According to Merriam- Webster, the definition of biocompatibility is: compatibility with living tissue or a living system by not being toxic, injurious, or physiologically reactive and not causing immunological rejection.

Biocompatibility is the degree to which a given substance does not elicit an immune response from a particular individual.

Dental toxicity is the complex condition resulting from both the cumulative effects derived from the placement of biologically incompatible materials in the mouth and their potential to do harm.

Restorative materials replace the function and appearance of a natural tooth. However, no restorative material can fully replace its biological original, especially at a vital or energetic level.

The kinds of materials available for use in dental restorations are incredibly varied. A wide range of compounds are utilized in dentistry such as dental composites, resins, and implants. The successful clinical use of dental materials relies on their physiochemical properties as well as biological and toxicological reliability. Different local and systemic toxicities of dental materials have been reported. Placement of these materials in oral cavity for a long time period might yield unwanted reactions. An extensive variety of materials is used in dentistry including filling materials, restorative materials, intracanal medicines, prosthetic materials, different types of implants, liners, and irrigants. The increasing rate in development of the novel materials with applications in the dental field has led to an increased consciousness of the biological risks and tempting restrictions of these materials. The biocompatibility of a biomaterial used for the replacement or filling of biological tissue such as teeth always had a high concern within the health care disciplines for patients. (SOURCE) 

The metallic materials commonly used in conventional dentistry are mercury dental amalgams, nickel, copper, gold, aluminum, titanium, silver and casting alloys.

The mouth is a hostile environment and when various metals are present, they corrode and the material can then relocate to another area of the body, far from the oral cavity. The problem is that when health starts to decline, the cause may be toxicity caused by dental materials, but often doctors will not explore this possibility.

A comprehensive analysis of published data indicates that heavy metals such as arsenic cadmium, chromium, lead, and mercury, occur naturally. However, anthropogenic activities contribute significantly to environmental contamination. These metals are systemic toxicants known to induce adverse health effects in humans, including cardiovascular diseases, developmental abnormalities, neurologic and neurobehavioral disorders, diabetes, hearing loss, hematologic and immunologic disorders, and various types of cancer. The main pathways of exposure include ingestion, inhalation, and dermal contact. The severity of adverse health effects is related to the type of heavy metal and its chemical form, and is also time- and dose-dependent. Among many other factors, speciation plays a key role in metal toxicokinetics and toxicodynamics, and is highly influenced by factors such as valence state, particle size, solubility, biotransformation, and chemical form. Several studies have shown that toxic metals exposure causes long term health problems in human populations. Although the acute and chronic effects are known for some metals, little is known about the health impact of mixtures of toxic elements. Recent reports have pointed out that these toxic elements may interfere metabolically with nutritionally essential metals such as iron, calcium, copper, and zinc. However, the literature is scarce regarding the combined toxicity of heavy metals. Simultaneous exposure to multiple heavy metals may produce a toxic effect that is either additive, antagonistic or synergistic.

A recent review of a number of individual studies that addressed metals interactions reported that co-exposure to metal/metalloid mixtures of arsenic, lead and cadmium produced more severe effects at both relatively high dose and low dose levels in a biomarker-specific manner. These effects were found to be mediated by dose, duration of exposure and genetic factors. Also, human co-exposure to cadmium and inorganic arsenic resulted in a more pronounced renal damage than exposure to each of the elements alone. In many areas of metal pollution, chronic low dose exposure to multiple elements is a major public health concern. Elucidating the mechanistic basis of heavy metal interactions is essential for health risk assessment and management of chemical mixtures. Hence, research is needed to further elucidate the molecular mechanisms and public health impact associated with human exposure to mixtures of toxic metals. (SOURCE) 

Several heavy metals are found naturally in the earth crust and are exploited for various industrial and economic purposes. Among these heavy metals, a few have direct or indirect impact on the human body. Some of these heavy metals such as copper, cobalt, iron, nickel, magnesium, molybdenum, chromium, selenium, manganese and zinc have functional roles which are essential for various diverse physiological and biochemical activities in the body. However, some of these heavy metals in high doses can be harmful to the body while others such as cadmium, mercury, lead, chromium, silver, and arsenic in minute quantities have delirious effects in the body causing acute and chronic toxicities in humans. (SOURCE)  

This paper is an excellent example of a case study where the patient was exposed to multiple metal based dental materials, including mercury, as well as cross‐reactions between nickel and palladium, causing systemic hypersensitivity or toxicity. (SOURCE) 

“Nickel: Human Health and Environmental Toxicology” reports that nickel contact can cause a variety of side effects on human health, such as allergy, cardiovascular and kidney diseases, lung fibrosis, lung and nasal cancer. Although the molecular mechanisms of nickel-induced toxicity are not yet clear, mitochondrial dysfunctions and oxidative stress are thought to have a primary and crucial role in the toxicity of this metal. Recently, researchers, trying to characterize the capability of nickel to induce cancer, have found out that epigenetic alterations induced by nickel exposure can perturb the genome. (SOURCE) 

The antimicrobial and cytotoxic effects of a copper-loaded zinc oxide phosphate cement was investigated by Wassmann et al, (2020) and concluded within the limitations of this study, there is no evidence for improved antibacterial or antifungal properties of the tested copper-loaded cement, either in vitro or in vivo. In fact, C. albicans showed a significantly higher initial adhesion to Co-ZOP compared with conventional ZOP. These findings may result from a low surface allocation of copper in the Co-ZOP. Furthermore, both tested cements exhibited significant cytotoxicity against human and animal cell cultures. Based on the results of this study, no clinical recommendation can be given for the use of the tested Co-ZOP. (SOURCE A, SOURCE B, SOURCE C) 

Composite resins release ions such as fluoride, strontium, and aluminum. Some other ions are implicated in the color of the restorative material and these metal elements may interfere with the biocompatibility of the resin because they are implicated in the Fenton reaction producing reactive oxygen species (ROS) that are cytotoxic. The concentration of F- and Sr2+ ions is too low to be cytotoxic. In contrast, Cu2+, Al3+, and Fe2+ are present in toxic concentrations. The cytotoxic cascade was shown to be enhanced by metals such as aluminum and iron present in various amounts in composite resins and RM-GIC. (SOURCE) 

According to Alexandrov et al., in their paper titled “Synergism in aluminum and mercury neurotoxicity (2018)” aluminum and mercury are common neurotoxic contaminants in our environment – from the air we breathe to the water that we drink to the foods that we eat. It is remarkable that to date neither of these two well-established environmental neurotoxins (i.e. those having a general toxicity towards brain cells) and genotoxins (those agents which exhibit directed toxicity toward the genetic apparatus) have been critically studied, nor have their neurotoxicities been evaluated in human neurobiology or in cells of the human central nervous system (CNS). The effects aluminum + mercury together on other neurologically important signaling molecules or the effects of other combinations of common environmental metallic neurotoxins to human neurobiology currently remain not well understood but certainly warrant additional investigation and further study in laboratory animals, in human primary tissue cultures of CNS cells, and in other neurobiologically realistic experimental test systems. (SOURCE)