Your browser doesn't support javascript.
loading
[Critical analysis of reference studies on aluminium-based adjuvants toxicokinetics]. / Adjuvants aluminiques des vaccins : analyse critique des études toxicocinétiques de référence.
Masson, J-D; Crépeaux, G; Authier, F-J; Exley, C; Gherardi, R K.
Afiliação
  • Masson JD; Inserm U955 E10, centre expert de pathologie neuromusculaire, « Biologie du système neuromusculaire ¼, hôpital Henri-Mondor, faculté de médecine, université Paris-Est-Créteil, 94010 Créteil, France.
  • Crépeaux G; Inserm U955 E10, centre expert de pathologie neuromusculaire, « Biologie du système neuromusculaire ¼, hôpital Henri-Mondor, faculté de médecine, université Paris-Est-Créteil, 94010 Créteil, France; École nationale vétérinaire d'Alfort, 7, avenue du Général-de-Gaulle, 94700 Maisons-Alfort, France.
  • Authier FJ; Inserm U955 E10, centre expert de pathologie neuromusculaire, « Biologie du système neuromusculaire ¼, hôpital Henri-Mondor, faculté de médecine, université Paris-Est-Créteil, 94010 Créteil, France.
  • Exley C; Aluminium and Silicon Research Group, The Birchall Centre, Lennard-Jones Laboratories, Keele University, ST5 5BG, Staffordshire, Royaume-Uni.
  • Gherardi RK; Inserm U955 E10, centre expert de pathologie neuromusculaire, « Biologie du système neuromusculaire ¼, hôpital Henri-Mondor, faculté de médecine, université Paris-Est-Créteil, 94010 Créteil, France. Electronic address: romain.gherardi@aphp.fr.
Ann Pharm Fr ; 75(4): 245-256, 2017 Jul.
Article em Fr | MEDLINE | ID: mdl-28576261
ABSTRACT
We reviewed the three reference toxicokinetic studies commonly used to suggest innocuity of aluminum (Al)-based adjuvants. A single experimental study was carried out using isotopic 26Al (Flarend et al., 1997). This study ignored adjuvant cell capture. It was conducted over a short period of time (28 days) and used only two rabbits per adjuvant. At the endpoint, Al retention was 78% for aluminum phosphate and 94% for aluminum hydroxide, both results being incompatible with quick elimination of vaccine-derived Al in urines. Tissue distribution analysis omitted three important retention sites the injected muscle, the draining lymph node and bone. Two theoretical studies have evaluated the potential risk of vaccine Al in infants, by reference to the oral Minimal Risk Level (MRL) extrapolated from animal studies. Keith et al., 2002 used a too 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. (2011) only considered absorbed Al, with erroneous calculations of absorption duration. They ignored particulate Al captured by immune cells, which play a role in systemic diffusion and the neuro-inflammatory potential of the adjuvant. MRL they used was both inappropriate (oral Al vs injected adjuvant) and far too high (1mg/kg/d) with regard to experimental studies of Al-induced memory and behavioral changes. Both paucity and serious weaknesses of these studies strongly suggest that novel experimental studies of Al adjuvants toxicokinetics should be performed on the long-term, including post-natal and adult exposures, to ensure innocuity and restore population confidence in Al-containing vaccines.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adjuvantes Imunológicos / Hidróxido de Alumínio Limite: Animals / Humans Idioma: Fr Revista: Ann Pharm Fr Ano de publicação: 2017 Tipo de documento: Article País de afiliação: França

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adjuvantes Imunológicos / Hidróxido de Alumínio Limite: Animals / Humans Idioma: Fr Revista: Ann Pharm Fr Ano de publicação: 2017 Tipo de documento: Article País de afiliação: França