Benzenesulfonic acid, 4-(branched alkyl derivs.) and benzenesulfonic acid, 4-(linear alkyl dervis.), calcium salts

Basic toxicokinetics

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:

2014

Report date:

2014

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

Test material information

Constituent 1

Reference substance name:

Benzenesulfonic acid, mono-C15-36 branched alkyl derivs., C24 rich and Octadecylbenzenesulfonic acid,calcium salts

IUPAC Name:

Benzenesulfonic acid, mono-C15-36 branched alkyl derivs., C24 rich and Octadecylbenzenesulfonic acid,calcium salts

Test material form:

other: liquid

Results and discussion

Main ADME results

Main ADME results 1

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.

Main ADME results 2

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.

Main ADME results 3

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.
The available data suggest that orally administered calcium sulfonate target substance will be absorbed to a limited extent, even though micellular solubilisation, pinocytosis and persorption cannot be ruled out. This thesis is supported by the LD50 value of 10000 mg/kg bw available for the calcium sulfonate read across substance CAS 70024-69-0, which shows that the substance is not acutely toxic after oral exposure.
Moreover, it has a low vapour pressure (0.01 Pa at 25°C), which indicates only low availability for inhalation. The high molecular weight and the high LogPow also indicate no possibility for absorption through aqueous pores. Based on this data and even though the LogPow value above 0 indicates the potential for absorption directly across the respiratory tract epithelium (which is unlikely as the substance is ionisable), it can be expected that the calcium sulfonate target substance is marginally available in the air for inhalation and any inhaled substance is expected not to be absorbed.
Due to it’s molecular weight and the results for acute toxicity, the chemical is not likely to be absorbed to a significant extent and the use of a factor of 10 % for the estimation of dermal uptake is justified.

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. It’s not possible to foresee protein binding, which 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, mono-C15-36 branched alkyl derivs., C24 rich and Octadecylbenzenesulfonic acid, 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:

The major routes of excretion for substances from the systemic circulation are the urine and/or the faeces (via bile and directly from the gastrointestinal mucosa). For non-polar volatile substances and metabolites exhaled air is an important route of excretion. Substances that are excreted favourable in the urine tend to be water-soluble and of low molecular weight (below 300 in the rat) and be ionized at the pH of urine. Most will have been filtered out of the blood by the kidneys though a small amount may enter the urine directly by passive diffusion and there is the potential for reabsorption into the systemic circulation across the tubular epithelium. Substances that are excreted in the bile tend to be amphipathic (containing both polar and nonpolar regions), hydrophobic/strongly polar and have higher molecular weights and pass through the intestines before they are excreted in the faeces and as a result may undergo enterohepatic recycling which will prolong their biological half-life. This is particularly a problem for conjugated molecules that are hydrolysed by gastrointestinal bacteria to form smaller more lipid soluble molecules that can then be reabsorbed from the GI tract. Those substances less likely to recirculate are substances having strong polarity and high molecular weight of their own accord. Other substances excreted in the faeces are those that have diffused out of the systemic circulation into the GI tract directly, substances which have been removed from the gastrointestinal mucosa by efflux mechanisms and non-absorbed substances that have been ingested or inhaled and subsequently swallowed. Non-ionized and lipid soluble molecules may be excreted in the saliva (where they may be swallowed again) or in the sweat. Highly lipophilic substances that have penetrated the stratum corneum but not penetrated the viable epidermis may be sloughed off with or without metabolism with skin cells.
For benzenesulfonic acid, mono-C15-36 branched alkyl derivs., C24 rich and Octadecylbenzenesulfonic acid, calcium salts no data is available concerning its elimination. Concerning the fate of the metabolites formed of benzenesulfonic acid, mono-C15-36 branched alkyl derivs., C24 rich and Octadecylbenzenesulfonic acid, 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.

Any other information on results incl. tables

Background:

There is data available on the physico-chemical properties of the calcium sulfonate target substance. The calcium sulfonate target substance is a viscous, dark brown coloured liquid with a relatively high molecular weight (MW >= 817.31 and <= 1111.87 g/mol, Anon., 2013). It has a pour point of -9 °C (Anon., 2013). Via TGA, the thermal decomposition and relative weight per cent value was observed. Overall weight loss onset occurs at 183 ˚C for the oil portion of the substance whereas for the soap fraction, overall weight loss onset occurs at 417 ˚C (Anon., 2013. In addition, the target substance has a low vapour pressure, 0.01 Pa at 25°C (Wintermute, 2013). Its relative density was reported to be 0.9432 (Anon., 2013). The calcium sulfonate read across substances (CAS 70024-69-0 and CAS 61789-86-4) are slightly soluble in water (1.69 mg/L at 20°C (Fox and White, 2011a) and 0.113 mg/L at 20°C, (Fox and White, 2011b)). The partition coefficient LogPow of the calcium read across substances has been estimated to be > 5.47 (CAS 70024-69 -0; Fox and White, 2011a) or 6.65 (Fox and White, 2011b).

