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

Endpoint summary

Description of key information

 The substance Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium salts (generic name: 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. 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 sodium sulfonate target substance 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.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

100

Additional information

Toxicokinetic behaviour of the sodium sulfonate target substance

The toxicokinetic profile of the Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium salts (generic name: C20-24 sodium sulfonate) was not determined by actual absorption, distribution, metabolism or excretion measurements. Rather, the physical chemical properties of the sodium sulfonate target substance and acute, irritation and repeated-dose toxicity data on the target substance as well on the analogue calcium and sodium read across substances were used to predict toxicokinetic behaviour of the sodium sulfonate target substance.

Toxicological profile of the sodium sulfonate target substance

The Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium salts (generic name: C20-24 sodium sulfonate) is a viscous, dark brown coloured liquid with a relatively high molecular weight range (MW = 432.64 - 516.79 g/mol; calculated by EPIWIN US EPA). It has a melting point at 9°C (Fox, 2015c). A study shows that it decomposes at approximately 300 °C (Fox, 2015c) and has a low vapour pressure, 0.0259 Pa at 25°C (Tremain, 2015c). Its relative density was reported to be 0.959 at 20 °C (Fox, 2015c). The sodium sulfonate target substance is slightly soluble in water (0.255 mg/L at 20 °C; Fox, 2015d). While the partition coefficient Log10Pow of the undissociated sodium sulfonate target substance has been experimentally determined to be in the range of 7.06 -12.53 (Tait and Laud, 2000), a key value of 7.99 was considered as relevant.

The C20-24 sodium sulfonate was shown not to be skin irritating (Kern, 1999a) but eye irritating (Kern, 1999d). In addition, several sodium and calcium sulfonate read across substances have been shown not to be acutely toxic when administered to rats orally (LD50 > 5000 mg/kg bw), or dermally (LD50 > 2000 mg/kg bw). Moreover, the calcium sulfonate read across substance (CAS 70024-69-0) was shown neither to be a skin nor an eye irritant (Hoff, 2002a; Hoff, 2002b; Buehler, 1990a; Buehler, 1990b; Swan, 1972; Kern, 1999b and Buehler, 1991a/b; Swan, 1972; Kern, 1999e). The sodium sulfonate target substance (Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium salts) was shown not to bear a potential to cause allergic reactions if the substance of high TBN (Smedley, 2015b); however, the low TBN substance caused skin sensitization in guinea pigs in a modified Buehler test (Smedley, 2015a). Repeated oral exposures to the calcium sulfonate read across substance analog of 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, 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 115733-09-0) was also tested in an one-generation study with NOAEL of greater than 500 mg/kg/bw (Bjorn, 2004). Concerning gene mutation, the analog of calcium sulfonate read across substance (CAS 70024-69-0) was shown not to bear genotoxic potential in bacterial strains (Sanitised, H., 1989) and the calcium sulfonate read across substance (CAS 68783 -96 -0) not to be mutagenic in OECD 476 study (Sanitised, D, 1984) and not to induce chromosome aberrations in OECD 473 study (Sanitised, M., 1995). Moreover, the calcium sulfonate read across substance (Analogue of CAS 70024-69-0) was shown not to induce micronuclei (Sanitised, I., 1989).

The calcium sulfonate read across substance (CAS 115733-09-0) was reported not to induce significant adverse effects in the one-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 sodium sulfonate target substance (Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium salts) is not favourable for absorption, due to its molecular weight (MW = 432.64 -516.79 g/mol), water solubility (0.255 mg/L) and logPow (>4). 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 but this mechanism may be of particular importance for the sodium sulfonate target substance since it is again poorly soluble in water. The substance does bear, however, surface activity; therefore an enhancement of absorption is theoretically possible. The substance is not irritating to skin but irritating to eyes so that an enhancement of absorption cannot be ruled out.

The above mentioned properties determine the absorption of the sodium sulfonate target substance to be, generally, rather limited, based on the absorption-hindering properties (molecular weight, slight water solubility and high LogPow) and the observed effects in toxicological experiments.

Oral route

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 sodium sulfonate target substance is, however, not expected to hydrolyse (due to its low water solubility).

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 administered sodium sulfonate 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 greater than 5000 mg/kg bw available for the sodium and calcium sulfonates read-across substances, which shows that the substance is not acutely toxic after oral exposure.

Additionally, only few clinical findings were observed in the repeated dose toxicity studies with the read-across substances that could point either to a limited absorption potential of sodium and calcium sulfonates or to their low toxicity. In details, reduced body weight gain was observed in animals of 28-day study with a read-across substance (Rush, 2003; CAS 115733-09-0), which significance was questionable; clinical signs i.e. post dosing salivation and dark material around the nose in the mid and high dose groups were 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 was noted in 28-day study (Wong, 1989; Analog of CAS 70024-69-0).The effects in these studies were assessed to be treatment related but not adverse.

Based on these data, 50 % oral absorption is considered appropriate for the purpose of DNEL derivation in case of route-to-route extrapolation.

