We reviewed the three toxicokinetic reference studies commonly used to suggest that aluminum (Al)-based adjuvants are innocuous. [Flarend et al., Keith et al., & Mitkus et al.]
A single experimental study was carried out using isotopic 26Al (Flarend et al., Vaccine, 1997). This study used aluminum salts resembling those used in vaccines but ignored adjuvant uptake by cells that was not fully documented at the time.
[With R]esults being incompatible with rapid elimination of vaccine-derived Al…
Keith et al. (Vaccine, 2002) used a high MRL [minimum risk level] (2 mg/kg/d), an erroneous model of 100% immediate absorption of vaccine Al, and did not consider renal and blood-brain barrier immaturity.
Mitkus et al. (Vaccine, 2011) only considered solubilized Al, with erroneous calculations of absorption duration. Systemic Al particle diffusion and neuro-inflammatory potential were omitted. The MRL they used was both inappropriate (oral Al vs. injected adjuvant) and still too high…
The occurrence of myalgia and arthralgia, chronic fatigue and neurological disorders following multiple injections of aluminum-containing vaccines against hepatitis B, tetanus and human papilloma virus (HPV) has been reported in many countries: Australia, Canada, Denmark, France, United Kingdom, Italy, Israel, Japan, Mexico, Portugal, and USA.
To date, aluminum adjuvants per se have, perhaps surprisingly, not been the subject of any official experimental investigation, and this being in spite of the well-established neurotoxicity of aluminum.
For a long time specialized international meetings have held that Al injected by the vaccine route was essentially rapidly eliminated from the body in the urine…
It is essential to take into account that in these preliminary toxico-kinetic studies, neither the form of aluminum (soluble) nor the route of administration (IV) corresponded to the vaccine situation, where aluminum is subcutaneously (SC) or in- tramuscularly (IM) injected in nano/microparticle form.
The point is crucial: the dynamics of Al adjuvants have very little relevance to any ‘normal’ exposure to Al in everyday life, and injection of Al citrate into the blood doesn’t really tell you much at all about normal chronic exposure to Al via any route and including vaccination.
[A]uthors were probably unaware of particles capture by immune cells. The fact that once injected into a tissue, agglomerates of adjuvant are rapidly captured by the cells of the innate immune system and thus rapidly taken away from the dissolving effect of the chelating agents present in the interstitial fluid was fully demonstrated several years later…
Rather than talking about the reassuring nature of these results, an inverse conclusion should have been made by the authors from a vaccine safety perspective, highlighting the low dissolution and low elimination of Al adjuvants, especially the hydroxide-based adjuvant, and the need for further long-term studies on a larger number of animals. The regulatory agencies themselves would have been well advised to order complementary toxico-kinetic studies in order to avoid the propagation of hazardous information on the rapid elimination of Al adjuvants.
[I]t should be noted that the issue of the blood-brain barrier has not been taken into account even though the development of the nervous system is notoriously sensitive to toxic exposures.
The issue of blood-brain barrier immaturity is an important issue in the potential toxicity of Al adjuvants. In its report, the French National Academy of Pharmacy considers that “the blood-brain barrier, which is incompletely formed in the pre-natal and post-natal stages, is more permeable to toxic substances.
Strictly speaking, MRL [minimum risk level] used for vaccine risk modeling should be defined on the basis of animal experiments carried out with Al adjuvants, monitored for their particle parameters to be in accordance with those of the vaccines, and injected IM, rather than studies with soluble forms of Al [chloride or lactate] added to food or drinking water.
Another limitation of the Mitkus study is that it does not take into account that the adjuvant can migrate away from the muscle in its particulate form.
In mice Al hydroxide particles are indeed transported… first to the draining lymph nodes and then… to the bloodstream, then reaching distant organs such as the spleen or even the brain, where slow and delayed accumulation can be observed…