Sodium methanolate

Endpoint summary

Description of key information

Sodium methanolate is classified as corrosive to the skin according to Annex VI of the CLP regulation (EC 1272/2008). At non-irritant concentrations / dose levels, no systemic effects are expected after repeated exposure to sodium methanolate via any route. It is unlikely that exposure to sodium methanolate at non-irritant concentrations / dose levels would result in exposure to toxic doses of the hydrolysis / dissociation products, in particular methanol.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No data are available on the repeated dose toxicity of sodium methanolate. Sodium methanolate is classified as corrosive to the skin according to Annex VI of the CLP regulation (EC 1272/2008). The abiotic hydrolysis of sodium methanolate with tissue water results in the formation of methanol and sodium hydroxide. The latter dissociate into the corresponding cations (Na⁺) and anions (OH^-). For hazard assessment of sodium methanolate at potentially non-irritating concentrations / dose levels, information on the hydrolysis / dissociation products was taken into account.

The major health hazard (and the mode of action) of sodium hydroxide (CAS No. 1310-73-2) is local irritation and/or corrosion as sodium hydroxide is also classified as corrosive to the skin according to Annex VI of the CLP regulation (EC 1272/2008). At concentrations between 0.5 and 2%, it is classified as skin and eye irritant. As outlined below, repeated exposure to Na⁺and OH^-ions at non-irritant concentrations is unlikely to produce systemic toxic effects by any route and under normal handling and use conditions (European Commission, 2007; OECD, 2002). Therefore, hazard assessment mainly focused on the repeated dose toxicity of methanol (CAS No. 67-56-1).

 

Oral

Sodium hydroxide

Sodium hydroxide in aqueous solution is completely dissociated into the corresponding ions (Na⁺and OH^-). Due to the neutralization of OH^-by gastric hydrochloric acid (HCl) and the quick and efficient blood pH regulation mechanisms (buffer capacity of extra cellular body fluids, respiratory and renal compensation mechanisms), an alkalosis due to the OH-ions after sodium methanolate oral dosage in non-irritating conditions is prevented (European Commission 2007; OECD, 2002). 

The hazard of repeated human exposure to sodium has been focused on the effects of sodium on the prevention and control of hypertension. A dietary salt intake of 2.0 to 3.0 g was reported to be a moderately restricted intake; 3.1 to 6.0 g was reported as normal intake, while a dietary intake of > 6 g of sodium ions per day was considered an excessive intake (European Commission, 2007; OECD, 2002). An intake of 6 g per day for a 60 kg individual would correspond to a daily dose of 100 mg/kg bw of sodium ions per day. To reach an excessive intake of sodium from exposure to sodium methanolate and intake of more than 235 mg sodium methanolate/kg bw per day would be needed. Given the corrosive properties of sodium methanolate, it is unlikely that humans would be exposed to toxic dose levels of sodium ions under normal handling and use conditions. Consequently, under the same conditions, it is unlikely that repeated oral exposure to non-irritating concentrations of sodium methanolate results in systemic toxic effects.

 

Methanol

There are several reliable studies in different species available for the hydrolysis product methanol (please refer to the endpoint summary of methanol for details). For the lowest NOAEL of 500 mg/kg bw/day, the corresponding approximate dose of sodium methanolate is 840 mg/kg bw/day, which is already in the acutely toxic dose range. Due to the corrosive nature of sodium methanolate it is unlikely that oral exposure to sodium methanolate could result in an uptake of toxic doses of methanol. Consequently, it is unlikely that repeated oral exposure to non-irritating concentrations of sodium methanolate results in systemic toxic effects related to methanol.

 

Dermal

Sodium hydroxide

When humans are dermally exposed to non-irritating concentrations, the dermal uptake of sodium hydroxide is expected to be low due to the low absorption of water-soluble ions (ECHA: Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance, June 2017). For this reason the dermal uptake of sodium hydroxide is expected to be limited under normal handling and use conditions. Under these conditions the uptake of OH^-via exposure to sodium hydroxide, is not expected to change the pH in the blood. Furthermore, the dermal uptake of sodium via exposure to the corresponding hydroxide is much less than the uptake of sodium via food under these conditions (European Commission 2007; OECD, 2002). Thus, it is unlikely that repeated dermal exposure to non-irritating concentrations of sodium methanolate results in systemic toxic effects referring to the dermal uptake of sodium or hydroxide ions.

