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Acute dermal toxicity (limit test) and skin irritation studies were conducted in New Zealand white rabbits to ascertain the systemic toxicity and skin-injury potential of chemically-neutralized Chemical Agent Identification Sets (CAIS). Studies also included the assessment of oxidant/solvent systems and solvent induced toxicity. The toxicity limit test consisted of a 24-hr occluded exposure to 1.0 ml/kg of 'test article.' Dermal irritation studies were based on a 4-hr occluded exposure to 0.5 ml of 'test article.' Chemical neutralization of CAIS resulted in complex product solutions (wastestreams) containing ppm levels of agent and an array of degradation products. Findings from the skin irritation testing of wastestreams and oxidant/solvent systems indicate that wastestream-induced skin effects (edema and erythema) were equivalent to or less in severity than the skin effects produced by exposure to oxidant/solvent systems. Systemic effects were not observed in 4/5 wastestream-exposed groups; however, 2/5 wastestream-treated groups exhibited systemic effects. Lethality was noted in only 1/5 wastestream-treated groups. Limit test data indicate that agents (HD, HN, or L) were destroyed by reaction with oxidant to less toxic materials.

Rabbit sperm cells developed hyperactivated motility when incubated in medium N. Hyperactivated but not normal progressive motility was inhibited by lead and cadmium, two metals implicated in fertility dysfunction. A metal of military interest, Cr+6, had a similar outcome on rabbit sperm, suggesting that it may also have the same property as cadmium and lead. Two metals, zinc and mercury, without fertility effects did not suppress hyperactivated motility. The rabbit sperm-medium M-hyperactivated motility system may have a role in the in vitro assessment of the antifertility effects of chemicals.

The teratogenicity of vaporized methlyphosphonic difluoride (DF) was investigated using the rat and rabbit as the experimental models. Pregnant rats and rabbits were exposed. Dams and does exposed exhibited nasal exudate and raspy breathing. These dams also had significantly lower body weights on the last three of four weighings. There were, however, no differences between the control litters and the DF-exposed litters for the parameters: litter number, mean body weight, mean crown-rump length, visceral or skeletal malformations. It was concluded that DF is not teratogenic in the rat or rabbit by the inhalation route at the concentrations tested. Keywords: Fetus; Teratogenic compounds; Gestation; Organogenesis; Pregnant.

Toxicity studies were conducted to determine the acute effects of single exposures to a white phosphorus screening smoke. Results indicate that the smoke is moderately toxic in rats (16% mortality at Ct of 62,200 mg min/cu m; 99% mortality at Ct of 248,250 mg min/cu m) and highly toxic in guinea pigs (16% mortality at Ct of 4600 mg min/cu m; 99% mortality at Ct of 7439 mg min/cu m). Surviving animals appear fully recovered 2 weeks after exposure, based on appearance, blood chemistries, lung function tests, and pathology.

Implantation of body armor fragments in the soldier could be a consequence of failure of the armor to protect the individual in combat. This study was an evaluation of the possible deleterious effects of candidate body armor materials implanted at various sites in animals. Boron carbide, Woven Roving PRD 49-IV yarn, Phillips 95-5XP film, and titanium were implanted subcutaneously in monkeys. All these materials plus calcium hexaboride, silicon hexaboride, and aluminum oxide were implanted subcutaneously in mice. No systemic toxicity either on a long- or short-term basis was identified. Local tissue reaction in excess of that found in controls was seen at the sites of silicon hexaboride implantation in mice, Phillips 95-5XP in monkeys, and Woven Roving in both animals. Malignant neoplasms were demonstrated with PRD 49-IV (4/110), Phillips 95-5XP film (4/30), and boron carbide (1/94) in mice. No subcutaneous tumors occurred at other than the implant sites.

Pregnant dams were exposed to DF-2 smoke, of tank exhaust for 1 hr and to noise from the tank's engine for 20-30 sec. One litter in the DF-2 smoke group had three fetuses with major, gross malformations and two with visceral abnormalities. The DF-2 smoke group also showed the greatest number of fetuses with sites of low bone ossification. Males in the DLM study and the males and females in the single generation (SG) reproduction study were exposed to DF-2 smoke or exhaust for 15 or 60 min. Unexposed dams were mated to DLM males from the 15-min exhaust group during the males' second week of post-exposure. These females had significantly more resorptions than the noise controls for the same mating period. The major malformations observed in the teratology study occurred in rather isolated instances. Retarded bone ossification was indicated in the DF-2 smoke group but without significantly lower body weights. Nothing indicates that DF-2 smoke caused fetal growth retardation. Observances in the DLM study were not strong enough to suspect a mutational effect, and the observations in the SG study gave no support for adverse effects on reproduction.

