Reaction mass of (2-methoxymethylethoxy)propanol and [2-(2-methoxymethylethoxy)methylethoxy]propanol and sodium methanolate

Endpoint summary

Additional information

Sodium Methanolate and Methanol (See also Section 13 of this document):

Sodium methanolate (CAS No. 124-41-4) is the principle component of toxicological concern for the glycol ether heavies. This is due to the high pKa value for methanol (15.5), which results in the rapid and complete conversion of the sodium methanolate to sodium hydroxide and methanol upon reaction with water (OECD, 2006). The toxicological properties of the sodium hydroxide become the prevalent concern and dictate that the primary effects of exposure to the methanolate will be corrosivity to the skin and mucous membranes (OECD, 2006). This corrosivity will sufficiently limit exposure to both the methanolate and to free methanol.

Methanol is rapidly absorbed by the oral, dermal and inhalation routes of exposure and distributed rapidly and equally to all parts of the exposed organism. In humans and primates, formate accumulation occurs at methanol doses in excess of 500 mg/kg (OECD, 2006) and is associated with blindness and CNS effects. An equivalent dose of sodium methanolate would be 840 mg/kg (OECD,2006). Such a dose of the methanolate is already acutely toxic (LD₅₀values in rats of 800 to 1687 mg/kg) resulting in pathological findings associated with the severe corrosivity of the test material (OECD, 2006). It is therefore highly unlikely that single or repeated exposures to methanolate at non-corrosive levels would result in uptake of toxic doses of methanol.

Dipropylene and Tripropylene Glycol Methyl Ethers (See also Section 13 of this document):

The propylene glycol ethers as a class are rapidly absorbed and distributed after oral administration and less rapidly absorbed after dermal exposure but with subsequent rapid distribution (OECD, 2003). Using dipropylene glycol methyl ether (DPGME, CAS No. 34590-94-8) as example, after oral administration approximately 60% of a¹⁴C DPGME dose was excreted in urine, while 27% was eliminated as¹⁴CO2 within 48 hours. Less than 3% of the dose was recovered in feces, indicating that the test material was effectively absorbed. Metabolites identified in the urine include sulfate and glucuronide conjugates, propylene and dipropylene glycol, propylene glycol methyl ether and some unchanged DPGME. Tripropylene glycol methyl ether (TPGME, CAS No. 25498-49-1) was similarly metabolized to yield tripropylene glycol, dipropylene glycol and propylene glycol as well as an oxidation product of dipropylene glycol, dipropylene glycol monomethyl ether (DPGME), TPGME and the sulfate conjugate of TPGME. Less than 5 per cent of the dose was recovered as unchanged TPGME.

According to Venieret al.(2004), DPGME is absorbed through full thickness human skin in vitro at a moderate rate with a permeation coefficient of 0.11 cm-hr (x10^-3). The short-term dermal absorption rates at 10 and 60 minutes have been determined for DPGME using human abdominal skin from cadavers mounted in anin vitrostatic diffusion cell model. The 10-minute absorption rate was calculated to be 658.6 μg/cm²/h. The 60-minute absorption rate was calculated to be 228.5 μg/cm²/h.

OECD (2003). Propylene Glycol Ethers: SIDS Initial Assessment Report for SIAM 17, Arona, Italy, 11-14 November, 2003.

OECD (2006). Category of Methanolates: SIDS Initial Assessment Report for SIAM 22, Paris, France, 18-21 April, 2006.

Venier, M., Adami, G., Larese F., G. Maina, G., and Renzi, N. (2004). Percutaneous Absorption of 5 Glycol Ethers Through Human Skin In Vitro. Toxicol. In Vitro 18:665-671.