5-sulphosalicylic acid

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

other: expert statement

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The toxicokinetic profile of 5-sulphosalicylic acid (CAS 97-05-2) was assessed based on existing toxicity studies and the physical-chemical properties of the substance.

Data source

Reference

Reference Type:

review article or handbook

Title:

Guidance on Information Requirements and Chemical Safety Assessment; Chapter R.7c: Endpoint specific guidance, version 3,

Author:

ECHA

Year:

2017

Bibliographic source:

ISBN 978-92-9495-838-9

Materials and methods

Objective of study:

absorption

distribution

excretion

toxicokinetics

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The toxicokinetic profile of 5-sulphosalicylic acid (CAS 97-05-2) was assessed based on existing toxicity studies and the physical-chemical properties of the substance.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

5-sulphosalicylic acid

EC Number:

202-555-6

EC Name:

5-sulphosalicylic acid

Cas Number:

97-05-2

Molecular formula:

C7H6O6S

IUPAC Name:

2-hydroxy-5-sulfobenzoic acid

Test material form:

solid: crystalline

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

An absorption of 100% is assumed for the oral and dermal route. 10% by inhalation route is considered

Main ADME results 2

Type:

distribution

Results:

5-suphosalicylic acid is expected to be distributed widely through the body via blood circulation. No accumulation is expected.

Main ADME results 3

Type:

excretion

Results:

The main excretion route is urinary excretion.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Oral absorption
Generally, absorption by passive diffusion is favoured for substances with moderate log P values (between -1 and 4). 5-sulphosalicylic acid has a low log P (-2.13). Thus, no ready absorption by passive diffusion is expected. However, based on the low molecular weight (218 g/mol) and due to its high solubility in water (987 g/L), 5-sulphosalicylic acid may be absorbed by passing through aqueous pores or being carried through the epithelial barrier by the bulk passage of water.
Taken together, based on the physical-chemical properties an oral absorption rate of 100 % is assumed for 5-sulphosalicylic acid as worst-case assumption.

Dermal absorption
Based on the pH of 0.55, the test substance is considered to be corrosive to the skin (Skin Corr Cat. 1 (H314)). Therefore, the substance is expected to destroy the barrier function of the skin. Generally, absorption in the stratum corneum is favoured for substances with a molecular weight below 100 g/mol, but it is also possible for substances with a molecular weight of below 500 g/mol. To cross the lipid-rich stratum corneum a certain degree of lipophilicity is required. Log P values between 1 and 4 favour dermal absorption (values between 2 and 3 are optimal). So, the log P of 2.13 indicates that 5-sulphosalicylic acid is not able to be absorbed by the stratum corneum. However, based on its corrosivity it is able to destroy this skin barrier. To partition into the viable part of the epidermis, a substance must be sufficiently soluble in water (>1 mg/L). So, based on the high water solubility (987 g/L) 5-sulphosalicylic acid is able to partition into the lower epidermis and thus, be taken up by the systemic circulation.
Although the physical-chemical properties of 5-sulphosalicylic acid indicate only a limited potential for dermal absorption, an absorption rate of 100 % is assumed due to its corrosivity.

Respiratory absorption
Due to the vapour pressure of 0.005441 Pa at 20°C 5-sulphosalicylic acid has a low volatility and thus the availability as a vapour can be excluded. As the substance is a solid particulate, the substance can be available for inhalation as particles. The particle size distribution of the substance was assessed via laser diffraction.
The following particle size distribution was determined:
D10 = 67.5 µm
D50 = 370.6 µm
D90 = 936.9 µm
In humans, particles with aerodynamic diameters below 100 μm have the potential to be inhaled. Particles with aerodynamic diameters below 50 μm may reach the thoracic region and those below 15 μm the alveolar region of the respiratory tract. Thus, based on the measured particle size distribution of 5-sulphosalicylic acid (D10 = 67.5 µm; D50 = 370.6 µm; D10 = 67.5 µm), respiratory exposure cannot fully be excluded. However, only a minor percentage of the particles, if any, will be able to reach the thoracic region; only 10% of the particles have diameters smaller than 67.5 µm. Because of the high water solubility these particles are expected to be dissolved within the mucus in the upper air way and not to reach the alveolar region. Additionally, particles caught within the mucus might be absorbed through aqueous pores. However, this absorption mechanism is considered for substances with molecular weights below around 200. Since the molecular weight 5-sulphosalicylic acid is somewhat above 200, diffusion is expected to be low.
Based on the available data, it can be concluded that inhalatory exposure may be possible for a limited percentage of the particles. These are not considered to be able to reach the alveolar region and be absorbed via inhalation. Inhalable fractions are expected to be caught by the mucous within the upper respiratory tract and diffusion processes are limited. Thus, absorption or translocation from the lung to the circulation is assumed to be minimal. Therefore, the inhalation absorption factor is set at 10 %.

Details on distribution in tissues:

Due to the low molecular weight (218 g/mol) and the high water solubility (987 g/L), 5-sulphosalicylic acid is expected to be widely distributed in the body via blood circulation. It may diffuse through the aqueous pores of cell membranes. Based on the low log P (< 3) no accumulation in fatty tissue or stratum corneum is expected.

