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Description of key information

In accordance with Annex VIII, Column 1, Item 8.8.1, of Regulation (EC) 1907/2006 and ‘Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance’ (ECHA, 2017), an assessment of the toxicokinetic behaviour of the test substance is conducted to the extent that can be derived from the relevant available information. This comprises a qualitative assessment of the available substance specific data on physicochemical properties. Butylmonoglycol sulphate, Na-salt (CAS 67656-24-0) is expected to be readily absorbed via the oral route. Low absorption via the inhalation route is expected. Medium-high (40%) absorption is assumed via dermal route. After oral absorption, the test substance is readily distributed throughout the organism. No bioaccumulation is expected. The test item is then expected to be excreted via the urine.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Basic toxicokinetics

There are no studies available in which the toxicokinetic behaviour Butylmonoglycol sulphate, Na-salt (CAS 67656-24-0) was investigated. In accordance with Annex VIII, Column 1, 8.8.1, of Regulation (EC) 1907/2006 and with ‘Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance’ (ECHA, 2017), an assessment of the toxicokinetic behaviour of Butylmonoglycol sulphate, Na-salt was conducted to the extent that can be derived from the relevant available information. This comprises a qualitative assessment of the available substance specific data on physico-chemical and toxicological properties according to Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2017).

 

Physico-chemical properties

Butylmonoglycol sulphate, Na-salt is a mono-constituent substance. The substance has a molecular weight of 220.2 g/mol.

 

It is a solid at 20 °C with a water solubility of > 2054 g/L at 20 °C. The log Kow is < -2.7 at 20 °C and vapour pressure is < 0.001 Pa at 20 °C, 25 °C and 50 °C. 

 

Absorption

Absorption is a function of the potential for a substance to diffuse across biological membranes. The most useful parameters providing information on this potential are the molecular weight, the octanol/water partition coefficient (log Kow) value and the water solubility. The log Kow value provides information on the relative solubility of the substance in water and lipids (ECHA, 2017).

 

Oral

In general, molecular weights below 500 and log Kow values between -1 and 4 are favourable for absorption via the gastrointestinal (GI) tract, provided that the substance is sufficiently water soluble (> 1 mg/L). Lipophilic compounds may be taken up by micellar solubilisation by bile salts, but this mechanism may be of particular importance for highly lipophilic compounds (log Kow > 4), in particular for those that are poorly soluble in water (≤ 1 mg/L) as these would otherwise be poorly absorbed (ECHA, 2017).

 

The high water solubility (> 2054 g/L) and the low log Kow value (< -2.7) of the substance indicate that oral absorption is likely to occur.

 

The available data on acute oral toxicity indicate the substance has low acute toxicity. In the acute oral toxicity study performed with a 50% solution of Butylmonoglycol sulphate, Na-salt, no mortality was observed in 5 male and 5 female rats administered 3000 mg/kg bw by gavage. No clinical signs of toxicity were observed during the 14-day observation period, no effects on body weight were noted, and the gross necropsy showed no treatment-related macroscopic changes (Hüls, 1987). The LD50 value was > 3000 mg/kg bw. Since no toxic effects were observed no conclusion can be drawn from this study whether the test substance was orally absorbed or not.

 

The potential of a substance to be absorbed in the GI tract may be influenced by chemical changes taking place in GI fluids as a result of metabolism by GI flora, by enzymes released into the GI tract or by hydrolysis. These changes will alter the physicochemical characteristics of the substance and hence predictions based upon the physico-chemical characteristics of the parent substance may no longer apply or apply to a lesser extent (ECHA, 2017). 

 

In conclusion, based on the available information Butylmonoglycol sulphate, Na-salt is assumed to be readily absorbed via oral route.  

 

Dermal

The dermal uptake of liquids and substances in solution is higher than that of dry particulates, since dry particulates need to dissolve into the surface moisture of the skin before uptake can begin. Molecular weights below 100 g/mol favour dermal uptake, while for those above 500 g/mol the molecule may be too large. Dermal uptake is anticipated to be low if the water solubility is < 1 mg/L; low to moderate if it is between 1-100 mg/L; and moderate to high if it is between 100-10000 mg/L. Log Kow values in the range of 1 to 4 (values between 2 and 3 are optimal) are favourable for dermal absorption, in particular if the water solubility is high. For substances with a log Kow 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. Log Kow values above 6 reduce the uptake into the stratum corneum and decrease the rate of transfer from the stratum corneum to the epidermis, thus limiting dermal absorption (ECHA, 2017).

