1,3-Benzenediol, 4-(1-phenylethyl)-

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

480-070-0

EC Name:

-

Cas Number:

85-27-8

Molecular formula:

C14H14O2

IUPAC Name:

4-(1-phenylethyl)benzene-1,3-diol

Details on test material:

Test item: SymWhite 377
Physical state: Solid, white to beige powder
Storage conditions: Ambient temperature, dark, dry and in original container
no further information on test material was stated

Applicant's summary and conclusion

Conclusions:

statement on ADME please refert to "executive summary" or to the report attached.

Executive summary:

Inhalation absorption:

The high water solubility and the moderate lipophilicity (log Pow = 2.11) initially indicate that the substance may easily be absorbed by the respiratory tract epithelium, whereas the low volatility indicates a marginal potential for inhalation of vapours. It was therefore considered necessary to address the potential for inhalation absorption as follows:

 

The potential for dust inhalation is considered moderate, since during measurements of the particle size distribution, clear indications of a high tendency for agglomeration of particles were observed, necessitating dry sieving of the test material prior to testing. As a consequence, approx. 26% of the material was > 250 µm.

 

Furthermore, the material was subjected to a test to determine the potential of the dust to be airborne (modified Heubach procedure (DIN 55992-1:2006)), yielding an MMAD of 26.5 µm with a GSD of 1.7. Based on this information, the fractional deposition in the respiratory tract was calculated with the MPPD model.

 

The results of this calculation can be briefly summarised as follows: the deposition frequency in the entire respiratory tract is ~ 52%, corresponding to the large particle size of approx. 26.5 µm which renders the particles only partly inhalable. The bulk of this material (i.e. 99.7%) is deposited in the extra-thoracic region, and will therefore be translocated to the GI tract within a few minutes; only a minimal amount (~0.2%) of the material present in air will be deposited in the tracheobronchial region, also cleared to the GI tract by mucociliary flow. Merely 0.04% in of the material present in air will be deposited in the alveolar region. Thus, only minimal amounts penetrate to the deep lung tissue, whereas the overwhelming bulk of inhaled material is cleared rapidly to the GI tract, where oral bioavailability will determine its uptake.

 

For current lack of other information on oral bioavailability and in light of the physicochemical characteristics, it may be assume as a worst-case that the absorption factor both from the alveolar region and the GI tract is 100%, thus yielding an overall inhalation absorption factor of 52% based on particle-size dependant deposition in the lung.

 

Oral absorption:

SymWhite377 is readily water soluble (3.85 g/L) and moderately lipophilic, and therefore may be assumed to readily dissolve in gastrointestinal fluid and subsequently be easily available for passage through the epithelial barrier of the GI tract by passive diffusion.

Dermal absorption:

see IUCLID endpoint 7.1.2 "dermal absorption"

Distribution:

Since SymWhite377 is a small water-soluble molecule it may be assumed to diffuse through aqueous channels and pores and to distribute to tissues widely and readily.

Metabolism and elimination:

Based on the available data, no definitive conclusions can be drawn on the likely metabolism or elimination of the substance. However, due to the low molecular weight and the good water solubility, urinary excretion is likely to be the favourable route of excretion for SymWhite377.