Sodium 4-hydroxybenzenesulphonate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Type of information:

other: Assessment based on available physicochemical properties and toxicological data

Adequacy of study:

weight of evidence

Study period:

2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Assessment based on available physicochemical properties and toxicological data as per ECHA guidance R7.c

Justification for type of information:

None

Data source

Reference

Reference Type:

other: Internal review

Title:

Unnamed

Year:

2018

Materials and methods

Objective of study:

other: Assessment of basic toxicokinetic properties

Test guideline

Qualifier:

according to guideline

Guideline:

other: ECHA Guidance R7.c

Deviations:

not applicable

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium 4-hydroxybenzenesulphonate

EC Number:

212-550-0

EC Name:

Sodium 4-hydroxybenzenesulphonate

Cas Number:

825-90-1

Molecular formula:

C6H6O4S.Na

IUPAC Name:

sodium 4-hydroxybenzenesulphonate

Test material form:

solid

Specific details on test material used for the study:

None

Radiolabelling:

no

Results and discussion

Any other information on results incl. tables

Absorption

Oral/gastrointestinal absorption:

Based on the molecular weight of 196.2g/mol, Sodium 4-hydroxybenzenesulfonate, is expected to favour oral absorption. With the high water solubility of 92.4 g/L, Sodium 4-hydroxybenzenesulfonate may readily dissolve into the gastrointestinal fluids and be absorbed via passive diffusion.

 

Sodium 4-hydroxybenzenesulfonate and structurally similar sodium xylenesulfonate were found to be of low acute oral toxicity. toluene-4-sulfonic acid did not lead to test substance related adverse effects, as NOAEL was adjudged to be >500 mg/kg bw/day, the highest tested dose in the 28-day oral toxicity study. However, sodium xylenesulfonate was determined to have a NOAEL of 763 mg a.i./kg bw/day in a 90-day oral feeding study conducted in rats, as the LOAEL was determined to be 4092 mg a.i./kg bw/day (next and highest dose tested) on the basis of relative spleen weight loss in males seen at this dose level.

 

The findings from the repeated dose toxicity study with sodium xylenesulfonate were indicative of absorption taking place from the gastrointestinal tract, which can be considered to be the case with Sodium 4-hydroxybenzenesulfonate as well. Hence, on the basis of hydrophilic nature and the findings of the toxicological studies as discussed above, Sodium 4-hydroxybenzenesulfonate is expected to be absorbed by the gastrointestinal tract when administered orally.

 

Dermal absorption:

Sodium 4-hydroxybenzenesulfonate has a molecular weight of 196.2 g/mol, which does not favour dermal absorption. With high degree of solubility in water (92.4 g/L) and low partition coefficient (Log Pow -2.79), dermal uptake is expected to be low as Sodium 4-hydroxybenzenesulfonate can be considered to be too hydrophilic in nature to cross the lipid rich environment of the stratum corneum.The surface tension of 72.41 mN/m for Sodium 4-hydroxybenzenesulfonate also suggests a low dermal uptake from skin surfaces.

 

Sodium 4-hydroxybenzenesulfonate is neither corrosive nor irritating to the skin. However, it did lead to slight irritation on the skin of exposed rabbits which was reversed (within 72 hours in one animal and within 24 hours in remaining two animals). Toluene-4-sulfonic acid was not sensitising to the skin of guinea pigs. sodium xylenesulfonate was found to induce epidermal hyperplasia in a 90-day dermal toxicity study conducted in mice, however, no systemic toxic effects were reported in the study (NIH, 1998). Hence, taking into consideration the hydrophilic nature and absence of systemic signs in the dermal toxicity studies, Sodium 4-hydroxybenzenesulfonate is expected to have minimal absorption potential via dermal route.

 

Respiratory absorption:

Sodium 4-hydroxybenzenesulfonate exists as a solid and expected to have low volatility based on high melting point of >350°C, and hence may not be available in inhalable forms. Further, the high water solubility (92.4 g/L), indicates that the dust will be trapped in the mucus if it happens to enter the respiratory tract, thereby further limiting the absorption. No toxicity studies via inhalation route are available for Sodium 4-hydroxybenzenesulfonate or structurally similar substances. Nonetheless, taking into account the physicochemical properties, respiratory absorption potential of Sodium 4-hydroxybenzenesulfonate is considered to be poor.

Distribution

The available toxicological information does not provide any clear indication of a mechanism for distribution. However, being a hydrophilic substance, systemic distribution of Sodium 4-hydroxybenzenesulfonate will be limited by the rate at which it crosses cell membranes. Access to the central nervous system (CNS) or testes is likely to be restricted by the blood-brain and blood-testes barriers. Accumulation in body fat is unlikely to occur.

Metabolism

In the available toxicity and/or genetic toxicity studies with Sodium 4-hydroxybenzenesulfonate, there was no evidence to suggest that the test substance may be metabolised. Further, the high water solubility of Sodium 4-hydroxybenzenesulfonate suggests that metabolism would be limited and not required to facilitate renal excretion.

Excretion

Route of excretion for Sodium 4-hydroxybenzenesulfonate has not been investigated. However owing to the hydrophilic nature of the substance, it is expected to be predominantly excreted via urine.

Applicant's summary and conclusion

Conclusions:

Sodium 4-hydroxybenzenesulfonate would be absorbed primarily in gastrointestinal tract, while poor absorption via dermal and inhalation exposure is expected. Systemic distribution would most likely be restricted owing to the hydrophilic nature, while metabolism would be limited and it will be predominantly excreted via urine.

Executive summary:

Sodium 4-hydroxybenzenesulfonate would be absorbed primarily in gastrointestinal tract, while poor absorption via dermal and inhalation exposure is expected. Systemic distribution would most likely be restricted owing to the hydrophilic nature, while metabolism would be limited and it will be predominantly excreted via urine.