# Extrapolation factor for differences in time of exposure

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Biene
Extrapolation factor for differences in time of exposure

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?

USEtox Team
Extrapolation to account for exposure duration

In the supporting information of Rosenbaum et al. (2011) it is described that:

• generally, an extrapolation factor for differences in time of exposure of 2 for subchronic to chronic exposure and 5 for subacute to chronic exposure is applied in USEtox™, and
• in the given example, an extrapolation factor of 1 is used, because the data reported in the original source have already been adjusted for time of exposure.

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.

Biene
Calculating ED50 data by estimatin from NOAEL

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.

• ED50a,t,j = NOAELa,t,j * AFN
• ED50h,j = (ED50a,t,j * BW * LT * N) / (AFa * AFt * 106)

To get constant values I have to modify AFt:

1. AFt (Methyl methacrylate) = 1
• NOAEL = 136 mg/kg/d
• USEtox_Oral ED50 = 535 kg/lifetime
2. AFt (Methanol) = 2
• NOAEL = 500 mg/kg/d
• USEtox_Oral ED50 = 984 kg/lifetime

But why do I have to vary the factor? Do I need several  information?

USEtox Team
RE: Calculating ED50 data by estimation from NOAEL

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

• NOEL to ED50 extrapolation factor: 9
• Body weight: 70 kg
• Life time: 70 years
• Conversion factor from days to years: 365 days/year
• Animal to human interspecies extrapolation factor: e.g. 4.1 for rat
• Exposure duration to chronic exposure extrapolation factor: 2 for sub-chronic and 5 for acute effects

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)