Teratologic studies of solvent refined coal process materials.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to D L Springer.
Explore the source record for details and available documents.
On days 12-16 of gestation pregnant rats were exposed to heavy distillate (HD), the highest-boiling material derived from the solvent refined coal-II (SRC-II) process, and the litters were examined at day 21. Adverse biological effects were observed in the group of animals exposed to an aerosol concentration of 0.66 mg 1-1 [1.8 microgram, mass medium aerodynamic diameter (MMAD)]; groups of animals exposed to lower aerosol concentrations (0.084 and 0.017 mg 1-1) were largely unaffected. Embryo lethality during mid- and late gestation appeared attributable to the coal liquid exposure. Fetuses from pregnant rats in the high exposure group were smaller in weight and length than fetuses from control animals, and skeletal ossification was reduced. Increased incidences of small lungs and cleft palate were observed in fetuses from the high exposure group. Pregnant rats in the high-exposure group gained less weight than controls during gestation; the reduced weight gain was accounted for by the reduced size of the fetuses and placentas. Even though maternal body weight (exclusive of the products of conception) was unaffected by the exposure, the weights of the maternal thymus, lung and spleen were altered in the high exposure group.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A method is described for collection of metabolic 15N2 from in vitro preparations or intact rats administered 15N-containing compounds. The methods enables routine collection and mass spectrometric measurement of as little as 10 mumol 15N2 respired by a rat over a 24-h period. A device is described that includes either an animal chamber or a tissue reaction vessel in a closed recycling atmosphere, with automatic O2 replenishment and removal of CO2 and water. It is capable of sustaining moderate vacuum and is coupled to a high-vacuum manifold designed to process the contained atmosphere and respiratory gases. The starting atmosphere is an 80:20 mix of sulfur hexafluoride and O2. Recovery of 15N2 gas from the system without an animal present was 101.3 +/- 5.75%. When 15N2 gas was very slowly infused iv into an animal, recovery was 89.1 +/- 5.38%. Use of the method in studies of the fate of [15N]hydrazine in rats indicated that about 15% of the administered hydrazine is rapidly converted to 15N2, followed by slower conversion of an additional 7-10% over the next several hours.
Studies of the disposition of hydrazine administered to mammals have not succeeded in accounting for more than a modest fraction of the dose, nor have the excretory products been completely identified. We have utilized 15N-labeled hydrazine and conventional methods to account for about 75% of single doses of about 0.5 LD50 (1 mmol/kg). In 48 h, about 30% appeared in urine as hydrazine and about 20% emerged as a derivative that is acid-hydrolyzable to hydrazine. About 25% was converted to N2 gas, most of which appeared less than 30 min after administration. The percentage converted to N2 at 4 h increased only slightly with dose between 0.5 and 2.0 mmol/kg. Disappearance of hydrazine from blood was biphasic with half-times of 0.74 and 26.9 h.
Explore the source record for details and available documents.
The most common procedure to identify hemoglobin adducts has been to cleave the adducts from the protein and characterize the adducting species, by, for example, derivatization and gas chromatography/mass spectrometry. To extend these approaches we used electrospray ionization mass spectrometry (ESI-MS) to characterize adducted hemoglobin. For this we incubated [14C]acrylamide with the purified human hemoglobin (type A0) under conditions that yielded high adduct levels. When the hemoglobin was separated by reversed-phase high-performance liquid chromatography (HPLC), 65% of the radioactivity copurified with the beta-subunit. Three adducted species were prominent in the ESI mass spectrum of the intact beta-subunit, indicating acrylamide adduction (i.e., mass increase of 71 Da) and two additional unidentified moieties with mass increments of 102 and 135 Da. Endoproteinase Glu-C digestion of the adducted beta-subunit resulted in a peptide mixture that, upon reversed-phase HPLC separation, provided several radiolabeled peptides. Using ESI-MS we identified these as the V91-101 and V102-122 peptides that represent the cysteine-containing peptides of the beta-subunit. These results provide definitive information on acrylamide-modified human hemoglobin and demonstrate that ESI-MS provides valuable structural information on chemically adducted proteins.