LD50半数致死剂量.pdf 3页VIP

Environment, Health and Safety Committee [EHSC] Note On “ LD50 ” [ LETHAL DOSE 50% ] This Note is designed to provide guidance to RSC members, though it This Note was produced by may also be useful to others with a particular interest in the subject. It a Working Party of the Environment, Health and is an update of the original version which was issued in 1996. Safety Committee [EHSC] of the Royal Society of The LD50 test and its variants were often undertaken as a result of Chemistry with expert legislative requirements. These tests are now considered obsolete input from the Society’s and nowadays they would rarely if ever be performed in the United Occupational and Kingdom and many other countries. Internationally accepted Environmental Toxicology Group. alternative tests have been developed. These use fewer animals and “absence of evident toxicity”, rather than death, as their criterion. They The Society is a registered have been accepted by most regulators as valid alternatives to LD50 Charity. Its Royal Charter testing. obliges it to serve the public interest by acting in an independent advisory capacity. Nonetheless LD50 values are still quoted and enquiries received by the In order to meet this obligation the members of the EHSC are Royal Society of Chemistry suggest that there is still a need for drawn from a wide range of information about their meaning. This Note aims to provide basic backgrounds and serve on the information about LD50 but does not pretend to be a full or definitive committee as individual experts explanation. Readers are urged to obtain more detailed information if and not as representatives of their employer. this is required. Also this paper does not address the complex ethical arguments surrounding the use of animal experiments to obtain LD50 The EHSC welcomes comments on this Note. Please send them and related data. to the committee secretary : WHAT IS AN LD50? Health, Safety and Environment Officer Royal Society of Chemistry “LD50” is an abbreviation for “Lethal Dose 50%.” It is sometimes also Burlington House referred to as the “Median Lethal Dose”. Although the LD50 is no Piccadilly London longer the only measure available for assessing the acute toxicity of W1J 0BA single doses of a substance, for historical reasons it is probably still the most commonly cited measure. Tel: 020 7440 3337 Fax: 020 7437 8883 Email: hazellr@ The LD50 for a particular substance is essentially the amount that can be expected to cause death in half (ie 50%) of a group of some EHSC Notes are updated from time to time and the most up to particular animal species, usually rats or mice, when entering the date versions can be found on animal’s body by a particular route. For example if the substance is the Society’s website swallowed the figure is an ‘oral LD50’whereas if its absorbed through the skin it’s a ‘dermal LD50 ‘. LD50 figures are derived by mathematical You may also wish to visit the calculation from the results of tests on animals and hence should not chemistry societies’network at be regarded as biologically precise values. In general the amounts of a substance required to kill animals from different species are Version 2 – 31/7/01 approximately related to the animals’body weights. Therefore LD50 figures are usually reported in units of milligrams of the substance per kilogram body weight for the animal species concerned. The LC(t)50 (lethal concentration 50% for exposure time t) is a similar and widely used measure for acute toxicity by inhalation. The LC(t)50 is essentially the concentration of a substance that can be expected to cause death in half [ie 50%] of a group of some particular species when entering the body over the specified period of time. “LC(t)50”figures are usually reported as milligrams of the substance per cubic metre (or litre) of the atmosphere to which the animal is exposed for the specified time [ t ]. Generally, no account is taken of body weight when comparing values for different species. Conventionally, the median lethal dose (MLD) is quoted as an LD50 when the exposure is by swallowing, skin contact or injection and as an LC(t)50 when exposure is by breathing it in. When quoting an LD50 the information must include the substance, the route of entry and the animal species. For example sodium cyanide has an oral LD50 of 15 mg/kg in rats. The LC(t)50 of a substance should state the duration [ t ] and species. From the above it will be clear that the smaller the LD50 or LC(t)50 figure the less the amount of the substance needed to cause death. In environmental toxicology the concentration of a substance which may be lethal to wildlife may also be expressed as LC(t)50 figures where the concentration [ c ] refers to the concentration in the relevant environmental medium. Perhaps the most common such use is LC(t)50 in water to indicate aquatic concentrations lethal to fish species. However LC(t)50 values can also be given for a substance in soil or other materials. WHAT USE IS AN LD50 FIGURE? Most users of a substance will need to know its toxicity to humans. It requires expert judgement to assess the relevance to humans of toxicity data derived from animals, including LD50 figures. Under European law the supplier of a chemical substance must assign it to a defined toxic hazard category using criteria set out in the legislation. The supplier may use LD50 figures, among other data, when deciding how to categorise the substance. Alternatively they can use a categorisation system based on a lack of “evident toxicity”. Information from either procedure may be used to classify the acute lethal hazard of a substance as set out in the regulatory requirements (eg “very toxic if swallowed”). LD50 and LC(t)50 values themselves give no information about other, non-lethal, effects of the substance, nor about cumulative, chronic, reproductive or irritant effects. The law requires that the supplier of a substance must classify and label it to show the hazard categories to which it belongs and provide a material safety data sheet (MSDS) that gives, amongst other things, the hazard categories that apply to the substance. The relevant MSDSs will provide much, but not all, of the information that must be taken into account when making a COSHH assessment and deciding on appropriate control measures for use in the workplace. [Information will also be needed on the circumstances of use and hence the likely exposures.] The MSDS also provides information needed when classifying wastes as “special wastes”. Information on the LC(t)50 values can also be used when preparing safety reports for toxic major accident hazards. Some people have doubts about the ethics of using animals to obtain toxicity data. The complex ethical, legal and scientific issues involved are beyond the scope of this paper. However, toxicologists have developed new procedures that reduce the numbers of animals used for acute toxicity testing and they continue to seek alternative, non-animal based procedures for assessing acute toxicity. 2 FURTHER READING th Hayes, A., Principles and Methods of Toxicology, Taylor and Francis, 4 Ed, 2001, Chapter 18 Gad, S., Acute Toxicology Testing, The Telford Press, 1988, Chapter 7 The British Toxicology Society, A New Approach to Classification of Substances and Preparatio