1-benzyl-3-carboxylatopyridinium sodium chloride

Endpoint summary

Description of key information

The organic salt 1-benzyl-3-carboxylatopyridinium sodium chloride will readily dissociate into its respective ions, once in contact with an aqueous solution.
Based on the physicochemical properties, it is unlikely that relevant amounts of the 1-benzyl-3-carboxylatopyridinium ion become systemically available following oral exposure and hence will be mainly excreted via the faeces. Dissociated sodium and chloride ions will be absorbed within the GI tract by physiological transport mechanisms with excess amount being mainly excreted via the kidney in the urine.
Uptake into the systemic circulation following dermal exposure is very limited due to the solid and ionic nature of the salt.
Based on the low vapour pressure, particle size and high water solubility, it is unlikely that relevant amounts of the substance will become systemically bioavailable via inhalation.
Based on the physicochemical properties 1-benzyl-3-carboxylatopyridinium sodium chloride methyl sulphate is not considered to be bioaccumulative.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

1 Physico-Chemical Data on 1-benzyl-3-carboxylatopyridinium sodium chloride

 

The organic salt 1-benzyl-3-carboxylatopyridinium sodium chloride appearsin solid form at standard ambient temperature and pressure.The molecular weight (Mw) of the substance is 271.6747 g/mol and the molecular formula is C₁₃H₁₂NO₂^.Cl^.Na. The melting point is estimated to be higher than 270°C at ambient pressure (EPIWIN).The substance has a very low vapour pressure which can be regarded as negligible for the present assessment.

The substance is very well water soluble (> 1000 g/L, estimated via EPIWIN) as expected for salts like this. When placed in an aqueous solution, the substance immediately dissociates into the 1-benzyl-3-carboxylatopyridinium ion (Mw: 231.32g/mol), a sodium ion (Mw: 22.99g/mol) and a chloride ion (Mw: 35.45 g/mol.)The logPow value of the salt is expected to be around zero. The present toxicokinetic assessment focuses mainly on the1-benzyl-3-carboxylatopyridinium ion, as sodium and chloride ions are a natural and essential component of the human diet and pose no health hazard with regard to this assessment.

2 Toxicokinetic analysis of 1-benzyl-3-carboxylatopyridinium sodium chloride

 

Absorption

 

Oral route:

Within the gastrointestinal (Gl) tract the substance immediately dissociates into its respective ions. The ionic nature, the high water solubility and low LogPow of the 1-benzyl-3-carboxylatopyridinium ion will drastically limit an uptake into the systemic circulation by passive diffusion. More specifically, the ion appears to be too lipophobic in order to diffuse through the walls of the GI tract. Also, based on the Mw, uptake of the ion via aqueous pores is unlikely.

On the other hand, dissociated sodium and chloride ions are rapidly taken up by active physiological transport processes or pass through aqueous pores with the bulk passage of water (Renwick, 1994).

With regards to toxicological data, in an acute oral systemic toxicity study in rats (OECD 423), the LD50 value for 1-benzyl-3-carboxylatopyridinium sodium chloride was determined to be higher than 2000 mg/kg bw (limit dose). In this study no systemic effects were noted.

Furthermore, the substance was repeatedly administered to rats via the oral route. Again, no adverse effects were observed in the animals up to the highest dose level of 1000 mg/kg bw/day.

Overall, based on the physicochemical properties and on the results of the toxicological evaluation, absorption of concerning amounts of the 1-benzyl-3-carboxylatopyridinium ion into the systemic circulation following oral administration is unlikely. On the other hand, dissociated sodium and the chloride ions are readily taken up through the wall of the GI tract by normal physiological processes.

Inhalation route:

Based on the very low vapour pressure and the fact that the substance appears in solid form, inhalation exposure under normal use conditions is unlikely. Even if inhaled, the hydrophilic ions will dissolve and be retained within the mucus of the respiratory tract. Instead of being absorbed, the ions may be coughed or sneezed out of the body.

