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Critical analysis of reference studies on the toxicokinetics of aluminum-based adjuvants.
- Source :
-
Journal of inorganic biochemistry [J Inorg Biochem] 2018 Apr; Vol. 181, pp. 87-95. Date of Electronic Publication: 2017 Dec 28. - Publication Year :
- 2018
-
Abstract
- We reviewed the three toxicokinetic reference studies commonly used to suggest that aluminum (Al)-based adjuvants are innocuous. 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. It was conducted over a short period of time (28days) and used only two rabbits per adjuvant. At the endpoint, Al elimination in the urine accounted for 6% for Al hydroxide and 22% for Al phosphate, both results being incompatible with rapid elimination of vaccine-derived Al in urine. Two theoretical studies have evaluated the potential risk of vaccine Al in infants, by reference to an oral "minimal risk level" (MRL) extrapolated from animal studies. Keith et al. (Vaccine, 2002) used a high MRL (2mg/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 (1mg/kg/d) regarding recent animal studies. Both paucity and serious weaknesses of reference studies strongly suggest that novel experimental studies of Al adjuvants toxicokinetics should be performed on the long-term, including both neonatal and adult exposures, to ensure their safety and restore population confidence in Al-containing vaccines.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Absorption, Physiological
Adjuvants, Immunologic blood
Adjuvants, Immunologic metabolism
Adjuvants, Immunologic pharmacokinetics
Adolescent
Adult
Age Factors
Aluminum blood
Aluminum metabolism
Aluminum urine
Aluminum Compounds blood
Aluminum Compounds metabolism
Aluminum Compounds pharmacokinetics
Animals
Child
Coordination Complexes blood
Coordination Complexes metabolism
Coordination Complexes urine
Humans
Infant
Renal Elimination
Toxicity Tests
Toxicokinetics
Adjuvants, Immunologic adverse effects
Aluminum toxicity
Aluminum Compounds adverse effects
Coordination Complexes toxicity
Vaccines adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3344
- Volume :
- 181
- Database :
- MEDLINE
- Journal :
- Journal of inorganic biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 29307441
- Full Text :
- https://doi.org/10.1016/j.jinorgbio.2017.12.015