The lymphotoxic action of vanadate.

The acute toxicity of ammonium metavanadate (15.5 mg/kg) in mice was investigated to examine the induction of lymphoid necrosis to (1) verify the reproducibility of the lesions in the thymus, lymph nodes, and spleen; (2) determine whether the necrosis of lymphoid tissue previously observed during the first 3 days post-treatment but absent at 14 days was the result of differences in sensitivity of the mice or the result of recovery from the effects of vanadium; and (3) determine whether differences in the presence and the degree of necrosis between thymus and spleen were correlated with differences in the uptake of vanadium in these tissues. A timed sacrificed study was conducted in conjunction with a 48V tracer. In this study, BALB/C mice were injected subcutaneously (s.c.) with ammonium metavanadate solution (15.5 mg/kg). Groups of mice were sacrificed at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 21, and 28 days postexposure. Lymphoid necrosis was found in the thymus, spleen, lymph nodes, and bone marrow, with the necrosis being most severe in the thymus. The necrosis was moderate at 0.5 days, most severe at 2 to 3 days, with recovery beginning at 4 days, and proceeding to full recovery at 14 to 28 days. At 0.5 days post-treatment, the concentration of vanadium in thymus and spleen was 4.4 and 8.3 micrograms/g, respectively. At all post-treatment periods, with the exception of the 1- and the 4-day periods, the concentration of vanadium in spleen was significantly higher than in the thymus, p less than 0.05. The treated animals showed neurological signs (ataxia, convulsion, dyspnea, and paralysis of hind legs) between 5 min and 54 hr post-treatment, but the concentration of vanadium in the brain was very low during this period (less than 5.2% of blood concentration).

Toxicity of an acute dose of agent VX and other organophosphorus esters in the chicken.

The neurotoxicities of single doses of a chemical warfare agent VX [phosphonothioic acid, methyl-S-(2-[bis(1-methylethyl)amino/ethyl) O-ethyl ester], a metabolite of the agricultural chemical parathion, paraoxon, PO (phosphonothioic acid, diethyl paranitrophenyl ester), and the known neuropathic agents DFP] phosphorofluoridic acid, bis(1-methylethyl) ester] and TOCP (phosphoric acid, tri-o-tolyl ester) were compared in the chicken. Single injections (subcutaneous, sc) of VX as high as 150 micrograms/kg (5 times the LD50, intramuscular, im) were tolerated by laying tens if atropine and 2-pralidoxime were used as antidotes before and immediately after injection. The 150 of VX for inhibition of chicken brain acetylcholinesterase was approximately 5 X 10(-10). Plasma acetylcholinesterase, but not butyrylcholinesterase, was depressed 2 h after injections of 2-20 micrograms VX/kg im without antidotes. Levels of plasma enzymes such as creatine kinase, indicative of tissue damage, were increased after exposure to both VX and PO. Injections of up to 150 micrograms/kg of VX with antidotes did not cause locomotor or histological signs of organophosphorus-induced delayed neuropathy, but single injections of 400 mg TOCP/kg did.

Comparative pulmonary fibrogenic potential of selected particles.

The comparative intrapulmonary fibrogenic potential of a number of chemically and physically characterized ashes and dusts was studied. Sprague-Dawley rats were exposed through intratracheal instillation to 5, 15, or 45 mg of stack-collected coal fly ash, electrostatic precipitator hopper-collected coal fly ash, bag-house filter-collected coal-oil mixture fly ash, Dowson and Dobson quartz, heated montmorillonite clay, and Mt. St. Helens volcano ash. Following a 3-month postexposure period, the animals were killed and subjected to histological examination. Some fibrosis was produced by all the ashes. However, the effects differed both qualitatively and quantitatively among the various exposure groups. The most severe fibrosis was found in the quartz-treated animals, followed in order of intensity by the heated clay, volcano, ash, hopper coal ash, stack coal ash, and coal-oil mixture ash. No effects were found in the saline-exposed control rats.

Structure of the human respiratory acinus.

Silicone rubber corrosion casts of the human lung in a state of end inspiration were used to study several specimens of the human pulmonary acinus. Four of the acini were measured in detail with respect to duct length and diameter, the number of alveoli per duct, and the branching pattern of the ducts. The acini were found to have irregular branching patterns, including dichotomous, trichotomous, and side branches. There were, on the average, eight to 12 duct generations and about 7.1 X 10(3) alveoli per acinus. The polygonal alveoli had an average diameter of 250 micrometers. The lengths and diameters of the ducts varied considerably; however, the dimensions tended to decrease in the more proximal portions of the acini. The number of alveoli per duct also varied, with an average of ten alveoli per duct. On the basis of measurements, two models, a "surrogate path" model and an model being more useful for calculations such as particle deposition in the airways, and the average path model being most illustrative of the anatomical structures.

Anatomy of the nasal-pharyngeal airway of experimental animals.

Silicone rubber casts were prepared of the nasal, pharyngeal and laryngeal regions of two rats, a rhesus monkey, and three beagle dogs and one for each species selected for detailed measurements. Cross-sections of the casts were made and the area and perimeter of each section measured using an image analyzing computer. Considerable anatomical differences were found between the species. Some of the differences, such as the sharp bend in the nasopharynx of the monkey, could be related to normal posture. One of the main differences was the greater complexity of the turbinate region of the dog as compared to the corresponding area of the monkey.

Replica casts of the entire respiratory airways of experimental animals.

A method is presented for producing silicone rubber replica casts of the entire respiratory airways (nasal cavity, pharyngeal region, and lungs) for toxicological assessment of inhaled particles and gases. Established methods for producing casts of the lungs are combined with other methods for faithful casting of the nasopharyngeal region to simultaneously cast all the respiratory regions of a given animal. The resulting detailed, flexible casts can be examined for comparison of the features and relative positions of the regions of the respiratory tracts of various animal species.

Morphology of the guinea pig respiratory tract.

A morphologic description of the airways of the guinea pig was developed from measurements of casts of the lungs and nasal cavity and from measurements of frozen sections of the lungs. The lengths, diameters, branching pattern, and numbers of elements of the respiratory tract formed the basis for a representative model of the system. The branching pattern is irregular to the pulmonary region but regularly dichotomous thereafter. The nasopharyngeal-tracheobronchial region contributes 2.64 cm3 of the total respiratory volume of 21.62 cm3. The alveoli contribute 16.31 cm3 of the 18.98 cm3 pulmonary region. The nasal region consists of convoluted and irregular airways with a functional volume of 0.48 cm3.