Sodium hydrogen-5-sulphoisophthalate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Type of information:

other: expert opinion

Adequacy of study:

supporting study

Study period:

22 January 2013

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

other: expert opinion

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Objective of study:

other: toxicokinetic assessment

Principles of method if other than guideline:

Expert judgement in the assessment of toxicokinetic parameters based on available data.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium hydrogen-5-sulphoisophthalate

EC Number:

228-845-2

EC Name:

Sodium hydrogen-5-sulphoisophthalate

Cas Number:

6362-79-4

Molecular formula:

C8H6O7S.Na

IUPAC Name:

Sodium 3,5-dicarboxybenzenesulfonate

Constituent 2

Reference substance name:

288-845-2

IUPAC Name:

288-845-2

Constituent 3

Reference substance name:

Sodium-3,5-dicarboxybenzenesulfonate

IUPAC Name:

Sodium-3,5-dicarboxybenzenesulfonate

Constituent 4

Reference substance name:

5-(Sodiosulfo)isophthalic acid

IUPAC Name:

5-(Sodiosulfo)isophthalic acid

Test material form:

other: white powder

Details on test material:

- Name of test material (as cited in study report): 5-(sodiosulfo)isophthalic acid
- Physical state: white powder
- Analytical purity: 99.4%
- Lot/batch No.: 6F21174000
- Expiration date of the lot/batch: 2 December 2013
- Stability under test conditions: stable
- Storage condition of test material: At room temperature in the dark. The material is hygroscopic and must be stored in a well-sealed container.

Radiolabelling:

no

Test animals

Species:

other: none

Strain:

other: none

Administration / exposure

Route of administration:

other: oral, dermal and inhalation

Vehicle:

unchanged (no vehicle)

Details on exposure:

see assessment

Results and discussion

Main ADME results

Type:

absorption

Results:

assumed 100% by inhalation; 50% by oral/dermal

Any other information on results incl. tables

ASSESSMENT

Oral Bioavailability:

The subject material is a water soluble and ionizable material with a measured octanol/water partition coefficient (log) of -1.7 and a moderate molecular weight (MW=268). Such a material should readily dissolve in the gastro-intestinal fluid. However, the presence of ionizable groups will reduce the absorption potential. Given some measured systemic effects in experimental animals following oral exposures, absorption from the gastrointestinal tract cannot be precluded. Once absorbed, the highly ionized nature of the material suggests rapid elimination primarily through the urine. The material should not accumulate or bioconcentrate in tissues. However, to provide a most conservative estimate and for risk assessment purposes, a 50% absorption of the subject material by the oral route is assumed.

Dermal Bioavailability

Compounds most readily absorbed through the relatively impervious stratum corneum skin layer are those of moderate lipophilicity and having both some water and fat solubility. The subject material is highly water soluble but is of a low lipophilicity, as evidenced by a low octanol/wate partition coefficient. Such a material should not be readily absorbed through the skin. However, to provide a most conservative estimate and for risk assessment purposes, a 50% absorption of the subject material by the dermal route is assumed.

Inhalation Bioavailability

Based on the particle size distribution measured for the subject material, inhalation exposure should result primarily in deposition of material in the upper nasopharyngeal reagion of the repiratory tract and with little or no exposure of the alveolar region. However, due to subsequent uptake of the water soluble material into the mucous coating of the respiratory tract with subsequent oral exposure due to swallowing, the material should be considered to be bioavailable by the inhalation route. However, to provide a most conservative estimate and for risk assessment purposes, a 100% absorption by the inhalation route is assumed.

Applicant's summary and conclusion

Conclusions:

A toxicokinetic assessment based on the measured and known physical chemical properties of the material and on all available toxicological data was performed. It is concluded that once absorbed from the gastrointestinal tract, the subject material should be rapidly eliminated from the body though the urine. For the purposes of risk assessment, 50% absorption following oral or dermal exposures and 100% absorption following inhalation exposures is assumed. This represents a most conservative estimate.