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Benzene: ED50_inh = ED50_ing?

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Biene
Biene's picture
Benzene: ED50_inh = ED50_ing?

Trying to understand how to fill in the gaps in USEtox substance data I wonder why the given data for ED50_inh of benzene does not differ from ED50_ing of benzene because CPDB published different values for both routes.

USEtox Team
USEtox Team's picture
Understading effect input data in USEtox

Thank you for your question.

The reason why human carcinogenic effect data for both exposure routes, i.e. inhalation and ingestion, are available in USEtox™ for benzene has to do with the fact that toxicity data for humans are preferred in the procedure. There are data from the WHO on the slope factor for benzene carcinogenity after inhalation expsoure in humans.

As benzene cause systemic effects (leukemia), expected to be rather independent of the route of exposure, route to route extrapolation is applied to derive the effect factor after oral exposure as well. Therefore, although reported data are in principle preferred compared to extrapolated data on the basis of the slope factor (q*), the exception is if the slope factor is available on the basis of human exposure (which is indicated in the USEtox™ database organics file, sheet "Hum-carc", columns P and Q).

Biene
Biene's picture
Finding ED50 data

It is really difficult to find ED50 data or NOAEL in database. Is there any other possibility to calculate human toxicity potential?

For instance, in my opinion the H- or R-phrases contained in safety data sheets provide a good impression about toxicity. Why are they not included in USEtox?

Moreover, I do not agree with extrapolation from the ingestion to inhalation route of entry as USEtox does sometimes because of missing data. Effects caused by inhalation rank higher than those which followed oral or dermal uptake. DNEL supplies inhalation data for several substances listed in an excel sheet. But there is the problem of conversion.

Would it be possible to modify USEtox calculation in order to calculate human toxicity potential with DNEL data?

USEtox Team
USEtox Team's picture
Using different ED50 data in USEtox

Thank you for your questions.

USEtox® is a scientific consensus model and the choices made are based on scientific research outputs of which a consensus is reached, baring in mind that the level of uncertainty related to the calculations is relatively small, and data availability relatively large. You may, however, very well use other data than implemented in USEtox®, but be aware that there might not be consensus on using or interpreting these data in this context.

There may always be other opinions for certain factors or calculation procedures than those used in USEtox®, for example in regards to the extrapolation between exposure routes. However, using other data than implemented in USEtox® may not save you from applying route-to-route extrapolation, as this is e.g. also done for most DNEL values (see REACH guidelines to derive DNEL). In addition, it might be difficult to derive an ED50 from DNEP, if you do not know which underlying dose descriptor (NOAEL, benchmark dose, etc.) was used to obtain a certain DNEP and how to extrapolate from this descriptor to ED50; note that in USEtox®, mostly NOEL (not NOAEL!) is used as original dose descriptor.

Extrapolation between inhalation and ingestion based on scientific consensus as applied in USEtox® is fully described in Rosenbaum et al. 2011, but be aware that due to the lack of scientific consensus, no extrapolation to dermal exposure is available in USEtox®.