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Biomedical subjects

L F Rubin

Publications and source records attributed to L F Rubin.

At least 19 recordsLinked to original sources
PubMed1994

Subchronic and chronic inhalation toxicity of antimony trioxide in the rat.

Fischer 344 rats were exposed by inhalation to Sb2O3 (antimony trioxide) dust at exposure levels of 0, 0.25, 1.08, 4.92, and 23.46 mg/m3 for 6 hr/day, 5 days/week for 13 weeks followed by a 27-week observation period. Subsequently, an inhalation oncogenicity study was conducted at exposure levels of 0, 0.06, 0.51, and 4.50 mg/m3 for 12 months followed by a 12-month observation period. The Sb2O3 in the subchronic study had a mass median aerodynamic diameter (MMAD) of 3.05 +/- 0.21 microns (mean +/- SD) with a geometric standard deviation (GSD) of 1.57 +/- 0.06. In the chronic study, the MMAD was 3.76 +/- 0.84 and the GSD was 1.79 +/- 0.32. Except for the eyes, no adverse clinical observations were attributed to Sb2O3 in either study. In the subchronic study, corneal irregularities were seen after about 2 weeks of exposure and did not abate during the observation period. In the chronic study, ophthalmoscopic evaluation at 24 months revealed a dose-related increase in cataracts of 11, 24, 28, and 32% (both sexes combined) for each group, respectively. Body weights were significantly lower (6%) than the control group's weights in the 23.46 mg/m3 males in the subchronic study. These rats did not recover this weight during the 27-week observation period. Body weights of the females in both studies and males in the chronic study were unaffected. There were no Sb2O3 effects on clinical chemistry or hematology in either study. Mean absolute and relative lung weights were significantly increased in the 4.92 and 23.46 mg/m3 groups in the subchronic study. The 23.46 mg/m3 group's lung weights did not recover to control levels during the 27-week observation period. Lung weights for rats in the chronic study were unaffected. Microscopic changes in the lungs in the subchronic and chronic study were limited to subacute-chronic interstitial inflammation, increased numbers of alveolar-intraalveolar macrophages, foreign material in the alveolar-intraalveolar macrophages in the peribronchial and perivascular (chronic study only) lymphoid aggregates and in the peribronchial lymph nodes, granulomatous inflammation/granulomas, and fibrosis. In the chronic study, any observed neoplasms occurred with comparable incidence among all groups and were within the historical range for controls. Clearance of Sb2O3 from the lung was burden dependent and was reduced by 80% in the 4.50 mg/m3 group in the chronic study. The previously reported studies, which found Sb2O3 to be a carcinogen, were run at higher lung burdens. Under the exposure conditions of the current study, Sb2O3 was not a carcinogen.

Administration, Inhalation↗
PubMed1990

On the etiology of subcapsular lenticular opacities produced in dogs receiving HMG-CoA reductase inhibitors.

The administration of high dosages of various hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors has resulted in the development of subcapsular lenticular opacities in dogs. While dogs receiving cataractogenic doses of HMG-CoA reductase inhibitors experienced profound decreases in circulating serum cholesterol concentrations (40-60% reductions in total serum cholesterol), a causal relationship between serum cholesterol lowering and cataractogenesis was not established. A strong relationship was demonstrated, however, between the systemic exposure to inhibitor (plasma drug levels) and the cataractogenic potential of the various compounds studied. Analysis of lenses from dogs chronically dosed with various HMG-CoA reductase inhibitors revealed the presence of low drug levels in the lens (less than 500 ng equivalents g-1), but no correlation was observed between the amount of drug associated with the lens after chronic treatment and cataract development. In addition, no abnormalities in cholesterol content or sterol composition were observed in clear and/or cataract containing lenses from dogs chronically dosed with HMG-CoA reductase inhibitors. The kinetics of drug appearance in the aqueous and lens cortex was assessed after doses of various HMG-CoA reductase inhibitors, and suggested somewhat higher but not statistically significant peak concentrations of inhibitor were achieved by compounds which produced a higher incidence of cataracts. These data have suggested that high doses of HMG-CoA reductase inhibitors may increase lenticular exposure to drug via the aqueous humor by producing a substantial systemic exposure to drug substance. This may result in an increased concentration of inhibitor in the outer cortical region of the lens where cholesterol synthesis is critical, thereby resulting in the development of opacities. The production of lenticular changes by a HMG-CoA reductase inhibitor of diverse chemical structure establishes, with reasonable assurance, that these lens changes are mechanism based (i.e. a product of the biochemical mechanism of action of this class of compounds). An extrapolation of these findings to patients receiving therapeutic dosages enables a favorable risk evaluation since the doses to be employed clinically are much lower and result in a far lower systemic exposure to drug substance.

