Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium salts

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: assessement of toxicokinetic behaviour based on physico-chemical properties and toxicological data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: An assessment of the toxicokinetic behaviour of target substance magnesium sulfonate salt was performed, taking into account the chemical structure, the available physico-chemical-data and the available toxicological data.

Data source

Reference

Reference Type:

other: Expert statement

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Objective of study:

absorption

distribution

excretion

metabolism

Test guideline

Qualifier:

according to guideline

Guideline:

other: Technical guidance document, Part I, 2003; ECHA guidance R7C., 2014

Deviations:

no

GLP compliance:

no

Remarks:

not applicable

Test material

Test material information

Constituent 1

Reference substance name:

Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium salts

EC Number:

946-212-5

Molecular formula:

Too complex

IUPAC Name:

Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium salts

Test material form:

other: liquid

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

The target substance sodium sulfonate is not favourable for absorption via all routes of exposure, due to its molecular weight (MW =432.64-516.79 g/mol), water solubility (0.255 mg/L), vapour pressure (0.0259 Pa at 25°C) and logPow (7.99).

Main ADME results 2

Type:

distribution

Results:

The distribution in tissues is expected to be limited based only on physico-chemical properties. The substance is not expected to cross biological membranes extensively.

Main ADME results 3

Type:

distribution

Results:

However, distribution throughout the body is apparent due to the findings in the repeated dose toxicity studies with read-across substances.

Main ADME results 4

Type:

excretion

Results:

The metabolites are expected to be eliminated via the urine and via the bile. The parent substance is expected rather to be eliminated via the faeces.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The absorption of Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium salts is expected to be, rather limited, based on the absorption-hindering properties (high molecular weight, slight water solubility and high LogPow) and the observed effects in toxicological experiments. The substance is not acutely toxic by oral (LD50 > 5000 mg/kg bw) and dermal exposure routes (LD50 > 2000 mg/kg bw). However, reduced body weight gain observed in animals of 28-day study with a read-across substance (Rush, 2003; CAS 115733-09-0), clinical signs i.e. post dosing salivation and dark material around the nose in the mid and high dose groups observed in the one-generation study with the same substance (Bjorn, 2004; CAS 115733-09-0) and reduction in mean serum cholesterol at highest dose level in 28-day study (Wong, 1989; Analog of CAS 70024-69-0) point to a certain absorption potential, which is considered to be minimal. The effects in these studies were assessed to be treatment related but not adverse.

Details on distribution in tissues:

There are no measured data available on distribution of the target substance in tissues of animals. The information can be gathered from gross and histopathological findings in treated animals in long-term studies. No remarkable findings were noted in the animals at necropsy and no meaningful microscopic lesions were observed in any of the treated F0 females in the one-generation study (Bjorn, 2004; CAS 115733-09-0) and in 28-day study with the same substance (Rush, 2003; CAS 115733-09-0). Only slight irritating effects of stomach (primary organ of exposure) were noted in animals of 28-day study with analog of CAS 70024-69-0). Based on these findings, either no extensive distribution potential or low toxicological activity can be concluded for the target substance sodium sulfonate. The high LogPow would indicate the possibility to reach the intracellular compartment, but the molecular weight of the un-metabolised substance is relatively high, so that a limited distribution potential can be concluded based only on physico-chemical parameters. However, minimal findings in the reapeted dose toxicity studies, even though they were not adverse, point to a certain distribution potential in the organism.

Details on excretion:

For Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium salts, no data is available concerning its elimination. Concerning the fate of the metabolites formed of sodium sulfonate, they should be eliminated mainly via the urine and to a smaller extent via the bile. The parent compound, if not absorbed into systemic circulation and does not undergo the first-pass metabolism, is expected to eliminate via the faeces.

Metabolite characterisation studies

Metabolites identified:

not specified

Details on metabolites:

Hydrolysis in the gastrointestinal tract does not apply for the target substance sodium sulfonate. Its metabolism is very likely to occur via the Cytochrome P450 group of metabolising enzymes. The primary and secondary sites of metabolism are the carbon atoms of the chain, where it branches, which can be subject to aliphatic hydroxylation. The tertiary sites of metabolism are the terminal carbon-atoms of the chain, which can also be hydroxylated. On the other hand, the long carbon chains are subject to initial omega- and then successive beta-oxidation, probably followed by oxidative scission of the aromatic ring and desulfonation. Hydroxylated intermediates can react in phase 2 of the biotransformation with different molecules, leading to the formation of conjugates with glucuronic acid, activated sulphate or activated methionine.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Based on the physico-chemical properties of the C20-24 sodium sulfonate and on the toxicity data of the structurally related read-across substances, the sodium sulfonate is of low toxicological activity. It is expected to be absorbed by oral route of exposure to a certain extent, while no or limited absorption potential is expected in case of inhalation or dermal routes of exposure, respectively. The substance is expected to distribute throughout the body whereby without adverse effects to organs and tissues. The substance is expected to eliminate via the urine and via the faeces.

Executive summary:

The C20-24 sodium sulfonate is expected to be absorbed to a limited extent after oral exposure, based on its high molecular weight, its low water solubility, its high LogPow and absence of toxicity in the oral acute toxicity studies and minimal clinical findings in the long-term toxicity studies with the read-across substances. Concerning the absorption after exposure via inhalation, as the chemical has 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 sodium 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 and its high LogPow. Concerning its distribution in the body the sodium sulfonate target substance is expected to be distributed into the intravasal compartment and possibly also into the intracellular compartment, athough the extent of the distribution cannot be predicted. The substance does not indicate a significant potential for accumulation, when taking into account the predicted behaviour concerning absorption and metabolism. Similarly to other alkyl benzene sulfonates, the C20-24 sodium sulfonate is expected to be significantly extensively metabolised (metabolism by cytochrome P450 enzymes, followed by omega- and beta-oxidation and cleavage of the aromatic ring and desulfonation) and to be eliminated mainly via the urine and also via the bile.