Scientific review of inhalation DNEL to bis(2-methoxyethyl ether)

Introduction
Derived inhalation No Effect Levels (DNELs) has been set for occupational exposure to bis(2-methoxyethyl)ether (diglyme) according to REACH principles. DNEL is the level of exposure above which humans should not be exposed.

Methods
Experimental data from three inhalation animal studies have been used to calculate DNELs. The main targets in male animals after repeated intake of diglyme are reproductive organs. The no-observed-adverse-effect level (NOAEL) in these studies was 30 ppm (167 mg/m3); the lowest-observed-adverse-effect level (LOAEL) was 100 ppm (558 mg/m3). In teratogenicity studies with rats diglyme showed dose-dependent effects on fetal weights, number of resorptions, and incidence of variations and malformations in a wide variety of tissues and organ systems. The LOAEL was 25 ppm (140 mg/m3). Changes in the haematopoietic system occurred in both sexes and involved the bone marrow, spleen, thymus, leukocytes, and erythrocytes. The NOAEL for female rats was 370 ppm (2065 mg/m3). The LOAEL was 1100 ppm (6138 mg/m3).

Results
Estimated DNELs values show significant differences and amount from 0,6 to 26 mg/m3, depending on chosen critical effect. The OEL value to diglyme of 10 mg/m3 was established based on reproductive toxicity. The DNEL to reproductive is 2,2 mg/m3.

Discussion
It indicates that the OEL does not provide the appropriate level of protection required by REACH.