Inhalation route

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.

The sodium sulfonate target substance (Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium salts) has a low vapour pressure (0.0259 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 sodium sulfonate is marginally available in the air for inhalation and any inhaled substance is expected not to be absorbed. However, according to ECHA guidance R.8, in the absence of experimental data on absorption, worst case assumption should be used in case of route-route extrapolation (50 % for the starting route and 100% for the end route). In a 28 -day inhalation study with a structural analogue calcium sulfonate (CAS 61789 -86 -4; Hoffman, 1987) clinical signs and microscopic lesions of lungs were reported in animals of all treatment groups whereby the mid and the highest treatment groups (150 and 250 mg/m³) were mostly affected while the effects in the lowest treatment group (50 mg/m³) do not represent an adverse effect of treatment.The effects are not severe (as defined in ECHA guidance on CLP) and seem to be rather local effects: an accumulation of intraalveolar macrophages and hyperplasia/ hypertrophy of bronchiole epithelium. Since no inhalation repeated dose toxicity study is available for Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium salts and the effects were observed in the 28 -day inhalation study with the read-across substance (Hoffman, 1987), 100 % absorption is considered for inhalation route while 50% absorption is assumed for oral route (the starting route) (please see above).

Dermal route

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 above 500 are normally not able to penetrate the skin. 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; ECHA guidance R7.C, 2014). 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 sodium sulfonate the molecular weight of around 500 g/mol (432.64 - 516.79), indicates already a marginal potential to penetrate the skin. This is accompanied by a low hydrophilicity of the substance (logPow of 7.99) and low water solubility (0.255 mg/L). Even though the stratum corneum is open for lipophilic substances, the epidermis is very resistant against penetration by highly lipophilic substances (logPow >4). However, the amount of sodium sulfonate,which is absorbed following dermal exposure into the stratum corneum is unlikely to be transferred into the epidermis. Although the substance shows characteristics of a surfactant, it is not irritating to skin, and therefore an enhancement of dermal absorption can be ruled out.

In support of this hypothesis (the low dermal absorption), the systemic toxicity ofthe calcium sulfonate read across substance CAS 70024-69-0 and of CAS 115733-09-0via 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, logPow of 7.99, low water solubility (0.255 mg/L) and the results for the dermal acute toxicity, the use of a factor of 10 % for the estimation of dermal uptake for sodium sulfonate is justified(Schuhmacher –Wolz et al.,2003; TGD, Part I, 2003; ECHA guidance R.7C, 2014).

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 sodium sulfonate no data is available for distribution patterns. 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, no extensive distribution potential can be concluded for the target substance sodium sulfonate. 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 rather 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 the sodium sulfonate target substance ( Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium 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 magnesium 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 sodium sulfonate target substance (Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium 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. According to the modelling results, Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium 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, where it branches, 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, probably 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 sodium sulfonate target substance (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 predicted by TOXTREE, the metabolitesshould be eliminated mainly via the urine and to a smaller extent via the bile. The parent substance, if not absorbed into systemic circulation and does not undergo the first-pass metabolism, is expected to eliminate via the faeces.

The following information is taken into account for any hazard/ risk assessment

Prediction using TOXTREE

A representative chemical structure of Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium salts was assessed by Toxtree (v.2.5.0) modelling tool for possible metabolism. SMART Cyp is a prediction model, included in the tool, which identifies sites in a molecule that are labile for the metabolism by Cytochromes P450.

Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium 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, where it branches, 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 subject to aliphatic hydroxylation.

ADME Studies on Related Alkyl/aryl Sulfonates

Linear alkylbenzene sulfonates (LAS), alpha-olefin sulfonates (AOS) and alkyl sulfates (AS)

The World Health Organization (WHO assessment of alkyl/aryl sulfates and sulfonates (ISBN 92 4 157169 1, 1996), shows that linear alkylbenzene sulfonates (LAS), alpha-olefin sulfonates (AOS) and alkyl sulfonates (AS) are readily absorbed by the gastrointestinal tract, widely distributed throughout the body and extensively metabolised. The parent compound and metabolites are excreted primarily via the urine and faeces, although there are marked differences between the isomers in the route of excretion. Although few data are available, it would appear that dermally applied LAS are not readily absorbed through the skin, although prolonged contact may compromise the epidermal barrier and permit more extensive absorption.They can undergo omega- and beta-oxidation, which is followed by oxidative scission of the aromatic ring and desulfonation. For LAS, the parent compounds and the metabolites are excreted mainly through the kidneys and via the bile. AOS and AS are mainly excreted via the urine.

