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“The Dose makes the Poison” Paracelcus (1567)

“The Dose makes the Poison” Paracelcus (1567). Ferguson cut-off Chemical concentration in the water needed to produce the internal concentration in the organism required to trigger the effect exceeds the chemical’s water solubility. Internal concentrationfor acute toxicity : 5 mmol/kg

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“The Dose makes the Poison” Paracelcus (1567)

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  1. “The Dose makes the Poison” Paracelcus (1567)

  2. Ferguson cut-off Chemical concentration in the water needed to produce the internal concentration in the organism required to trigger the effect exceeds the chemical’s water solubility.

  3. Internal concentrationfor acute toxicity : 5 mmol/kg Fish-water Bioconcentration Factor : 0.04 8 105.5 = 12,600 Water Concentration needed : 5 / 12,600 = 4 .10-4 mmol/L Water Solubility : 1.7 .10-5 mmol/L

  4. Toxic Effect = f(concentration at the active site, concentration at the active site required to trigger the effect) Toxic Effect = f(EXPOSURE, POTENCY) Toxic Effect = f(EXPOSURE, TOXICITY)

  5. What is the difference? • Dose makes the Poison • Toxic Effect = f(concentration at the active site, concentration at the active site required to trigger the effect)

  6. To agree or not agree? Chemicals that cause the same effect at the same internal concentration have the same potency / toxicity

  7. Non-Polar Narcosis • similarity with mode of action of anaesthetics (chloroform) • Internal Concentration : 3 to 6 mmol/kg • fairly universal among organisms & chemicals • basic toxicity • mechanism is unknown but chemicals are believed to affect membrane fluidity or thickness which affects Na-K pump in cells, which is reponsible for transmission of nerve impuleses

  8. Concentration 1 1 in water (umol/L)

  9. FISH 1FISH 2 Volume Total (m3) 1 1 Volume Water (m3) 0.9 0.5 Volume Lipid (m3) 0.1 0.5 Concentration in water 1.10-6 1.10-6 (mol/m3) ZW 1 1 fW 1.10-6 1.10-6 fL 1.10-6 1.10-6 ZL 104 104 Cw 1.10-6 1.10-6 CL 1.10-2 1.10-2 VW.CW 0.9 . 10-6 0.5 . 10-6 VL.CL 0.1 . 10-2 0.5 . 10-2 Vi.Ci ~0.1 . 10-2 ~0.5 . 10-2 Ci ~0.1 . 10-2 ~0.5 . 10-2

  10. Dose makes the Poison Toxic Effect = f(EXPOSURE, POTENCY) Toxic Effect = f(EXPOSURE, TOXICITY) Toxic Effect = f(concentration at the active site, concentration at the active site associated with the effect)

  11. Toxic Effect = f(fugacity at the active site, fugacity at the active site associated with the effect) f(f at the active site, f at the active site associated with the effect)

  12. Toxic Effect = f(fugacity at the active site, fugacity at the active site associated with the effect) f(f at the active site, f at the active site associated with the effect)

  13. CEPA Framework for Evaluating DSL Chemicals Substances on the DSL Persistent and or Inherently Toxic PHASE 1: Bioaccumulative no Categorization No further action under this Yes program PHASE 2: Is the Substance a Screening Assessment Screening level Track 1 Substance? risk assessment Add to the Priority Add to Schedule 1 No Further Action Substances List for Outcomes List of Toxic Substances for at this Time Further Assessment Possible Regulatory Actions

  14. “inherent Toxicity” • iT is the “hazard a substance presents to the environment” • iT can be represented by the toxic effect caused by a substance that has not been masked or mitigated by some factor or parameter; that is, the toxicity found in a study (or predicted) due solely to the test substance • iT is a judgement - based evaluation of a chemical’s impact on • the environment • Proposed Cut-off value is : 1 mg/L

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