User Guide to Thresholds and Classification - Environmental ...

142User Guide for Thresholds and ClassificationsAre any of the acute toxicity values ‗outliers‘? Acute toxicity values can vary from study to study,between species, within a species, or between sexes.RelevanceIs the route of exposure tested relevant to likely human exposure to the substance?Were the acute toxicity values reported in preferred laboratory species? (The preferred test speciesfor evaluation of acute toxicity by the oral and inhalation routes is the rat, while the rat or rabbit ispreferred for evaluation of acute dermal toxicity.)If there are acute toxicity values in animal species that are not preferred laboratory species, is theanimal used considered to be a relevant indicator of acute toxicity exposure in humans?The appropriate LD 50 value should, therefore, be the most reliable and relevant LD 50 value.10.2.3. Reliable informationThe EPA acknowledges that the use of reliable information to determine threshold within clause 2(1)(d) ofSchedule 4 to the Hazardous Substances (Minimum Degrees of Hazard) Regulations 2001 should be linkedto evident toxicity. Evident toxicity means clear signs of toxicity following the administration of a testsubstance sufficient for hazard assessment and such that an increase in the dose administered can beexpected to result in the development of severe toxic signs and probable mortality.It is also important to note that an epidemiological study in humans that shows evident toxicity has notoccurred is also important information that should be considered when determining whether classification ofa substance is necessary (provided it is well established that human exposure did occur).10.2.4. Lowest toxic doses and lowest lethal dosesSome acute toxicity databases give information on the lowest lethal doses (LD LO ) or the lowest toxic doses(TD LO ). Similarly inhalation concentrations are sometimes found (LC LO and TC LO ). This information can bederived from an animal study or human exposure. These values in humans tend to be based on anecdotalexposure to a single dose or occupational exposure, so uncertainty may exist about the actual dose taken.If an LD LO is available, this may be used directly in the calculations for the toxicity of a mixture. However, theresultant value may result in an overly conservative classification. How to calculate the toxicity of a mixture isdescribed in section 10.3.If a TD LO is available, then a general indication of acute toxicity may be inferred from the value. The TD LO isthe lowest dose known to cause a toxic effect, as opposed to a result from a standardised acute toxicitytesting method that gives rise to the lethal dose capable of killing 50% of the test animals (LD 50 ). It can,therefore, be assumed that the LD 50 for the substance would be greater (a larger amount) than the TD LO .10.2.5. Precedence of human data over animal dataWhen direct human data show an acute effect (for example, the LD LO is established or clinical signs of acutetoxicity in humans are observed), this effect takes precedence over negative results from animal studies.10.2.6. Low viscosity substances with an aspiration hazardJanuary 2012 EPA0109