I’ve been using a nano-hydroxyapatite toothpaste multiple times per day this past month and I’m having unexplained intermitent hand and arm numbness when I wake in the morning. I’m also having headaches, back muscle and skin patch pain for no apparent reason. Could my toothpaste be to blame? I switched to a new one tonight after reading about the possible dangers of nano-hydroxyapatite, specifically when in the form of microscopic needle shapes. Update: After about two months, it seems the symptoms may be getting slowly better, but time will tell. I’m not prepared to draw any conclusions at this point, but I will be avoiding this substance in the future.
While nano-hydroxyapatite has shown promise as a remineralizing agent in oral care products, there are significant safety concerns that have been raised by regulatory bodies in the European Union (EU) that have not been adequately addressed in the United States.
Safety Concerns Raised by the EU
The Scientific Committee on Consumer Safety (SCCS) in the EU has reviewed multiple studies on the safety of nano-hydroxyapatite and found that needle-shaped particles in particular are of concern. Some key findings:
- Oral administration of needle-shaped nano-hydroxyapatite particles can lead to systemic effects related to hepatoxicity in animal studies
- Dermal exposure to nano-hydroxyapatite caused changes in lipid peroxidation, reduced glutathione, mild inflammatory cell infiltration, and proliferation of bronchial-associated lymphoid tissue in the lungs
- The SCCS concluded that “the available information indicates that nano-hydroxyapatite in needle-shaped form is of concern in relation to potential toxicity”
As a result, the EU has banned the use of needle-shaped nano-hydroxyapatite in cosmetic products. Regulations state that for nano-hydroxyapatite to be considered safe, at least 95.8% of particles must have an aspect ratio less than 3, with the remaining 4.2% not exceeding 4.9.
Genotoxic Potential and Toxicity Risks
The SCCS has also expressed concerns about the genotoxic potential of hydroxyapatite (nano) in oral-care cosmetic products, particularly when the available data is insufficient to exclude such risks.
Inhalation Exposure
The SCCS has also raised concerns about the lack of data on consumer safety from inhalation exposure, particularly in relation to sprayable products that could lead to exposure of the lungs to nanoparticles by inhalation.
Effects on Blood and Platelets
Studies have shown that nano-hydroxyapatite (N-HAP) can negatively affect red blood cells and platelets by adhering to their membranes. This can lead to changes in sedimentation, aggregation, and potentially even calcification of blood cells. In animal studies, there was a statistically significant increase in red blood cells, hemoglobin, and hematocrit, accompanied by a decrease in platelet counts.
Damage to DNA
Research has also found that N-HAP can damage human DNA in vitro, leading to dose-dependent increases in sister chromatid exchanges, micronucleus formation, chromosome aberration rates, and 8-oxo-2-deoxyguanosine levels. This suggests that N-HAP may have genotoxic effects.
Effects on Organs
Animal studies have revealed that N-HAP can cause histopathological changes in organs such as the liver, kidneys, and lungs. In the kidneys, N-HAP has been shown to cause vacuolar degeneration of nephric tubule epithelium. In the liver, N-HAP has been linked to free radical damage and changes in lipid peroxidation and glutathione levels.
Systemic Effects
The available information suggests that some forms of nano-hydroxyapatite might exert systemic effects after administration by the dermal and oral routes, with potential distribution to the liver, kidneys, and lungs.
Inflammatory Response
If nHAP particles cause tissue irritation or damage, the body may initiate an inflammatory response. This involves the release of signaling molecules that attract immune cells to the site of exposure, helping to isolate and eliminate the foreign material.
Normally, the immune response is to recognized foreign invaders and then to engulf foreign particles through a process called phagocytosis. Can Macrophages ingest nHAP particles, potentially reducing their presence in tissues and preventing further damage? The physical characteristics of particles, including size and shape, significantly affect macrophage uptake.Research indicates that macrophages can efficiently clear particles in the range of 1-5 µm, with larger particles often leading to frustrated phagocytosis, where the macrophages are unable to fully engulf them.
Bioaccumulation of nHAP
Does nHAP bioaccumulate? Does it end up in particular tissues more than others in the human body?
The bioaccumulation of nano hydroxyapatite (nHAP) in the human body is a topic of ongoing research, particularly regarding its potential to accumulate in specific tissues. Here are the key points related to this issue:
1. Potential for Accumulation: Nano hydroxyapatite, especially in needle-shaped forms, has been shown to potentially accumulate in the body. Due to their small size and unique shape, these nanoparticles may evade some of the body’s natural clearance mechanisms, leading to their retention in biological tissues.
