Showing papers by "Gerald L. Kennedy published in 1993"
TL;DR: The deposition and clearance of lung-deposited Kevlar para-aramid fibrils (subfibers) have been investigated as part of a subchronic and chronic inhalation toxicity testing program.
18 citations
TL;DR: Enhanced metabolism of DMF resulting from multiple 500 ppm DMF exposures and together with saturation ofDMF metabolism suggest using exposure levels below 500 ppm in a chronic bioassay.
Abstract: Whole-body inhalation exposures to N,N-dimethylformamide (DMF) were conducted with rats and mice. The exposure concentrations were 10, 250, and 500 ppm DMF. The exposure routines consisted of single 1-, 3-, or 6-hour exposures and ten 6-hour exposures (ten exposure days in 2 weeks). Area under the plasma concentration curve (AUC) values were determined following exposure for DMF and “N-methylformamide” [“NMF” represented N-methylformamide plus N-(hydroxymethyl)-N-methylformamide (DMF-OH)].The DMF AUC values increased 8- and 29-fold for rats and mice, respectively, following single six-hour exposures to 250 and 500 ppm DMF. These data are indicative of saturation of DMF metabolism. peak “NMF” plasma concentrations for rats and mice, following single 6–hour exposures, did not increase as DMF exposure concentrations increased from 250 to 500 ppm. In addition, the “NMF” plasma levels in rats following a single 6-hour 500 ppm DMF exposure did not decay by 24 hours post exposure. These “NMF” plasma data...
16 citations
TL;DR: Kennedy, G.L., Jr., Brock, W.J., Banerjee, A.K., the authors suggest that all chemicals found to have LD50 values lower than 1000 mg/kg be initially assigned a skin notation until more definitive work proves otherwise.
Abstract: The skin notation with a threshold limit value (TLV) indicates that significant quantities of the chemical may be absorbed through that route to produce unwanted systemic effects. The relationship between the dermal LD50 for a given chemical and the occurrence of skin irritation in the TLV was examined. An association was found, but it was weak. We suggest that all chemicals found to have LD50 values lower than 1000 mg/kg be initially assigned a skin notation until more definitive work proves otherwise. Further, effects that can be produced following repeated dermal exposures using reasonable dose concentrations need to be evaluated for the purpose of a skin notation. Extrapolation of dermal effects following information from other routes of administration needs to be carefully considered, particularly when the absorption and distribution of the chemical following various routes (including dermal) are known. Kennedy, G.L., Jr.; Brock, W.J.; Banerjee, A.K.: Assignment of Skin Notation for Threshol...
16 citations
TL;DR: Male rats were exposed by inhalation from 10 to 300 ppm Dimethylacetamide (DMAc) for either 3, 6, or 12 hrs/day for a total of 10 exposures and recovery from these liver changes was not complete after 14-day post-exposure period.
Abstract: Male rats were exposed by inhalation from 10 to 300 ppm Dimethylacetamide (DMAc) for either 3, 6, or 12 hrs/day for a total of 10 exposures (5 exposures, 2 rest days, 5 exposures). Rats were observed daily for signs of DMAc-related effects, growth was monitored by body weights, clinical laboratory tests and microscopic examination of the liver, testes epididymides, and nasal passages were conducted. One half of the rats in each group was allowed a 14-day post-exposure period to evaluate the reversibility of DMAc-induced changes. No clinical signs of toxicity or DMAc-related gross changes at necropsy were seen in any of the rats although 1 rat exposed to 300 ppm for 12 hours per day died following the seventh exposure. Slight (< 5%) decreases in body weight gain were seen in rats exposed to 300 ppm for 6 or 12 hrs/day. Serum cholesterol levels were elevated in rats exposed to either 100 or 300 ppm (all exposure durations) and in rats exposed to 30 ppm for 12 hours. Total serum protein concentration...
14 citations
TL;DR: Male and female cynomolgus monkeys received whole-body inhalation exposures to dimethylformamide at concentrations of 30, 100, and 500 ppm for 6 hours a day, 5 days a week over a 13-week period to study saturation of DMF metabolism as inhaled DMF concentrations increased from 100 to 500 ppm.
Abstract: Male and female cynomolgus monkeys received whole-body inhalation exposures to dimethylformamide (DMF) at concentrations of 30, 100, and 500 ppm for 6 hours a day, 5 days a week over a 13–week period. serial blood samples were drawn at the conclusion of the first day of exposure and following 15, 29, 57, and 85 days of testing. Area under the plasma concentration curve (AUC) values were determined for DMF and “NMF” [N-methylformamide (NMF) plus N-(hydroxymethyl) -N-methylformamide (DMF-OH)]. Urine samples were also collected and assayed for DMF, NMF and DMF-OH.The systemic exposure to DMF increased disproportionately as the airborne DMF concentrations increased. DMF AUC values increased 19- to 37-fold in male and 35- to 54-fold in female monkeys as the inhalation concentrations increased 5–fold (100 to 500 ppm). These data are consistent with saturation of DMF metabolism as inhaled DMF concentrations increased from 100 to 500 ppm. AUC values, peak plasma concentrations, and plasma half-lives were ...
13 citations