cobalt were diagnosed with cobalt induced cardiomyopathy. Cardiomyopathy is also an effect of occupational exposure to cobalt dust and even joint implants, such as MOM prostheses. In addition to cardiomyopathy, cobalt induced hypothyroidism is another potential health consequence. Hypothyroidism is a decrease in thyroid gland and hormonal function. This can cause weight gain and loss of muscle tone. The risk of hypothyroidism on those with bio-mechanical issues of their MOM prostheses is significant since weight gain and loss of muscle tone increases the interference of normal, daily activities. Cobalt exposure from MOM prostheses causes a systemic response in the blood and organs, as well as the possibility for tissue destruction.

Metal Toxicology Expert Part 7: What are the potential long term health issues of having high levels of cobalt and chromium?

The symptoms and health outcomes you, and your general practitioner, should be aware of resulting from cobaltism include cardiomyopathy, a swelling of the heart, hypothyroidism, and neuro-toxic consequences on Central Nervous System function.

Metal Toxicology Expert Part 8: Effects of high levels of Chromium in the blood

Chromium ions in the valence state are the key with respect to the types of health consequences that we expect. The type of chromium, as well as exposure, is also important in order to differentiate among the various health consequences. The difference between exposure to chromium 3 (trivalent chromium) and chromium 6 (hexavalent chromium) is large. Chromium 6 is a well known carcinogen which can lead to cancer. There are issues of exposure to hexavalent chromium, and how this exposure informs us to health consequences in terms of known mutagenic effects. In joint divisions and wear debris in metal on metal joints, the form of chromium and metal ions released is chromium 3. Chromium 6 does not apply to metal on metal hip implants and wear debris. However, chromium 3 can produce carcinogenic mechanisms by stimulating inflammatory mechanisms within the immune system. There are publications and scientific studies that demonstrate that chromium can promote inflammatory process and inflammation cascades. Inflammation is known to be a progression factor in the progression of certain cancers. Inflammation is an immune response and a way to deal with foreign agents. From this perspective, inflammation is beneficial. However, the problem arises when the inflammatory process is unregulated. During that deregulation, the body’s response and initiation of inflammatory processes, then contributes to the development of disease. Chromium 3 can promote inflammatory processes and this mechanism of action could contribute to cancer.

Metal Toxicology Expert Part 9: effects of metal wear debris from metal on metal hip implants

Metal on metal (MOM) wear debris particles can cause soft tissue damage. Specifically, this is damage to the muscle, acetabular capsule, and connective tissues surrounding the hip replacement. Soft tissue damage is caused by tissue necrosis, or tissue death, that occurs as a function of wear debris particles that are deposited in the periarticular region. The formation of pseudo-tumors is also seen with MOM hip replacements. The contribution of pseudo-tumors, in terms of long term health consequences, is currently unknown. The expectation and possibility exists that if you have a poorly functioning implant it will continue to release wear debris particles which could result in increased levels of cobalt and chromium. If you have a MOM device, and it is functioning improperly, you should voice your concerns to your clinician about the possibility of increased levels of cobalt and chromium. Individuals who are not having any pain or evident problems with their hip also need to be evaluated in consultation with their physicians as to what is critically indicated in terms of cobalt-chromium levels. In definition of normal cobalt-chromium levels, there are no standards or authoritative body that demonstrates what is considered a high level of cobalt and its consequences.

Metal Toxicology Expert Part 10: Cobalt blood levels after hip replacement

Cobalt is not an accumulating toxicant, or accumulating metal. For instance, lead is an example of an accumulating metal. Most of the lead we are exposed to is stored in our bones, and as we age is released from our bones. Cobalt, on the other hand, is not a bone seeking element. Most of the cobalt in our bodies, approximately 50%, is stored in the liver as part of Vitamin B12. Blood levels of Cobalt are an indication of ongoing, recent exposure. Anyone with an elevated blood cobalt level demonstrates that the cobalt is coming from some source albeit occupational or environmental. If these sources are not indicated in individuals, then the source is coming from wear debris in their hip implant. Therefore, the elevation of cobalt blood levels illustrates ongoing, continued exposure. The body handles this level of Cobalt in the blood by excreting it via the kidneys and so it appears in the urine. After revision of the hip implant, the expectation is that blood and urine cobalt levels will decrease over time. The life stage of a red blood cell is approximately 3 months and most of the cobalt is associated with red blood cells. You would expect that as red blood cells turnover, post-revision, that those cobalt levels are going to decrease. Every toxicology issue deals with exposure and effect: even if cobalt levels decrease post-revision, there are still long term health consequences. In this situation, an effect from the cobalt exposure is a stimulated immune response. Even in the absence of continued exposure to these metal ions, the possibility for long term immunological reactions and inflammatory processes still exists.

Metal Toxicology Expert Part 11: Should all metal on metal hip implants be revised?

Occupational studies and literature show that a certain level of exposure in the environment over a period of time will produce cobalt levels in blood and urine. These occupational studies indicate that when a patient is exposed to 5 parts per billion of cobalt they should be removed from that environment. However, it is more difficult to advise a patient on revision surgery if they are not having any problems with their metal on metal hips. Their advice should come from their treating surgeon and treating physicians who are in a better position to make an informed decision on this matter. There are potential long term consequences as a result of this exposure and potential risks involved with another surgery. There are additional risks of initiating long term biomechanical problems because the concern may or may not be relevant.

Metal Toxicology Expert Part 12: Do high cobalt and chromium levels cause cancer?

There are in-vitro and in-vivo studies indicating mutagenesis in patients suffering from corrosive wear of Metal on metal (MOM) hip prostheses. Mutagenesis is mutation of the structural integrity of DNA, and chromosomal abnormalities, as a result of exposure to mutagens such as cobalt and chromium. This does not mean that MOM prostheses necessarily cause cancer but indicates that a mutagenesis response is a mechanism which possibly contributes to cancer. Currently, there are no studies stating that individuals with poorly functioning implants will get cancer. The research connecting poorly implanted prostheses leading to cancer is still unknown and unavailable. However, there is some research illustrating that corrosive wear debris from improperly implanted devices may contribute to cardiomyopathy, hypothyroidism and even neuro-toxic outcomes. It is essential to communicate and follow-up with your health care provider or treating surgeons who can test and assess your health care secondary to implantation of these devices.

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