PRINCIPLES OF TOXICOLOGY - Biology East Borneo

1.8 EXTRAPOLATION OF ANIMAL TEST DATA TO HUMAN EXPOSURE 31Here again, it may be assumed that α = 100 percent, and that (BR) × (t) is 20 m 3 for a 24-h period (theUSEPA has recommended this value). Since environmental exposures include a more diverse populationthan the workplace (e.g., the old, the sick, the young), one might choose to use a UF larger than100, one possibly as high as 1000. Thus, for a constant daily exposure the formula reduces toSHDAAAL =20 m 3 = N mg / m3/ dayAgain using PCP as an example, the following calculation can be made:AAAL =5.8 mg / kg per day100020 m 3 / day60 kgwhere AAAL = 1.7 × 10 –2 mg/m 3 per day, or 17 µg/m 3 . This value could be used as an acceptable24-h concentration of PCP in the ambient air.Another approach to establishing an AAAL is to use the estimated permissible concentration (EPC).This approach uses an established OEL and applies two factors: one to take into account the potentialincreased exposure time for environmental exposures (i.e., 24 h per day for 7 days per week versus 8h per day for 5 days per week); and an increased UF for the differences in populations between theworkplace and the general community. The EPC can be calculated as follows:EPC =OEL100(4.2) = OEL420The value of 100 is used as an UF and the 4.2 value is used simply for the increased exposure time of168 h per week (24 h per day for 7 days per week) versus a 40-h workweek (i.e., 168/40 =4.2). Usingthe PCP example, the following can be calculated:AAAL =0.5 mg / m3420= 1.19 × 10 −3 mg / m 3 , or 1.2 µg/m 3Both of these approaches could be used for environmental exposures, but the first approach ispreferable, assuming that the NOEL data for the most significant adverse effect (in this case, thatoccurring at the lowest dose) of a chemical are known.For water consumption, one might adopt a 1000-fold UF and assume the average individual ingests2 L of water per day. In this scenario, the safe water concentration for PCP becomes 174 µg/L or 174ppb [(5.8 mg/kg per day × 60 kg) ÷ 1,000 = 348 µg/day of PCP is the SHD, which when divided bythe water ingestion rate of 2 L/day of water becomes 174 µg/L.)]If the route of environmental exposure to PCP were via the ingestion of food, then the level of PCPconsidered safe for a particular food item would be dependent on how much of the item is consumedeach day. For this example let us assume that the fish ingestion rate is 20.1 g/day for the average fishconsumer and 63 g/day for the high-end consumer (assuming this represents the 95th percentile). Asafe fish concentration for PCP could be calculated as follows:1. For the average ingestion rate:5.8 mg / kg daily60 kg1000Fish concentration =20.1 g / dayFish concentration (for average consumption rate) = 0.0173 mg/g = 17.3 µg/g or 17.3 ppm.