Sodium methanolate

Endpoint summary

Description of key information

The abiotic hydrolysis of sodium methanolate with tissue water results in the formation of sodium ions, hydroxide ions and methanol. Exposure to non-irritant levels of sodium methanolate via the dermal or inhalation route is not expected to lead to relevant uptake of the ionic degradation products sodium ions or hydroxide ions in amounts that would exceed the normal physiological levels. Uptake of sodium following oral exposure to sodium methanolate can be considered negligible compared to the uptake of sodium via food. Exposure to hydroxide ions from sodium methanolate exposure could potentially increase the pH of the blood and lead to alkalosis. However, the pH of the blood is regulated between narrow ranges (pH 7.0 to 7.8) and an excessive pH of the blood is prevented by the bicarbonate buffer system, respiration and renal compensation mechanisms. The hydrolysis product methanol is fast absorbed and metabolised, so that no bioaccumulation is expected.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

According to the OECD SIDS of sodium and potassium methanolate (OECD, 2006), the abiotic hydrolysis of sodium methanolate with tissue water results in the formation of sodium ions, hydroxide ions and methanol. Information on the toxicokinetics, metabolism and distribution data of sodium hydroxide and methanol can be found in the respective OECD SIDS dossiers (OECD, 2002, OECD, 2004). For sodium hydroxide, comprehensive information is also available in the corresponding European Union Risk Assessment Report (European Commission, 2007).

Exposure to non-irritant levels of sodium methanolate via the dermal or inhalation route is not expected to lead to relevant uptake of the ionic degradation products sodium ions or hydroxide ions in amounts that would exceed the normal physiological levels.

Exposure to hydroxide ions from sodium methanolate exposure could potentially increase the pH of the blood and lead to alkalosis. However, the pH of the blood is regulated between narrow ranges (pH 7.0 to 7.8) and an excessive pH of the blood is prevented by the bicarbonate buffer system, respiration and renal compensation mechanisms (European Commission, 2007; OECD, 2002).

The sodium ion is a normal constituent of the blood and an excess is excreted in the urine (European Commission, 2007; OECD, 2002). Uptake of sodium following oral exposure to sodium methanolate can be considered negligible compared to the uptake of sodium via food (3.1 to 6 g/day; European Commission, 2007; OECD, 2002). For sodium hydroxide it was concluded that "under normal handling and use conditions (non-irritating) neither the concentration of sodium in the blood nor the pH of the blood will be increased, and therefore, NaOH is not expected to be systemically available in the body" (European Commission, 2007; OECD, 2002).

According to the OECD SIDS of methanol (OECD, 2004), methanol is readily absorbed by inhalation, ingestion and dermal contact and partitions rapidly and equally throughout the organism in relation to the water content of organs and tissues. A small amount is excreted unchanged by the lungs and kidneys. Half-lives of methanol in the body are roughly 2.5 to 3 hours at doses less than 100 mg/kg bw. At high doses disproportionate increases of the parent compound in blood are obtained in rodents, but not in humans. On the other hand, in humans the metabolite formate accumulates at high doses. This important difference mirrors the different enzymes and enzyme capacities involved in the oxidative pathway from methanol to carbon dioxide. Specifically, two different rate-limiting processes have been identified: in rodents, high doses (after inhalation of 2.5 – 3.3 mg/L) lead to the saturation of catalase, resulting in the accumulation of methanol whereas formate levels remain low, whereas in primates (especially humans), the parent compound is well oxidized and does not accumulate, but formate increases disproportionately.

From studies in humans and monkeys exposed to concentrations of 0.26 – 2.6 mg/L (administered for 6 to 8 hours), it can be concluded that methanol remains close to 50 mg/L in blood. At inhalation exposures of 2.6 mg/L, rats also exhibit methanol blood levels that are not much higher (at about 80 mg/L), whereas the level in mice was 400 mg/L. At a higher inhalation exposure (6.5 mg/L), humans show the lowest blood methanol level (at 140 mg/L), followed by monkeys, rats, and mice, with the level in mice being more than 10 times higher than humans. Formate accumulation in primates has been observed at methanol doses greater than 500 mg/kg bw.

The corresponding dose levels for sodium methanolate that would lead to accumulation of formate in primates would be 840 mg/kg bw. Such dose levels are already in the acutely toxic dose range. The methanol dose that saturates the folate pathway in humans is estimated to be 210 mg/kg bw, which corresponds to sodium methanolate doses of ca. 354 mg/kg bw. Due to the corrosive nature of the sodium methanolate it is unlikely that exposure to sodium methanolate could result in an uptake of toxic doses of methanol.

 

 

References not included as study summaries in IUCLID:

OECD SIDS Initial Assessment Report for SIAM 22 (2006): Category of Methanolates: Sodium Methanolate, Potassium Methanolate (CAS No: Sodium Methanolate: 124-41-4; Potassium Methanolate: 865-33-8).

OECD SIDS Initial Assessment Report for SIAM 14 (2002): Sodium Hydroxide (CAS No: 1310-73-2).

European Union Risk Assessment Report (2007): Sodium Hydroxide (CAS No: 1310-73-2).

OECD SIDS Initial Assessment Report for SIAM 19 (2004): Methanol (CAS No: 67-56-1).