['An', 'Unscheduled', 'DNA', 'Synthesis', '(UDS)', 'assay', 'in', 'rat', 'primary', 'hepatocytes', 'was', 'conducted', 'to', 'assess', 'the', 'potential', 'of', 'Tobacco', '57.561', 'to', 'produce', 'DNA', 'damage', 'as', 'indicated', 'by', 'increased', 'DNA', 'repair', 'synthesis.', 'Five', 'treatments', 'ranging', 'from', '0.1', 'to', '5.0', 'wl/mL', 'were', 'analyzed', 'for', 'UDS', 'which', 'represented', 'an', 'adequate', 'range', 'of', 'toxicities', 'for', 'analysis.', 'Tobacco', '57.561', 'did', 'not', 'cause', 'a', 'significant', 'increase', 'in', 'UDS', 'as', 'measured', 'by', 'an', 'increase', 'in', 'net', 'nuclear', 'grain', 'counts', 'compared', 'to', 'untreated', 'control', 'hepatocytes', '(i.e.,', 'an', 'increase', 'of', 'at', 'least', '5', 'counts', 'over', 'control).', 'This', 'material', 'was', 'therefore', 'considered', 'negative', 'in', 'this', 'assay,', 'suggesting', 'DNA', 'alterations', 'were', 'not', 'produced', '(Microbiological', 'Associates,', 'Inc.,', 'MBA', 'Study', 'No.', 'T5671.380,', '1987).', 'Tobacco', '57.561', 'was', 'evaluated', 'in', 'an', 'in', 'vitro', 'cytogenetic', 'assay', 'for', 'its', 'ability', 'to', 'induce', 'chromosomal', 'aberrations', 'in', 'Chinese', 'Hamster', 'Ovary', '(CHO)', 'cells', 'with', 'and', 'without', 'metabolic', 'activation.', 'No', 'increases', 'in', 'chromosome', 'aberrations', 'were', 'observed', 'in', 'the', 'non-activated', 'or', 'in', 'the', 'rat', 'S9-activated', 'test', 'systems', 'at', 'levels', 'of', '1250', 'to', '5010', 'wg/mL,', 'and', 'it', 'was', 'concluded', 'that', 'Tobacco', '57.561', 'was', 'negative', 'in', 'the', 'CHO', 'cytogenetics', 'assay', '(Hazleton', 'Laboratories', 'America,', 'Inc.,', 'HLA', 'Study', 'No.', '10842-0-437,', '1989).', 'The', 'acute', 'toxicity', 'of', 'Tobacco', '57.561', 'was', 'evaluated', 'after', 'a', 'single', 'intraperitoneal', 'injection', 'of', 'various', 'doses', 'to', 'Sprague-Dawley', 'rats', 'in', 'a', '0.9%', 'NaCl', 'vehicle', 'followed', 'by', 'a', '14', 'day', 'observation', 'period.', 'The', 'LDSO', 'was', 'greater', 'than', '5000', 'mg/kg', 'of', 'body', 'weight', 'for', 'both', 'male', 'and', 'female', 'rats,', 'and', 'the', 'sexes', 'combined.', 'The', 'only', 'clinical', 'signs', 'observed', 'in', 'this', 'study', 'were', 'sporadic', 'incidences', 'of', 'soft', 'feces', 'at', 'all', 'dosage', 'levels', '(Hazleton', 'Laboratories', 'America,', 'Inc.,', 'HLA', 'Project', 'No.', '642-142,', '1984).', 'The', 'acute', 'toxicity', 'of', 'Tobacco', '57.561', 'was', 'evaluated', 'at', 'Lorillard', 'Research', 'Center', 'after', 'a', 'single', 'intraperitoneal', 'injection', 'of', 'various', 'doses', 'in', 'a', '1.0%', 'methylcellulose', 'vehicle', 'to', 'male', 'Swiss-Webster', 'mice', 'followed', 'by', 'a', '24', 'hour', 'observation', 'period', '(Lorillard,', '1982).', 'The', 'LD,', 'was', 'estimated', 'to', 'be', 'greater', 'than', '5000', 'mg/kg', 'for', 'male', 'mice', 'in', 'thie', 'study.', 'A', 'rangefinding', 'study', 'was', 'conducted', 'in', 'Sprague-Dawley', 'rats', '(2', 'males,', '2', 'females', 'per', 'dose', 'level)', 'to', 'determine', 'the', 'maximum', 'tolerated', 'dose', '(MTD)', 'after', 'a', 'single', 'oral', 'administration', 'of', 'Tobacco', '57.561', 'in', 'a', '1%', 'methylcellulose', 'vehicle', 'followed', 'by', 'a', 'five-day', 'observation', 'period.', 'Lethargy', 'was', 'observed', 'in', 'both', 'females', 'dosed', 'at', '5000', 'mg/kg', 'at', 'the', 'three-hour', 'observation', 'interval,', 'but', 'this', 'was', 'not', 'considered', 'a', 'sign', 'of', 'toxicity', 'since', 'it', 'did', 'not', 'persist.', 'Therefore,', 'the', 'MTD', 'was', 'estimated', 'to', 'be', 'greater', 'than', '5000', 'mg/kg', 'for', 'male', 'and', 'female', 'rats', '(Borriston', 'Laboratories,', 'Inc.,', 'Project', 'No.', '251-K(2),', '1982).', ' ', 'A', 'study', 'was', 'performed', 'to', 'assess', 'the', 'acute', 'cardiovascular', 'and', 'respiratory', 'effects', 'of', 'Tobacco', '57.561', 'by', 'its', 'intravenous', '.', 'administration', 'in', 'anesthetized', 'male', 'beagle', 'dogs.', 'A', 'battery', 'of', 'tests', 'monitored', 'effects', 'on', 'cardiac', 'function,', 'systemic', 'circulatory', 'function,', 'segmental', 'vascular', 'function', 'and', 'respiratory', 'parameters', 'LO96PSLE']