Latest Documents


  • 8-September-2009

    English

    Test No. 436: Acute Inhalation Toxicity – Acute Toxic Class Method

    The method described by this Test Guideline provides information that allows hazard assessment for short-term exposure to a test article by inhalation, and allows the substance to be classified according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS). The test method is based on a stepwise procedure, each step using 3 animals of each sex (the preferred species is rat). Animals are exposed in  inhalation chambers to a pre-defined concentration for 4 hours. Absence or presence of compound-related mortality of the animals at one step will determine the next step. Animals in severe pain or distress should be humanely killed. The starting concentration is selected from one of four fixed levels corresponding to GHS categories 1-4 for gases, vapours or aerosols. Animals are observed daily for clinical signs of toxicity for a total of at least 14 days. Animals' body weights should be determined at least weekly. All the animals should be subjected to gross necropsy.

  • 8-September-2009

    English

    Test No. 452: Chronic Toxicity Studies

    The objective of these chronic toxicity studies is to characterize the profile of a substance in a mammalian species (primarily rodents) following prolonged and repeated exposure.
    The Test Guideline focuses on rodents and oral administration. Both sexes should be used. For rodents, at least 20 animals per sex per group should normally be used at each dose level, while for non-rodents a minimum of 4 per sex per group is recommended. At least three dose levels should be used in addition to the concurrent control group. Frequency of exposure normally is daily, but may vary according to the route chosen (oral, dermal or inhalation) and should be adjusted according to the toxicokinetic profile of the test substance. The duration of the exposure period should be 12 months. The study report should include: measurements (weighing) and regular detailed observations (haematological examination, urinalysis, clinical chemistry), as well as necropsy procedures and histopathology.

  • 8-September-2009

    English

    Test No. 437: Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants

    The Bovine Corneal Opacity and Permeability test method (BCOP) is an in vitro test method that can be used to classify substances as 'ocular corrosives and severe irritants'. The BCOP uses isolated corneas from the eyes of cattle slaughtered for commercial purposes, thus avoiding the use of laboratory animals. Each treatment group (test substance, negative/positive controls) consists of a minimum of three eyes where the cornea has been excised and mounted to a holder. Depending on the physical nature and chemical characteristics of the test substance, different methods can be used for its application since the critical factor is ensuring that the test substance adequately covers the epithelial surface. Toxic effects to the cornea are measured as opacity and permeability, which when combined gives an In Vitro Irritancy Score (IVIS) for each treatment group. A substance that induces an IVIS superior or equal to 55.1 is defined as a corrosive or severe irritant.

  • 8-September-2009

    English

    Test No. 453: Combined Chronic Toxicity/Carcinogenicity Studies

    The objective of a combined chronic toxicity/carcinogenicity study is to identify carcinogenic and the majority of chronic effects, and to determine dose-response relationships following prolonged and repeated exposure.

    The rat is typically used for this study. For rodents, each dose group and concurrent control group intended for the carcinogenicity phase of the study should contain at least 50 animals of each sex, while for the chronic toxicity phase of the study should contain at least 10 animals of each sex.  At least three dose levels should be used, in addition to the concurrent control group for both the chronic toxicity phase and the carcinogenicity phase of the study. The three main routes of administration are oral, dermal, and inhalation. The Test Guideline focuses on the oral route of administration.

    The period of dosing and duration of the study is normally 12 months for the chronic phase, and 24 months for the carcinogenicity phase. The study report should include:  measurements (weighing) and regular detailed observations (haematological examination, urinalysis, clinical chemistry), as well as necropsy procedures and histopathology. All these observations permit the detection of neoplastic effects and a determination of carcinogenic potential as well as the general toxicity.

  • 8-September-2009

    English

    Test No. 231: Amphibian Metamorphosis Assay

    This Test Guideline describes an amphibian metamorphosis assay intended to screen substances which may interfere with the normal functioning of the hypothalamo-pituitary-thyroid axis. The assay was validated with the species Xenopus laevis, which is recommended for use in the Guideline. The assay uses three test chemical concentrations and the necessary controls, including a carrier control if necessary. The assay starts with tadpoles at the development stage 51 on the Nieuwkoop and Faber scale and is extended for a duration of 21 days. Four replicate test vessels are used for each treatment level and control(s). After 7 days of exposure, a sub-set of tadpoles from each treatment level is sampled for the measurement of the length of the hind-limb. At termination of 21-day exposure period, developmental stage, snout-to-vent length and hind limb length are measured on all remaining tadpoles. A sub-set of tadpoles from each treatment level is fixed (whole-body or dissected) for histopathology of the thyroid gland.

