A Quick, Simple, Conversion System to Extrapolate Safe Reference Doses from Animal Data to Human Data
When discussing the idea of chemical doses, safety has to be the number one focus and the main deciding factor when researching a drug. It is useful when designing the initial stages for testing to calculate a threshold below which the probability of harm is almost non-existent. This is how a calculated, presumed “safe” level of exposure is found. This is traditionally found by diving of a NOAEL (No Observable Adverse Effect Level), a LOAEL (Lowest Observable Adverse Effect level), using a Benchmark Dose (BMD), a Benchmark Concentration (BMC) or by uncertainty factors to address interspecies and Interindividual variation (IPCS, 1987, 1994).
When there are sources of uncertainty or unaccounted for variability, the magnitude that the NOAEL, LOAEL, BMD, or BMC exceeds the estimated exposure (the “margin of safety” or “margin of exposure) will be considered as well.
“Inter- and intraspecies considerations are an essential part of extrapolation to humans for all of these approaches (IPCS, 1999b) and were described in EHC 210 as follows:
a) Interspecies consideration: comparison of the data for animals with a representative healthy human. Species differences result from metabolic, functional and structural variations.
b) Intraspeciesor interindividual consideration: comparison of the representative healthy human with the range of variability present within the human population in relation to the relevant parameters. “
http://www.inchem.org/documents/ehc/ehc/ehc210.htm
When human data is available, the relationship between dose and toxicity is easiest determined. When human data is not available it must be derived from ...
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...r other variance considerations and will be decided based on expert judgment and is normally found to be less than 10. For instance I use a factor of 2 when using data from oral administration to apply it to subcutaneous data.
My adapted model of for detailed specificity was based on the core principles of (Dourson et al., 1996)
Factors are based on allometric scaling, which was originally predicted mathematically and subsequently substantiated by empirical investigations (Schneider et al., 2004). The factors are derived according to the formula:
(body weight human/body weight animal)^0.25 =
(body weight human/body weight animal)________________________________________
(body weight human/body weight animal)^0.75
Body Weights Used in Calculations: Human (70kg), Dog (18kg), Monkey (4kg), Rabbit (2kg), Guinea Pig (.8kg), Rat (.25kg), Mouse (.03kg)