2-(phenylmethoxy)naphthalene

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Assessment of available data

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to (EC) No. 1907/2006, the toxicokinetic properties of a substance may be assessed based on the physico-chemical properties (section 4).

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

The toxicokinetic properties are predicted taking into account the physico-chemical properties of the substance.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-(phenylmethoxy)naphthalene

EC Number:

405-490-3

EC Name:

2-(phenylmethoxy)naphthalene

Cas Number:

613-62-7

Molecular formula:

C17H14O

IUPAC Name:

2-(benzyloxy)naphthalene

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

not relevant

Results and discussion

Any other information on results incl. tables

Data from in vivo studies, which were designed to identify the toxicokinetic properties of the substance, are not available. Studies considering the endpoints acute and long-term toxicity are available and show a low toxicological hazard. This means, that absorption, distribution, metabolism and excretion (ADME) can only be derived from available physical-chemical data and in the case of metabolism additionally from the available study.

To estimate the toxicokinetic properties of the substance the following information was considered (cited from IUCLID5 data file, section 4):

Parameter	Value used for CSR
Molecular weight	234.29 g/mol
Melting point	100.5 – 102.5 °C
Boiling point	148 - 150 °C (at 103.1 kPa, determined under reduced pressure) decomposition at 323 °C
Density	1.25 g/cm^3(at 20 °C)
Vapour pressure	0.000045 Pa (at 25 °C)
Partition coefficient n-octanol/water (log POW)	5 (at 21 °C)
Water solubility	0.027 mg/L (at 25 °C)
pH	Not relevant
pKa	Not relevant
Particle size	83.3 % < 100 µm; 4.96 % < 10.2 µm

 

Absorption:

Based on above data the substance may not be absorbed through the skin in relevant amounts as the log P_OWis above the threshold value. (molecular weight < 500 g/Mol, -1 < log P_OW< 4, see EUROPEAN COMMISSION HEALTH & CONSUMER PROTECTION DIRETORATE-GENERAL: Guidance Document on Dermal Absorpiton Sanco/222/2000 rev. 7 19 March 2004). Additionally no dermal toxicity or irritation was noted in the performed studies.

For exposure assessments a default value of 10 % of absorption after dermal exposure may be appropriate.

The uptake after direct inhalation of the substance may be relevant due to the high proportion of inhalable particles. Uptake by inhalation after evaporation is unlikely, the substance is a solid at room temperature and has a very high boiling point together with a very low vapour pressure.

For exposure assessments a default value of 100 % of absorption after inhalative exposure may be appropriate.

The absorption after oral ingestion cannot be calculated due to lack of data; by default absorption of 100 % may be appropriate, until specific data will be available, although such a high absorption is rather unlikely.

  

Distribution:

The substance is highly lipophilic and has a poor water solubility. Therefore lipid-rich compartments will be preferred. Nevertheless, the low water solubility will be the limiting factor for the bioavailability of the substance once entered the body.

Due to the log Pow of 5 a high potential for bioaccumulation is expected.

 

Metabolism and Excretion:

Taking into account the structural elements of the formula it follows that typical functional groups for phase II metabolic reactions are not present (like hydroxyl- or amine-groups).

These functional groups can be introduced by phase I metabolic enzymes which are the most likely pass way of metabolic activity with this substance.

A cleavage of the ether is possible by oxidising Phase I Enzymes like Cyp 450 Enzymes. The resulting metabolites of this cleavage can be Naphthen-2-ol and Benzylaldehyde. These metabolites can be subject to further Phase I reactions.

Based on this functionalisation phase II reactions can occur. The potentially introduced functional groups can be the substrate for sulfotransferases, acetyltransferases and for glucuronidation.

In the case of the metabolite Benzylaldehyde, it is known that further oxidation to benzoic acid takes place followed by the conjugation with glycine. The conjugate, hippuric acid is readily excrated.

All of these reactions will increase the relatively low water solubility of the substance and improve urinary excretion, which may be the most relevant way of excretion for this substance.

But even when the water solubility stays low, a renal excretion of the unchanged molecule is possible.

Another relevant pathway for excretion may be by feces, especially for the fraction, which has not been absorbed in the gastrointestinal tract after oral uptake.

Excretion by exhalation does not seem to be relevant.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): high bioaccumulation potential based on study results
Based on the physicochemical data the toxicokinetic properties of Benzotriazole are assesssed.

Executive summary:

Absorption: for the inhalative and oral route, an absorption of 100% are assumed,

for the dermal route no relevant absorption is estimated and 10% are assumed.

Distribution: no information

Metabolism and Excretion: no inherent groups for phase II reactions are present in the parent molecule. The molecule can be substrate for phase I metabolic enzymes.

Renale and fecal excretion are the prominent excretion routes.