Dodecyl benzenesulfonate (DOBC)

The percutaneous absorption of DOBC surfactant was studied in in vitro studies in rats and humans (Howes, 1975). Two test solutions of the [14C]DOBC were used, the first a 3 mM solution in 25 % v/v Polyethylene Glycol 400 in water and a second 3 mM suspension in water. 0.25 mL of the test solution was applied to the rat skin (4.9 cm²) and 0.1 mL to the human epidermal samples (0.78 cm²).The concentration of the test material in the solutions was 1.2 mg/mL. After 2, 6 and 24 hours (rats) or after 0.5, 1, 2, 3, 4, 6, 7, 8, 24 and 48 hours (human) of exposure, the skin samples were washed with excess of water and the radioactivity was measured in the rinsings and in the tested skin samples to determine the penetration rates. The results show no measurable penetration (<0.1 µg/cm²) of DOBS through the rat skin up to 24 hours. DOBC did not penetrate human epidermis as well (<0.1 µg/cm²). 30% [14C] DOBS was recovered in the rinsings and 70% remained associated with the skin of rats. 30-50% of [14C] DOBC retained in the human epidermis after rinsing.

To calculate percutaneous absorption rates, penetration of 0.1 µg/cm², the lower limit of detection, was taken as worst-case. Based on the applied amount of 0.25 mL to the rat skin (4.9 cm²) and 0.1 mL to the human epidermis (0.78 cm²) and ´the concentration of DOBC in vehicle of 1.2 mg/mL, 0.16% and 0.065% absorption was calculated for the rat skin and human epidermis, respectively. Monitoring at 2, 6, and 24 hours after exposure to rat and human skin showed no measurable percutaneous penetration of 14C (< 0.1 µg/cm²) for DOBS.

Howes (1975) also studied the in vivo dermal absorption of DOBC in rats (Howes, 1975).The [14C]-labelled DOBS was applied (0.2 ml) as a 3 mM aqueous suspension over 7.5 cm² of skin for 15 min. The applied dose resulted in 250 µg per test site. Then the test solution was rinsed off with distilled water and the animals were fitted with either restraining collars or non-occlusive protection patches and placed in the metabolism cages for collection of excreta. The expired CO2, urine, faeces and the carcasses of the animals, after excision of the treated skin, was monitored for 14C at 24 h after treatment. The excised skin was monitored for 14C and examined by autoradiography. Autoradiography of the skins showed heavy deposition of the surfactant on the skin surface and in the upper regions of the hair follicles. 11± 4 µg/cm² was recovered in the excised skin of rats, 135 µg in the rinsing and < 2 µg in the protection patches, so the total recovery was complete. All the tissue and excreta samples examined did not contain quantifiable amounts of 14C. The penetration of the DOBC was below the limit of detection (<0.1 µg/cm²). Based on the amount applied (250 µg) and the penetration of 0.1 µg/cm², rat skin absorption would result in 0.3%.

The turnover (elimination) of [14C]-labelled DOBC was also measured by injecting three animals intraperitoneally and three animals subcutaneously with 0.1 or 0.5 mL of surfactant solution (Howes, 1975). Two test solutions of the [14C] DOBS were used, the first a 3 mM solution in 25% v/v Polyethylene Glycol 400 in water and a second a 3 mM suspension in water. The administered dose resulted in 1.02 mg/kg bw. The animals were placed in sealed metabolism cages where urine, faeces and expired air were collected and monitored for 14C. After 6 or 24 h the animals were killed and the radioactivity in their carcasses was measured. The rate and route of excretion of 14C from intraperitoneally administered [14C] surfactant solutions were the same as that from subcutaneously administered solutions. Most of the administered 14C was recovered in the urine at 24 h after dosing (78%). 22% and 1.5% of applied dose were recovered in carcasses and in faeces, respectively. Less than 0.1% radioactivity was measured in the expired air.

Conclusion:

The toxicology profile for the Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium salts (generic name: C20-24 sodium sulfonate) and the sodium and calcium sulfonate read across substances indicate that oral and dermal absorption is expected to be limited. The in vitro and in vivo studies with DOBC and other related alkyl/aryl sulfates and sulfonates provide additional evidence that the skin absorption is expected to be low. No measurable skin penetration could be determined in the in vitro and in vivo studies in rats and/or humans (Howes, 1975). According to WHO (1996), alkyl benzene sulfonates (ABS) are readily absorbed by the gastrointestinal tract, widely distributed throughout the body and extensively metabolised. However, since linear ABS (LAS) are defined as substances with the shorter hydrocarbon chain length (C10 -C13) than the target substance sodium sulfonate ( Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium salts), absorption and distribution pattern of the target substance are expected to be rather limited. This is based on well-known principle that homologue substances with the longer hydrocarbon chain are more lipophilic and their molecular weight is higher resulting in their limited absorption and distribution compared to their low molecular and less hydrophobic counterparts. Nevertheless, a certain absorption potential of the target substance sodium sulfonate by oral route of exposure was also confirmed by the findings in the repeated dose toxicity studies with the read-across substances. Even though the sodium and calcium sulfonates are widely distributed throughout the body, in analogy with ABS, they are of low toxicological activity and do not destroy the organs and their function. This statement is confirmed by the fact that no remarkable gross or histopathological findings in organs or tissues of treated animals were noted in the available long-term studies with calcium sulfonates. Similarly to ABS, the C20-24 sodium sulfonate is expected to be metabolised and to be excreted via the urine or via the faeces.