both exposure and toxicity are expressed on the same basis, e.g., micrograms per kilogram, micrograms per square meter, or micrograms per 1,000 kilocalories. To clarify this concept, assume that pesticide X is used on food A. The residue at the point of consumption is found to be 100 µg/100 g (1  µg/g) of food A. If the average adult consumption of food A is found to be 210 g with a total energy intake of 3,000 kcal/day (Table 3-5) and the average 2-year-old male infant consumes the same proportion of his total calories—1,200—as food A (Table 3-5), the following data apply:

Adult: 210 g of food A in a 3,000 kcal total intake

2 year old: (1,200 kcal ÷ 3,000 kcal) × 210 g food A = 84 g food A

Adult exposure = 210 g × 1 µg/g = 210 µg of pesticide X

2-year-old exposure = 84 µg × 1 µg/g = 84 µg of pesticide X

If these intakes are then scaled by weight, surface area, or calories for both adult and child, the value of intake of pesticide X becomes 70 µg/1,000 kcal for both (see Table 3-7).

If toxicity is evaluated on the same basis as exposure is assessed (i.e., on the basis of weight, surface area, or calories metabolized) using the same ratio of dosages, the results will be identical whatever basis is used. For example, if the no-observed-effect level (NOEL) were 6 µg/kg for the adult and 13 µg/kg for the child, then the NOEL expressed on the basis of surface area would be 228 µg/m2 in the adult and 300 µg/m2 in the child. On a metabolic rate basis, the NOEL for adult and child would both be 140 µg/1,000 kcal. Thus, on whatever basis one calculated toxicity, both the infant and adult would be consuming X at half the NOELs for their age group. Similar calculations would be needed to translate these ratios from the human species to the species to be used for toxicity testing.

Because the diets of small children are limited in diversity, it would be reasonable for the 2 year old to consume twice as much of food A as the adult as a proportion of his total energy intake. In this situation, the amount of residue ingested by the infant would be 13 µg/kg, 300 µg/m2, and 140 µg/1,000 kcal. Because of the relative increase in intake by the child compared to the adult, the child would be at the child's NOEL whatever the basis of the calculation.

If the efficacy or toxicity of a compound is not related to its rate of metabolism, using energy consumption as a basis for relating dosages probably would not provide equivalent levels of toxicity. In acute toxicity, for example, if the toxicity depended on peak concentration, comparable dosage would be on a simple weight basis because volumes of distribution based on body water compartments are more closely related directly to weight than to surface area or metabolic rate. Even under such circumstances, differences in rates of absorption, extent of protein binding,



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement