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

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via inhalation route

Dose descriptor:

NOAEC

6 061 mg/m³

Additional information

A propylene glycol ethers category has been recognized under the OECD HPV program (OECD, 2003). As a class, these materials are absorbed rapidly and distributed throughout the body following inhalation and oral exposures. Metabolism and excretion are similar for the category members, with elimination primarily though the urine and expired air.

No fertility studies are available for the glycol ethers heavies mixture. A 2-generation reproduction toxicity test is available for the structural analogue to dipropylene glycol methyl ether, propylene glycol methyl ether (PGME). In this 2-generation inhalation reproduction study, no adverse fertility or reproductive effects were observed at 1,000 ppm PGME. The NOAEL for paternal toxicity is 300 ppm and for offspring toxicity is 1000 ppm. Effects appear to be secondary to parental weight loss.

Both PGME and DPM have undergone repeated dose toxicity testing at substantial doses with extensive histopathological analysis of reproductive organs (OECD, 2003). Results from these repeated dose tests indicate that neither PGME nor DPM cause toxicity to the testes. Specifically, no reduction in testicular weights, no damage to the sperm or sperm producing cells, and no damage to the epididymis or seminiferous tubules were reported. Likewise, no damage to female reproductive organs was found.

Sodium methanolate has not been tested for reproductive effects. Methanol, the degradation product of sodium methanolate, had no effect on reproductive parameters when tested in a 2-generation study by inhalation in female monkeys (Macaca fascicularis) at a maximum exposure concentration of 1800 ppm (2.358 mg/L). The NOAEC for this study was 1800 ppm.

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

Short description of key information:
A 2-generation inhalation reproduction study with propylene glycol methyl ether (PGME) in Sprague-Dawley rats failed to produce any adverse effects on fertility or reproduction. Similarly, a 2-generation inhalation study with methanol in female monkeys failed to produce any significant reproductive effects.

Effects on developmental toxicity

Description of key information

Developmental toxicity studies with a number of representative members of the propylene glycol ethers category indicate a general lack of developmental toxicity.  It has been recognized that information on developmental effects of methanol in humans is inadequate but that based on studies in animals, effects are not anticipated at levels of exposure from dietary sources or from occupational exposures.

Effect on developmental toxicity: via inhalation route

Dose descriptor:

NOAEC

2 358 mg/m³

Additional information

No developmental toxicity studies are available for the glycol ethers heavies mixture. Developmental toxicity studies with representative members of the propylene glycol ethers tested by various routes of exposure all indicate an absence of developmental effects (OECD, 2003).

Methanol, the degradation product of sodium methanolate, has been tested by inhalation in monkeys (Macaca fascicularis) at a maximum exposure concentration of 1800 ppm (2.358 mg/L). The assigned NOAEC value for both teratogenicity and fetotoxicity was 1800 ppm.

A recent review by the Center for the Evaluation of Risks to Human Reproduction concluded that there was a concern for developmental effects in pregnant women at acutely toxic or near toxic doses of methanol (NTP, 2003). However, this review did also state that such effects should not occur at blood methanol levels less than 10 mg/L and that such blood levels are not expected from normal dietary or occupational exposures.

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

NTP (2003). NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Methanol, Center for the Evaluation of Risks of Human Reproduction, National Toxicology Program, U.S. Department of Health and Human Services, NIH Publicatin No. 03-4478, September, 2003.

Justification for classification or non-classification

The propylene glycol ether components of the glycol ethers heavies mixture display a general lack of significant reproductive and developmental toxicity effects. Although animal studies with methanol are not conclusive, reproductive and developmental toxicity is generally considered of minimal concern at exposure levels that are below acutely toxic dose levels. Thus, the reaction mass containing DPM, TPM, and sodium methanolate should not be classified for reproductive or developmental toxicity.