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Biomedical subjects

R F McConnell

Publications and source records attributed to R F McConnell.

21 records · Page 2Linked to original sources
PubMedDate not supplied

Strain as a determinant factor in the differential responsiveness of rats to chemicals.

The beneficial effects derived from the use of chemicals in agriculture, energy production, transportation, pharmaceuticals, and other products that improve the quality of life are clearly established. However, continued exposure to these chemicals is only advantageous in conditions where the benefit far outweighs toxic manifestations. By law, determination of risk of toxicity necessitates the use of laboratory animals to establish whether chemical exposure is safe for humans. To simulate the human condition, it is incumbent upon investigators to choose a species in which pharmacokinetic and toxicokinetic principles are established and resemble those of humans. Some of the advantages to the use of rat in chemical toxicity testing include (a) similarities in metabolism, anatomy, and physiological parameters to humans; (b) the short life span, especially for carcinogenesis study; (c) the availability, ease of breeding, and maintenance at a relatively low cost; and (d) the existence of a large database to enable comparison of present to reported literature findings. However, the choice of rat can be complicated by several factors such as sex, age, and nutrition, but especially strain, where currently there are over 200 different strains of rat known to exist. The aim of this review is to demonstrate that there are differences in the responsiveness of rat strains to chemicals and that the susceptibility observed is dependent on the tissue examined. It is evident that the genotype differs among strains, and this may be responsible for differences in sensitivities to chemicals. Awareness of strain as a factor in susceptibility to toxicant action needs to be taken into account in interpretation of relevance of risk of toxicity for humans.

Animals↗
PubMedDate not supplied

Systemic and histopathologic changes in Beagle dogs after chronic daily oral administration of synthetic (ethinyl estradiol) or natural (estradiol) estrogens, with special reference to the kidney and thyroid.

ABSTRACT Four groups of 3 male and 3 female sexually mature Beagle dogs were treated daily po with either ethinyl estradiol (EE) or estradiol (E2). A fifth group of 4 males and 4 females acted as a control group. Three groups of dogs were treated with EE: One group was treated at dose levels of 2.0, 1.5, and 1.0 mg/kg for 6 mo; the other 2 groups received either 0.5 mg/kg or 1.0 mg/kg for 1 yr. The fourth group was treated with 5.0 mg/kg E2 for 1 yr. Results obtained for the clinical, hematological, and biochemical parameters and the histopathologic findings of most organs and tissues in EE- and E2-treated dogs were essentially comparable to those documented in the literature for dogs treated with synthetic or natural estrogens. Chronic treatment with EE or E2 induced similar effects, with the exception of mesothelial proliferation of the genital serosa, which was observed in EE-treated dogs only. Additional new estrogen-related findings were observed in the kidneys and thyroid glands of EE- and E2-treated dogs. Increased interstitial fibrous tissue occurred at the corticomedullary junction and in the outer cortex of the kidney. It appeared to originate primarily from the perivascular fibrous tissue of branches of the renal arteries and veins. Extension of this lesion into the renal parenchyma resulted in secondary atrophic changes of tubules and glomeruli. The treatment relationship and specific characteristics of this renal alteration differentiated it from other chronic renal interstitial and vascular diseases. Squamous metaplasia of urogenital tract epithelia, including renal cortical tubule epithelium, occurred as expected in both EE- and E2-treated dogs. Unexpectedly, squamous metaplasia of thyroid follicular epithelium also occurred. It was present in scattered follicles of both EE- and E2-treated dogs. The renal and thyroid changes did not alter clinicopathological function tests for either of these organs. These 2 new findings extend the list of estrogen-related effects in the dog.

Administration, Oral↗