 

Dermal route:

The physicochemical properties of 1-benzyl-3-carboxylatopyridinium sodium chloride do not favour dermal absorption. As the substance is a solid at room temperature, it has to dissolve into the surface moisture of the skin before any potential uptake can take place. Once dissolved, the ionic nature of the constituents will drastically hinder dermal uptake.

The assumption that no dermal absorption occurs is further strengthened by the results obtained from dermal toxicity testing. In an acute dermal toxicity study (OECD 402), the substance did not cause any local or systemic effects and the LD50 was determined to be greater than 2000 mg/kg bw (limit dose). Topical application of the substance onto the skin of rabbits caused no considerable irritation as observed in a skin irritation/corrosion study (OECD 404). No evidence of tissue damage was observed which in turn could have favoured direct absorption into the systemic circulation.

Furthermore, no indication of systemic absorption was evident with respect to the results obtained in a Buehler sensitisation test (OECD 406) conducted on guinea pigs. Here, no immunological response was triggered and no signs of systemic toxicity were present.

Overall, the physicochemical properties and the findings from the dermal toxicity and sensitisation studysupport that practically no absorption into the systemic circulation is expected after dermal application.

 

Distribution

 

Based on the physicochemical properties and the lacking systemic toxicity of the substance as observed in the oral toxicity studies, concerning amounts of the 1-benzyl-3-carboxylatopyridinium ion are not expected to become systemically available. However, in the unlikely event that a certain amount of the highly water soluble ion enters the systemic circulation, distribution within the body via the blood stream will occur. Here the transport efficiency to the body tissues will be drastically limited by the rate at which the ion crosses cell membranes. More specifically, access to the central nervous system or the testes is most likely to be restricted by the blood-brain and blood-testes barriers (Rozman and Klaassen, 1996).

Absorbed sodium and chloride ions are distributed with the blood stream and remain either in extra cellular compartments or enter the intracellular compartments in order to maintain homeostasis.

Based on the physicochemical properties value, the ion or its potential metabolism products are not expected to bioaccumulate in the human body.

 

Metabolism

 

As stated above, systemic absorption of the 1-benzyl-3-carboxylatopyridinium ion is unlikely. However, if a limited amount of the ion is absorbed into the systemic circulation, it cannot be ruled out that the ion may be metabolised by Phase I enzymes while undergoing functionalisation reactions (e.g. hydroxylation of the phenol structure) aiming to further increase the ion’s hydrophilicity. Furthermore, Phase II conjugation reactions may covalently link an endogenous substrate to the cation or its Phase I metabolite in order to ultimately facilitate excretion.

 

Excretion

 

Due the limited GI absorption, the vast majority (if not all) of the dissociated 1-benzyl-3-carboxylatopyridinium ions are readily excreted via the faeces. In case that any amount of the ion reaches the systemic circulation, it is most likely that the ion itself or its final metabolites are excreted via the urine.

The majority of excess amounts of sodium and chloride ions are ultimately excreted from the body via the urine with minor amounts being excreted with the sweat (Holbrooket al.,1984).

 

3 Summary

 

The organic salt 1-benzyl-3-carboxylatopyridinium sodium chloride will readily dissociate into its respective ions, once in contact with an aqueous solution.

Based on the physicochemical properties, it is unlikely that relevant amounts of the 1-benzyl-3-carboxylatopyridinium ion become systemically available following oral exposure and hence will be mainly excreted via the faeces. Dissociated sodium and chloride ions will be absorbed within the GI tract by physiological transport mechanisms with excess amount being mainly excreted via the kidney in the urine.

Uptake into the systemic circulation following dermal exposure is very limited due to the solid and ionic nature of the salt.

Based on the low vapour pressure, particle size and high water solubility, it is unlikely that relevant amounts of the substance will become systemically bioavailable via inhalation.

Based on the physicochemical properties 1-benzyl-3-carboxylatopyridinium sodium chloride methyl sulphate is not considered to be bioaccumulative.

 

4 References

 

 

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Rozman K.K., Klaassen C.D. (1996) Absorption, Distribution, and Excretion of Toxicants. In Klaassen C.D. (ed.) Cassarett and Doull's Toxicology: The Basic Science of Poisons. McGraw-Hill, New York.

 

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