Acceptable daily intake NOELs calculation

This method of calculation is based on the use of animal toxicity data to determine limits. As mentioned earlier, this method is particularly suited for determining limits for materials that are not used medically. This method is based upon the concepts of acceptable daily intake (ADI) and no observed effect level (NOEL) developed by scientists in the Environmental Protection Agency [7], the U.S. Army Medical Bioengineering Research and Development Laboratory [8], and the toxicology department at Abbott Laboratories [9], This method has also been recently used to calculate the limits of organic solvent residues allowed in APIs [10]. 

Atrazine appears to have a relatively low chronic toxicity via the oral route, but the data base is limited. The National Academy of Sciences (4) calculated an acceptable daily intake (ADI) using a no-observed-effect level (NOEL) from an 80 week mouse (dietary) tumorigenicity study (5) and an uncertainty factor of 1,000 a suggested guideline of... 

As described elsewhere in this Volume, the aim of the toxicological (and microbiological) studies is to allow the identification of a no-observed effect level (NOEL) and the calculation of an acceptable daily intake (ADI) (11). The safety file specifies the types of toxicological study that are usually required to allow the construction of the toxicological profile of a veterinary drug active ingredient and to identify the NEL. These include the following ... 

For adverse responses which demonstrate thresholds, the usual evaluation involves identification of a no observable effect level — NOEL — in the swat sensitive animal species or, in some cases, the calculation of the threshold for the effect. The NOEL is divided by a suitable safety factor, to establish an acceptable daily intake (ADl) in man (9 ). Safety factors vary from 10 to 2,000 depending upon the toxic response observed as well as the duration of the anisial studies. The ADI refers to the amount ingested and this amount is considered to be totally absorbed. 

Finally, researchers calculate a risk estimate from all the other data and analyses. There are various ways to report risk. One method is estabUshing allowable dose rates for humans. Typical units are acceptable daily intake (ADI), which derive from NOELs. Risk estimates may include a safety factor to protect sensitive people. If there are data from human studies, the safety factor is smaller compared to having data available from animal studies only. 

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