Registration Dossier

Administrative data

Endpoint:
dermal absorption
Type of information:
other: Expert statement
Adequacy of study:
key study
Study period:
2011-2013
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: An extensive Assessment of the toxicological behaviour of 3-(1-Pyridinio)-1-propanesulfonate was performed, taking into account the chemical structure, the available physico-chemical-data and the available (eco-)toxicological data.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
no guideline required

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
not applicable in this expert statement
Radiolabelling:
other: not applicable in this expert statement

Test animals

Species:
other: not applicable
Strain:
other: not applicable
Details on test animals and environmental conditions:
not applicable in this expert statement

Administration / exposure

Type of coverage:
other: all routes of administration are discussed in the expert statement
Duration of exposure:
not applicable in this expert statement
Doses:
not applicable
No. of animals per group:
not applicable
Details on study design:
not applicable

Results and discussion

Percutaneous absorption
Remarks on result:
other: 1-Propanesulfonic acid, 3-mercapto-, monosodium salt is expected to be poorly absorbed following dermal exposure into the stratum corneum, due to its LogPow of -2.94. Moreover, systemic toxicity after dermal exposure is low.

Any other information on results incl. tables

Absorption following dermal exposure

In order to cross the skin, a compound must first penetrate into the stratum corneum and may subsequently reach the epidermis, the dermis and the vascular network. The stratum corneum provides its greatest barrier function against hydrophilic compounds, whereas the epidermis is most resistant to penetration by highly lipophilic compounds. Substances with a molecular weight below 100 are favourable for penetration of the skin and substances above 500 are normally not able to penetrate. The substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. Therefore if the water solubility is below 1 mg/l, dermal uptake is likely to be low. Additionally LogPow values between 1 and 4 favour dermal absorption (values between 2 and 3 are optimal; TGD, Part I, Appendix VI). Above 4, the rate of penetration may be limited by the rate of transfer between the stratum corneum and the epidermis, but uptake into the stratum corneum will be high. Above 6, the rate of transfer between the stratum corneum and the epidermis will be slow and will limit absorption across the skin. Uptake into the stratum corneum itself may be slow. Moreover vapours of substances with vapour pressures below 100 Pa are likely to be well absorbed and the amount absorbed dermally is most likely more than 10% and less than 100 % of the amount that would be absorbed by inhalation. If the substance is a skin irritant or corrosive, damage to the skin surface may enhance penetration. During the whole absorption process into the skin, the compound can be subject to biotransformation.

In case of1-Propanesulfonic acid, 3-mercapto-, monosodium salt, the molecular weight is above 100 and below 500, which indicates a low potential to penetrate the skin. The small amount of1-Propanesulfonic acid, 3-mercapto-, monosodium salt,which is absorbed following dermal exposure into the stratum corneum, is most likely transferred into the epidermis, due to its LogPow. The systemic toxicity of1-Propanesulfonic acid, 3-mercapto-, monosodium saltvia the skin is surely low and this has been proven with the results of the acute dermal toxicity study, which showed no mortality after dermal application of 7500 mg/kg bw in rats.

Applicant's summary and conclusion

Conclusions:
An extensive Toxicological Statement for 1-Propanesulfonic acid, 3-mercapto, monosodium salt was performed (expert statement), taking into account the chemical structure, the available physico-chemical-data and the available (eco-)toxicological data, incl data on its structural analogue mesna.
Executive summary:

In order to assess the toxicological behaviour of1-Propanesulfonic acid, 3-mercapto-, monosodium salt, the available and predicted physico-chemical and toxicological data have been evaluated. According to its physico-chemical characteristics, the substance is expected to be poorly absorbed after oral exposure, based on its high water solubility (LogPow of -2.94) and its molecular weight. However, as its structural analogue mesnahas been shown to be surprisingly well absorbed, it is likely that MPS will be also well absorbed after oral exposure.Concerning the absorption after exposure via inhalation, as the chemical has low vapour pressure and a high water solubility, it is clear, that it is poorly available for inhalation. Given its hydrophilic properties - if absorbed - it is expected to be absorbed through aqueous pores.1-Propanesulfonic acid, 3-mercapto-, monosodium saltis also expected to be poorly absorbed following dermal exposure into the stratum corneum, due to its LogPow of -2.94. Moreover, systemic toxicity after dermal exposure to the skin is low and this has been proven with the results of the acute dermal toxicity study, which showed no mortality after dermal application of 7500 mg/kg bw in rats. Concerning its distribution in the body,the chemicalis expected to be distributed mostly in the intravasal/extracellular system, since it is a very hydrophilic substance. Moreover, it does not indicate a potential for accumulation.1-Propanesulfonic acid, 3-mercapto-, monosodium salt is expected to be either excreted unchanged via the urine or metabolised via Cytochrome P450s. It will be eliminated via urine, in cases as glucuronic acid conjugates. The possibility of protein binding can not be ruled out without adequate experimental data,because it is theoretically possible for the thiol-group to react with amino acids. However, for the structural analogue mesna there are data available which prove it to bind in rats to plasma albumin and to different immunoglobulins. This increases the probability of protein binding of MPS significantly.