The calcium sulfonate read across substances were shown not to be skin or eye irritating (Kern, T.G., 1999a/b; Swan, 1972, Hoff 2002a/b, Buehler, 1990a/b, 1991 a/b, Costello, 1986b, Ohees, 1968 c/d, Gabriel, 1981b/c, Kern, 1999).

Systemic toxicity is expected to be low; as the calcium sulfonate read across substances were non-toxic by ingestion (Swan, 1972 - LD50: > 10,000 - < 20,000 mg/kg bw; Sanitised, F., 1989 - LD50 < 5,000 mg/kg bw; Sanitised, A., 1981 - LD50 < 5,000 mg/kg bw, Sanitised, C., 1984 - LD50 >5.000 mg/kg bw; Sanitised, E., 1985 - LD50 >5.000 mg/kg bw; Ohees, P. 1968a - LD50 > 20,000 mg/kg bw; Regel, L., 1970 - LD50 > 10,000 mg/kg bw; Ohees, P., 1968b - LD50 > 20,000 mg/kg bw, Gabriel, K. L:, 1981a - LD50 > 16,000 mg/kg bw). In addition no toxicity was found after percutaneous absorption (Sanitised, G., 1989, LD50 < 2,000 mg/kg bw; Sanitised, B., 1981 - LD50 > 5,000 mg/kg bw, Sanitised, J., 1993 - LD50 > 2000 mg/kg bw, Costello, B. A:, 1986a - LD50 > 4000 mg/kg bw). The calcium sulfonate read across substance (CAS 75975-85-8) was shown to bear a potential to cause allergic reactions (Shults, 1993, Bonnette, 1993, Lees, 1996). However, the other calcium sulfonate read across substance (CAS 61789-86-4) was shown not to be skin sensitising (Kiplinger, 1992a/b/c, Blaszcak, 1992, Reagan, 1988). This was analysed in a weight-of-evidence approach (in conjunction with various human patch test data) and the conclusion was drawn, that, a low TBN calcium sulfonate target substance (C15-C36) (TBN < 300) is a skin sensitizer (Cat. 1B, H317) with a specific concentration limit (SCL) of 10%, in accordance with CLP 1272/2008. In contrast, a high TBN calcium sulfonate target substance (C15-C36) (TBN ≥ 300) is not a skin sensitizer. Repeated oral exposures to the calcium sulfonate read across substance CAS 70024-69-0 (28-day study) revealed a NOAEL of 500 mg/kg bw (based on a decrease in serum cholesterol and a LOAEL of 1000 mg/kg bw, the highest dose tested (Wong, Z., 1989). Additionally, the calcium sulfonate read across substance CAS 115733-09-0 showed a systemic NOAEL of 1000 mg/kg bw for rats (Rush, R.E:, 2003). The calcium sulfonate read across substance CAS 61789-86-4 was shown to have a dermal NOAEL of 1000 mg/kg bw (Laveglia, 1988). Concerning gene mutation, the calcium sulfonate read across substance CAS 70024-69-0 was shown not to bear genotoxic potential (Sanitised, C., 1989, and Sanitised, L., 1995) and the calcium sulfonate read across substance CAS 68783-96-0 not to be mutagenic (Sanitised, D. 1984, Sanitised, N., 1995). Moreover, the calcium sulfonate read across substance (Analogue of 70024-69-0) was shown not to induce micronuclei (Sanitised,I., 1989). In addition, the calcium sulfonate read across substances (CAS 68783-96-0 and CAS 61789-86-4) were also shown not induce micronuclei (Sanitised, N., 1995, Loveday, 1988b).

The calcium sulfonate read across substance (CAS 115733-09-0) was reported not to induce adverse effects in a 1-generation reproduction toxicity study (Bjorn, 2004).

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.

Absorption from the gastrointestinal tract

Regarding oral absorption, in the stomach, a substance will most likely be hydrolysed, because this is a favoured reaction in the acidic environment of the stomach.The calcium sulfonate target substanceis not expected to hydrolyse (due to its low water solubility). Accordingly, it is very unlikely for benzenesulfonic acid, mono-C15-36 branched alkyl derivs., C24 rich and Octadecylbenzenesulfonic acid, calcium salts to be hydrolysed in the stomach.

In the small intestine absorption occurs mainly via passive diffusion or lipophilic compounds may form micelles and be taken into the lymphatic system. Additionally, metabolism can occur by gut microflora or by enzymes in the gastrointestinal mucosa. However, the absorption of highly lipophilic substances (LogPow of 4 or above) may be limited by the inability of such substances to dissolve into gastrointestinal fluids and hence make contact with the mucosal surface. The absorption of such substances will be enhanced if they undergo micellular solubilisation by bile salts. Substances absorbed as micelles enter the circulation via the lymphatic system, bypassing the liver.

