Abstract |
This study was conducted for Union Carbide Corporation. It was designed to assess the potential toxicity of 12-Crown-4 (CAS No. 294-93-9) when administered to the skin of Sprague-Dawley CD rats at doses of 50, 100, and 250 mg/kg/day at a dose volume of 1.0 mL/kg, for nine days over a two week period, at concentrations of 50, 100 and 250 mg/mL, respectively. The control animals received the vehicle alone (distilled water) at the same dose volume and frequency as the treated animals. All groups contained 10 males and 10 females for selected sacrifice at the end of the dosing period. Also, the control and high dose groups had an additional 5 males and 5 females for sacrifice 4 weeks after the end of the dosing ('recovery animals'). Pilot studies with undiluted and diluted test material were performed to select doses for the main study. Study animals were observed twice daily for mortality/morbidity and for obvious pharmacologic and/or toxicologic effects. Clinical pathology laboratory studies were performed prior to the terminal and recovery euthanasias. Detailed physical examinations, skin evaluations, neurobehavioral examinations (Modified Irwin Screen), body weight, food consumption and water consumption measurements were performed pretest and at select intervals during the study. Selected animals were euthanized after nine days of treatment (Day 12), the remaining survivors were held for a 4-week recovery period and then euthanized on Day 38 of the study. Complete macroscopic postmortem examinations were conducted on all animals, selected organs were weighed and organ/body weight and organ/brain weight ratios were calculated. Histopathological evaluation of selected tissues was performed for all animals. |