impact

• What happens when a xenobiotic reaches a living organism

  1. Kinetic phase (metabolism + excretion)

  2. Dynamic phase (interaction with cell, tissues, organs -> cause toxic response)
• Kinetic phase

  Metabolism + excretion, how much in and out (bioaccumulation, trophic level high)
• Dynamic phase


  Interaction with cell, tissues, organs -> cause toxic response
• Dynamic approach: Kill? Provoke illness? Modify metabolism? Modify hormonal balance?
• Effect depend on exposure: Detrimental effect(s) on tissues, organs or biological processes depend on physical form, matrix and type of exposure
• Type of exposure


  • Route of exposure (solid, gas, liquid)
  • Oral, dermal etc.
  • Frequency of exposure
  • Length of exposure
  • Level = concentration
• Acute exposure


  High concentration, short time, immediate response, might clear away (e.g. occupational)
• Chronic exposure


  Low concentration, long time, lag time, persistent effect (e.g. environmental)
• Complex and diverse exposure patterns + biological variability = basic effect testing
• Standard ecotoxicity tests are performed following some guidelines (OECD) on simplified systems (allow comparison of different chemicals)
• Standard ecotoxicity tests


  • Single species
  • One matrix
  • Fixed concentration
  • Laboratory conditions allow comparisons of different chemicals
• Base set for industrial chemicals

  • Fish: acute (96 h) survival, chronic (7-200 d) on eggs or juveniles hatching success, growth
  • Crustaceans: acute (48 h) and chronic (21 d) -> survival and reproduction
  • Algae: growth inhibition (72 h)
  • Bacteria: growth inhibition
• Alive or dead, chronic exposure
• Algae growth inhibition test

  1. Cultures of green algae growing exponentially

  2. Exposure to one compound for 72 h, range of concentrations

  3. Replicate

  4. Toxic level reduce reproduction
• Dose-response relationship


  • LC50, EC50 + concentration required to observe of mortality/effect
  • LOEC = lowest conc. at which an effect is observed
  • NOEC = highest conc. at which no effect
  • There is no safe dose
• Toxicity scale for aquatic organisms: the higher the least toxic. A concentration of 100ml or more is required to observe 50% impact on survival, reproduction, etc.
• Phytotoxicity = increasing concentration of pharmaceutical in soil
• Terrestrial organisms


  • Soil dwelling organisms: invertebrates (earthworms, enchytraeids and collembolans), microorganisms (carbon transformation test)
  • Birds, bees: particularly sensitive to some pesticides -> rather monitoring than testing
• One specie-one compound-under laboratory conditions is not very realistic. Need SSD, consider food webs, effects of mixtures, pulsed and sequential exposure.
• Effects of mixtures


  • Additive (1+1=2)
  • Synergistic (1+1=3) Higher impact than think
  • Potentiation (0+1=2) Not effect on own but when combined with something then overall effect of mixture is higher
  • Antagonism (1+1=1) Effect is less then what we predicted
• Effects of mixtures are still poorly understood + Environment: complex and dynamic mixtures - Concentration not fixed, up and down. Changes in biota, temperature..
• Demonstrating a direct link between a chemical and a health outcome is very challenging (unless extremely high exposure). Mixture of toxicants, long latency, population migration, individual exposure difficult to measure -> No dose-response relationships, confounding factors (e.g. socio economic status, smoking), low number of cases -> difficulty in showing a significant difference compared to a control population
• Toxicity to humans: For existing and new chemicals, mostly based on extrapolation from toxicity tests on model organisms, analysed with health statistics. Animal testing very controversial as many scientists argue that toxicity cannot be extrapolated across species.
• Endocrine disruptors

  Substances that act like hormones in the endocrine system -> disruption of endogenous hormones functions. Effects include reduced fertility, skewed male/female sex ratios, loss of foetus, early puberty, brain/behaviour problems, impaired immune functions, difficult to measure. Dose–response controversy: effect at very low concentration not deducible from higher dose -> Difficulty in defining some regulatory maximum concentration.
• Sources of human exposure to endocrine disruptors

  • Food (PCB/DDT/PBDE)
  • Indoor air/dust
  • Water
• Wide range of effects
• "The dose makes the poison" or "the solution to pollution is dilution" (concentration goes down) -> Concept of dose-response relationship
• The effects of real exposure patterns (frequency, duration) and mixtures is difficult to predict