Kinetic evaluation of the ciliotoxicity of methyl- and propyl-p-hydroxybenzoates using factorial experiments.
The ciliotoxicity of methyl-p-hydroxybenzoate (methyl paraben, MHB) and propyl hydroxybenzoate (propyl paraben, PHB) was investigated. It is shown that at the concentrations used (0.28 and 0.38 mM) PHB exerted only mild toxicity. The MHB solutions used (1.18 and 2.36 mM) were much more ciliotoxic. There was, however, an order of magnitude difference in the concentrations used as a result of constraints imposed by their differing aqueous solubilities. There was no evidence of synergism in the ciliotoxicity of the two compounds when the MHB concentration was raised from 1.18 to 2.36 mM and the PHB concentration was raised from 0.28 to 0.38 mM in a 2(2) factorial experiment. At those levels the two compounds showed additive effects. On the other hand, clear synergism was evidenced by the fact that the ciliotoxicity of both MHB and PHB was dependent on whether the cilia were exposed to each hydroxybenzoate singly or in combination. The results combined with those of an earlier study, indicate that it is not possible to improve the selectivity of antimicrobial activity without also increasing ciliotoxicity.
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Drug Delivery Research Group, Queen's University of Belfast, UK.
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D000818:Animals; D002923:Cilia / Q000187:drug effects*; D004357:Drug Synergism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010226:Parabens / Q000633:toxicity*; D000091402:Prohibitins; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000473:pathology
D010226:Parabens; C000717332:Phb protein, rat; D000091402:Prohibitins; C015358:methylparaben; C006068:propylparaben