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At least 19 recordsLinked to original sources

Pertussis vaccine: mouse-weight-gain (toxicity) test.

Toxicity tests based on mouse-weight-gain (whether control of pertussis, DPT, cholera or typhoid vaccine) are not satisfactory, particularly since the vaccines may be adsorbed and non-adsorbed preparations. Comparison between results of tests in animals some of which were treated with vaccine and others with saline does not allow to make conclusions as valid as those supplied by a standard control vaccine (adsorbed and not adsorbed) instead of saline.

Animals

Relevance of parameters related to fertility and reproduction in toxicity testing.

Toxicity data of 37 compounds tested in both a subchronic study and one or more studies focused on reproduction were evaluated to obtain information on the significance of fertility and reproduction parameters in setting no-effect levels (NEL). It appeared that a) the test system aimed at reproduction and development was more sensitive than the subchronic study for 35% of the selected compounds and was equally sensitive for another 35%; b) for 65% of these compounds parameters related to reproduction and development were at least codecisive in determining the minimal-effect level (MEL); c) for 21% of all compounds, parameters related to reproduction were the most sensitive and therefore decisive for the MEL. It was concluded that reproduction in its broadest sense is a very sensitive tool in toxicity testing. The possibilities of either applying a simple screen of fertility and reproduction at an early stage of toxicity testing or incorporating fertility and reproduction parameters in the current subchronic study are discussed.

Animals

The effects of purified components of Bordetella pertussis in the weight gain test for the toxicity testing of pertussis vaccines.

The effects of highly purified preparations of three Bordetella pertussis components--pertussis toxin (PT), lipopolysaccharide (LPS) and filamentous haemagglutinin (FHA)--were examined in the mouse weight gain test, a toxicity test for pertussis vaccine. When these components were administered alone, PT enhanced initial weight gains of the mice, LPS produced an initial weight loss and FHA had no detectable effect on the weights of the mice. However, testing the components in combinations revealed that the effect of PT and LPS together was not simply the sum of their individual effects. This combination generally produced lower weights than LPS alone, particularly in the later stages of the test.

Animals

Situational smoke toxicity testing: hazard assessment as the 'front end' of a smoke toxicity test.

Traditionally, the toxic potency of the smoke from a material or product is part of the assessment of the fire hazard in a given scenario. The assessment also requires a knowledge of virtually all the details of the fire environment and, until they are identified, a 'safe' or 'acceptable' level of smoke toxicity is a term without meaning. This paper suggests a method of using the knowledge of these factors to simplify smoke toxicity testing. Faster, cheaper, and better-targeted smoke toxicity tests would result if the rest of the hazard assessment were carried out first. This is accomplished by determining or specifying all the relevant fire properties except the toxic potency, identifying the other environmental conditions (such as those typical of an aircraft cabin interior) and the desired tenability limits (such as the minimum necessary escape time), and then solving the equations for the buildup of toxic conditions in terms of the single remaining unknown, the toxic potency. The result is the greatest toxic potency which would meet the requirements of the analysis. In this approach, a material or product is acceptable if its smoke is no more toxic then the computed result and unacceptable if it is not. It would not be necessary to obtain an EC50 (product concentration which will cause an effect in half the animals) or dose-response profile, only the response at whatever dose is dictated by the analysis. Two sample cases are presented to illustrate the technique.

Administration, Inhalation

Test guideline. Behavioral toxicity testing in animal experiments according to section 9, para. 1, No. 2 of the Chemicals Act (Chemikaliengesetz) of the Federal Republic of Germany.

The German Chemicals Act requires that chemicals are tested for behavioral toxicity at stage 2 of the testing procedure, i.e. if more than 1000 annual tons are produced. For this purpose a guideline was developed according to which data on behavioral toxicity are to be collected, which are based on cageside observations during longterm exposure. The protocol covers outer appearance, as well as motor, sensory, autonomic and central nervous system functions. Data are to be reported in tabular form and should be evaluated by taking all aspects of the toxicological profile into account.

Animals

The lysosomal permeability test modified for toxicity testing with cultured heart endothelioid cells.

