Reading the article “Supporting Information: USEtox human exposure and toxicity factors for comparative assessment of toxic emission in Life Cycle Analysis: Sensitivity to key chemical Properties” by Rosenbaum I wonder why the extrapolation factor for differences in time of exposure is modyfied. I recognized that a factor of 2 is used for subchronic to chronic exposure and a factor of 5 for subacute to chronic exposure. In the example published in the paper a extrapolation factor for differences in time of exposure of AFt = 1 is used. What does it mean? When do I have to set AFt = 1?
Thank you for your question.
In the supporting information of Rosenbaum et al. (2011) it is described that:
In all cases, where original data are not yet adjusted for exposure duration (i.e. given as either acute or sub-chronic), the stated extrapolation factors need to be applied, while in cases where original data refer to chronic exposure or are already adjusted for time of exposure, no extrapolation is required, i.e. an extrapolation factor of 1 is used.
The article includes a list of data used in the acute-to-chronic extrapolation for non-carcinogens (Table S5). I tried to calculate the USEtox ED50 data by estimating from the no-observed adverse effect level (NOAEL) in order to compare the results.
To get constant values I have to modify AFt:
But why do I have to vary the factor? Do I need several information?
Thank you for your follow-up question. However, not sure I understand your problem correctly:
All information you need to calculate ED50 values from NOEL is
Example methyl methacrylate: you have NOEL = 136 mg/kg body weight/day (hence, you need to extrapolate from NOEL to ED50), rat as exposed species (hence, you need to extrapolate from rat to human exposure), and chronic exposure study (hence, no extrapolation to chronic exposure needed, i.e. AFt = 1):
ED50 = (136 mg/kg/day * 9 NOEL-to-ED50 * 70 kg * 70 years * 365 days/year) /
(4.1 rat-to-human * 1 chronic-to-chronic * 106 mg/kg)
= 535.16 kg/person/lifetime
Example methanol: you have NOEL = 500 mg/kg/day (hence, you need to extrapolate from NOEL to ED50), rat as exposed species (hence, you need to extrapolate from rat to human exposure), and sub-chronic exposure study (hence, you need to extrapolate to chronic exposure, i.e. AFt = 2):
ED50 = (500 mg/kg/day * 9 NOEL-to-ED50 * 70 kg * 70 years * 365 days/year) /
(4.1 rat-to-human * 2 sub-chronic-to-chronic * 106 mg/kg)
= 983.74 kg/person/lifetime
All information for your case (NOEL, exposed species and exposure duration) is given in the file Database_organics, sheet "Noncarc Oral", of which Table S5 in Rosenbaum et al. 2011 only extracted information relevant for the publication's context.
Additional comment: If you wish to have a full training in applying the USEtox model and interpreting its results, I can recommend to attend one of several workshops, webinars and training courses that we offer each year, see http://usetox.org/events for further information.