The available data suggest that orally administeredbenzenesulfonic acid, mono-C15-36 branched alkyl derivs., C24 rich and Octadecylbenzenesulfonic acid, calcium salts will be absorbed to a limited extent, even though micellular solubilisation, pinocytosis and persorption cannot be ruled out. This thesis is supported by the LD50 value of 10000 mg/kg bw available for the calcium sulfonate read across substance CAS 70024-69-0, which shows that the substance is not acutely toxic after oral exposure.

Absorption from the respiratory tract

Concerning absorption in the respiratory tract, any gas or vapour has to be sufficiently lipophilic to cross the alveolar and capillary membranes (moderate LogPow values between 0-4 favourable for absorption). The rate of systemic uptake of very hydrophilic gases or vapours may be limited by the rate at which they partition out of the aqueous fluids (mucus) lining the respiratory tract and into the blood. Such substances may be transported out of the lungs with the mucus and swallowed or pass across the respiratory epithelium via aqueous membrane pores. Lipophilic substances (LogPow >0) have the potential to be absorbed directly across the respiratory tract epithelium. Very hydrophilic substances can be absorbed through aqueous pores (for substances with molecular weights below and around 200) or be retained in the mucus.

Benzenesulfonic acid, mono-C15-36 branched alkyl derivs., C24 rich and Octadecylbenzenesulfonic acid, calcium salts has a low vapour pressure (0.01 Pa at 25°C), which indicates only low availability for inhalation. The high molecular weight and the high LogPow also indicate no possibility for absorption through aqueous pores. Based on this data and even though the LogPow value above 0 indicates the potential for absorption directly across the respiratory tract epithelium (which is unlikely as the substance is ionisable), it can be expected thatbenzenesulfonic acid, mono-C15-36 branched alkyl derivs., C24 rich and Octadecylbenzenesulfonic acid, calcium salts is marginally available in the air for inhalation and any inhaled substance is expected not to be absorbed.

Absorption following dermal exposure

In order to cross the skin, a compound must first penetrate into the stratum corneum and may subsequently reach the epidermis, the dermis and the vascular network. The stratum corneum provides its greatest barrier function against hydrophilic compounds, whereas the epidermis is most resistant to penetration by highly lipophilic compounds. Substances with a molecular weight below 100 are favourable for penetration of the skin and substances above 500 are normally not able to penetrate. The substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. Therefore if the water solubility is below 1 mg/l, dermal uptake is likely to be low. Additionally LogPow values between 1 and 4 favour dermal absorption (values between 2 and 3 are optimal; TGD, Part I, Appendix IV). Above 4, the rate of penetration may be limited by the rate of transfer between the stratum corneum and the epidermis, but uptake into the stratum corneum will be high. Above 6, the rate of transfer between the stratum corneum and the epidermis will be slow and will limit absorption across the skin. Uptake into the stratum corneum itself may be slow. Vapours of substances with vapour pressures below 100 Pa are likely to have enough contact time to be absorbed and the amount absorbed dermally is most likely more than 10% and less than 100 % of the amount that would be absorbed by inhalation. If the substance is a skin irritant or corrosive, damage to the skin surface may enhance penetration. During the whole absorption process into the skin, the compound can be subject to biotransformation.

In the case of benzenesulfonic acid, mono-C15-36 branched alkyl derivs., C24 rich and Octadecylbenzenesulfonic acid, calcium salts, the molecular weight is above 500, which indicates already a marginal potential to penetrate the skin. This is accompanied by a low hydrophilicity of the substance and even though the stratum corneum is open for lipophilic substances, the epidermis is very resistant against penetration by highly lipophilic substances. However, the amount of benzenesulfonic acid, mono-C15-36 branched alkyl derivs., C24 rich and Octadecylbenzenesulfonic acid, calcium salts, which is absorbed following dermal exposure into the stratum corneum is unlikely to be transferred into the epidermis. Although the substance does show characteristics of a surfactant, the calcium sulfonate target substance is not irritating to skin and eyes, and therefore this does not enhance dermal absorption.

In support of this hypothesis (the low dermal absorption), the systemic toxicity ofthe calcium sulfonate read across substance CAS 70024-69-0 and of 115733-09-0 via the skin is low (acute dermal toxicity, LD50 value of > 2000 and > 5000 mg/kg bw for rats, respectively).

