Sodium 2-mercaptoethanolate

Endpoint summary

Description of key information

Gastro intestinal-, respiratory- and dermal absorption are expected based on physico-chemical properties and systemic effects observed in in vivo studies. No bioaccumulation is expected due to high water solubility and a log kow  < 0. The high water solubility and low molecular weight make urinary excretion possible. The metabolite 2-mercaptoacetate was detected in the urine of a person who died from ingesting 2-mercaptoethanol (Eriksson et al., 1989) indicating that the substance can be metabolised.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100

Additional information

Toxicokinetics

Since no toxicokinetic studies are available for the test substance the assessment is based on the available physicochemical properties of both sodium 2-mercaptoethanolate and read across candidate 2-mercaptoethanol following the Endpoint specific guidance R.7c from ECHA.

1. The ratio of 2-mercaptoethanolate and 2-mercaptoethanol

The mercaptoethanolate ion is a conjugated base where 2-mercaptoethanol is its weak undissociated acid. The amount of dissociation depends on the pH and can be calculated with Henderson–Hasselbalch equation (pH = pKa + log [conjugated base (A-) / undissociated acid (HA)]). Based on the Henderson–Hasselbalch equation it is expected that 2-mercaptoethanol will not dissociate in an acidic environment. When the pH – pKa ≤ -2 no dissociation is expected and ca. 100% 2-mercaptoethanol is expected in solution. Complete dissociation into the mercaptoethanolate ion would be expected when pH – pKa ≥ 2. The pH in the human stomach ranges from 1.7 to 5 depending on the location in the stomach and the content in the stomach (fed or fasted). The pH of the intestines range from 5-8 depending on the specific parts of the intestine (ECHA guidance R7c). Furthermore the skin pH is ca. 5. Thus, overall the substance will be in an acidic environment/solution and for the determination of the toxicokinetics 2-mercaptoethanol will be used.

2. Physical chemical properties

2-mercaptoethanol is a liquid with a molecular weight of 78.13 g/mol. The log kow was determined at -0.056 at 25°C. 2-mercaptoethanol is very soluble in water. The boiling is 155.8 °C at 1013 hPa and the vapour pressure is 1.3 hPa. Based on the structure of the substance hydrolysis is unlikely

3. Absorption

Gastrointestinal absorption:

Non-ionised substances are able to readily diffuse across biological membranes in contrast with ionised substances. 2 -Mercaptoethanol contains a hydroxyl group (OH) and thiol group (SH) that are ionisable however as discussed in paragraph 1 this is not expected in an acidic environment. The molecular weight < 200 g/mol and the moderate log kow make 2-mercaptoethanol favourable for absorption by passive diffusion in the GI tract. Single and repeated dosing via the oral route resulted in systemic toxic effects. Repeated dosing resulted in organs damage, targeting the liver and heart. In conclusion, the test substance is likely to be absorbed by the gastointestinal tract.

Dermal absorption:

With a vapour pressure of 1.3 hPa, 2-mercaptoethanol will not evaporate in significant amounts from the skin and will be available for absorption. The molecular weight < 100 g/mol favours dermal uptake. However, with a log P of -0.056, 2-mercaptoethanol may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Although the physical chemical data indicate low dermal absorption, skin irritation studies showed that the substance is irritating/corrosive to the skin and this may enhance the penetration. Furthermore, dermal acute toxicity studies showed systemic toxicity after dosing, indicating absorption. In conclusion, the test substance is likely to be absorbed by the skin.

Respiratory absorption:

The moderate log kow and molecular weight < 200 g/mol favours absorption by the respiratory tract epithelium by passive diffusion. An acute inhalation study with 2-mercaptoethanol is available and resulted in systemic effects. The substance is likely to be absorbed via the respiratory tract. As signs of systemic toxicity are present in an oral toxicity study it is likely that the substance will also be absorbed if it is inhaled.

4. Metabolism

After oral intake of 2-mercaptoethanol in a poisoning case the metabolite 2-mercaptoacetate was measured in human urine (Eriksson et al., 1989).

5. Excretion

The high water solubility and low molecular weight make urinary excretion possible. The metabolite 2-mercaptoacetate was detected in the urine of a person who died from ingesting 2-mercaptoethanol. 

6. Accumulation

The substance is highly water soluble and the log P is <0 therefore it is unlikely that the substance will accumulate in tissues. Furthermore, the substance is metabolized and excreted via the urine.

7. References

Eriksson et al., 1989. Mercaptoethanol poisoning: report of a fatal case and analytical determinations. J. Anal. Toxicol. 13, 60-62 (cited in SIDS)