 

Methanol

There are no data available on the repeated dose toxicity of methanol by the dermal route. However, as described in 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, regardless of its exposure route. The effects of methanol on the CNS and retina in humans only occur at doses at which formate accumulates due to a rate-limiting conversion to carbon dioxide. In primates, formate accumulation was observed at methanol doses greater than 500 mg/kg bw (OECD, 2004; Tephly and McMartin, 1984, as cited in NTP, 2003). This value corresponds to a sodium methanolate dose of more than 840 mg/kg bw, which 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 (Kavet and Nauss, 1990, as cited in OECD, 2004), which corresponds to sodium methanolate doses of ca. 354 mg/kg bw. Repeated dermal exposure to such high sodium methanolate dose levels, is highly unlikely under normal handling and use conditions due to the corrosive properties of sodium methanolate. Consequently, it is unlikely that repeated dermal exposure to non-irritating concentrations of sodium methanolate results in systemic toxic effects related to methanol.

 

Inhalation

Sodium hydroxide

As already mentioned, health hazard of sodium hydroxide is mainly restricted to local (irritating/corrosive) effects at the portal of entry. Sodium hydroxide is not expected to be systemically available under normal handling and use conditions, and therefore systemic effects of sodium hydroxide after repeated inhalation exposure to non-irritating concentrations are not expected to occur (European Commission, 2007). In terms of hazard assessment for local effects after inhalation exposure to sodium hydroxide human survey data on respiratory tract irritation was taken into account (please refer to the endpoint summary of sodium hydroxide for details). A concentration of 1.0 mg/m³ was considered a NOAEC for local effects to the respiratory tract (European Commission, 2007). A sodium hydroxide concentration of 1 mg/m³ corresponds to an approximate sodium methanolate concentration of 1.35 mg/m³.

 

Methanol

Also for the inhalation route there are several reliable studies in different species available for the hydrolysis product methanol (please refer to the endpoint summary of methanol for details). The results of the studies in different species (rodents, monkeys) demonstrated a 100-fold greater susceptibility for methanol-related effects due to differences in metabolism of methanol. In rodents methanol is metabolised to carbon dioxide to a great extent, whereas in primates formate accumulation is responsible for the observed effects. Formate accumulation in primates has been observed at methanol doses greater than 500 mg/kg bw (OECD, 2004; Tephly and McMartin, 1984, as cited in NTP, 2003). The corresponding dose level for sodium methanolate that would lead to accumulation of formate in primates would be ca. 840 mg/kg bw. Such dose levels are already in the acutely toxic dose range. Due to the corrosive nature of sodium methanolate it is unlikely that repeated inhalation exposure to sodium methanolate could result in an uptake of toxic doses of methanol.

 

Human data

Methanol

Please refer to the endpoint summary of methanol for details on human data.

In the European Union, the occupational exposure limit for methanol is 260 mg/m³ (200 ppm) as an 8 hour TWA. In the US, the limit is 200 ppm as an 8 hour TWA and 250 ppm as a STEL. It has been assumed that an inhalation exposure to methanol of 260 mg/m³ for 8 hours does not lead to any adverse effects (IPCS/WHO, 1997; Kavet and Nauss, 1990; NTP, 2003; OECD, 2004). This exposure level corresponds to a systemic dose of 2600 mg methanol/day (assuming an inhalation volume of 10 m³ during an 8-hour working day) or 37 mg/kg bw day (for a 70 kg human). It would require doses of ca. 62.4 mg/kg bw/day of sodium methanolate to achieve a systemic dose of 2600 mg methanol/day. Conversely, this would require an 8-hour exposure to approximately 440 mg/m³ of sodium methanolate. Given the corrosive properties of sodium methanolate, inhalation exposure to such concentration levels is highly unlikely. Thus, it is unlikely that repeated inhalation exposure to non-irritating concentrations of sodium methanolate results in methanol-related systemic toxic effects.

 

Conclusion:

Sodium methanolate is classified as corrosive to the skin according to Annex VI of the CLP regulation (EC 1272/2008). At non-irritant concentrations / dose levels, no systemic effects are expected after repeated exposure to sodium methanolate via any route. It is unlikely that exposure to sodium methanolate at non-irritant concentrations / dose levels would result in exposure to toxic doses of the hydrolysis / dissociation products, in particular methanol.

 

References not included in IUCLID:

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).

Justification for classification or non-classification

The health hazard of sodium methanolate is dominated by its corrosive properties.The abiotic hydrolysis of sodium methanolate with tissue water results in the formation of sodium ions, hydroxide ions and methanol. At non-irritant concentrations, repeated exposure to sodium methanolate via any route will not result in exposure to toxic doses of any of its hydrolysis/dissociation products, in particular methanol. Therefore, the available information on the repeated dose toxicicty of sodium methanolate is conclusive but not sufficient for classification according to CLP (1272/2008/EC) / UN-GHS.