A modified lysosomal fragility test is described which is suitable for use with cultured cells. The permeability (fragility) of the lysosomal membranes of the cells to the substrate beta-glycerophosphate is measured by assessing the degree of particulate lysosomal straining seen after exposing the cells to the Gomori acid phosphatase staining reaction under carefully controlled conditions. Monolayer cultures of endothelioid cells from the hearts of neonatal rats have been used in all experiments. The time-course of lysosomal straining for cells exposed to various treatments (normal saline, isotonic sucrose, 0.25 m sucrose, distilled water, acetate buffer pH 5.0, cold acetone, neutral formalin, acetic-ethanol, Triton X-100, hydrocortisone, choloroquine and vitamin A) was compared with that of control cells stained under identical conditions. Statistical differences in staining between the test and control cells were determined by the Wilcoxin Signed Rank Test and also by regression analysis following a transformation designed to allow for the saturation character of the reaction. The success of the modified technique depends upon meticulous methodology. It is capable of demonstrating both lysosomal membrane labilization and stabilation, second- and third-stage lysosomal activation, and apparent lysosomal enzyme loss or destruction in situ. The technique also allows the degree of reversible or first-stage lysosomal activation to be subdivided on an almost continous basis and is suitable for investigating the effects of drugs and other agents on the integrity of the lysosome in situ.

Animals

[Safety evaluation of DE-020 eye drops--eye irritation test and subacute toxicity test in rabbits (author's transl)].

Basic experiments on safety evaluation of 0.3%, 1% and 3% solution of KW-1062 (DE-020 eye drops) were carried out. These eye drops applied topically to rabbits eyes had no undesirable local or systemic effects as follows: 1. Repeated instillations of DE-020 eye drops (One drop every 1 hr for 4 hrs) showed no significant irritation except only a temporary and slight congestion localized at the conjunctivae. 2. Daily instillation of DE-020 eye drops (3 times daily for 28 days) showed no abnormal findings in the eye mucosa, clinical signs, body weight, hematological examination, biochemical examination, autopsy, organ weight and histopathological examination.

Aminoglycosides

Complete programme for acute toxicity testing - not only LD50 determination.

The objective of any experimenter should be to obtain the maximum amount of useful information in the most economical manner possible. In this context, 'useful' means study both of the principal or anticipated actions of the compound under examination, and also detection of additional responses to it. For efficient evaluation, including greater statistical rigour, a continuous or graded response and quantitative measurement is preferable, although much can be done by simply analysis of the presence or absence of responses, even if these are complex or dependent upon subjective criteria. Consistency of experimental conditions, and of diagnostic criteria are essential, whether in single, exploratory or comparative tests. Acute toxicity tests, like other experiments, should be designed pragmatically, therefore, confirming to the properties of the substance under examination, but also with general or holistic coverage, albeit less specific, to detect unanticipated actions. Greater or lesser weight may be given to these two classes of method, depending on whether the test is done as part of a general screen of a previously unknown substance, or as a specific control measure done to assay one particular property. Extrapolation of the results to man or other species is only possible with the caution proper to any experiment done under restricted and highly artificial conditions, but the value of acute toxicity data has often been shown by experience gained in man.

Animals

Laboratory toxicity test of field trial typhoid vaccines.

It is important for the control of vaccines to develop methods for testing their toxicity in the laboratory. Two typhoid vaccines that had given different rates of reactions among vaccinated persons in extensive field trials provided a unique opportunity for exploring the validity of the laboratory assessment of their toxicity. An elaborate design of a toxicity test based on weight changes in intraperitoneally vaccinated mice is described in this paper. The results of the laboratory test reflected the experience gained in field studies.

Animals

Report of the Validation and Technology Transfer Committee of the Johns Hopkins Center for Alternatives to Animal Testing. Framework for validation and implementation of in vitro toxicity tests.

The development and application of in vitro alternatives designed to reduce or replace the use of animals, or to lessen the distress and discomfort of laboratory animals, is a rapidly developing trend in toxicology. However, at present there is no formal administrative process to organize, coordinate, or evaluate validation activities. A framework capable of fostering the validation of new methods is essential for the effective transfer of new technological developments from the research laboratory into practical use. This committee has identified four essential validation resources: chemical bank(s), cell and tissue banks, a data bank, and reference laboratories. The creation of a Scientific Advisory Board composed of experts in the various aspects and endpoints of toxicity testing, and representing the academic, industrial and regulatory communities, is recommended. Test validation acceptance is contingent upon broad buy-in by disparate groups in the scientific community-academics, industry and government. This is best achieved by early and frequent communication among parties and agreement upon common goals. It is hoped that the creation of a validation infrastructure composed of the elements described in this report will facilitate scientific acceptance and utilization of alternative methodologies and speed implementation of replacement, reduction and refinement alternatives in toxicity testing.

Animal Testing Alternatives