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Regul Toxicol Pharmacol ; 107: 104421, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31299268

RESUMO

Acute central nervous system (CNS) depression is the most sensitive toxicological effect associated with aliphatic hydrocarbon exposure. No observed effect levels for the CNS effects of aliphatic constituents decrease with increasing carbon number to C10 (Lammers et al., 2011; McKee et al., 2011), whereas constituents with carbon numbers > C10 do not produce CNS effects at maximally attainable vapor concentrations (Nilsen et al., 1988). Accordingly, as n-decane appeared to be the "worst case" for acute CNS effects among aliphatic hydrocarbon solvent constituents, experimental studies were conducted to more precisely define the no effect level. Rats were exposed for 8 h to n-decane, either constantly at 3000 mg/m3 or at higher levels using a discontinuous exposure protocol to assess the influence of fluctuating exposures. Neurobehavioral testing methods including visual discrimination performance and motor activity were used to assess performance, and concentrations of n-decane in blood and brain were measured to obtain pharmacokinetic data. No statistically significant differences were observed in the neurobehavioral tests, establishing 3000 mg/m3 as the no effect level for CNS effects in rats. These data support the recommended guidance value of 1050 mg/m3 for C9-C15 aliphatic hydrocarbons for use in calculating occupational exposure levels for complex hydrocarbon solvents and provide empirical evidence that advice from the ACGIH® that within a working day there should be no more than 3 fluctuations, not longer than 15 min and not exceeding 3 times the Threshold Limit Value (TLV®), is reasonable for this group of substances.


Assuntos
Alcanos/toxicidade , Sistema Nervoso Central/efeitos dos fármacos , Solventes/toxicidade , Administração por Inalação , Alcanos/sangue , Alcanos/farmacocinética , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Solventes/farmacocinética , Níveis Máximos Permitidos
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