Isomer-specific toxicity profiles of aminophenols

Details

• Personal Author:
  Lipscomb, Jane A. ; Perumal Kuppusamy S
• Description:
  Aminophenols are used in photographic processes, and in several fluorescent and hair dyes. Because the isomers differ in metabolism and the capabilities to cause toxicities in different organs, the repeated dose toxicity profiles for aminophenol isomers (ortho-, meta- and para-) are compared. Ortho aminophenol (OAP) is converted to 2-aminophenoxazine- 3-one by cytochrome c and excreted as sulfate and glucuronide conjugates. The critical effect is increased relative liver weight in male rats at 83 mg/kg-day on 12 days oral exposure. No observed adverse effect level (NOAEL) could not be identified. For meta aminophenol (MAP), only glucuronidation and sulfation conjugation reactions are reported. The critical effect is reduced body weight, tremors, and increased serum bilirubin in newborn rats of both sexes at 240 mg/kg-day on postnatal days 4-21 oral exposure. NOAEL is 80 mg/kg-day. Paraminophenol (PAP) is oxidized to p-benzoquinoneimine by renal tissue cytochrome P-450 and binds to renal protein. PAP acetylates and conjugates with glutathione for excretion. The critical effect is brown urine, increased epithelial cells in the urine, and increased proximal basophilic tubule in the kidney of both sexes of rats at 100 mg/kg-day on 28 days oral exposure. NOAEL is 20 mg/kg-day. The severe nephrotoxic effect of PAP, among other isomers, may be due to para arrangement on the benzene ring of hydroxyl and amino groups. OAP and PAP produced dose-related increases in developmental toxicity in Syrian Golden Hamsters with intraperitoneal injection. Although both positive and negative genotoxicity results are reported for all isomers, there is inadequate information to assess the carcinogenic potential for all of them. No repeated dose inhalation studies for all aminophenols are located. Taken together, each isomer target different organs. These kind of studies improve our understanding of the different risks posed by different arrangement of atoms in the molecule. [The findings and conclusions in this presentation are those of the authors and do not necessarily represent the views of the NIOSH or the US EPA.] [Description provided by NIOSH]
• Subjects:
  Acids Benzene Body Weight Energy Metabolism Environmental Exposure Kidney Diseases Laboratories Occupational Health Phenol Safety Toxicology Urogenital Diseases Urogenital System

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• Keywords:
  Amino Acids Amino Compounds Amino Groups Body Weight Chemical Binding Developmental Disorders Exposure Assessment Exposure Levels Genotoxicity Hydroxyl Groups Kidney Toxins Laboratory Animals Laboratory Testing Liver Damage Metabolism Molecular Structure Nephrotoxins Oral Cavity Organs Oxidation Phenols Proteins Renal Absorption Risk Assessment Sugars Sulfates Toxic Effects Xenobiotics

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Louisiana ; Ohio ; OSHA Region 5 ; OSHA Region 6
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  EID - Education and Information Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  150
• Issue:
  1
• NIOSHTIC Number:
  nn:20047703
• Citation:
  Toxicologist 2016 Mar; 150(1):402
• CAS Registry Number:
  2-Aminophenol (CAS RN 95-55-6) ; 3-Aminophenol (CAS RN 591-27-5) ; 4-Aminophenol (CAS RN 123-30-8)
• Federal Fiscal Year:
  2016
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 55th Annual Meeting and ToxExpo, March 13-17, 2016, New Orleans, Louisiana
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:892f31a2e55e068de8b20175bc0599faabf8fd055a478ae9b70b9bc0f0f9e04632d33de5e39a68bc153c05293bc9b244948747a19fdb6116dd483e0d281c71a9
• Download URL:
  https://stacks.cdc.gov/view/cdc/202706/cdc_202706_DS1.pdf
• File Type:
  [PDF - 442.40 KB ]