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EC number: 268-692-9
CAS number: 68133-60-8
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.
1 Physico-Chemical Data on 1-benzyl-3-carboxylatopyridinium
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
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.
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
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
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.
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
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
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.
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).
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.
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