GB 30000.26-2013Rules for classification and labelling of chemicals - Part 26: Specific target organ toxicity - Repeat exposure (English PDF)

1.0 Inhalation of dust/smoke/fog (rat) (mg/L)/(6h/d) 0.02 \u003cC<=0.2

5.2.9.8 in a guidance values and ranges mentioned in

5.2.9.7 for guidance purposes only, that is used as a weight of evidence approach He points to help make classification decisions. They do not have as strict demarcation values.

5.2.9.9 In animal studies repeated exposure, dose below the guidance value/concentration [for example, less than 100mg/(kg · d), orally] Observation Specific toxicity profile is possible, but the nature of the effect (for example, only in male rats known to be susceptible renal toxic effect of specific strains Observed in renal toxicity) may result in the decision not to classify. Conversely, in animal studies, it may be higher than the guideline value [for example, not Less than 100mg/(kg · d), by the oral route] specific toxicity was observed, and in addition, but also from other sources (such as other long-term administration RESEARCH Studies, or population-based case experience) supplementary information to support the conclusion that, given the weight of evidence, the classification is prudent practice.

5.2 Classification criteria for substances

5.2.1 All available weight of evidence, based on expert judgment, including the dose and duration of exposure have an effect/concentration Recommended guidance values (see 5.2.9), a substance classified as a specific target organ toxicant, and according to the nature and severity of the observed effects of the substance Quality in one of two categories as shown in Table 1. Table 1 specific target organ toxicity after repeated exposure Classification Standard Category

1 Humans produce significant toxic substances, or the basis of evidence obtained from studies in experimental animals, can be assumed after repeated exposure possible for people Class of significant toxic substances. The substance is classified according to the following categories 1.

--- Human cases or reliable and good quality evidence obtained in epidemiological studies;

--- Appropriate observation studies in experimental animals. In the trial, at generally low exposure concentrations produced human health Correlation significant and/or severe toxic effects. Guidance dose/concentration values are provided below (see 5.2.9) can be used as weight of evidence Use part of the assessment. Category

2 According to experimental evidence from animal studies it can be assumed that after repeated exposure may be hazardous to human health substances. According to observations appropriate studies in experimental animals will be classified as a Category 2 substance. In the experiment, generally moderate exposure concentrations Produces human health correlated significantly and/or severe toxic effects. The following provides guidance on dose/concentration values (see 5.2.9), In order to help in classification. In exceptional cases, human evidence can also be used a substance classified as Category 2 (see 5.2.9). A specific target organ both categories can be determined mainly by the impact of classified material or substance can be classified as general poison. Identify key Target organ toxicity (system) and classify, such as liver poison, nerve poison. Carefully evaluate the data and, where possible, not include secondary entry into force It should be, such as the liver or nervous system toxicant may produce secondary effects in the gastrointestinal system.

5.2.2 should determine the classification of hazardous substances relevant route of exposure.

5.2.3 Classification of existing heavy weight of all evidence (including the guidance provided below) basis, based on expert judgment.

5.2.4 The weight of evidence of all data, including human contingencies, epidemiological and experimental animal studies, including the weight, it is necessary to confirm points Specific target organ toxicity effect class. To do this, use a large number of industrial toxicology data collected over the years. Assessment should be based on all existing data, Published peer-reviewed studies and additional data accepted by regulatory agencies as the basis. Should be evaluated based on all existing data, Including additional data published studies and regulatory agencies adopt.

5.2.5 Specific organ toxicity assessment of the required information can be obtained from repeated exposure in humans, such as the home, the workplace or the surrounding environment Contact, or from experimental animal studies. The standard animal studies provide such information rats or mice is 28d, 90d or end Health Study (up to 2 years), this study include hematology, clinical chemistry and detailed macroscopic and microscopic examination to determine the target tissue / Toxic effects of organs. Data repeated dose studies conducted in other species may also be used to get. Other long-term exposure studies, for example, Such as carcinogenicity, neurotoxicity or reproductive toxicity, may also provide evidence for classification evaluate specific target organ toxicity.

5.2.6 In special cases, based on expert judgment, can have some human material specific target organ toxicity evidence classified Category 2.

a) when the weight of human evidence is not sufficiently convincing to warrant Category 1; and/or

b) Depending on the nature and severity of effects. In the classification should reference the human dose/concentration levels in animal studies and any available evidence should be consistent with the Category 2 classification. In other words, if there are also animal data on the substance that warrant Category 1 is justified, then the substance should be classified as Category 1.

5.2.7 Effect of support is considered classified

5.2.7.1 show that repeated exposure to the substance with a consistent and identifiable toxic effect of an association of reliable evidence, the classification can be supported. Evidence

5.2.10 Other matters

5.2.10.1 When using only animal data to determine the nature of the substance (of the new material is a typical practice for many existing substances is also So), the classification process would include reference to dose/concentration guidance values, they are regarded as one of the elements of the weight of evidence approach helps.

5.2.10.2 If you have a well-substantiated human data indicate specific target organ toxic effects can be reliably attributed to repeated exposure Or long-term exposure to the substance, then the substance may be classified. Regardless of possible dose, positive human data take precedence over animal data. Thus, when a substance because at or below the recommended dose animal testing/concentration guidance values when there is no specific target organ toxicity was observed While no classification, if subsequent human episode data showing a specific target organ toxic effect, to deal with the substance classification.

5.2.10.3 did not conduct specific target organ toxicity test substance may in some cases, the classification has proved to be appropriate, Efficient data structure activity relationships and expert judgment based on data from a structural analogue previously been classified on the basis of extrapolation, Together with substantial support, but also with reference to other important factors such as formation of common significant metabolites.

5.2.10.4 saturated vapor concentration may be as an additional element to provide for specific health and safety protection.

5.3 Classification criteria for mixtures

5.3.1 General Principles The mixture can be used with the same criteria as substances are classified or can also be classified under this section the following terms. As with substances, mixed Composition can be classified as a specific target organ toxicant exposure, target organ toxicant repeated exposure, or both.

5.3.2 There mixture Classification of mixtures when data If, as the criteria for substances, mixtures are reliable and good quality evidence of experience or appropriate studies in experimental animals from humans, that What can re-assessment of the mixture was classified by weight of evidence data. When evaluating data on mixtures should be careful, dose, duration, Observation or analysis, do not render the results inconclusive. No mixture

5.3.3 Classification of mixtures when data are. bridging principles

5.3.3.1 Data Use If the mixture itself has not been tested to determine its specific target organ toxicity, but the individual components of the mixture has been done and Similar testing of the mixture have been mastered sufficient data to adequately characterize the hazards of the mixture, then the frame in accordance with the following agreed Bridge principle to use these data. This ensures that the hazardous properties classification process to maximize the use of available data to the mixture, without For additional testing in animals.

5.3.3.2 Dilution If the tested mixtures to be diluted with a diluent, the diluent toxic and least toxic original ingredient in the same category or specific It is less, and is not expected to affect the toxicity of other ingredients, then the new diluted mixture may be classified as the original tested mixtures to the same category.

5.3.3.3 Batches The mixture had done a production batch of toxicity tests can be considered substantially the same manufacturer or under their control swells Another production of the same commercial product without testing the toxicity of the same production batch, unless there is reason believe that the untested production batch Toxicity has changed significantly. If the latter occurs, a new classification is required.

5.3.3.4 Concentration of highly toxic mixtures If the tested mixture of Category 1, a method of increasing the concentration of toxic components, then the higher the concentration of the resulting mixture should be classified in Of category 1, do not need another test. Interpolation within one toxicity category

5.3.3.5 within rang...