Potassium methanolate

Endpoint summary

Description of key information

The abiotic hydrolysis of potassium methanolate with tissue water results in the formation of potassium ions, hydroxide ions and methanol. Exposure to non-irritant levels of potassium methanolate via the dermal or inhalation route is not expected to lead to relevant uptake of the ionic degradation products potassium ions or hydroxide ions in amounts that would exceed the normal physiological levels. Potassium ions are normal constituents of body fluids. Potassium ions play an essential role in human physiology, but starts to be toxic at plasma concentrations exceeding 200 - 250 mg/L. Its concentration in blood is regulated principally by renal excretion/re-absorption and controlled by an effective feed-back autoregulation system. A systemic intoxication by potassium methanolate is therefore not expected. 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.

Additional information

According to the OECD SIDS for sodium and potassium methanolate (OECD, 2006), the abiotic hydrolysis of potassium methanolate under aqueous conditions results in the formation of potassium ions, hydroxide ions and methanol. Information on the toxicokinetics, metabolism and distribution data of potassium hydroxide and methanol can be found in the respective OECD SIDS dossiers (OECD, 2002; OECD, 2004).

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

Exposure to hydroxide ions from potassium 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).

Potassium ions are normal constituents of body fluids. K⁺plays an essential role in human physiology, but starts to be toxic at plasma concentrations exceeding 200 - 250 mg/L. Its concentration in blood is regulated principally by renal excretion/re-absorption and controlled by an effective feed-back autoregulation system (OECD, 2002). A systemic intoxication by potassium methanolate is not expected. For potassium hydroxide, SIAM 13 concluded: "Under normal handling and use conditions (non-irritating) neither the concentration of potassium in the blood nor the pH of the blood will be increased above normal limits and therefore KOH is not expected to cause systemically toxic levels in the blood. The renal excretion of K⁺can be elevated and the OH¯ ion is neutralised by the bicarbonate buffer system in the blood." (OECD 2002, OECD 2006)

According to the OECD SIDS for 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 potassium methanolate that would lead to accumulation of formate in primates would be 1000 mg/kg bw. Such a dose level is 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 potassium methanolate doses of ca. 460 mg/kg bw. Due to the corrosive nature of the potassium methanolate, it is unlikely that exposure to potassium 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 13 (2002): Potassium Hydroxide (CAS No: 1310-58-3).

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