1-(3-sulphonatopropyl)pyridinium

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Expert statement

Adequacy of study:

key study

Study period:

2014

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:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

Prediction based on the physico-chemical properties and on the toxicological data.

Test material

Test material information

Constituent 1

Reference substance name:

3-(1-Pyridinio)-1-propanesulfonate

IUPAC Name:

3-(1-Pyridinio)-1-propanesulfonate

Constituent 2

Reference substance name:

1-(3-sulphonatopropyl)pyridinium

EC Number:

239-491-3

EC Name:

1-(3-sulphonatopropyl)pyridinium

Cas Number:

15471-17-7

Molecular formula:

C8H11NO3S

IUPAC Name:

1-(2-hydroxy-3-sulphonatopropyl)pyridinium

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

The substance is expected to be well absorbed after oral exposure based on its low molecular weight (201.2 g/mol), its high water solubility (240.5 g/L) and its logPow of < -2.78. Absorption via inhalation and dermal routes is considered to be negligible.

Main ADME results 2

Type:

distribution

Results:

The substance is expected to be extensively and wide distributed throughout the body into the intravasal compartment.

Main ADME results 3

Type:

metabolism

Results:

No extensive metabolism is expected for the target substance due to its high hydrophilicity. The substance is expected to be excreted unchanged. Conjugation reactions or metabolism via Cytochrom P450 monoaminooxigenase cannot be ruled out.

Main ADME results 4

Type:

excretion

Results:

The substance is likely to be excreted via the urine.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

3-(1-Pyridinio)-1-propanesulfonate is favourable for absorption, when taking its molecular weight (201.24 g/mol) into account. In addition, the substance is very soluble in water (240500 mg/L), so it is apparent, that its absorption is also favoured. The value of the LogPow (< -2,78) shows the substance to be better soluble in water than in octanol (positive LogPow for lipophilic substances, negative LogPow for hydrophilic substances). Considering its water solubility and the value for LogPow below 0, the absorption into the body will still be favoured (LogPow between 0 and 4 are most favourable for absorption).
3-(1-Pyridinio)-1-propanesulfonate has a very low calculated vapour pressure (4.24 E-05 Pa at 25°C), which indicates a low availability for inhalation. However, the low LogPow indicates a potential for absorption through aqueous pores. The available acute toxicity data show that the substance was absorbed systemically if administered orally to rats. This was confirmed by the fact that three male rats of the 5000 mg/kg group showed mottled lungs (Ullmann and Sacher, 1983). The substance is, however, not toxic per se since no mortality, neither signs of toxicity nor other findings at necropsy were observed at the highest dose level of 5000 mg/kg bw.
3-(1-Pyridinio)-1-propanesulfonate has a very low calculated vapour pressure (4.24 E-05 Pa at 25 °C), which indicates a low availability for inhalation. However, the low logPow indicates a potential for absorption through aqueous pores. Furthermore, a certain amount of the substance can be available for inhalation due to its appearance form as powder. The average particle size is 32.1 µm (< 100 µm), indicating the potential to be inspired.
Concerning dermal absorption, 3-(1-pyridinio)-1-propanesulfonate has a molecular weight of 201.24 g/mol (above 100 and below 500), which indicates a certain potential to penetrate the skin. However, 3-(1-pyridinio)-1-propanesulfonate has negative logPow (-2.78) and high water solubility (240.5 g/L). Therefore, it is expected to be absorbed following dermal exposure to a limited extent into the stratum corneum and from there into the epidermis. Moreover, the systemic toxicity of 3-(1-Pyridinio)-1-propanesulfonate via the skin is low and this has been shown with the results of the acute dermal toxicity study, which showed no mortality after dermal application of 2000 mg/kg bw in rats.

Details on distribution in tissues:

In case of 3-(1-Pyridinio)-1-propanesulfonate, no data is available for distribution patterns. The distribution of 3-(1-Pyridinio)-1-propanesulfonate is expected to be limited to the intravasal compartment, due to its better solubility in water than in octanol (LogPow < -2.78).

Details on excretion:

Concerning the above mentioned behaviour predicted for its metabolic fate, it is likely that the parent substance will be excreted unchanged. However, if unchanged excretion is assumed, based on chemical structure of 3-(1-Pyridinio)-1-propanesulfonate, its molecular weight and its high water solubility, it is likely to be excreted via the urine. Concerning the fate of the metabolites formed of 3-(1-Pyridinio)-1-propanesulfonate, the hydroxylated carbon-atoms and the nitrogen, in cases linked to glucuronic acid, activated sulphate or activated methionine or acetylated by N-acetyltransferases should be eliminated via the urine.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Hydrolysis does not apply. However, metabolism is very likely to occur via the Cytochrome P450 group of metabolising enzymes. Using Toxtree, the chemical has been identified to bear primary, secondary and tertiary sites and has more than 4 sites for metabolism by the Cytochrome P450 group of metabolising enzymes. The primary and secondary sites of metabolism are the carbon atoms of the chain, which are predicted to be subject to aliphatic hydroxylation. The tertiary site of metabolism is the nitrogen-atom of the aromatic ring, which is predicted to be subject to N-oxidation.
The above mentioned functional groups can react in phase 2 of the biotransformation with different molecules, leading to the formation of conjugations. This is not necessary for 3-(1-Pyridino)-1-propanesulfonate as its water solubility is already very high and it can be eliminated via the urine without further metabolism. If further metabolism is taken into account, it is most likely that the hydroxyl-groups will be conjugated to glucuronic acid, activated sulphate or activated methionine.
The oxidised or hydroxylated nitrogen can be further metabolised by the monoaminooxigenase to an imine via dehydration, which can be hydrolysed to ammonia and an aldehyde. Furthermore this amino-group could be subject either conjugation with glucuronic acid, activated sulphate or to be subject to N-acetylation mediated by N-acetyltransferases. In conclusion, it is possible that the substance of interest will be subject to metabolism by cytochrome P450 enzymes.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: expert statement indicates no potential for bioaccumulation
An extensive Assessment of the toxicological behaviour of 3-(1-Pyridinio)-1-propanesulfonate was performed (expert statement), taking into account the chemical structure, the available physico-chemical-data and the available (eco-)toxicological data.

Executive summary:

In order to assess the toxicological behaviour of 3-(1-pyridinio)-1-propanesulfonate, the available and predicted physico-chemical and toxicity data have been evaluated. The substance is expected to be well absorbed after oral exposure, based on its low molecular weight, its high water solubility and its logP_owof < -2.78. Concerning the absorption after exposure via inhalation, as the chemical has a low vapour pressure, it is clear, that the substance has a low availability for inhalation. Given its hydrophilicity (logP_owof < -2.78), if any of the substance is available for inhalation, it is expected to be absorbed directly through aqueous pores. Moreover, the average particle size is 32.1 µm (< 100 µm), indicating the potential to be inspired. 3-(1-Pyridinio)-1-propanesulfonate is expected to be absorbed to a limited extent following dermal exposure into thestratum corneumand into the epidermis, due to its high water solubility and its logP_ow. The substance is expected to be extensively and wide distributed throughout the body into the intravasal compartment. The substance does not bear accumulative potential after repeated exposures. 3-(1-Pyridinio)-1-propanesulfonate is expected to be metabolised via the Cytochrome P450 group of metabolizing enzymes. However, elimination of unchanged or metabolised substance will occur mainly via the urine, either without or after conjugation to glucuronic acid, activated sulphate or activated methionine.