Butylmonoglycol sulphate, Na-salt is highly water soluble (> 2054 g/L). This, combined with a low log Kow (< -2.7), indicate that the test substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum and dermal uptake may be low. However, the dermal permeability coefficient (Kp) can be calculated from log Kow and molecular weight (MW) applying the following equation described in US EPA (2012), using the Epi Suite software: log(Kp) = -2.80 + 0.66 log Pow0.0056 MW. Using a water solubility of 2054 g/L and a log Kow of -2.7 Dermwin v2.02 calculated the Kp to be 1.53E-06 cm/h. The dermal flux was calculated to be 0.00314 mg/cm²h, indicating a medium-high dermal absorption potential.

  

An acute dermal toxicity study is available for the registered substance Butylmonoglycol sulphate, Na-salt (CAS 67656-24-0) which was conducted according to OECD TG 402 (Toxi-Coop, 2017). In this GLP study, single group of male and female animals (n=5 animals/sex) were exposed the test material at a concentration of 2000 mg/kg bw. No mortality occurred at a dose level of 2000 mg/kg bw in neither male nor females. No clinical signs of toxicity were recorded during the study period. No behavioral changes and no systemic toxic signs were noted during the study. The test item did not cause dermal irritation symptoms. In summary, the acute dermal LD50 value for male and female rats was considered to be > 2000 mg/kg bw.

 

If a substance shows skin irritating or corrosive properties, damage to the skin surface may enhance penetration. The available in vitro skin corrosion and skin irritation data on the target substance showed no cytotoxic effects on the viability of a reconstituted three-dimensional human epidermis model (EPISKIN-SM) consisting of normal human epidermal keratinocytes (Toxi-Coop, 2017 and 2018). In the acute dermal toxicity study, no signs of local irritation were noted (Toxi-Coop, 2017).

Taking all data into consideration, medium-high absorption is assumed as a worst case as no conclusion can be drawn from the dermal acute toxicity study.

 

Inhalation

Butylmonoglycol sulphate, Na-salt is a solid with low vapour pressure (< 0.001 Pa at 20 °C, 25 °C and 50 °C), and therefore very low volatility. Consequently, under normal use and handling conditions, inhalation exposure and availability for respiratory absorption of the substance in the form of vapour, gases or mists is not significant (ECHA, 2017). However, the substance may be available for absorption after inhalation of aerosols, if the substance is sprayed (e.g. as a formulated product). In humans, particles with aerodynamic diameters below 100 μm have the potential to be inhaled. Particles with aerodynamic diameters below 50 μm may reach the thoracic region and those below 15 μm the alveolar region of the respiratory tract. Particles deposited in the nasopharyngeal/ thoracic region will mainly be cleared from the airways by the mucocilliary mechanism and swallowed. The high water solubility (> 2054 g/L) and the low log Kow value (< -2.7) of the substance indicate that absorption may be possible. The moderate molecular weight of the test substance (220.2 g/mol), however, may have a limiting effect on the absorption rate. There is no experimental data on the effects of acute or long-term inhalation exposure to the target substance.

 

In conclusion, while absorption of the target substance via inhalation is possible, inhaling the substance is quite unlikely because it has a low vapor pressure and the substance is marketed and used in a non granular form.

 

Distribution and accumulation

Distribution of a compound within the body depends on the physico-chemical properties of the substance; especially the molecular weight, the lipophilic character and the water solubility. As discussed under oral absorption, Butylmonoglycol sulphate, Na-salt is assumed to be absorbed after oral exposure. The test item absorbed from the GI tract will be transported via the portal vein to the liver, where further metabolism can take place. Substances that are absorbed through the pulmonary alveolar membrane or through the skin enter the systemic circulation directly before transport to the liver where metabolism will take place.

Metabolism

No data are available regarding metabolism. Available genotoxicity data of the test substance do not show any genotoxic properties with metabolic activation. In particular, an Ames test was negative and therefore no indication of genotoxic reactivity is indicated.

Running the OECD Toolbox v. 3.4 one skin metabolite was found and 12 metabolites were identified from the rat liver S9 metabolism simulator as well as 27 metabolites from the microbial metabolism simulator.

 

Excretion

Based on its high water-solubility, Butylmonoglycol sulphate, Na-salt is expected to be excreted via the urine or metabolised. The fraction of the test substance that is not absorbed in the GI tract will be excreted via the faeces.

 

References

ECHA (2017). Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance. Version 3.0.