Subchronic inhalation toxicity of p-nitroaniline and p-nitrochlorobenzene in rats |
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| Affiliation: | 1. Monsanto Company, 800 North Lindbergh Boulevard, St. Louis, Missouri 63167 USA;2. Bio/Dynamics, Inc., East Millstone, New Jersey, 08873 USA;1. Pfizer Worldwide Research and Development, Drug Safety Research and Development, Sandwich, Kent, UK;2. Pfizer Worldwide Research and Development, Drug Safety Research and Development, Groton, CT, USA;1. Lhasa Limited, Granary Wharf House, Leeds West Yorkshire LS11 5PS, United Kingdom;2. GlaxoSmithKline R&D, Park Road, Ware, Hertfordshire SG12 0DP, United Kingdom;3. AstraZeneca, Charter Way, Macclesfield SK10 2NA, United Kingdom;4. New Drug Modalities, Drug Safety and Metabolism, IMED, AstraZeneca, Cambridge, United Kingdom;5. Takeda Pharmaceuticals International Co, Cambridge, MA 02139, United States;6. Merck KGaA, Biopharma, Non-Clinical Safety, HPC: U009/101, 64271 Darmstadt, Germany;7. Bayer AG, Pharmaceuticals Division, Genetic Toxicology, Müllerstr. 178, D-13353 Berlin, Germany;8. Novartis Institutes for Biomedical Research, Novartis AG, Werk Klybeck 135-118, 4057 Basel, Switzerland;9. Novartis Institutes for Biomedical Research, 181 Massachusetts Avenue, Cambridge, MA 02139, United States;10. UCB, 216 Bath Road, Slough SL1 3WE, United Kingdom;11. UCB BioPharma SPRL, Investigative Toxicology, Chemin du Foriest, B-1420 Braine-l’Alleud, Belgium;12. Genetic Toxicology, Drug Safety Research and Development, Pfizer Worldwide Research and Development, Groton, CT 06340, United States;13. Eli Lilly and Company, Erl Wood Manor Research Centre, Windlesham, Surrey GU20 6PH, United Kingdom;14. Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, United States;15. Sanofi R&D Preclinical Safety, Industriepark Hoechst, 65926 Frankfurt am Main, Germany;p. F. Hoffmann-La Roche Ltd, Roche Pharma Research & Early Development, Pharmaceutical Sciences, Roche Innovation Center, Basel, Grenzacherstrasse 124, Switzerland;q. EU Head Genetic Toxicology, Mechanistic & Investigative Toxicology, Discovery Sciences, Janssen Pharmaceutica, Turnhoutseweg 30, B-2340 Beerse, Belgium;1. School of Environmental Science and Engineering/Tianjin Engineering Research Center of Bio Gas/Oil Technology, Tianjin University, Tianjin 300072, China;2. School of Chemical Engineering, The University of Adelaide, Adelaide, SA 5005, Australia;3. Georgia Tech Shenzhen Institute, Tianjin University, Shenzhen 518071, China;1. College of Environmental Science and Engineering, Hunan University, Changsha 410082, PR China;2. Key Laboratory of Environment Biology and Pollution Control, Hunan University, Ministry of Education, Changsha 410082, PR China;3. Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore;4. Singapore Membrane Technology Center, Nanyang Environment and Water Research Institute, Nanyang Technological University, 639798, Singapore;1. Institute of Environmental Research at Greater Bay, Key Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, Guangzhou University, Guangzhou, Guangdong, 510006, China;2. School of Environmental Science and Engineering, Guangzhou University, Guangzhou, Guangdong, 510006, China;3. College of Packaging and Materials Engineering, Hunan University of Technology, Zhuzhou, 412007, China;4. School of Resources & Environment and Safety Engineering, University of South China, Hengyang, Hunan, 421001, China;5. Institute for Frontier Materials, Deakin University, Geelong, Victoria, 3216, Australia |
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| Abstract: | For evaluation of subchronic toxicity of the two single-ring nitroaromatics, p-nitroaniline (PNA) and p-nitrochlorobenzene (PNCB), groups of 10 male and 10 female Sprague-Dawley rats were exposed to an aerosol/vapor of PNA in isopropanol at target concentrations of 0, 10, 30, or 90 mg/m3 or to PNCB vaporized from a solution in ethylene glycol monoethyl ether at target concentrations of 0, 5, 15, or 45 mg/m3 for 6 hr/day, 5 days/week for 4 weeks. Clinical signs of toxicity, body weights, results of ophthalmoscopic exam, hematology and clinical chemistry tests, organ weights, gross and histopathological changes were recorded. Exposure to PNA or PNCB resulted in a dose-related increase in blood methemoglobin levels. Mean red blood cell counts, hematocrit, and hemoglobin were significantly decreased in mid and high level animals exposed to PNCB. Mean spleen weights (absolute and relative to body weight) were significantly increased at the high dose levels in the two studies. A slight increase in spleen weights was also observed at the low concentration level in the PNA study. Absolute and relative liver weights also were increased among animals exposed to 45 mg/m3 PNCB. Microscopic changes were observed mainly in the spleen and included an increase in intensity of extramedullary hematopoiesis and hemosiderosis with both compounds. Spleens of animals exposed to PNCB also exhibited congestion. Neither PNA nor PNCB exhibited significant toxicological effects other than those of methemoglobinemia, anemia, and splenic changes classically associated with nitroaromatics at levels significantly above presently accepted occupational standard. Our data suggest that the current TLV for PNA which is 3 mg/m3 will provide adequate protection to the workers. OSHA's PEL of 1 mg/m3 for PNCB is to be preferred over the current TLV of 3 mg/m3 to provide a comparable margin of safety. |
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