Uptake of 19 hydrocarbon vapors inhaled by F344 rats.

The comparative rates of uptake of 19 hydrocarbon vapors by rats were determined by a dual-column gas chromatograph method. The hydrocarbons ranged in volatility from propylene (BP -47.7 degrees C) to 1,2,4-trimethylbenzene (BP 169 degrees C). Representative compounds from the chemical classes of alkenes, alkynes, straight-chain and branched alkanes, alicyclics, and aromatics were examined. Trends observed included: (1) highly volatile hydrocarbons were less well-absorbed than less volatile hydrocarbons; (2) unsaturated compounds were better absorbed than saturated ones; and (3) branched hydrocarbons were less well-absorbed than unbranched ones. The data indicate that uptake rates among inhaled hydrocarbon vapors may be predicted from the molecular structures and physical properties of the hydrocarbons.

Evaluation of a real-time aerosol monitor (RAM-S) for inhalation studies.

Measurement of the aerosol concentration in inhalation toxicology studies is generally done by gravimetric and/or chemical analysis of filter samples taken over a known period of time at a fixed sampling flow rate. The value obtained represents the time-averaged concentration in an exposure chamber. However, the filter method does not provide information as to the stability of aerosol concentration in "real-time" nor as to the time required for the aerosol concentration to reach the target value during the start-up of exposures. In order to accomplish evaluation of aerosol stability and chamber rise and fall times, a direct measurement device is required. An available real-time aerosol monitor (RAM-S, GCA Corp., Bedford, MA) is a photometer which collects scattered light from an aerosol cloud at a 70 +/- 25 degrees angle. The output signal is 0 to 10 volt with three ranges corresponding to maximum aerosol concentrations of 200, 20, and 2 mg/m3. The performance of the RAM-S was evaluated in inhalation studies involving nickel sulfate hexahydrate, nickel oxide, nickel subsulfide, and azodicarbonamide. Several RAM-S units were calibrated by obtaining both filter samples and voltage readings of a RAM-S simultaneously. Results indicated that the response of the RAM-S instruments was linear. However, the voltage output per given aerosol concentration was different for each compound used. Furthermore, there was interinstrument variability in the voltage response to aerosol concentration of a given compound. At concentrations higher than 100 mg/m3, modification of the flow system in the RAM-S was made to increase the sheath air around the optical system and also to dilute the aerosol concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of acclimation to caging on nephrotoxic response of rats to uranium.

Animal studies of the toxicity and metabolism of radionuclides and chemicals often require housing of rats in metabolism cages for excreta collection. Response of rats to toxic substances may be affected by environmental factors such as the type of cage used. Dose-response studies were conducted to assess the effects of two types of cages on the nephrotoxic response of rats to uranium from implanted refined uranium ore (yellowcake). The LD50/21 days was 6 mg of uranium ore per kilogram body weight (6 mg U/kg). The 95% confidence limit (C.L.) was 3-8 mg U/kg for rats housed in metabolism cages beginning on the day of implantation (naive rats). However, for rats housed in metabolism cages for 21 days before implantation (acclimated rats) the LD50/21 days was 360 mg U/kg (95% C.L. = 220-650 mg U/kg), which was the same value obtained for rats housed continuously in polycarbonate cages. This significant difference (P less than 0.01) in response of naive rats compared to response of acclimated rats appeared related to a significantly lower water consumption by the naive rats.

Comparison of early lung clearance of yellowcake aerosols in rats with in vitro dissolution and IR analysis.

The lung retention of uranium was determined in rats that inhaled aerosols of commercial yellowcake powders obtained from two mills (Mill A and Mill D) and whose chemical composition and solubilities in vitro were significantly different. Analysis by IR absorption indicated Mill A yellowcake contained 82% ammonium diuranate (ADU) and 18% U3O8. The Mill D powder contained 25% ADU and 75% U3O8. In vitro dissolution studies indicated for the Mill A sample, approximately 85% of the uranium had a dissolution half-time (T 1/2) of less than one day, with the remainder dissolving with a half-time of 500 days. For the Mill D sample, 25% had T 1/2 less than one day and 75% had T 1/2 of 300 days. Groups of 50 rats were exposed by nose-only inhalation to aerosols of either the Mill A or the Mill D yellowcake. Rats were sacrificed in groups of five at intervals through six months after exposure. Selected tissues and excreta samples were assayed by fluorometry to determine their uranium contents. For the Mill A yellowcake, 78% initial lung (broncho-alveolar) burden cleared with T 1/2 of 0.5 days, and 22% with T 1/2 of 240 days. For the Mill D yellowcake, 25% initial lung burden cleared with T 1/2 of 3.5 days and 75% with T 1/2 of 110 days. Thus, the lung clearance of uranium in the rat mimicked the in vitro dissolution data and supported the contention that ADU should be considered as a Class D compound (T 1/2 = 0.5 days) and U3O8 behaves in the lung as a Class Y (T 1/2 greater than 100 days) material.

Predicted deposition rates of uranium yellowcake aerosols sampled in uranium mills.

Uranium aerosols generated during normal yellowcake packaging operations were sampled at four uranium mills. Samplers located in the packaging area were operated before, during and after drums of yellowcake were filled and sealed. Median aerosol concentrations in the packaging areas ranged from 0.04 micrograms U/1 to 0.34 micrograms U/1. The aerosols were heterogeneous and included a broad range of particle sizes such that 14% to 76% (by weight) of the airborne uranium was in particles with aerodynamic diameters greater than 12 micron. Air concentrations and particle-size distributions varied with time as larger particles settled or more aerosols were suspended. Aerosol characteristics could often be related to individual packaging steps. The results show that appreciable amounts of airborne uranium would be expected to deposit in the nasopharyngeal compartment of the respiratory tract if inhaled by a worker not wearing respiratory protection.

Influence of elastase-induced emphysema and the inhalation of an irritant aerosol on deposition and retention of an inhaled insoluble aerosol in Fischer-344 rats.

The purpose of this study was to assess the effects of elastase-induced pulmonary emphysema and the inhalation of an irritant aerosol (Triton X-100, a nonionic surfactant similar to those used in a number of pressurized consumer products) on pulmonary deposition and retention of an insoluble test aerosol, 59Fe-labeled Fe2O3. Untreated rats or rats pretreated by intratracheal instillation with elastase were exposed to an aerosol of 59Fe-labeled Fe2O3 either 18 hr or 7 days after exposure to aerosolized Triton X-100 which was administered in doses of 20, 100, or 200 micrograms/g of lung. Rats pretreated with elastase had significantly lower pulmonary deposition of 59Fe than the untreated controls (p less than 0.005). Pulmonary deposition of Fe2O3 was unaffected by pretreatment with Triton X-100. Elastase treatment alone had no effect on retention of Fe2O3. Triton X-100 administered 18 hr prior to exposure of rats to Fe2O3 aerosol resulted in dose-related increases in whole-body retention of 59Fe. When rats were exposed to Triton X-100 7 days before exposure to Fe2O3, increased retention of 59Fe was noted only in those treated at the highest Triton X-100 dose level (200 micrograms/g).