JECFA performs thorough safety assessments of natural and synthetic color additives through the application of principles for the safety assessment of food additives (WHO, 1987). JECFA considers data from a wide variety of sources in an attempt to capture all relevant data. Data from the literature, government sources, and industry are all considered. Industry has often proven to be a valuable source of data that may not be otherwise available.
JECFA may consider a new color additive upon the request of an interested party. For additives that have already been reviewed by JECFA and assigned an acceptable daily intake (ADI), JECFA may choose to review their past decision if the additive is manufactured through a new process, new specifications have been developed or a new impurity identified, new safety data become available, there have been significant changes in consumption patterns, or if improved safety assessment standards have been developed.
The Acceptable Daily Intake
The ADI is the safe level of human intake determined by JECFA to be supported by the best available scientific data. The ADI is expressed as milligrams (mg) of the additive that are consumed per kilogram (kg) body weight per day. The ADI is most often abbreviated as “mg/kg/day” and is listed by JECFA as a range such as “0-5 mg/kg/day”. The ADI can be used together with available data on the concentration of the additive in food, and consumption of relevant foods to determine whether the ADI has been met.
The ADI is based in part on the concept that food additives appropriate for inclusion in the human diet should be additives that are rapidly cleared and do not accumulate making it appropriate for the determination of an acceptable daily intake. Substances that accumulate after ingestion present significant toxicological issues and often render them inappropriate for human consumption. Therefore, current, accurate data related to the metabolism and pharmacokinetics of color additives is necessary for a sound safety assessment.
Embodied in the ADI concept is the premise that an adequate margin of safety is desirable when using animal studies to assess the safety of human consumption of food and color additives. A safety factor allows for species differences between humans and test animals, the relatively small number of test animals compared to the human population that may consume the additive, the potentially greater variety of disease processes in humans, difficulties in estimating human intake, and possible synergistic effects among additives. JECFA applies a safety factor of 100 when using animal studies to assign ADIs. The safety factor of 100 is based on the assumption that humans are 10 times more sensitive than test species, and that humans have 10 times the variability in sensitivity compared to test species.
The Determination of the ADI
The ADI is based on toxicology data. Critical to the relevance of the toxicology data is that the studies were conducted with appropriate doses. JECFA recommends that toxicology studies be conducted with low, mid, and high doses and that the doses be set through the use of short-term range-finding studies, especially in the case of lifetime studies.
In evaluating toxicology studies, JECFA will examine study design and conduct to assure that the study has been conducted according to appropriate standards. Once the evaluation of the study is complete, JECFA will determine a no-observed-adverse-effect level (NOAEL) for the study. After the overall evaluation of the available data is complete, JECFA will select the most relevant study as the basis for assigning an ADI; often this study is a lifetime toxicity/carcinogenicity study in rats. JECFA may then use the NOAEL from this study to assign an ADI. For example, it has been common for NOAELs in lifetime rat studies on color additives to be several hundred mg/kg/day; a NOAEL of 500 mg/kg/day yields an ADI of 0-5 mg/kg/day after the application of a 100-fold safety factor. On occasion, short-term mechanistic studies may serve as the basis for an ADI, as may clinical data when they are available. In the case of clinical data, JECFA may apply a 10-fold safety factor instead of 100-fold because the data were produced in humans.
JECFA Conclusions on Color Additives
The JECFA program is a sound, scientifically valid program that provides the best available safety assessments of color additives. JECFA has evaluated a number of color additives and provided ADIs. The color additives assigned ADIs by JECFA provide a sound basis for international harmonization efforts. JECFA has just begun a program to re-evaluate color additives, based on priority, due to colors being among those additives first evaluated by JECFA and the desire for ADIs to be based on the most up to date safety information.