User Guide to Thresholds and Classification - Environmental ...

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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
143User Guide for Thresholds and ClassificationsSome liquid substances and preparations present an aspiration hazard in humans because of their lowviscosity.The 6.1E acute oral toxicity classification is triggered if the substance has the following physical properties orhas known aspiration hazards in humans.The 6.1E acute oral toxicity classification is triggered if:a. The substance is a hydrocarbon with a kinematic viscosity of ≤20.5 mm 2 /s measured at 40°C orthere is reliable and good quality human evidence to indicate a human aspiration (note this isessentially the same as the GHS category 1); orb. The substance has a kinematic viscosity ≤14 mm 2 /s at 40°C, with evidence from existing animalstudies, and expert judgment which takes into account surface tension, water solubility, boiling pointand volatility (note this is essentially the same as the GHS category 2).The following formula provides a conversion between dynamic and kinematic viscosity:Dynamic viscosity (mPa.s) = kinematic viscosity (mm 2 /s)Density (g/cm 3 )A mixture is classified as 6.1E acute oral toxicity (aspiration hazard) if it contains:≥10% of a substance classified under criterion 1 , and has a kinematic viscosity of viscosity of ≤20.5mm 2 /s measured at 40°C (GHS Category 1); or≥10% of a substance classified under criterion 1 , and has a kinematic viscosity of viscosity of ≤14 mm 2 /smeasured at 40°C (GHS Category 2)A mixture which separates into two or more distinct layers, one of which contains ≥10% of an ingredientclassified according to either criterion, then the entire mixture is classified accordingly.The latest revision to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS)(United Nations, 2007) has included two separate classifications for substances that present an aspirationhazard. The EPA is reviewing the Hazardous Substances (Minimum Degrees of Hazard) Regulations 2001and the Hazardous Substances (Classification) Regulations 2001 in light of this revision to determinewhether these regulations should be amended.10.2.7. Specific considerations for inhalation toxicityConversionsValues for inhalation toxicity are based on four-hour tests in laboratory animals. For conversion of existinginhalation toxicity data generated from exposures other than four hours, the following formulae should beused.Dusts and mists: LC 50 (4 hours) = LC 50 (x hours) × (x/4)Vapours and gases: LC 50 (4 hours) = LC 50 (1 hour) × (1/2)Conversion of inhalation data for vapours, dusts, or mists specified as milligrams per cubic metre (mg/m 3 )to mg/L: mg/L = mg/m 3January 2012 EPA0109
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