4-tert-butylbenzoic acid

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: expert assessment/evaluation using various experimental results for argumentation

Adequacy of study:

key study

Reliability:

other: not applicable as data is not a study

Rationale for reliability incl. deficiencies:

other: data is contained in the EU risk assessment report of the substance - reliability is assumed. Reference to origin (Potts and Guy)

Data source

Reference

Reference 1

Reference Type:

other: EU risk assessment report

Title:

4.1.2.1 Toxicokinetics, metabolism and distribution; 4.1.2.1.3 Summary of toxicokinetics, metabolism and distribution

Author:

Federal Institute for Occupational Safety and Health, Division for Chemicals and Biocides Regulation, Germany

Year:

2009

Bibliographic source:

European Union Risk Assessment Report, 4-tert-butylbenzoic acid, CAS No: 98-73-7, EINECS No: 202-696-3, p. 46-47, Final Approved Version, July 2009

Reference 2

Reference Type:

publication

Title:

No information

Author:

Potts and Guy

Year:

1992

Bibliographic source:

Potts, RO and Guy, RH (1992). Predicting Skin Permeability. Pharmaceutical Research 9, 663-669

Materials and methods

Principles of method if other than guideline:

Assessment of toxicokinetics by argumentation with existing physico-chemical data

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-tert-butylbenzoic acid

EC Number:

202-696-3

EC Name:

4-tert-butylbenzoic acid

Cas Number:

98-73-7

Molecular formula:

C11H14O2

IUPAC Name:

4-tert-butylbenzoic acid

Results and discussion

Any other information on results incl. tables

Toxicokinetics, metabolism and distribution

Data on toxicokinetics, metabolism and distribution of 4-tert-butylbenzoic acid after oral, dermal and inhalative uptake in animals and humans are not available. Therefore, an estimation of absorption based on physico-chemical data and on results of toxicological investigations is performed. From physico-chemical properties (water solubility (47.1 mg/l), molecular weight (178.23 g/mol) and the octanol-water partition coefficient log Pow of 3.4) the substance can be assumed to have a probably good oral bioavailability. However, due to the pKa of 4.36, only small amounts of the substance may be present in the non-ionized form at the pH values present in small intestine (pH 4-6 according to TGD). This makes complete absorption from the small intestine unlikely. Toxic effects, which can be observed after acute and subacute oral application of the substance (a NOAEL cannot be derived; a LOAEL exists), are indicative of gastrointestinal absorption, but quantification is not possible. Therefore, oral absorption is assumed to be 100 % (default-value). Due to its molecular weight below 500 and a log Pow value between –1 and 4, 100 % dermal absorption can be assumed according to TGD. This assessment is further supported by calculations according to Potts and Guy (1992). Toxic effects, which can be observed after acute and repeated dermal application of PTBBA to the skin of rats are indicative of dermal absorption. Quantification is not possible. Therefore, dermal absorption is assumed to be 100 % (default-value). Based on the low vapour pressure of 0.057 Pa at 20°C and its physical state (crystalline solid at room temperature), inhalative uptake is possible if exposure to particle dust (where particle size is small enough) is given. Toxic effects which could be observed after acute and repeated exposure of rats towards particle dusts of 4-tert-butylbenzoic acid (maximal median mass diameter: 5.5 μm) are indicative of inhalative uptake. Quantification of inhalative uptake of PTBBA is not possible. Therefore, absorption via inhalation is assumed to be 100 % (default value).

Summary of toxicokinetics, metabolism and distribution

There are no data available on the toxicokinetics, metabolism and distribution of 4-tertbutylbenzoic acid after inhalation, oral and dermal exposure in animals or humans. Taking into account the physico-chemical properties of PTBBA (molecular weight 178 g/mol, water solubility of 47.1 mg/l, log Pow of 3.4, and vapour pressure of 0.057 Pa), the state of ionisation and available toxicological information an extent of absorption of 100% via inhalation, dermal and oral exposure will be assumed (default).