Dodecylbenzenesulphonic acid, compound with 2-amino-2-methylpropan-1-ol (1:1)

Endpoint summary

Description of key information

No experimental data on absorption, distribution and excretion is available for the target substance,dodecylbenzenesulphonic acid, compound with 2-amino-2-methylpropan-1-ol (1:1).

AMP 

Oral absorption in vivo

In rats AMP was absorbed following administration of an oral bolus dose. Almost 100% of the dose is excreted via the urine (91-99%) and feces (4-8%) within the course of the study (168 hours), the vast majority of the dose excreted within the first 24 hours. The substance is not metabolised prior to excretion and does not appear to accumulate in any tissues.

Dermal dosing in rats led to an absorption of approximately 40% of the dose, the majority of which was excreted in the urine. Of the absorbed dose, approximately a quarter remained in the skin at the dose site and it is not clear if this would subsequently have become systemically available. Based on this data there is no concern that AMP would accumulate in the body (Dow 2007).

 

Dermal absorption in vitro

The absorption and cutaneous disposition of [14C]-AMP in an Ultra PC 2000™ formulation, a 40% aqueous formulation, and a Neat Control Lotion B formulation were determined in rat and human skin. In rat skin the total absorbed dose as a percent of the applied dose ranged from 30.0 to 50.9 %. In human skin the total absorbed dose as a percent of the applied dose was less than in rats, and ranged from 6.65 to 16.7 %. In both species, absorbed [14C]-AMP was primarily recovered from the receptor fluid. No evidence of marked accumulation of [14C]-AMP in skin tissue was evident (Dow 2007).

 

The findings of both in vivo and in vitro studies indicate that absorption via the oral route is expected to be 100%, while a clear species difference is expected for dermal absorption. In general it is known that the rat skin absorbs substances more easily than does the human skin. This is here confirmed for the uptake of AMP, which is expected to be <20% in humans.

DDBSA

The sodium salt of DDBSA is readily absorbed by the gastro-intestinal tract after repeated exposure for 5 weeks (82% of the administered dose), but absorption via the skin is very low (0.07-0.3% of the administered dose). DDBSA is distributed to most organs, except the uterus, and the major part is metabolised in the liver to sulfophenyl carboxyl acids. NaDDBSA metabolites are eliminated primarily via the urine and feces (ca 30 and 50% respectively). No accumulation of DDBSA or its main metabolites has been observed[1][2].

AMP-DDBSA

Based on the physico-chemical characteristics of the two parts of the compound, taking into account that the compound will readily dissolve into the gastrointestinal fluids and thus be present in its dissociated form[3], the absorption after oral administration of the substance can be attributed to the absorption of AMP and DDBSA. As was found for the source substances, it is expected that absorption will be significant although the ionic nature of the parts will hamper absorption to a certain extent. The low vapour pressure indicates that AMP-DDBSA is non-volatile at room temperature and thus the exposure of the substance via inhalation route is unlikely. Therefore, absorption via inhalation is not further discussed. With dermal exposure the compound is expected to be present in its non-dissociated form and the uptake is expected to be very low based on high water solubility and low log Kow. AMP-DDBSA may be too hydrophilic to cross the lipid rich environment of the stratum corneum.

Based on the low Log Kow and high water solubility, both parts of the substance are not expected to remain in the body fluids and may be rapidly excreted via urine, as is seen in the information available on the individual components. No bioaccumulation is expected.

Concluding the absorption of AMP-DDBSA via the oral route is set at the default of 100%, while dermal absorption is set at the default value of 10%. This conclusion has been drawn in absence of data on toxicokinetics for the target substance. The metabolism and excretion data are based on the information on AMP and DDBSA. No other metabolic pathways are however expected for these kinds of substances.

Mode of action

      

For human toxicity the AMP part of the compound is expected to be most relevant.

The effect of AMP on the liver appears to be a result of interference with phospholipid synthesis in the hepatocytes. Various publications on AMP from the 1950's and 1960's have identified that it is capable of becoming incorporated into phospholipids in place of ethanolamine and/or choline and that it inhibits the uptake of choline by the liver cells. AMP also appears to inhibit the formation of choline in the liver via the conversion of ethanolamine to choline.

The transport of lipids from hepatocytes is fairly consistent throughout mammalian physiology, i.e. the use of a phospholipid based transport such as VLDL. Therefore, the effects observed in rats and dogs in the studies on AMP are likely relevant to man. However, the increase in hepatic lipids is only the first step in the toxicity to the liver, and further indicators of toxicity are only evident after some accumulation of lipids. There is no evidence of liver toxicity (e.g. increased liver weight, increase in liver enzymes in the blood etc.) at doses where lipid accumulation in hepatocytes is not apparent. It is also apparent that the liver toxicity is the most sensitive endpoint, occurring at doses lower than those causing other effects, such as increased post implantation loss.

[1](Lay JP et al., Elimination and biodistribution studies of [14C]Dodecylbenzene sulfonate in rats, following low dosing in the daily diet and single i.p. administration Toxicology letters, 17(1983), 187-192

[2]Howes D, The percutaneous absorption of some anionic surfactants J. Soc. Cosmet. Chem. 26 (1975): 47-63.

[3]Aromatic sulphonic acids are almost completely ionized in watery environments even at low pH. In principle the salts of these acids get dissociated when in contact with water, so forming back to the acids. This is particularly relevant for studies that are conducted in water (e.g., ecotoxicity and biodegradation) as well as for mammalian toxicity studies where the relatively high acidity of the acid form has an immediate and harsh local effect, whereas the salt form provides an indication of potential systemic toxicity beyond the site of application or initial contact.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10