Health animal toxicity

Testing on animals may provide initial information on the effect of a possible shortterm exposure on human health. Acute toxicity is defined as the toxic effect of a substance after a single oral, dermal, or inhalative application. For acute oral toxicity, for instance, LD50 is defined as the amount of substance expressed in mg per kg body weight which has a lethal effect on 50% of the test animals after a single oral application. Such tests are useful in that they assess the toxicity of a material relative to that of other known compounds. 

A manufacturer seeks approval from the FDA for the marketing of a new non-caloric sweetening agent. The manufacturer has conducted extensive animal toxicity testing on this new food additive, and has also provided to the FDA information about the chemical s use rates in foods and the expected rate of intake consumers might experience. Is it possible to predict whether the new additive will pose a health risk to consumers if it were to be approved for use in food ... 

Zhou et al. 2001, 2002). The available data indicate that the thyroid is a particularly sensitive target of acute oral exposure and justify using thyroid effects as the basis for an acute oral MRL, but acute effects of PBDEs on the liver are not as well characterized as thyroid effects. Other studies indicate that immunosuppression and neurobehavior are important and potentially critical health end points for acute exposure to PBDEs that need to be further investigated (see discussions of data needs for Immunotoxicity and Neurotoxicity). Studies in other species would help to clearly establish the most sensitive target and species for acute exposure, as well as which animal toxicity data are the most relevant to humans and useful for assessing acute health risks. 

In the GSK approach, each factor was given a score based on available physical property data (for example boiling point), life cycle impact data, or experimentally derived data (such as animal toxicity or ecotoxicity data). Related factors were associated together before the combined data was normalized between 1 (worst) and 10 (best) to give final scores for the headline categories (incineration, ecotoxic-ify, exposure potential, and so on). This approach enabled the envirorunental and health and safety properties of solvents of different types or classes to be easily compared alongside more conventional physical and solvent properties. In an ideal world, a similar approach would be taken with every single chemical to be able to... 

Blue pigment compounds show no toxicity in animal studies therefore it is not expected to cause any adverse effects on human health. No toxic effects were reported in humans when blue pigment compounds were used experimentally or therapeutically. 

The toxicities of alkyl halides vary a great deal with the compound. Although some of these compounds have been considered to be almost completely safe in the past, there is a marked tendency to regard each with more caution as additional health and animal toxicity study data become available. Perhaps the most universal toxic effect of alkyl halides is depression of the central nervous system. Chloroform, CHC13, was the first widely used general anesthetic, although many surgical patients were accidentally killed by it. 

Accurate exposure and biological monitoring data are crucial to the evaluation of residential exposure and risk estimates since the potential health risks associated with a pesticide depend on the amount of exposure to the pesticide, its toxicity and the susceptibility of the exposed population. Prediction of whether adverse health effects will occur in humans can be made by comparing the exposure estimate to the No Observed Adverse Effect Level (NOAEL) derived from the animal toxicity data. Uncertainty arises from the input data used in an assessment, e.g. variability in time-activity patterns, contact with exposure media, bioavailability, exposure duration, frequency of product use and differences in the route of exposure in humans from that in the animal studies (since absorption, distribution, metabolism and elimination kinetics may differ substantially by exposure route). 

In general, criteria developed to protect against noncancer effects are based on the assumption that there is a threshold below which no adverse health effects will occur. A critical evaluation of available human health and animal toxicity studies is performed to identify the most sensitive adverse effect relevant to humans. Noncancer exposure criteria are often based on an experimentally defined dose at which no adverse effects were observed (i.e., the no-observed-adverse-effect level - NOAEL). If no adequate NOAEL is available, the lowest dose at which adverse effects were observed (lowest-observed-adverse-effect level - LOAEL) is used. Another commonly used approach is to fit study data to dose-response models to identify appropriate values (e.g., dose corresponding to the upper bound of the 10% response level or BMDLio) as the basis for deriving the exposure criteria. 

TERA scientists analyze available human and animal toxicity data to determine the potential for human health effects from exposure to chemicals. These assessments can include hazard assessments and deter-mination/evaluations of mode of action and weight of evidence determinations for relevance of particular endpoints/effects to humans from environmental or occupational exposures. When adequate data are available, TERA derives noncancer and cancer risk estimates for various routes of exposure. TERA frequently publishes the results of the finalized assessment in peer reviewed journals and posts the assessments on its website. 

There is no statutory prohibition, in any of the current Federal health and safety laws, in making daily regulatory decisions utilizing quantitative safety/risk assessment based upon extrapolation from animal toxicity studies. Indeed, the court cases already discussed, from 1914 to the present, lead inexorably to this approach. 

This data usually reflects the results of animal testing. The table of relative acute toxicity criteria given below was published by the National Institute for Occupational Safety and Health (NIOSH) in the Registry of the Toxic Effects of Chemical Substances (RTECS) in 1967. It is widely used to interpret animal toxicity data. As the table below indicates, for animal toxicity data, the lower the number, the greater the toxicity. The measures of toxicity used in the table, LD50 and LC50, (and others) are explained in the section that follows the table. 

The European - United States Paediatric Formulation Initiative (Eu-US PEI) has established that there is a pressing need for a single authoritative comprehensive database of adverse effects of excipients for paediatrics. Safety and Toxicity of Excipients for Paediatrics (STEP) Database holds all the animal toxicity and human health data, regulatory information and toxicological reviews of excipients. STEP acts as repository for all the scientific communities to share the data for better understanding and paediatric medicines development (European Paediatric Eormu-lation Initiative. STEP Database. See [3]). 

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