Butanedioic acid, sulfo-, monoesters with lanolin alcs., disodium salts

Endpoint summary

Description of key information

According to the Directive (EC) No. 1907/2006 (REACH), annex VIII, assessment of the toxicokinetics, metabolism and distribution of the substance to the extent can be derived from the relevant available information.

The metabolism and distribution of Sulfosuccinate of Lanolin Alcohol could be described by the sterol part Lanolin Alcohol  and a Sulfosuccinic portions of the molecule, represented by Dioctyl Disodium Sulfosuccinate.

Additional information

According to the Directive (EC) No. 1907/2006 (REACH), annex VIII, assessment of the toxicokinetics, metabolism and distribution of the substance can be derived from the relevant available information.

No specific literature is available for Sulfosuccinates of Lanoline Alcohol and due to its complexity it was preferred considering directly the pathways of metabolites. This information, reported in several publications, have been taken into consideration to evaluate the toxicokinetics behaviour, metabolism and distribution.

Sulfosuccinate of Lanoline Alcohol is an ester formed by a steroid alcohol (Lanoline) and a Sulfosuccinic acid.

The Lanolin Alcohol (considered for the sterol portion) is a mixture of alcohols comprised of about two-thirds sterols and one-fourth aliphatic alcohols.

The whole molecule can be then metabolised by esterases in those two parts, and, in order to give an indication of the metabolism and the distribution, they will be described separately.

ABSORPTION AND DISTRIBUTION

In general, the gastrointestinal tract, the respiratory system and the skin are the most important natural routes by witch substances usually enter an organism and are organized in different ways. After a substance has been absorbed, it is distributed throughout the body via the bloodstream.

The major ways of metabolism for this substance are the oral and the dermal route, due to the presence of the esterase enzyme in the gastrointestinal system (lipidic metabolism) and on skin.

The sulfosuccinic part, represented by Dioctyl Disodium Sulfosuccinate (DSS), is well absorbed after oral uptake.

Surface-active agents are known to be absorbed through the skin and probably through mucous membranes (Smythe et al., 1941, GDCh, 2004).

Lanoline is mainly composed by sterols, with pathway is here represented by Cholesterol, that enters the intestinal tract from two major sources the diet and bile.

Before absorption, cholesterol must be solubilized by mixed micelles containing conjugated bile acids and hydrolytic products of triglycerides and lecithin fatty acids, monoglycerides and lysolecithin.

Absorption of cholesterol occurs in the upper intestine where micelles are swollen by fatty acids and monoglycerides; absorption is less in the lower intestine, possibly due to disruption of micelles by fat absorption. Before incorporation into chylomicrons most of the cholesterol in the mucosa becomes esterified and after, transported.

After transport in to the blood, the uptake of LDL by cells appears to be mediated by LDL-binding receptors on the surface of cells. From the surface of the cells, Cholesterol can be metabolised.

Lanolin and its derivatives are also used for their emollient properties on the skin, nails and hair. Emollient act to decrease the rate of evaporation by forming a barrier or occlusive material on the skin surface permitting hydration or rehydration from the deeper layers (Kammerau et al., 1976; CIR 2011). Therefore dermal absorption should be considered.

Furthermore, Lanoline contains unsaturated fatty alcohols, esters, sterol and terpenols, autoxidation may occur and chemical autoxidation products are unknown. However, peroxides and epoxides have been suggested as likely structures (Stutsman, 1977; CIR 2011).

METABOLISM AND EXCRETION

Once Cholesterol reacts with the surface of cells, it binds receptors, which are regulated in turn by cells need for cholesterol.

When LDL binds to high affinity receptors, it enters the cell by absorptive endocytosis and is incorporated into endocytotic vesicles (endosomes) that fuse with lysosomes.

Within the lysosome, the lipoprotein is dismantled: apoprotein B of the LDL coat is degraded to amino acids, and cholesterol esters, containing mostly polyunsaturated fatty acids (linoleic acid). The resulting unesterified cholesterol is discharged into the cell cytoplasm, where it can be incorporated into cell membranes, reesterified for storage within the cell, or excreted out of the cell. The esterification reaction, occurring through action of acyl CoA: cholesterol acyltransferase (ACAT), usually attaches a saturated fatty acid (palmitic acid) or monounsaturated fatty acid (oleic acid) to the cholesterol molecule; esterification is apparently stimulated by excess cholesterol to prevent abnormal accumulation of free (unesterified) cholesterol in membranes (Scott M. Grundy, 1978).

Maximum blood levels of the Sulfosuccinate DSS (representative of the sulfosuccinic part of the registering substance) are reached in humans after two hours. Elimination occurs rapidly in the form of metabolites, mainly in the faeces of humans and dogs and in the urine of rats and rabbits.

The major route of elimination is the gastrointestinal tract by urine and faeces. The tissues contained only traces.

No unchanged DSS appeared to be present in the urine, and only a small amount was present in the faeces (WHO, 1975).

In addition, DSS produced water, sodium and chloride secretion into the in vivo rat cecum, stimulating fluid and electrolyte secretion which is mediated by increased mucosal cyclic adenosine 3':5' monophosphate (Donowitz M., 1975).

The hypothesis that Dioctyl Sodium Sulfosuccinate (DSS) induces intestinal fluid accumulation by inhibiting Na, K-ATPase activity and/or by increasing mucosal prostaglandin E2 (PGE2) content was tested in rats. Eighteen hours after its intragastric administration, DSS (260 mg/kg body weight) significantly decreased jejunal and colonic Na, K-ATPase activity in saline-treated rats. DSS increased jejunal and colonic PGE2 content in control rats. Although jejunal adenylate cyclase and phosphodiesterase activities were not affected by DSS (520 mg/kg body weight), they were significantly stimulated in the colon. Inhibition of intestinal Na, K-ATPase activity and increase in mucosal PGE2 content might contribute to the net water accumulation induced in the rat intestine by DSS (Rachmilewitz D. et al., 1975).

In conclusion, the substance Sulfosuccinate of Lanoline Alcohol, salified, can be considered well metabolised, having not bioaccumulation potential on human tissues and organs.