5 research outputs found
In vivo and ex vivo percutaneous absorption of [14C]-bisphenol A in rats: a possible extrapolation to human absorption?
Bisphenol A (BPA) is a monomer used mainly in the synthesis of polycarbonates and epoxy resins. Percutaneous absorption is the second source of exposure, after inhalation, in the work environment. However, studies on this route of absorption are lacking or incomplete. In this study, percutaneous BPA absorption was measured in vivo and ex vivo in the rat, and ex vivo in humans. An approximately 12-fold difference in permeability between rat skin and human skin was found, with permeability being higher in the rat. In addition, inter- and intra-individual variability of up to tenfold was observed in humans. No accumulation of BPA in the skin was found during exposure. The skin clearance rate following exposure was estimated at 0.4Â ÎŒg/cmÂČ/h. Ex vivo and in vivo percutaneous absorption fluxes of BPA in the rat were in the same range (about 2.0Â ÎŒg/cmÂČ/h), suggesting that extrapolation to the in vivo situation in humans may be possible. The European tolerable daily intake (TDI) of BPA is 50Â ÎŒg/kg body weight. However, many research projects have highlighted the significant effects of BPA in rodents at doses lower than 10Â ÎŒg/kg/day. A 1-h occupational exposure over 2,000Â cmÂČ (forearms and hands) may lead to a BPA absorption of 4Â ÎŒg/kg/day. This is 8% of the European TDI and is very close to the value at which effects have been observed in animals. This absorption must therefore be taken into account when evaluating risks of BPA exposure, at least until more relevant results on the toxicity of BPA in humans are available
Modifications de lâamplitude du rĂ©flexe de lâoreille moyenne aprĂšs inhalation de solvant. ConsĂ©quences physiologiques pour les expositions au bruit
The middle-ear reflex (MER) reduces acoustic energy carried by the high intensity noises rich in low frequencies at entering the cochlea. His bilateral trigger thus protects the cochlea. Disruption of this reflex by solvents can increase cochleo-traumatic effects of noise, especially among industrial workers, where noise and solvent are often associated. The main objective of this work was to develop a screening test capable of identifying the volatile substances that could modify the reflex. Moreover, the choice of solvents allowed us to study the mode of action of solvents on the neurons involved in the reflex circuit. For this purpose, Brown Norway rats were anesthetized and then exposed to aromatic solvents selected according to their lipophilicity (log Kow) and/or their structure. The amplitude of the MER is determined by measuring cubic distortion product oto-acoustic emissions. For that, aromatic solvents appear to act directly on the neuronal targets involved in the acoustic reflex circuit, rather than on membrane fluidity. The affinity of this interaction is determined by stereospecific parameters rather than lipophilocity. Additionally, NMR spectra for brain microsomes confirmed that brain lipid fluidity was unaffected by toluene exposure. In conclusion, the MER can be used to detect hazardous volatiles substances for the hearing when co-exposed to noise. Moreover, this study revealed that aromatic solvents have a neuropharmacological and/or cochleotoxic action that can act separately on the hearing of workers exposed to noise and solvents simultaneously.Le rĂ©flexe de lâoreille moyenne (ROM) diminue lâĂ©nergie acoustique portĂ©e par les bruits riches en basses frĂ©quences et de fortes intensitĂ©s qui pĂ©nĂštrent dans la cochlĂ©e. Son dĂ©clenchement bilatĂ©ral permet ainsi de protĂ©ger la cochlĂ©e. La perturbation de ce rĂ©flexe par des solvants peut accroĂźtre les effets cochlĂ©o-traumatisants du bruit, notamment chez les salariĂ©s du secteur industriel, oĂč bruit et solvant sont souvent associĂ©s. Lâobjectif principal de ces travaux Ă©tait dâĂ©laborer un test de criblage capable dâidentifier les substances volatiles susceptibles de modifier le rĂ©flexe. De plus, le choix des solvants nous a permis dâĂ©tudier le mode dâaction des solvants sur les neurones impliquĂ©s dans lâarc rĂ©flexe. Pour cela, des rats Brown Norway anesthĂ©siĂ©s ont Ă©tĂ© exposĂ©s par inhalation aux solvants aromatiques choisis selon leur