Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

No bioaccumulation potential

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

For this endpoint, the read across between PWH/ammonium and PWH/sodium salt is valid and therefore the waiving.

The read across justification is attached on section 13 of the dossier.

INTRODUCTION

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

 

In the case of Paraffin waxes and Hydrocarbon waxes, chloro, sulfochlorinated, saponified, specific studies, nor specific literature data on toxicokinetics and metabolism are available. Nevertheless the substance resulted non-toxic for acute and repeated human toxicity, but some effects have been observed at 30 mg/kg bw on rats and for daphnia at very low concentration. Furthermore the substance is classified as irritant for skin and eye. No concern about mutagenicity , carcinogenicity or reproduction system is evident from performed tests.

 

Toxicokinetics, metabolism and distribution of the substance was evaluated considering:

-                     Physical-chemical properties

-                     Experimental data of toxicological tests

Literature data in general were also evaluated for completeness sake. 

 

PHYSICO/CHEMICAL PROPERTIES

The substance, physically a paste, but sold already in liquid form, is a typical high molecular weight surfactant, not formally soluble in water, but dispersible in stable micelles, as measured by TOC during water solubility test. The affinity for non polar phase seems low, therefore it can be treated biologically as an hydrophilic substance and no potential for bioaccumulation is expected.

 

SUMMARY OF TOXICOLOGICAL DATA

Acute Toxicity

In all of the acute toxicity tests (oral and dermal) no signs of systemic toxicity was recorded and no abnormalities were noted. No gross organ changes were . At necropsy In the remaining animal of the main study, swollen abdomen was noted and at the internal examination, gas content and swelling were observed in the stomach, duodenum, jejunum, ileum, caecum and colon. During dermal toxicity test, clinical signs recorded during the observation period were limited to the treatment site, in which redness (from marked to slight) and/or scabs were generally observed during the study.

Skin/eye irritation

The test substance has been tested only in vitro, but results seem consistent and lead to classification both for skin and eye. Furthermore, during dermal acute toxicity test the same irritating effect and the complete recovery has been noted

 

Sensitisation

The Buhler test has been performed on the test substance and the results indicate that the test item may elicit a sensitisation response in the guinea pig, since there was evidence of response at challenge following a period of induction exposure to the test item. This result indicates that the substance is absorbed and systemically available

Repeated dose toxicity

During the repeated dose oral toxicity test (30, 180 and 500 mg/Kg bw) no clinical signs related to treatment were observed.Treatment-related findings were seen in the stomach of the high and intermediate dosed groups of both sexes, and in the liver of the male high and intermediate dosed animals, and in the females of all treated groups.

Stomach (non-glandular): the treatment-related changes, seen in the non-glandular stomach of the high and intermediate dosed groups of both sexes, were generally dose-related in incidence and/or severity, and consisted of mild to moderate diffused hyperplasia of the squamous epithelium, which was associated with mild thickening (i.e., hyperkerathosis) of the keratin layer. Sporadically, subchronic inflammation of the submucosa and focal erosion were also noted. No other organs seem affected by the treatment.

 

Mutagenesis

All tests present the same results: no traces of mutagenicity and no significative cytotoxicity.

 

Reproduction

No effects on reproductive organs and fertility index have been reported during OECD 422 on rats and the faetus seem completely developed at all doses.

 

TOXICOKINETICS, METABOLISM AND DISTRIBUTION EVALUATION

 

The gastrointestinal tract, the respiratory system and the skin are the most important natural routes by which toxic 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.

A characteristic of biological membranes is that due to their lipid nature, they are readily permeable to lipophilic (= hydrophobic) substances; however is not to be forget that hydrophilic compounds can also pass biological membranes, albeit at a much lower rate than lipophilic substances.

 

Paraffin waxes and Hydrocarbon waxes, chloro, sulfochlorinated, saponified is a hydrophilic substance and based on the very low affinity with the n-octanol phase, demonstrated by Pow result, it is expected to have a low potential to cross biological membranes.

The available literature is usually focused on the sulphited functionality and can be applied also in this case:

Primary n-alkanesulfonates are metabolised to bisulfite and the corresponding aldehyde (Thysse and Wanders, 1972; Schöberl and Bock, 1980). The metabolic pathway of SAS is not fully investigated. Thysse and Wanders (1974) isolated an alkane sulfonate hydroxylase which was able to desulfonate n-C12-SAS forming 2-Dodecanone. Swisher (1987) suggested that the first step in metabolism is the formation of a ketobisulfite, which forms the ketone and bisulfite. The ketone may be further oxidized to an alkylacetate ester. Ester cleavage yields acetate and an alcohol which is further metabolised via ß-oxidation. Based on this metabolic pathway, the formation of recalcitrant metabolites is unlikely. This was also proven experimentally in a special test for the detection of recalcitrant metabolites (Gerike and Jasiak, 1985, 1986).

 

Salts of strong acids like sulfonates are known to be poorly absorbed into living cells because the charged species are hindered to cross membranes (Boethling & Mackay, 2000). Bioconcentration studies with radiolabelled homologues of the surfactant Linear Alkylbenzenesulfonate (LAS) gave BCF values allowing calculation of an average BCF= 66 L/kg (HERA, 2002b).

The absorption behaviour of charged species is taken into account by the QSAR calculation programme BCFWIN from US EPA (US EPA, 2000d) which uses different Kow dependent equations for ionic compounds. As for SAS no measured BCF values are available a QSAR approach was used and applied to 8-Hexadecansulfonic acid sodium salt (C16-SAS)

 

The pharmacokinetics of chloroparaffins has been investigated with 14 C-labelled (both terminal [1-14C] and uniform label) and with 36Cl-labelled substances administered orally or by intravenous injection to rodents and quails. Metabolic studies have revealed dechlorination and oxidative chain length reduction but the mechanisms have not yet been investigated (Darnerud, P., J. Brandt: Environm. Pollut. (Series A) 27, 45 (1982))].

After oral administration to rats, the half-life for short chain paraffins C14 –C17 with 52% chlorine was given as less than one week in the liver and 8 weeks in adipose tissue. Repeated administration did not lead to accumulation (Birtley, R., D. Conning, J. Daniel, D. Ferguson, E. Longstaff, A. Swan: Toxicol. appl. Pharmacol. 54,514 (1980)). Chloroparaffins are not completely absorbed from the digestive tract; the less chlorinated substances are better absorbed than those with high chlorine content. The accumulation of short chain chloroparaffins in organs and tissues with high metabolic activity (liver, kidney, intestinal mucosa, bone marrow, pancreas and salivary glands) after intravenous or oral administration to rats or quails is also inversely proportional to the chlorine content [Darnerud, P. O., A. Biessmann, J. Brandt: Arch. Toxicol. 50, 217 (1982)].