Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: assessment based on information available
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP assessment report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Objective of study:
other: toxicokinetic assessment
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
An expert assessment was made based on all data available.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): phenyltolylethane; PTE
- - Physical state: liquid
- Analytical purity: >=95%

Test animals

Species:
other: none

Administration / exposure

Route of administration:
other: oral, dermal and inhalation
Vehicle:
other: not applicable
Details on study design:
A toxicokinetic assessment has been performed based on available physico-chemical properties and toxicological data of the substance.

Results and discussion

Any other information on results incl. tables

Based on similar structure and physicochemical properties PTE and related substances are theoretically expected to have similar adsorption, distribution, metabolism and excretion behavior. As the relevant physicochemical properties of PTE are available, this toxicokinetic assessment is based on the physicochemical properties of PTE.

 

The low molecular weight (196.29) of PTE favours absorption in the gastro-intestinal tract by passive diffusion, however, the low water solubility (0.0167 mg/L) and the high log Pow (5.1-5.3) of PTE render absorption in the gastro-intestinal tract by passive diffusion to be unlikely. PTE may be taken up by micellular solubilisation as PTE is poorly soluble in water and has a high log Pow. Therefore, for risk assessment purposes, the oral absorption of PTE is set at 50% (1). The results of the toxicity studies with PTE and related substances do not provide reason to deviate from this proposed oral absorption percentage.

 

Although PTE may be expected to distribute widely throughout the body based on the small molecular weight, the lipophilicity and low water solubility of PTE disfavour a wide distribution. The lipophilicity of PTE also predicts that the intracellular concentration may be higher than the extracellular concentration, particularly in fatty tissues. Based on the relatively high lipophilicity PTE may accumulate (1). Absorbed PTE might undergo oxidation which may be followed by conjugation (2). The conjugates are expected to be excreted via the urine as they are still expected to be low molecular weight compounds.

 

The low vapour pressure (0.44 Pa) indicates that PTE is not available for inhalation as a vapour. The low water solubility (0.0167 mg/L) enhances penetration to the lower parts of the respiratory tract. In combination with the high log Pow (5.1-5.3) PTE is expected to be taken up by micellular solubilisation in the lower respiratory tract. For risk assessment purposes the inhalation absorption of PTE is set at 100%.

 

Since the log Pow is high (5.1-5.3), PTE is expected to be taken up in the stratum corneum, but further transfer to the epidermis is predicted to be low based on the low water solubility (0.0167 mg/L). According to the criteria given in the REACh guidance (1): 10% dermal absorption will be considered in case MW>500 and log Pow <-1 and >4, otherwise 100% dermal absorption. As dermal absorption is generally not expected to be higher than oral absorption, 50% dermal absorption of PTE is proposed.

 

Based on the present data, no additional conclusions can be drawn on the distribution, metabolism and excretion of PTE after dermal and inhalatory absorption.


1.    Guidance for the implementation of REACH. Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance. European Chemical Agency, May 2008.

2.    A. Parkinson. In: Casarett and Doull’s Toxicology, The basic science of poisons. Sixth edition. Ed. C.D. Klaassen. Chapter 6: Biotransformation of xenobiotics., 2001.

3.    Category approach for REACH registration of phenyltolylethane (PTE). WIL Research Projectno 500789.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
For the risk assessment oral absorption is set at 50%, dermal absorption at 50% and inhalation absorption at 100%.
Executive summary:

A toxicokinetic assessment has been performed based on available physico-chemical properties and toxicological data of the substance. For the risk assessment oral absorption is set at 50%, dermal absorption at 50% and inhalation absorption at 100%.