lipophilie (log Kow) et/ou selon leur structure. Lâamplitude du ROM a Ă©tĂ© dĂ©terminĂ©e grĂące Ă la mesure de lâintensitĂ© du produit de distorsion acoustique. Les rĂ©sultats montrent que les effets des solvants sur le ROM sont conditionnĂ©s par les paramĂštres stĂ©rĂ©ospĂ©cifiques des molĂ©cules et non par leur lipophilie. Par ailleurs, lâanalyse RMN des microsomes de cerveaux de rats confirme que le toluĂšne nâinfluence pas la fluiditĂ© membranaire. En conclusion, le ROM est un bon outil pour dĂ©tecter des substances dangereuses pour lâaudition en cas de co-exposition avec du bruit. De plus, nous pouvons dire que les solvants aromatiques ont une action neuropharmacologique et/ou cochlĂ©otoxique qui peuvent retentir de façon distincte sur lâaudition des sujets co-exposĂ©s au bruit et Ă des solvants
Alterations in the amplitude of acoustic middle-ear reflex after inhalation solvent. Physiological consequences for exposure to noise
Le rĂ©flexe de lâoreille moyenne (ROM) diminue lâĂ©nergie acoustique portĂ©e par les bruits riches en basses frĂ©quences et de fortes intensitĂ©s qui pĂ©nĂštrent dans la cochlĂ©e. Son dĂ©clenchement bilatĂ©ral permet ainsi de protĂ©ger la cochlĂ©e. La perturbation de ce rĂ©flexe par des solvants peut accroĂźtre les effets cochlĂ©o-traumatisants du bruit, notamment chez les salariĂ©s du secteur industriel, oĂč bruit et solvant sont souvent associĂ©s. Lâobjectif principal de ces travaux Ă©tait dâĂ©laborer un test de criblage capable dâidentifier les substances volatiles susceptibles de modifier le rĂ©flexe. De plus, le choix des solvants nous a permis dâĂ©tudier le mode dâaction des solvants sur les neurones impliquĂ©s dans lâarc rĂ©flexe. Pour cela, des rats Brown Norway anesthĂ©siĂ©s ont Ă©tĂ© exposĂ©s par inhalation aux solvants aromatiques choisis selon leur lipophilie (log Kow) et/ou selon leur structure. Lâamplitude du ROM a Ă©tĂ© dĂ©terminĂ©e grĂące Ă la mesure de lâintensitĂ© du produit de distorsion acoustique. Les rĂ©sultats montrent que les effets des solvants sur le ROM sont conditionnĂ©s par les paramĂštres stĂ©rĂ©ospĂ©cifiques des molĂ©cules et non par leur lipophilie. Par ailleurs, lâanalyse RMN des microsomes de cerveaux de rats confirme que le toluĂšne nâinfluence pas la fluiditĂ© membranaire. En conclusion, le ROM est un bon outil pour dĂ©tecter des substances dangereuses pour lâaudition en cas de co-exposition avec du bruit. De plus, nous pouvons dire que les solvants aromatiques ont une action neuropharmacologique et/ou cochlĂ©otoxique qui peuvent retentir de façon distincte sur lâaudition des sujets co-exposĂ©s au bruit et Ă des solvants.The middle-ear reflex (MER) reduces acoustic energy carried by the high intensity noises rich in low frequencies at entering the cochlea. His bilateral trigger thus protects the cochlea. Disruption of this reflex by solvents can increase cochleo-traumatic effects of noise, especially among industrial workers, where noise and solvent are often associated. The main objective of this work was to develop a screening test capable of identifying the volatile substances that could modify the reflex. Moreover, the choice of solvents allowed us to study the mode of action of solvents on the neurons involved in the reflex circuit. For this purpose, Brown Norway rats were anesthetized and then exposed to aromatic solvents selected according to their lipophilicity (log Kow) and/or their structure. The amplitude of the MER is determined by measuring cubic distortion product oto-acoustic emissions. For that, aromatic solvents appear to act directly on the neuronal targets involved in the acoustic reflex circuit, rather than on membrane fluidity. The affinity of this interaction is determined by stereospecific parameters rather than lipophilocity. Additionally, NMR spectra for brain microsomes confirmed that brain lipid fluidity was unaffected by toluene exposure. In conclusion, the MER can be used to detect hazardous volatiles substances for the hearing when co-exposed to noise. Moreover, this study revealed that aromatic solvents have a neuropharmacological and/or cochleotoxic action that can act separately on the hearing of workers exposed to noise and solvents simultaneously
Membrane fluidity does not explain how solvents act on the middle-ear reflex
International audienc