Guidelines for Canadian Drinking Water Quality: Guideline Technical Document – Nitrate and Nitrite

Table of Contents

• Part I. Overview and Application
  • 1.0 Guidelines
  • 2.0 Executive summary
    • 2.1 Health effects
      • 2.1.1 Nitrate
      • 2.1.2 Nitrite
    • 2.2 Exposure
    • 2.3 Analysis and treatment
  • 3.0 Application of the guideline
    • 3.1 Monitoring
• Part II. Science and Technical Considerations
  • 4.0 Identity, use and sources in the environment
    • 4.1 Identity
    • 4.2 Major uses and sources
    • 4.3 Environmental fate
  • 5.0 Exposure
    • 5.1 Water
    • 5.2 Food
    • 5.3 Air
    • 5.4 Consumer products
    • 5.5 Soil
  • 6.0 Analytical methods
  • 7.0 Treatment technology
    • 7.1 Municipal scale
      • 7.1.1 Ion exchange
      • 7.1.2 Reverse osmosis/nanofiltration
      • 7.1.3 Electrodialysis/electrodialysis reversal
      • 7.1.4 Biological denitrification
      • 7.1.5 Emerging treatment technologies
      • 7.1.6 Nitrification in the distribution system
      • 7.1.7 Formation of nitrate or nitrite from other treatment technologies
    • 7.2 Residential scale
  • 8.0 Kinetics and metabolism
    • 8.1 Absorption
    • 8.2 Distribution
    • 8.3 Metabolism
      • 8.3.1 Endogenous nitrate formation
    • 8.4 Excretion
    • 8.5 Physiologically-based pharmacokinetic models
  • 9.0 Health effects
    • 9.1 Effects in humans
      • 9.1.1 Acute toxicity
      • 9.1.2 Subchronic toxicity
        • 9.1.2.1 Thyroid effects
        • 9.1.2.2 Insulin-dependent type 1 diabetes mellitus
        • 9.1.2.3 Balkan endemic nephropathy (BEN)
      • 9.1.3 Long-term exposure and carcinogenicity
        • 9.1.3.1 Gastrointestinal tract tumours
        • 9.1.3.2 Non-Hodgkin's lymphoma (NHL)
        • 9.1.3.3 Brain tumours
        • 9.1.3.4 Urinary tract tumours
        • 9.1.3.5 Other tumour sites (upper aerodigestive tract, pancreas, thyroid gland)
      • 9.1.4 Reproductive and developmental toxicity
    • 9.2 Effects on experimental animals
      • 9.2.1 Acute toxicity
      • 9.2.2 Short-term exposure
        • 9.2.2.1 Methaemoglobinaemia
        • 9.2.2.2 Thyroid effects
        • 9.2.2.3 Effects on the vascular system and adrenals
        • 9.2.2.4 Effects on kidneys
      • 9.2.3 Long-term exposure and carcinogenicity
        • 9.2.3.1 Ingested nitrate
        • 9.2.3.2 Ingested nitrite
      • 9.2.4 Concurrent administration of nitrate/nitrite with nitrosatable compounds
        • 9.2.4.1 Short-term exposure leading to cancer
        • 9.2.4.2 Long-term exposure leading to cancer
        • 9.2.4.3 Studies on interactions with antioxidants
        • 9.2.4.4 Conclusion
      • 9.2.5 Genotoxicity of the concurrent administration of nitrite and nitrosatable compounds
        • 9.2.5.1 In vivo
        • 9.2.5.2 In vitro
      • 9.2.6 Genotoxicity of nitrate and nitrite
        • 9.2.6.1 In vivo
        • 9.2.6.2 In vitro
      • 9.2.7 Reproductive and developmental toxicity
        • 9.2.7.1 Reproductive effects
        • 9.2.7.2 Developmental effects
    • 9.3 Endogenous formation of N-nitroso compounds
      • 9.3.1 Chemistry of endogenous N-nitrosation
        • 9.3.1.1 Acid-catalysed nitrosation
        • 9.3.1.2 Cell-mediated nitrosation
      • 9.3.2 Inhibitors of (acid-catalysed) N-nitrosation
        • 9.3.2.1 Vitamin C (ascorbate + dehydroascorbic acid)
        • 9.3.2.2 Vitamin E (tocopherol) and other compounds
      • 9.3.3 In vitro and in vivo findings on endogenous nitrosation
    • 9.4 Mode of action
      • 9.4.1 Non-cancer
        • 9.4.1.1 Methaemoglobinaemia
        • 9.4.1.2 Thyroid effects
      • 9.4.2 Cancer effects
  • 10.0 Classification and assessment
    • 10.1 Nitrate
    • 10.2 Nitrite
    • 10.3 Cancer risk related to endogenous nitrosation
      • 10.3.1 Quantitative risk assessment
        • 10.3.1.1 Estimation of endogenous formation of nitrosamines: exposure model
        • 10.3.1.2 Estimation of cancer risk
      • 10.3.2 Example of calculation for NDMA
      • 10.3.3 Risk characterization
    • 10.4 Comparison of cancer and non-cancer risk assessment
    • 10.5 International considerations
  • 11.0 Rationale
    • 11.1 Nitrate
    • 11.2 Nitrite
  • 12.0 References
• Appendix A: List of Acronyms