Upper Respiratory Tract Uptake of Acrylate Ester and Acid Vapors

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Abstract
Inhalation exposure of the rodent to either of the esters ethyl acrylate (EA) or methyl methacrylate (MMA) results in nasal olfactory injury. The current study was designed to provide inhalation dosimetric data for these ester vapors as well as for their carboxyl-esterase metabolites, acrylic acid and methacrylic acid. Toward this end, uptake of these vapors was measured in the surgically isolated upper respiratory tract (URT) of the male F344 rat under constant-velocity unidirectional inspiratory (200 mllmin) or cyclic (207 mllmin mean inspiratory flow rate) flow conditions over a wide range of inspired concentrations. To examine the potential influences of carboxylesterase metabolism, uptake of the ester vapors was measured in naive (non-pretreated) rats and in rats pretreated with the carboxylesterase inhibitor bis-nitrophenylphosphate (BNPP). The URT uptake of EA averaged 24, 25, and 18% under cyclic flow at inspired concentrations of approximately 5, 25, and 100 ppm, respectively. Overall, uptake under unidirectional flow averaged 2% less than under cyclic flow; a statistically significant difference between the two flow conditions was observed at 5 but not 25 or 100 ppm. BNPP pretreatment reduced URT EA uptake by approximately one-third (p < .0001) indicating a large fraction of inspired EA is metabolized by carboxylesterase in the nose. The URT uptake of MMA averaged 18, 20, and 16% (cyclic flow) at inspired concentrations of approximately 25, 100, or 500 ppm. Deposition of MMA was 3% less on the average in the unidirectional than cyclic flow groups (p < .01). MMA deposition at the high concentration was significantly less efficient (p < .05) than at the two lower concentrations. BNPP pretreatment decreased MMA uptake on the average by one-third (p < .05), indicating this ester is also extensively metabolized by nasal carboxylesterase. Both EA and MMA exposure decreased nasal nonprotein (NP5H) content by approximately 25% (p < .05) at their respective high exposure concentrations, but not at the lower exposure concentrations. Based on delivered dose rate, EA was estimated to be three- to fivefold more potent in producing this effect than MMA. Acrylic and methacrylic acid deposition efficiencies averaged 95% or greater under unidirectional flow. (Cyclic flow studies were not possible due to vapor adsorption on the cyclic flow pump). Nasal NPSH levels were not decreased by exposure to either acid (p > .05) even at delivered dose rates twofold or more greater than for the esters, suggesting the nasal NPSH lowering effect is attributable to the ester vapors themselves, not their acid metabolites.