Initial Submission: Pathological Evaluations, 90-Day Inhalation Toxicity Study with Ethyl Acetate in Rats, with Cover Letter dated 08/02/1996

摘要

Ten rats/sex designated for the 90-day clinical pathology examination from the control (0 ppm) and high concentration (1500 ppm) groups, and all surviving rats from the low (350 ppm) and intermediate (750 ppm) concentration groups were sacrificed by carbon dioxide anestbesia and exsanguination and necropsied after approximately 90 days on study. Liver, kidneys, lungs, heart, spken, brain, adrenal glands, testes (right), and ovaries from rats sacrificed by design at tbc end of the exposure period wcm weighed wet at necropsy. All rats on study were given a complete g:oss examination and represcatative samples of the following tissues were saved at necropsy: liver, kidneys, lungs, heart, skoletal muscle, spleen, aorta, brain (cerebrum, midbrain, cerebellum, medullalpons), spinal cord (cavical, thoracic, lumbar), stomach, duodenum. jejunum, ileum, pancreas, cecum, colon, rectum, mesenteric lymph node, salivary glands, mandibular lymph node, harderian glands, exorbital lacrimal glands, thymus, adrenal glands, sciatic nerve, pituitary gland, thyroid gland, pamthyroid glands, trachea, esophagus, pharynx/larynx, eyes, skin, mammary gInds (female), ovaries, uterus, vagina, urinary bladder, prostate, seminal vesicles, testes (right), femur (including joint), sternum, bone marrow (femur, stemum), nose (4 sections) and selected gross lesions. Gross lesions which were diagnosed at necropsy and for which microscopic examination was not appropriate (e.g., fluid, rufQed fur, missing anatomic parts) were generally not collected. Selected gross lesions for which a microscopic diagnosis would not be additive (e.g., osteoarthritis, pododermatitis, chronic dermatitis of the tail. urinary calculi. and deformity of the teeth, too. tail. or pinna) were saved but were generally not processco for microscopic evaluation. All tissues were fixed in 10% neutral buffered formalia except testes, and eyes which were fixed in Bouin's solution. The lungs were inflated with 10% neutral buffered formalia after weighing. All tissues, including selected gross lesions, collected from rats in the high-concentration and control groups that were sacrificed at the end of the exposure period and from early death rats (found dead, accidentally killed, sacrificed in extremis) during this period, were processed, embedded in paraffin, cut at a nominal thickness of 5 micrometers, stained with homatoxylin and easin (H&E) and examined microscopically. Nose, pharyndlarynx, liver, kidneys, lungs and selected gross lesions from rats in the low- and intermediate-concentration groups were also processed to slides and examined microscopically.