In conclusion, the evaluation of all the available indicators and the results of toxicity studies allow the allocation of the chemical in question into the group of chemicals with a low dermal absorption. In detail, due to it’s molecular weight and the results for acute toxicity, the use of a factor of 10 % for the estimation of dermal uptake for benzenesulfonic acid, mono-C15-36 branched alkyl derivs., C24 rich and Octadecylbenzenesulfonic acid, calcium salts is justified(Schuhmacher –Wolz et al.,2003; TGD, Part I, 2003).

Distribution

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. It’s not possible to foresee protein binding, which 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, mono-C15-36 branched alkyl derivs., C24 rich and Octadecylbenzenesulfonic acid, 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.

Accumulation

It is also important to consider the potential for a substance to accumulate or to be retained within the body. Lipophilic substances have the potential to accumulate within the body (mainly in the adipose tissue), if the dosing interval is shorter than 4 times the whole body half-life. Although there is no direct correlation between the lipophilicity of a substance and its biological half-life, substances with high LogPow values tend to have longer half-lives. On this basis, there is the potential for highly lipophilic substances (LogPow >4) to accumulate in biota which are frequently exposed. Highly lipophilic substances (LogPow between 4 and 6) that come into contact with the skin can readily penetrate the lipid rich stratum corneum but are not well absorbed systemically. Although they may persist in the stratum corneum, they will eventually be cleared as the stratum corneum is sloughed off. A turnover time of 12 days has been quoted for skin epithelial cells.

Accordingly, the high LogPow and the predicted behaviour concerning absorption and metabolism of benzenesulfonic acid, mono-C15-36 branched alkyl derivs., C24 rich and Octadecylbenzenesulfonic acid, calcium salts might indicate a potential for accumulation in the body. This, however, is limited as the absorption is expected to be low via all routes of exposure and because metabolism of the calcium sulfonate target substance is expected to influence this initial prediction.

Metabolism:

Route specific toxicity results from several phenomena, such as hydrolysis within the gastrointestinal or respiratory tracts, also metabolism by gastrointestinal flora or within the gastrointestinal tract epithelia (mainly in the small intestine), respiratory tract epithelia (sites include the nasal cavity, tracheo-bronchial mucosa [Clara cells] and alveoli [type 2 cells]) and skin.

As specified above,hydrolysis does not apply for benzenesulfonic acid, mono-C15-36 branched alkyl derivs., C24 rich and Octadecylbenzenesulfonic acid, calcium salts. 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 (Chemservice, S.A., 2013). According to the modelling results, benzenesulfonic acid, mono-C15-36 branched alkyl derivs., C24 rich and Octadecylbenzenesulfonic acid, calcium salts, 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.

Excretion:

The major routes of excretion for substances from the systemic circulation are the urine and/or the faeces (via bile and directly from the gastrointestinal mucosa). For non-polar volatile substances and metabolites exhaled air is an important route of excretion. Substances that are excreted favourable in the urine tend to be water-soluble and of low molecular weight (below 300 in the rat) and be ionized at the pH of urine. Most will have been filtered out of the blood by the kidneys though a small amount may enter the urine directly by passive diffusion and there is the potential for reabsorption into the systemic circulation across the tubular epithelium. Substances that are excreted in the bile tend to be amphipathic (containing both polar and nonpolar regions), hydrophobic/strongly polar and have higher molecular weights and pass through the intestines before they are excreted in the faeces and as a result may undergo enterohepatic recycling which will prolong their biological half-life. This is particularly a problem for conjugated molecules that are hydrolysed by gastrointestinal bacteria to form smaller more lipid soluble molecules that can then be reabsorbed from the GI tract. Those substances less likely to recirculate are substances having strong polarity and high molecular weight of their own accord. Other substances excreted in the faeces are those that have diffused out of the systemic circulation into the GI tract directly, substances which have been removed from the gastrointestinal mucosa by efflux mechanisms and non-absorbed substances that have been ingested or inhaled and subsequently swallowed. Non-ionized and lipid soluble molecules may be excreted in the saliva (where they may be swallowed again) or in the sweat. Highly lipophilic substances that have penetrated the stratum corneum but not penetrated the viable epidermis may be sloughed off with or without metabolism with skin cells.

For benzenesulfonic acid, mono-C15-36 branched alkyl derivs., C24 rich and Octadecylbenzenesulfonic acid, calcium salts no data is available concerning its elimination. Concerning the fate of the metabolites formed ofbenzenesulfonic acid, mono-C15-36 branched alkyl derivs., C24 rich and Octadecylbenzenesulfonic acid, calcium salts, the metabolites should be eliminated mainly via the urine and to a smaller extent via the bile.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
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 expected to be distributed throughout the body, possibly reaching also the intracellular compartment, due to its hydrophilicity 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, mono-C15-36 branched alkyl derivs., C24 rich and Octadecylbenzenesulfonic acid, 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 substanceis 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 intravasal compartment and possibly also 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.