Details on excretion:

The molecular weight of below 300 g/mol and the high water solubility of (987 g/L) favour urinary excretion. Therefore, urinary excretion is expected to be the major route of excretion.

Applicant's summary and conclusion

Conclusions:

The absorption rate of 5-sulphosalicylic acid is assumed to be 100 % via the oral and dermal route. It is considered to be 10 % by inhalation route. The substance is expected to be distributed widely through the body via blood circulation. No accumulation is expected. The main excretion route is urinary excretion.

Executive summary:

Toxicokinetic Statement for 5-sulphosalicylic acid (CAS 97-05-2)

General

The toxicokinetic profile of 5-sulphosalicylic acid (CAS 97-05-2) was assessed based on existing toxicological studies toxicity and the physical-chemical properties of the substance.

Substance identity

 

Table 1: Physical-chemical properties of 5-sulphosalicylic acid

Substance ID	5-sulphosalicylic acid (CAS 97-05-2)
Molecular Weight [g/mol]	218
Physical state	solid
Water Solubility (20°C)	987 g/L
Log P	-2.13
Vapour Pressure (20°C)	0.005441 Pa
Particle size distribution (average)	D10 = 67.5 µm D50 = 370.6 µm D90 = 936.9 µm

 

Oral absorption

Generally, absorption by passive diffusion is favoured for substances with moderate log P values (between -1 and 4). 5-sulphosalicylic acidhas a low log P (-2.13). Thus, no ready absorption by passive diffusion is expected. However, based on the low molecular weight (218 g/mol) and due to its high solubility in water (987 g/L), 5-sulphosalicylic acidmay be absorbed by passing through aqueous pores or being carried through the epithelial barrier by the bulk passage of water.

Taken together, based on the physical-chemical properties an oral absorption rate of 100 % is assumed for 5-sulphosalicylic acid as worst-case assumption.

 

Dermal absorption

Based on the pH of 0.55, the test substance is considered to be corrosive to the skin (Skin Corr Cat. 1 (H314)). Therefore, the substance is expected to destroy the barrier function of the skin. Generally, absorption in thestratum corneumis favoured for substances with a molecular weight below 100 g/mol, but it is also possible for substances with a molecular weight of below 500 g/mol. To cross the lipid-rich stratum corneum a certain degree of lipophilicity is required. Log P values between 1 and 4 favour dermal absorption (values between 2 and 3 are optimal). So, the log P of ‑2.13 indicates that5-sulphosalicylic acid is not able to be absorbed by the stratum corneum. However, based on its corrosivity it is able to destroy this skin barrier. To partition into the viable part of the epidermis, a substance must be sufficiently soluble in water (>1 mg/L). So, based on the high water solubility (987 g/L)5-sulphosalicylic acid is able to partition into the lower epidermis and thus, be taken up by the systemic circulation.

Although the physical-chemical properties of5-sulphosalicylic acid indicate only a limited potential for dermal absorption, an absorption rate of 100 % is assumed due to its corrosivity.

Respiratory absorption                                                       

Due to the vapour pressure of0.005441 Paat 20°C5-sulphosalicylic acid has a low volatility and thus the availability as a vapour can be excluded. As the substance is a solid particulate, the substance can be available for inhalation as particles. The particle size distribution of the substance was assessed via laser diffraction.

The following particle size distribution was determined:

D10 = 67.5 µm
D50 = 370.6 µm
D90 = 936.9 µm

In humans, particles with aerodynamic diameters below 100 μm have the potential to be inhaled. Particles with aerodynamic diameters below 50 μm may reach the thoracic region and those below 15 μm the alveolar region of the respiratory tract. Thus, based on the measured particle size distribution of5-sulphosalicylic acid (D10 = 67.5 µm; D50 = 370.6 µm; D10 = 67.5 µm), respiratory exposure cannot fully be excluded. However, only a minor percentage of the particles, if any, will be able to reach the thoracic region; only 10% of the particles have diameters smaller than 67.5 µm. Because of the high water solubility these particles are expected to be dissolved within the mucus in the upper air way and not to reach the alveolar region. Additionally, particles caught within the mucus might be absorbed through aqueous pores. However, this absorption mechanism is considered for substances with molecular weights below around 200. Since the molecular weight 5-sulphosalicylic acid is somewhat above 200, diffusion is expected to be low.

Based on the available data, it can be concluded that inhalatory exposure may be possible for a limited percentage of the particles. These are not considered to be able to reach the alveolar region and be absorbed via inhalation. Inhalable fractions are expected to be caught by the mucous within the upper respiratory tract and diffusion processes are limited. Thus, absorption or translocation from the lung to the circulation is assumed to be minimal. Therefore, the inhalation absorption factor is set at 10 %.

 

Distribution and Accumulation

Due to the low molecular weight (218 g/mol) and the high water solubility (987 g/L),5-sulphosalicylic acid is expected to be widely distributed in the body via blood circulation. It may diffuse through the aqueous pores of cell membranes. Based on the low log P (< 3) no accumulation in fatty tissue or stratum corneum is expected.

 

Elimination

The molecular weight of below 300 g/mol and the high water solubility of (987 g/L) favour urinary excretion. Therefore, urinary excretion is expected to be the major route of excretion.