NOELs safety risk assessment

Data on the safety studies were submitted to international agencies like the Joint Expert Committee for Food Additives of the WHO and FAO (JECFA), and the Scientific Committee on Food (SCF) of the EC. Both committees endorsed acesulfame K as a food additive. Initial acceptance was based on an NOEL of 900mg/kg in dogs which were considered to be the most sensitive species. Therefore Acceptable Daily Intake (ADI) values of 0-9 mg/kg of body weight were allocated.8 9 Evidence that rats would be an appropriate model for risk assessment was the reason for JECFA to change the ADI to 0-15 mg/kg of body weight on the basis of a no-effect level of 1500-3000 mg/kg in rats.10 Countries allocating their own ADI values like the USA and Canada have come to the same conclusion. The SCF still retains its 0-9 mg/kg ADI.11... 

Under this broad concept of risk assessment are encompassed all of the essential problems of toxicology that traditional safety assessment schemes have dealt with, but they have been recast to provide a means for answering a different question — that Isr the question of risk. There are other Important differences as well. Risk assessment does not rely on the biologically and statistically dubious concept of a NOEL, but takes into account all of the available dose-response data. It treats uncertainty not by the application of... 

The development of an ADI is essentially the same in the NAS procedures, the EPA Food Tolerance procedures, and the NACA proposal for groundwater. An ADI is determined by dividing the NOEL in the most sensitive species by a suitable Safety Factor (SF). Safety Factors for subchronic or repeat administration are usually 1,000 for chronic or lifetime studies, 100 is used. Species conversions can be based upon mg/kg, ppm in the food, or body surface area conversion [29]. Currently, non-oncogenic effects are considered on an mg/kg basis without attempts to correct for species differences. Risk assessment procedures for oncogenic risk employed by the EPA are based upon surface area extrapolations in an attempt to relate to man [30]. 

For example, the Ontario risk assessment uses a no observable effect level (NOEL) of 0.001 ug/kg/day (6.73) and a safety factor of 100 to obtain a maximum allowable dally intake of 1 X 10" 1 g/kg/day (= 10 pg/kg/day) for humans (74). In contrast, EPA has used a value of 6.4 X 10" 5 g/kg/day which suggests cancer risks that are 1670 fold higher. The United States Food and Drug Administration (FDA) has, on the other hand, accepted risks associated with the ingestion of up to 13 pg/kg/day. (Table IX). 

Once the NOEL and the exposure to workers are known, the margin of safety (MOS) can be calculated. It then remains to be determined whether the MOS is adequate. Obviously the acceptability of a margin will depend upon the severity and reversibility of the toxic effect. Historically, a margin of 100-fold has been accepted for many toxic effects (19). This allows for a factor of 10 for extrapolation from animals to man, and a factor of 10 to allow for differences in sensitivity from one person to another. However much larger factors (up to 5000) have been used when the effects are more severe. A more complicated procedure is utilized when the product is a proven animal carcinogen. However, any method of risk analysis requires reliable assessment of both NOEL and exposure. 

The main purpose of the toxicity tests just described is to provide a data base that can be used to evaluate the hazard and assess the risk associated with the use of a pesticide. In practice the no observable effect level (NOEL) found in the most sensitive animal species tested in chronic studies is used. To extrapolate a safe dose for human consumption, a safety factor of 100 is usually used. For example, if the NOEL in the most sensitive animal species e.g. the dog from the chronic feeding study, was 10 mg/kg of body weight, then the acceptable daily intake (ADI) for man would be... 

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