Animals↗
PubMed1990

Albino versus pigmented animals for ocular toxicity testing.

The capability of uveal and retinal tissue to accumulate exogenously administered materials, coupled with the existence of anatomic, physiologic and biochemical ocular abnormalities in albino animals, evokes the question of whether albino animals are suitable for testing novel compounds for untoward ocular effects. Examples of special susceptibilities of either pigmented or non-pigmented animals to novel compounds exist. The best way to avoid unanticipated oculotoxic effects from the administration of novel compounds is to use both pigmented and unpigmented strains.

Albinism↗
PubMed1989

Chronic morpholine exposure of rats.

The chronic toxicity and carcinogenic potential of morpholine were evaluated in 60 Sprague-Dawley rats/sex/group receiving morpholine at mean inhalation exposure concentrations of 0, 10, 50 and 150 ppm for 6 hr/day, 5 days/week, for 104 weeks. Survival, body weight gains, organ weights, hematology, and clinical chemistries were normal in exposed groups and comparable to those of the control animals. The incidences of palpable tissue masses and of histologically confirmed neoplasia were comparable among all groups, including the control groups, and were typical of the strain and age of the rats tested. In-life clinical examinations revealed increased incidences of irritation around the eyes and nares, chromadacryorrhea, and urine stains on the fur, predominantly in high-dose animals. Morpholine exposure was associated with corneal irritation seen by ophthalmoscopic examination and confirmed microscopically as keratitis limited to the highest exposure group. Irritation of the maxillary and nasoturbinates as indicated by infiltration of neutrophils, focal squamous metaplasia of the turbinate epithelium, and necrosis of the turbinate bone was observed in high-dose animals. Therefore, chronic exposure of rats to morpholine for 2 years at concentrations of 150 ppm or less revealed no carcinogenic potential or chronic systemic toxicity. Consistent with its known irritating properties, morpholine produced only local irritation, which was limited almost exclusively to high-dose animals.

Administration, Inhalation↗
PubMed1983

Hyaloid artery patency in neonatal beagles.

The patency of the hyaloid artery in neonatal Beagles was evaluated after liquid latex perfusion. As early as postpartum day 5, some pups had closure of the most distal branches of the vessels of the posterior lens tunica, but in these, many larger branches were open. Other pups at postpartum days 5 and 6 had substantially all of the blood vessels of the posterior tunica vasculosa lentis open. Few tunica vessels were patent in any pups beyond day 13, and none was patent after day 17. Persistent hyaloid remnants at the optic disk were evident in 3 of 16 pups 17 to 28 days old, but absent in the others.

Aging↗
PubMed1975

Protothecosis with ocular involvement in a dog.

An 8 1/2-year-old Collie dog was referred for evaluation of chronic diarrhea as well as sudden blindness and leukokoria of the right eye. An organism morphologically similar to Prototheca sp was recovered from the subretinal fluid and was found at necropsy in the eyes, gastrointestinal tract, lungs, lymph nodes, kidneys, heart, abdominal fat, and omentum.

Animals↗
PubMed1975

Exophthalmos secondary to zygomatic adenocarcinoma in a dog.

An 8-year-old Labrador Retriever developed unilateral exophthalmos over a 1-year period. Contrast radiography, surgical exploration, and histologic examination revealed the cause to be an adenocarcinoma arising from the zygomatic salivary gland or duct.

Adenocarcinoma↗
PubMed1975

The electroretinogram in dogs with inherited cone degeneration.

The electroretinogram (ERG) of hemeralopic Alaskan malamute dogs contains only rod components. There is absence of the photopic b-wave which is normally elicited with red light stimuli during dark adaptation and, using flicker stimulation, only the first or rod branch of the flicker fusion response curve is present. At high stimulus intensity levels, the flicker response of hemeralopes is absent. A normal ERG is recorded from affected dogs using blue light stimuli and low intensity white light. In the adult hemeralope, the retina contains no cones.

Animals↗