2. Tissue Distribution: Research indicates that nHAP can be found in various tissues after exposure. Specifically, studies have shown statistically significant changes in liver enzyme markers following oral administration of nHAP, suggesting that the liver may be one of the primary sites of accumulation. Other tissues, such as the lungs and kidneys, could also be affected due to the particles’ ability to enter systemic circulation and distribute throughout the body[6].
3. Factors Influencing Distribution: The accumulation and distribution of nHAP in tissues can be influenced by several factors, including the size, shape, and surface properties of the nanoparticles. Needle-shaped nHAP, in particular, is noted for its potential toxicity and ability to interact with cellular structures, which may lead to localized accumulation and adverse effects[6].
In summary, while the exact mechanisms and extent of bioaccumulation of nano hydroxyapatite in the human body require further investigation, current evidence suggests that these nanoparticles can accumulate in various tissues, particularly the liver. The unique properties of nHAP, especially in its needle-shaped form, may enhance its retention in the body, raising concerns about potential long-term health effects.
Unknowns and Future Research Directions
Despite these findings, there are still many unknowns regarding the effects of N-HAP on the body. Further research is needed to understand its effects on the gut, its systemic absorption from oral products, and its potential to pass the blood-brain barrier. Additionally, the long-term effects of N-HAP on the body, including its potential for carcinogenicity and reproductive toxicity, have not been fully studied.
Particle Shape and Size
The particle shape, size, and aspect ratio of nano-hydroxyapatite have been investigated as possible safety concerns, with the SCCS specifying that only rod-shaped particles with certain aspect ratios are considered safe for use in oral cosmetic products.
Coating and Surface Modification
The SCCS has emphasized that the particles must not be coated or surface-modified to be considered safe for use in oral cosmetic products.
Regulatory Differences Between the EU and US
These health concerns and regulatory specifications highlight the EU’s more cautious approach to the use of nano hydroxyapatite in cosmetic products, emphasizing the need for careful evaluation of the safety of nanomaterials in consumer products. However, in the United States, nano-hydroxyapatite products containing needle-shaped particles are still being marketed and sold, with little oversight from the FDA. While the FDA generally recognizes nano-hydroxyapatite as safe, it has not yet been fully approved as a medical device for regenerative dentistry practices.
FDA Consultations and Safety Concerns
- The FDA has been made aware of infant formula containing a nano-form of hydroxyapatite but has not taken action despite concerns raised about chronic exposure to nano-hydroxyapatite.[1]
- The FDA guidance indicates that there is a lack of safety data for food substances engineered on the nanometer scale, which raises questions about the safety of nano-hydroxyapatite in food products.
- There are challenges in regulating nano-hydroxyapatite, with issues related to labeling requirements, lack of differentiation between types of hydroxyapatite, and limited data on its potential carcinogenicity and reproductive toxicity.
- The cooperation of product developers is crucial for generating exposure data to enable risk assessment of nano-hydroxyapatite in various products, but there have been difficulties in securing this cooperation.
Given these concerns and the gaps in safety data and regulatory oversight highlighted in the sources, it is understandable to question the FDA’s recognition of nano-hydroxyapatite as safe.
How to Avoid Nano-Hydroxyapatite
To avoid nano-hydroxyapatite, steer clear of dental products, supplements and sports drinks containing it. Be wary of any products with unspecified particle sizes or sources. Discuss any concerns with your healthcare provider.
Conclusion
Dental professionals and consumers should be aware of these safety concerns and advocate for stricter regulation of nano-hydroxyapatite products in the US, in line with the EU’s precautionary approach. Manufacturers should also be transparent about the particle morphology in their products and avoid using needle-shaped nano-hydroxyapatite. More research is still needed to fully understand the potential risks of nano-hydroxyapatite, but the EU’s stance serves as an important warning that should not be ignored. Prioritizing safety should be paramount when it comes to oral care products, especially those targeting vulnerable populations like children.
More Reading
[1] http://www.centerforfoodsafety.org/files/efsa-nanomaterial-in-food-comment-from-icta-and-center-for-food-safety-3418-final_67169.pdf
[2] https://www.todaysrdh.com/nano-hydroxyapatite-varnish-does-research-support-caries-prevention-efficacy-and-safety/
[3] https://www.sciencedirect.com/science/article/abs/pii/S1742706118304306
[4] https://betterbiom.com/blogs/learn/is-nano-hydroxyapatite-safe
[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667430/
[6] https://bubbleandbee.com/hydroxyapatite-part-2/
[7] https://health.ec.europa.eu/publications/hydroxyapatite-nano_en
[8] https://www.sciencedirect.com/topics/chemistry/bioaccumulation
[9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5044975/
[10] https://study.com/learn/lesson/bioaccumulation-concept-examples.html
[11] https://www.acs.org/education/whatischemistry/landmarks/rachel-carson-silent-spring/rachel-carson-poster.html
