Tests chronic

Chronic tests are those conducted over a significant part of the life span of the test animal. The duration of a chronic study is generally one year or more. Typically rat and dog are the preferred species for carcinogenicity studies, rats and mice are used. 

The MTD has been defined for testing purposes by the US Environmental Protection Agency (EPA) as  

This dose is determined by extrapolation from subchronic studies. 

The requirements for animal facilities, housing, and environmental conditions are as described for subchronic studies. Special attention must be paid to diet formulation because it is impractical to formulate all of the diets for 2-year study from a single batch. In general, semisynthetic diets of specified components should be formulated regularly and analyzed before use for test material content. 

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Testing to identify hazards should be tiered, starting with short-term screening, followed by subchronic and chronic tests. 

Panter, G.H., Hutchinson, T.H., and Hurd, K.S. et al. (2006). Development of chronic tests for endocrine active chemicals—Part 1. An extended fish early-life stage test for oestrogenic active chemicals in the fathead minnow (Pimephales promelas). Aquatic Toxicology 77, 279-290. 

Dose-effect dependence is shared by many OPC in both the acute and chronic tests. The higher dose of an anti-cholinesterase substance, the higher degree of both acetyl cholinesterase (AChE) inhibition in neural tissue and intoxication evidence. 

Under Article 7(1), if the country that receives a notification concludes that further data and information are needed for performing health and environmental assessments of the new substance, it may require the notice submitter to provide those data. This may involve completion of the Annex VII base set (for PMN s that invoke the "escape clause"), and/or performance of further tests specified in Annex VIII, in addition to those contained in Annex VII.(24) Annex VIII specifies a series of sub-chronic and chronic tests, as well as other extensive (and expensive) data requirements that may be required as a part of followup notifications once a chemical enters commercial production and its production volume increases substantially. 

Category A lists three types of studies for human health effects basic acute toxicity tests, a 28-day animal study (referred to in other discussions as a "sub-chronic" test), and a series of two (or more) screening tests for mutagenicity and carcinogenicity. 

The use of a battery of environmental bioassays for the management of hazardous wastes is applied in the Czech Republic [176]. This battery of environmental bioassays has included representatives of producers, consumers, and destructors D. magna (possible substitution by D. pulex), acute, reproduction, chronic test Scenedesmus quadricauda S. capricomutum), as bottle test or in microwell plates Poecillia reticulate (Danio rerio), acute, chronic, embryolarval tests 5. alba (Lactuca sativa), germination test, 72 hours. 

Under the sponsorship of the National Cancer Institute and the National Toxicology Program, two chronic tests of CN and CS administered by inhalation are under way. > Preliminary data obtained in the subchronic studies preparatory to the definitive inhalation carcinogenicity tests are presented in the sections of this chapter dealing with CS and CN. One probable adverse effect, to judge from... 

Dobrokhotov, V.B. Enikeev. M.I. (1977) The mutagenic action of benzene, toluene and a mixture of these hydrocarbons in a chronic test. Gig. Sanit., 42, 32-34 (in Russian)... 

Male and female mice from an outbred strain are handled by the best animal husbandry techniques, as described for acute, subchronic, and chronic tests, and are treated either with the solvent, 0.5 LD50, or 0.1 LD50 of the test chemical. Animals are killed at several time intervals up to 2 days the bone marrow is extracted, placed on... 

The enormous cost of multiple-species, multiple-dose, lifetime evaluations of chronic effects has already made the task of carrying out hazard assessments of all chemicals in commercial use impossible. At the same time, quantitative structure activity relationship (QSAR) studies are not yet predictive enough to indicate which chemicals should be so tested and which chemicals need not be tested. In exposure assessment, continued development of analytical methods will permit ever more sensitive and selective determinations of toxicants in food and the environment, as well as the effects of chemical mixtures and the potential for interactions that affect the ultimate expression of toxicity. Developments in QSARs, in short-term tests based on the expected mechanism of toxic action and simplification of chronic testing procedures, will all be necessary if the chemicals to which the public and the environment are exposed are to be assessed adequately for their potential to cause harm. 

Acute aquatic tests normally last 2 to 4 days depending on the test organisms. Chronic tests for invertebrates, like daphnia, last for 21 to 28 days and may involve several generations of offspring. We are always looking for test organisms that will reach maturity faster so we can evaluate the effect of the test substance on multiple generations in a shorter period of time. 

Chronic toxicity Rodent and non-rodent species. 6 months or longer. Required when drug is intended to be used in humans for prolonged periods. Usually run concurrently with clinical trial. Goals of subacute and chronic tests are to show which organs are susceptible to drug toxicity. Tests as noted above for subacute. 3 dose levels plus controls. 

Other standardized/validated test methods reported in the literature include acute/chronic tests performed with algae (e.g, OECD, 2002a ISO, 2003), fish cells (Gagne and Blaise, 2001), invertebrates (Borgmann and Munawar, 1989 Trottier et al., 1997 Pereira et ah, 2000 OECD, 2001 a,b), Lemnaceae (OECD, 2002b), and with toxicity tests conducted at different trophic levels (Nebeker et ah, 1984 U.S. EPA, 2002a,b). 

Geis, S.W., Fleming, K.L., Mager, A. and Reynolds, L. (2003) Modifications to the fathead minnow (Pimephales promelas) chronic test method to remove mortality due to pathogenic organisms, Environmental Toxicology and Chemistry 22 (10), 2400-2404. 

Jop, K.M., Askew, A.M., Terrio, K.F. and Simoes, A T. (1992) Application of the short-term chronic test with Ceriodaphnia dubia in identifying sources of toxicity in industrial wastewaters, Bulletin of Environmental Contamination and Toxicology 49 (5), 765-771. 

Sakai, M. (2002a) Use of chronic tests with Daphnia magna for examination of diluted river water, Ecotoxicology and Environmental Safety 53 (3), 376-381. 

Sakai, M. (2002b) Determination of pesticides and chronic test with Daphnia magna for rainwater samples, Journal of Environmental Science and Health, Part B, 37(3), 247-254. 

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