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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: assessment of toxicokinetic behaviour based on physico-chemical properties
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: An assessment of the toxicokinetic behaviour of the calcium sulfonate target substance was performed, taking into account the chemical structure, the available physico-chemical-data and the available toxicological data.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
other: Expert statement
Title:
Unnamed
Year:
2013

Materials and methods

Objective of study:
absorption
distribution
excretion
metabolism
Test guideline
Qualifier:
according to guideline
Guideline:
other: Technical guidance document, Part I, 2003
Deviations:
no
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Benzenesulfonic acid, di-C10-14-alkyl derivs., calcium salts
EC Number:
939-603-7
Cas Number:
1471316-72-9
Molecular formula:
not applicable (UVCB substance)
IUPAC Name:
Benzenesulfonic acid, di-C10-14-alkyl derivs., calcium salts
Test material form:
other: liquid

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
The absorption of the calcium sulfonate target substance is rather limited, based on the absorption-hindering properties (high molecular weight, slight water solubility and high LogPow) and the observed effects in toxicological experiments.
Type:
distribution
Results:
Even though the high LogPow would indicate the possibility to reach the intracellular compartment, this seems to be unlikely as the molecular weight of the un-metabolised substance is fairly high. Therefore, the distribution is expected to be limited.
Type:
excretion
Results:
The metabolites formed of the calcium sulfonate target substance, the metabolites should be eliminated mainly via the urine and to a smaller extent via the bile.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
In general, absorption of a chemical is possible, if the substance crosses biological membranes. This process requires a substance to be soluble, both in lipid and in water, and is also dependent on its molecular weight (substances with molecular weights below 500 are favourable for absorption). Generally, the absorption of chemicals which are surfactants or irritants may be enhanced, because of damage to cell membranes.
The calcium sulfonate target substance is not favourable for absorption, due to its molecular weight (MW >= 817.31 and <= 1111.87 g/mol), limited water solubility (1.69 mg/L) and a logPow (>6.65). Such lipophilic low water soluble substances are hindered to be absorbed because the dissolving in the gastrointestinal fluids is impaired. On the other hand, any lipophilic compound may be taken up by micellular solubilisation and this mechanism may be of particular importance for the calcium sulfonate target substance since it is poorly soluble in water. The substance does bear, however, surface activity; therefore an enhancement of absorption is theoretically possible, but it is not irritating to skin or eyes confirming that no further enhancement of absorption seems to be applicable.
The above mentioned properties determine the absorption of the calcium sulfonate target substance to be, rather limited, based on the absorption-hindering properties (molecular weight, slight water solubility and high LogPow) and the observed effects in toxicological experiments.
Details on distribution in tissues:
In general, the following principle applies: the smaller the molecule, the wider the distribution. A lipophilic molecule (LogPow >0) is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues. Protein binding can limit the amount of a substance available for distribution. Furthermore, if a substance undergoes extensive first-pass metabolism, predictions made on the basis of the physico-chemical characteristics of the parent substance may not be applicable.
In case of benzenesulfonic acid, di-C10-14-alkylderivs., calcium salts, no data is available for distribution patterns. Even though the high LogPow would indicate the possibility to reach the intracellular compartment, this seems to be unlikely as the molecular weight of the un-metabolised substance is so high. Therefore, the distribution is expected to be limited.
Details on excretion:
For benzenesulfonic acid, di-C10-14-alkylderivs., calcium salts no data is available concerning its elimination. Concerning the fate of the metabolites formed of benzenesulfonic acid, di-C10-14-alkylderivs., calcium salts, the metabolites should be eliminated mainly via the urine and to a smaller extent via the bile.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Hydrolysis does not apply for the calcium sulfonate target substance]. However, its metabolism is very likely to occur via the Cytochrome P450 group of metabolising enzymes, as it has been predicted with the TOXTREE modelling tool. According to the modelling results, the calcium sulfonate target substance, containing the structural alerts: cation, anion, sulfonic acid derivative and aromatic compound (Class 1: At least one functional group), is expected to be well metabolized by the Cytochrome P450 group of metabolizing enzymes. The primary and secondary sites of metabolism are the carbon atoms of the chain, next to aromatic ring, which are predicted to be subject to aliphatic hydroxylation. The tertiary sites of metabolism are the terminal carbon-atoms of the chain, which is predicted to be also subject to aliphatic hydroxylation.
Moreover, it is possible that the long carbon chains are subject to initial omega- and then successive beta-oxidation, possibly followed by oxidative scission of the aromatic ring and desulfonation. The above mentioned functional groups can react in phase 2 of the biotransformation with different molecules, leading to the formation of conjugations. This might be necessary for the parent compound, as its water solubility is fairly low and it cannot be eliminated via the urine without further metabolism. Further metabolism is most likely the conjugation of the hydroxyl-groups with glucuronic acid, activated sulphate or activated methionine.
In conclusion, it is likely that the substance of interest will be subject to metabolism by cytochrome P450 enzymes, followed by omega- and beta-oxidation and cleavage of the aromatic ring and desulfonation.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results based on high logPow and the predicted low absorption and extensive metabolism.
The calcium sulfonate target substance was evaluated regarding its toxicokinetic behaviour. Due to its physico-chemical properties it is reasonable to assume, that the calcium sulfonate target substance is absorbed after oral and poorly after dermal exposure. In addition, it is assumed to be poorly absorbed after exposure via inhalation. The calcium sulfonate target substance is not expected to be distributed throughout the body extensively. However, if absorbed, it is epected to distribute into the intracellular compartment, due to its high lipophilicity. However, it does not indicate a significant potential for accumulation, due to extensive metabolism. The calcium target substance is expected to be extensively metabolised (omega- and beta-oxidation, probably followed by oxidative scission of the aromatic ring and desulfonation) and to be eliminated via urine or to a minor extent via the faeces.
Executive summary:

In order to assess the toxicological behaviour of benzenesulfonic acid, di-C10-14-alkyl derivs., calcium salts, the available physico-chemical and toxicological data for it and its near calcium read across substances have been evaluated. The calcium sulfonate target substance is expected to be absorbed to a limited extent after oral exposure, based on its high molecular weight, its low water solubility and its high LogPow. Concerning the absorption after exposure via inhalation, as the chemical is considered to have a low vapour pressure, is highly lipophilic, has a high LogPow, and has a rather high molecular weight, it is clear, that the substance is poorly available for inhalation and will not be absorbed significantly.The calcium sulfonate target substance is also not expected to be absorbed following dermal exposure into the epidermis, due to its low water solubility and its fairly high molecular weight. Concerning its distribution in the body the calcium sulfonate target substanceis expected to be distributed into the intracellular compartment. The substance does not indicate a significant potential for accumulation, when taking into account the predicted behaviour concerning absorption and metabolism. The calcium sulfonate target substanceis expected to be extensively metabolised (metabolism by cytochrome P450 enzymes, followed by omega- and beta-oxidation and cleavage of the aromatic ring and desulfonation) andto be eliminated mainly via the urine and also via the bile.