  • 8-September-2009

    English

    Test No. 232: Collembolan Reproduction Test in Soil

    This Test Guideline is designed for assessing the effects of chemicals on the reproduction of collembolans in soil. The parthenogenetic Folsomia candida is the recommended species for use, but an alternative species such as sexually reproducing Folsomia fimetaria could also be used if they meet the validity criteria. This Guideline can be used for testing both water soluble and insoluble substances but it is not applicable to volatile ones. The Guideline aims to determine toxic effects of the test substance on adult mortality and reproductive output expressed as LCx and ECx respectively, or NOEC/LOEC value. The number of treatment concentrations varies depending on endpoints to be determined. For a combined approach to examine both the NOEC/LOEC and ECx, eight concentrations in a geometric series with four replicates for each concentration as well as eight control replicates should be used. In each test vessel, 10 juveniles F. candida (or 10 males and 10 females adults F. fimetaria) should be placed on 30 g of modified OECD artificial soil using a 5 % organic matter content. The duration of a definitive reproduction test is 4 weeks for F. candida or 3 weeks for F. fimetaria.

  • 8-September-2009

    English

    Test No. 230: 21-day Fish Assay - A Short-Term Screening for Oestrogenic and Androgenic Activity, and Aromatase Inhibition

    This Test Guideline describes an in vivo screening assay for certain endocrine active substances where sexually mature male and spawning female fish are held together and exposed to a chemical during a limited part of their life-cycle (21 days). This assay covers the screening of oestrogenic and androgenic activity, and aromatase inhibition. The assay was validated on the fathead minnow (Pimephales promelas), the Japanese medaka (Oryzias latipes) and the zebrafish (Danio rerio); however zebrafish does not allow the detection of androgenic activity. At termination of the 21-day exposure period, depending on the species used, one or two biomarker endpoint(s) are measured in males and females as indicators of oestrogenic, aromatase inhibition or androgenic activity of the test chemical; these endpoints are vitellogenin and secondary sexual characteristics. Vitellogenin is measured in fathead minnow, Japanese medaka and zebrafish, whereas secondary sex characteristics are measured in fathead minnow and Japanese medaka only.

  • 8-September-2009

    English

    Test No. 455: The Stably Transfected Human Estrogen Receptor-alpha Transcriptional Activation Assay for Detection of Estrogenic Agonist-Activity of Chemicals

    This Test Guideline describes an in vitro assay, which  provides mechanistical information, and can be used for screening and prioritization purposes. The test system utilises the hERalpha-HeLa-9903 cell line derived from a human cervical tumor and stably transfected. This cell line can measure the ability of a test chemical to induce hERalpha-mediated transactivation of luciferase gene expression. The cells are exposed to 7 non-cytotoxic concentrations of the test chemical for 20-24 hours to induce the reporter gene products. Four reference chemicals should be included in each experiment: a strong estrogen (17beta-estradiol), a weak estrogen (17alpha-estradiol), a very weak estrogen (17alpha-methyltestosterone) and a negative control (corticosterone). The activity of the luciferase enzyme is measured in a luminometer. A test chemical is considered to be positive if the maximum response induced is equal to or exceeds 10% of the response of the positive control (1 nM 17alpha-estradiol) in at least two of two or two of three runs.

    Software to be used with TG 425, 432, 455. Click here. Software not part of the Mutual Acceptance of Data.

  • 8-September-2009

    English

    Test No. 451: Carcinogenicity Studies

    The objective of a long-term carcinogenicity study is to observe test animals for a major portion of their life span for the development of neoplastic lesions during or after exposure to various doses of a test substance by an appropriate route of administration.

    This Test Guideline is intended primarily for use with rats and mice, and for oral administration. Both sexes should be used. Each dose group and concurrent control group should contain at least 50 animals of each sex. At least three dose levels and a concurrent control should be used. Animals are dosed with the test substance daily (oral, dermal or inhalation administration) and the mode of exposure should be adjusted according to the toxicokinetic profile of the test substance. The duration of the study will normally be 24 months for rodents. For specific strains of mice, duration of 18 months may be more appropriate. Termination of the study should be considered when the number of survivors in the lower dose groups or the control group falls below 25 per cent. The results of these studies include: measurements (weighing, food consumption), and, at least, daily and detailed observations, as well as gross necropsy and histopathology.

  • 8-September-2009

    English

    Test No. 412: Subacute Inhalation Toxicity: 28-Day Study

    This revised Test Guideline 412 (TG 412) has been designed to fully characterize test article toxicity
    by the inhalation route following repeated exposure for a limited period of time (28 days), and to provide data for quantitative inhalation risk assessments.

    Groups of at least 5 male and 5 female rodents are exposed 6 hours per day for 28 days to a) the test article at three or more concentration levels, b) filtered air (negative control), and/or c) the vehicle (vehicle control). Animals are generally exposed 5 days per week but exposure for 7 days per week is also allowed. Males and females are
    always tested, but they may be exposed at different concentration levels if it is known that one sex is
    more susceptible to a given test article. This guideline allows the study director the flexibility to
    include satellite (reversibility) groups, bronchoalveolar lavage (BAL), neurologic tests, and additional
    clinical pathology and histopathological evaluations in order to better characterize the toxicity of a test
    article.

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