Registration Dossier

Administrative data

Description of key information

The repeated dose toxicity of the glycol ether components of the glycol ethers heavies is generally low.  Although methanol, the degradation product of sodium methanolate, is of concern based on a number of effects noted including ocular and neurological effects, these effects are generally only seen at high exposure concentrations.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
500 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
1 300 mg/m³
Study duration:
chronic
Species:
monkey

Additional information

Repeat dose toxicity information is not available for the glycol ethers heavies mixture. Repeated dose oral toxicity testing in not justified based on a lack of any identified consumer uses or consumer exposure scenarios. Thus, exposure by the oral route is assumed to be minimal. Based on the highly corrosive nature of the glycol ethers heavies mixture, dermal repeated dose toxicity testing is also not scientifically justified. The measured low vapor pressure of the mixture precludes significant exposure by the inhalation route. Exposure to particles or droplets of the test substance is not anticipated.

 

Supporting Information:

 

A number of repeated dose toxicity studies are available for the glycol ether components of the glycol ethers heavies mixture, DPM and TPM (OECD, 2003). Few effects have been seen with these materials even at high exposure concentrations and effects observed were generally mild including increased liver and kidney weights without accompanying histopathology. A subchronic inhalation study in rats with DPM is illustrative of the effects observed. Male and female rats were exposed by whole-body to vapors of DPM at 0, 15, 50 or 200 ppm for 6 hours/day, 5 days/week for 13 weeks. The NOAEL in this study was 200 ppm, based on a lack of treatment-related findings (Landry et al., 1984).

 

Methanol, the degradation product of sodium methanolate, exhibits potential hazardous properties for human health that include neurological effects, CNS depression, and ocular effects (OECD, 2004; NTP, 2003). These effects are generally seen at high exposure concentrations. Thus, oral gavage administration of methanol to rats at dose levels up to 2500 mg/kg bw/day (actual ingested) for 90 days caused decreased brain weights at the highest dose and elevated SGPT and SAP (not statistically significant). Liver weights were increased at the highest dose level but without accompanying histopathological findings. There were no differences between dosed animals and controls in body weight gain, food consumption, or gross or microscopic evaluations. The NOAEL from this study was 500 mg/kg bw/day.  Monkeys (Macaca fascicularis) exposed for 29 months to methanol by inhalation at exposure concentrations up to 1000 ppm (1.3 mg/L) displayed no clear toxicological effects even at the highest exposure concentration. An NOAEL of 1000 ppm can be assigned to this study based on the lack of evidence for clear irreversible effects of exposure to methanol up to the highest dose level tested (OECD, 2004).

 

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

 

OECD (2004). Methanol: SIDS Initial Assessment Report for SIAM 19, Berlin, Germany, 18-20, 2004.

 

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 repeated dose toxicity of the glycol ether components of the glycol ethers heavies mixture is generally low. Similarly, although methanol, the degradation product of sodium methanolate, has associated toxicities including ocular, CNS depression and neurological effects, these are generally only seen at high dose levels. Thus, no hazard classification is recommended for the glycol ethers heavies.