Minimal acute toxicity test

In general, traditionally designed acute toxicity tests can be divided into three types that can be called the minimal acute toxicity test, the complete acute toxicity test, and the supplemented acute toxicity test. Of these, the minimal protocol is by... 

Schutz, E. andFuchs, H. (1982). A new approach to minimizing the number of animals in acute toxicity testing and optimizing the information of the test results. Arch. Toxicol. 51 197— 220. 

Due to the different fate of lubricants during their use, e.g. contamination by fuel and combustion products of engine oils, the toxicity of used lubricants may be significantly different than that of fresh oils. Fluids which are considered environmentally friendly must not only be biodegradable, but also relatively nontoxic, in both their initial form and degradation products. Their effects on flora and fauna must be minimal. There are two common tests to evaluate toxicity the Microtox and the Rainbow Trout bioassay. Considerable environmental toxicity testing has been carried out on esters fluids. Esters cause minimal acute toxicity by ingestion and skin absorption. 

Simplified notifications, for substances produced or imported at less than one tonne per year. Minimal data are required. These data include melting point, water solubility, and octanol-water partition coefficient. For organic substances, the simplified notification must also include data from a test of ready biodegradability and, if the substance is not readily biodegraded, a test report on acute aquatic toxicity (ideally to fish). An earthworm acute toxicity test may be required. For inorganic substances, testing on acute aquatic toxicity (and, under certain circumstances, acute toxicity to earthworms) is required [145,146]. 

Douglas, M.T., D. 0. Chanter, I.B. Pell, and G.M. Burney. 1986. A proposal for the reduction of minimal numbers required for the acute toxicity to fish test (LC50 determination). Aquat. Toxicol. 8 243-249. 

The third health effect bioassay employed utilizes acute toxicity in whole animals (rats). Since the major objective of the Level 1 biological testing procedure is to identify toxicology problems at minimal cost, a two-step approach is taken to the initial acute in vivo toxicology evaluation of unknown compounds. The first is based on a... 

A Guidance Document on Acute Inhalation Toxicity Testing is being developed and presently exists as a draft (OECD 2004b). The document recommends the Acute Toxic Class (ATC) Method with a group size of three animals per sex, if the objective of the test is solely related to hazard classification. Limits for particle-size distribution of aerosolized test substances are suggested. The preferred mode of exposure is the nose-only, head-only, or head/nose-only exposure technique, because this mode of exposure minimizes exposure or uptake by noninhalation routes. 

Quinazolines - SL-512 (1 ) caused minimal gastrointestinal toxicity, was equipotent to phenylbutazone in acute models of inflammation, and was less effective in chronic models such as the adjuvant rat.H9 Comparisons of with Indomethacin and phenylbutazone (most potent analog is shown) were sufficiently favorable to warrant further testing of members... 

This approach appears somewhat irrational and without much scientific merit, since many of these new molecules are minimally toxic or nontoxic by this sort of acute evaluation. As in the case of interferons or monoclonal antibodies, the toxic effects observed in humans might not be predicted from safety assessments in rodents. An appropriate test species should be selected. Is the rat or mouse the appropriate species to evaluate a species-specific rDNA protein such as human growth hormone or interferons, or would nonhuman primates be more suitable Does the nonhuman primate really offer any advantages There is some consensus that the nonhuman primate may be a more appropriate species for testing some rDNA human proteins. 

Thyroid effects were produced in rats in acute-duration studies at doses as low as 3 mg/kg/day (reduced serum levels of T4 hormone) but not at 1 mg/kg/day, in intermediate-duration studies at doses as low as 0.05 mg/kg/day (increased number and decreased size of follicles), and in chronic-duration studies at doses as low as 1.3 mg/kg/day. The no-observed-adverse-effect level (NOAEL) of 1 mg/kg/day is used herein as the basis for an acute-duration minimal risk level (MRL) for oral exposure. The acute-duration lowest-observed-adverse-effect level (LOAEL) for hepatic effects is identical to the LOAEL for acute thyroid toxicity, but is a less appropriate basis for the MRL because organ functional implications are not as clear. The intermediate-duration LOAELs for thyroid and hepatic effects are also comparable to each other, but neither of these LOAELs are suitable for an intermediate MRL because reproductive and developmental toxicity occurred at a lower dosage. The thyroid LOAEL for chronic-duration exposure is unsuitable for deriving a chronic MRL because decreased survival occurred at the same dose (lower doses were not tested), and thyroid, liver, and other effects occurred at lower doses in intermediate-duration studies. 

Lecithin-based o/w MEs for parenteral use were formulated using polysorbate 80, IPM (Isopropyl myristate), lecithin, and water at different lecithin-polysorbate 80 weight ratios [115]. The formulated systems were shown to be highly stable and of minimal toxicity when evaluated in vitro. Phospholipid-based ME formulations of all-trans retinoic acid (ATRA) for parenteral administration were prepared and tested in vitro [116]. ATRA is effective against acute promyelocytic leukemia with highly variable oral bioavailability. Parenteral ME of ATRA was prepared using pharmaceutically acceptable ingredients, namely phospholipids and soybean oil. The inhibitory effect of ATRA on two human cancer cell lines (HL-60 and MCF-7) was not affected by incorporation into a ME formulation. 

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