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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

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

A critical review of the optimum duration of chronic rodent testing for the determination of non-tumourigenic toxic potential: a report by the BTS Working Party on Duration of Toxicity Testing.

This review indicates that for the detection of non-neoplastic toxic effects: 1. Four decades of accumulated literature provide no lead as to the optimum duration of repeat dose toxicity testing required for all classes of chemicals, although 6 months repeated administration appears adequate for pharmaceuticals. 2. Three month studies predicted the 2 year outcome for 70% of the compounds evaluated in this pilot study using data published by the US National Toxicology Program. 3. In spite of the limitations of this pilot study, this finding is considered encouraging as it is close to that generated previously on more detailed confidential pharmaceutical data. This suggests that the exercise should now be expanded using confidential surveys of industrial data to determine the concordance resulting from the evaluation of a larger group of chemicals.

Animals

Acute and prolonged toxicity tests.

An answer to the question of whether acute and prolonged toxicity tests are good candidates for standardization is developed by reviewing (1) the factors that are presumed to influence the results of these tests and (2) the collaborative studies that have been reported in the literature. In regard to acute toxicity tests it is clear that competent laboratories give due consideration for the control of factors that are known to influence these tests. Also competent laboratories using their own procedures provide reliable results, even though the procedures vary from laboratory to laboratory. In regard to prolonged toxicity tests there are no examples of controlled collaborative investigations which could be used to evaluate interlaboratory variation and its relation to the protocols involved. It is recommended that guidelines rather than rigid protocols would be an appropriate approach for improving the quality and accuracy of these toxicologic tests. Examples of such guidelines are given.

Biological Assay