Registration Dossier

Diss Factsheets

Administrative data

Link to relevant study record(s)

Description of key information

The HYDROTOPES Category comprises the following 6 substances:
STS - Sodium toluene 4-sulphonate (CAS 657-84-1, EC 211-522-5)
SXS - Sodium (xylenes and 4-ethylbenzene) sulphonate (EC 701-037-1)
NH4XS - Ammonium (xylenes and 4-ethylbenzene) sulphonate (EC 943-024-5)
SCS - Sodium p-cumenesulphonate (CAS 15763-76-5, EC 239-854-6)
KCS - Potassium p-cumenesulphonate (CAS 164524-02-1, EC 629-764-9)
NH4CS - Ammonium p-cumenesulphonate (CAS 680972-33-2, EC 811-484-5) 
In addition CaXS (Calcium Xylenesulphonate, CAS 28088-63-3, EC 248-829-9) was evaluated for complete the assessment despite it is not registered under REACH.

A multiple homogeneous layer model was used to derive an estimate of dermal penetration for hydrotropes. The mathematical model simulates the uptake of a chemical substance through the skin into a central sink compartment below the skin. The model uses the substance's diffusion and partitioning coefficients and calculates the total (cumulative) fraction of the substance that enters the stratum corneum for a specific exposure duration. The model does not include any metabolism and the model is believed to represent an upper bound estimate of the potential uptake of the substance through the skin. The differential equations used to describe the model are numerically integrated using MATLAB software.Four exposure scenarios were modelled to derive exposure-specific uptake percentages. They included hand washing laundry, laundry pre-treatment, manual dish washing, and hard surface cleaning. These scenarios covered the product-relevant ranges of exposure durations and chemical concentrations.
Dermal penetration simulations based on a mechanistic model of the process of uptake of chemical substances in skin predicts that the dermal penetration of a generic hydrotrope is less than 0.6% of the applied amount (over a wide range of exposure scenarios). Simulations show that for an exposure extending to 23 hours, the dermal uptake does not exceed 2.8% of the applied amount, regardless of the applied amount (concentration) within the range of 0.0002% to 10%. 10% is considered an upper bound of the concentration of hydrotropes in consumer products. Irritation can be an issue at concentrations above 10% and so would need to be managed in the workplace.
Based on this state-of-science modelling, a 2.8% dermal absorption factor can be used as an upper bound value in general population exposure dose calculations for hydrotropes.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
Absorption rate - dermal (%):

Additional information

In addition to the toxicokinetic studies on rats and dogs (Dreyfuss et al, 1971) there are two toxicokinetic studies on closely related substances which provide useful supporting information.

Ho et al. (1981) investigated the toxicokinetics of p-toluene sulphonic acid. Whilst this is not a hydrotropes category member it does share the same organic anion as Sodium toluene sulphonate. Following iv bolus dosing of rats the substance is present (80% of the administered dose) in the blood one minute post-dosing. At eight minutes post-dosing there was still 20% of the substance present in the blood. There was no substance present in the bile at any of the time points up to 70 minutes. Tissue distribution of total radioactivity following dosing shows that there are low levels in the liver indicating that the substance is able to leave the liver (across the hepatic cell membrane) and travel to other sites in the body. Distribution of radioactivity in the kidneys sees a rise from 4.6% at 6 minutes to 27.2% at 35 minutes post-dosing. This paper also states that the substance is poorly absorbed across the jejenum and ileum.

Kano et al (1985) investigated the toxicokinetics of Sultamicillin tosilate (SBTPC) and p-toluene sulphonic acid. Sultamicillin tosilate is a prodrug that is hydrolysed in vivo into two metabolites and the salt of sultamicillin. The absorption, distribution and excretion and p-toluene sulphonic acid was investigated. Whilst p-toluene sulphonic acid is also not a hydrotropes category member it does share the same organic anion as sodium toluene sulphonate. Following oral dosing in rats at a dose of 200 mg/kg bw it was reported that there was negligible levels of the substance present in the blood. Distribution of the substance was higher in the kidneys than in the blood or other tissues/organs. There was no indication of accumulation of the substance in the organs/tissues examined. The metabolites of the substance is excreted in the unchanged parent compound primarily in the urine with 87% excreted in the urine and 1.2% in faeces by 24 hours post-dosing. At 96 hours post-dosing there was 96.4% total excretion.

Overall the findings of both studies are consistent with the findings from Dreyfuss et al., (1971) and demonstrate rapid urinary excretion of the unchanged parent substance.


NFH Ho et al, Specific Liver-Site Delivery and Enhanced Intestinal Absorption by the Drug-Bile Acid Carrier Mechanism. Optimization of drug delivery, 1982, 17, 80-89.

H Kano et al. The absorption, distribution and excretion of Sultamicillin tosilate in experimental animals. Chemotherapy, 1985, 33 (S-2), 128-153.