Additives risk/safety assessment

GLP embodies a set of principles that provide a framework within which studies are planned, performed, monitored, recorded, reported and archived. These studies are undertaken to generate data by which the hazards and risks to users, consumers, and third parties, including the environment, can be assessed for pharmaceuticals, agrochemicals, veterinary medicines, industrial chemicals, cosmetics, food and feed additives, and biocides. GLP helps assure regulatory authorities that the data submitted are a true reflection of the results obtained during the study and can therefore be relied upon when making risk/safety assessment decisions. 

Rationale These descriptions provide broad orientation, and as well accurate identification. They briefly explain how the species of interest is actually identified in relation to others. Additionally, the description may give particular characteristics of the plant to aid in defining the scope of a risk/safety assessment. Although an exact identification often is based on experience i.e. recognition) or on regional publications, rigorous or subtle analysis using specialist resources sometimes is required. 

The possibility is expressly left open for topics of additional information that is pertinent to environmental risk/safety assessment, as a section in the main text of the document, and/or as appendices. 

In risk characterization, step four, the human exposure situation is compared to the toxicity data from animal studies, and often a safety -margin approach is utilized. The safety margin is based on a knowledge of uncertainties and individual variation in sensitivity of animals and humans to the effects of chemical compounds. Usually one assumes that humans are more sensitive than experimental animals to the effects of chemicals. For this reason, a safety margin is often used. This margin contains two factors, differences in biotransformation within a species (human), usually 10, and differences in the sensitivity between species (e.g., rat vs. human), usually also 10. The safety factor which takes into consideration interindividual differences within the human population predominately indicates differences in biotransformation, but sensitivity to effects of chemicals is also taken into consideration (e.g., safety faaor of 4 for biotransformation and 2.5 for sensitivity 4 x 2.5 = 10). For example, if the lowest dose that does not cause any toxicity to rodents, rats, or mice, i.e., the no-ob-servable-adverse-effect level (NOAEL) is 100 mg/kg, this dose is divided by the safety factor of 100. The safe dose level for humans would be then 1 mg/kg. Occasionally, a NOAEL is not found, and one has to use the lowest-observable-adverse-effect level (LOAEL) in safety assessment. In this situation, often an additional un-... 

Information and data from toxicological tests are essential requirements of the food additive petition. The Redbook 2000 Toxicology Principles for the Safety Assessment of Food Ingredients (16) provides guidance to industry concerning the appropriate tests for the determination of safety. The Redbook discusses concern levels as a method to determine recommended toxicology tests for food and color additives. A level of concern can be assigned based on the potential health risk of the food additive. 

In addition, current Food and Drug Administration (FDA) guidelines outline a series of short-term and in vitro tests for the safety assessment of bound residues together with their chemical characterization (5). A study of reversibility of adduct formation is also included and as with the Joint FAO/WHO Expert Committee on Food Additives (JECFA) recommendation, drugs are investigated in an individual manner. It seems likely that the JECFA and FDA approaches, at least in general terms, will become widely adopted in this particular area of hazard and risk assessment. 

JECFA has been meeting since 1956, initially to evaluate the safety of food additives. Its mandate has been expanded to contaminants, natural toxins, and residues of veterinary drugs in food. The Committee has also developed principles for the safety assessment of chemicals in food that are consistent with the current thinking on risk assessment, and take account of recent developments in toxicology and other relevant sciences. These principles were originally published in 1987, as Environmental Health Criteria 70 Principles for the safety assessment of food additives and contaminants in food. 

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