A model system was developed for studies of the direct effects of high pressure oxygen on skin growth and viability. The data demonstrate the feasibility of the system in studies of the effects of hyperoxygenation by exhibiting the toxicity of 100% oxygen under the conditions employed.

Beta-diethylaminoethyl-diphenylpropylacetate (SKF-525-A), a surface- active agent, inhibits sickling of erythrocytes from individuals with homozygous sickle cell anemia (SS cells) in vitro. Sickling was prevented when SS cells were incubated in .0003 M SKF-525-A, washed free of excess drug, and then deoxygenated in humidified nitrogen atmosphere. Polymerization of sickle hemoglobin and submembrane vesicles could be demonstrated in these cells by electron microscopy. At .0003 M SKF-525-A approximately 10% of the cells lysed. Incubation of pretreated cells at 37C without added oxygen for 24 hours did not produce significant additional lysis. Irreversibly sickled cells were unaffected by drug treatment. Preliminary studies suggest that the oxygen affinity of sickle hemoglobin in the intact cell is not altered by SKF-525-A. It is hypothesized that inhibition of sickling is the result of drug-induced alterations of the cell membrane.

Crude cartilage powder does not accelerate cellular proliferation in newly established human fetal skin fibroblast cultures at concentrations of 0.3 or 30 microg/ml. Collagen biosynthesis is not increased in confluent cultures of human fetal or adult skin fibroblasts by addition of saline or distilled water extracts of cartilage powder at medium concentrations of 30 or 100 microg/ml. Neither N-acetyl glucosamine nor its polymeric form, chitin, has a consistent stimulatory or inhibitory influence on collagen biosynthesis in confluent cultures at final concentrations of 5.0, 50, or 500 microg/ml. The results are taken as evidence that cartilage powder and its extracts and related compounds to not directly influence collagen production in the tissue culture system. The suggestion is made that perhaps the known effects of cartilage powder on wound tensile strength in vivo are exerted by an indirect mechanism as through provision of a matrix material for collagen aggregation. (Author)

Studies were initiated in tissue culture to determine whether activation of alkaline phosphatase is directly related to the biosynthesis of collagen in human diploid skin fibroblasts. Prednisolone 21-phosphate added to monolayer cultures every 3 days with medium change induced a linear increase in specific activity of alkaline phosphatase which began on the fourth day and reached 7 times the control level by the 13th day. Under the same experimental conditions, addition of ascorbate induced an increase in the specific activity of the enzyme to 2.5 times the control level. Prednisolone phosphate did not affect accumulation of collagen-hydroxyproline in cell monolayers when compared to control cultures. Addition of ascorbate, however, resulted in rapid accumulation of hydroxyproline. The addition of prednisolone and ascorbate together resulted in an increased rate of collagen biosynthesis on the fourth. When prednisolone and ascorbate were added in combination, the induction of alkaline phosphatase was 5 times the control level by the 13th day. The accumulation of hydroxyproline, however, was no greater in these cultures by the 13th day than in cultures to which ascorbate alone was added. These studies demonstrate that the activity of alkaline phosphatase induced by prednisolone phosphate is not directly related to the biosynthesis of collagen in human skin fibroblasts in tissue culture. (Author)

Magnesium-dependent adenosine triphosphatase (ATPase) activity of unfixed, isolated, intact skeletal muscle mitochondria, frozen-thawed mitochondria, and digitonin-disrupted submitochondrial particles was localized ultrastructurally after incubation in a Wachstein-Meisel reaction medium and correlated with biochemical ATPase activity. The reaction precipitate was localized within the matrix of intact and partially disrupted mitochondria and between membranous fragments in the submitochondrial particles. These findings are consistent with an ATPase activity residing within the headpieces of the mitochondrial cristae with deposition of reaction product within the adjacent matrix. The effects of various activators, inhibitors, nucleotides, and disruptive procedures on this localization are described. (Author)

Electron-dense deposits were observed in skeletal-muscle mitochondria exposed in vivo and in vitro to a partially purified Clostridium perfringens alpha toxin. Depressed oxidative functions in the toxin-exposed, isolated mitochondria were concomitant with the electron-dense deposits. The mitochondria are suggested as the cellular site of action of the alpha toxin. (Author)