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Description of key information

NOAEL (29 days, gavage; rat): 250 mg/kg bw/d
Oral (read across to 2-Methoxyethanol, a possible metabolite of Triethylene glycol dimethyl ether):
NOEL (14 days, drinking water study, male mouse): 200 mg/kg bw/d
NOEL (14 days, drinking water study, female mouse): 600 mg/kg bw/d
NOAEL (13 weeks, drinking water study, male/female mouse): < 2000 ppm
NOAEL (14 days, drinking water study, male rat): 200 mg/kg bw/d
NOEL (14 days, drinking water study, female rat): 400 mg/kg bw/d
NOAEL (13 weeks, drinking water study, male rat): < 750 ppm
Inhalation read across to Diethylene glycol dimethyl ether due to structural similarities):
NOEC (2 weeks, 6h/d, nose only, female rat): 370 ppm (corresponding to 589 mg/kg bw/d); NOAEC (male rat): 110 ppm (corresponding to 175.1 mg/kg bw/d)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
250 mg/kg bw/day
Study duration:

Additional information

A 29 day oral toxicity study was performed in rats. The animals were exposed to 0, 62.5, 250 and 1000 mg/kg bw/d. All animals survived and no clinical signs were noted at any dose level. No neurological or ophthalmological effects or changes in mucosa were noted. Except of the males of the 1000 mg/kg bw/d group which showed a decreased body weight gain, the body weight gain of all animals was not affected. There were no effects upon the mean daily food and water consumption observed in all test groups. There were no changes in haematology and clinical chemistry noted at 62.5 and 250 mg/kg bw/d dose groups. At 1000 mg/kg bw/d the leucocyte count was decreased in male rats; the thrombocyte count was decreased in all animals of the high dose group. At 1000 mg/kg bw/d the bilirubin and creatinin concentration was significantly increased. Relative organ weights were within the control range with the exception of a decreased testis and epididymides weight (absolute and relative) of the males in the high dose group. The absolute and relative thymus weight was also significantly decreased in all animals of the 1000 mg/kg bw/d group. Females of the 250 mg/kg bw/d group had decreased thymus weight. The size of testes was reduced in males of the 1000 mg/kg bw/d dose group. No microscopic changes occurred at any dose level with the exception of changes of the testes, epididymides and spermatogenesis in male rats of the 1000 mg/kg bw/d dose group which caused oligo- and aspermia. In both males and females involution of thymus was observed in the high dose group.

Since there is a strong evidence that to 2-Methoxyethanol is possible a metabolite of Triethylene glycol dimethyl ether a read across to the 2 and 13-week drinking water study with 2-Methoxyethanol in rats and mice might be justified to estimate possible systemic effects of the glycol ether via oral route.

In summary, the major target organs for toxicity of 2-Methoxyethanol were testes in males (decrease in testicular and epididymal weight) and the haematopoetic system (lymphoid depletion) in both species.


To assess the inhalation toxicity of Diglyme (a structural analog to Triethylene glycol dimethyl ether), groups of 20 male and 10 female rats were exposed by nose-only inhalation 6 hours/day, 5 days/week for 2 weeks to either 0 (control), 110, 370 or 1100 ppm Diglyme. 2-Methoxyethanol was applied as positive control. Rats were sacrificed immediately following exposure, after a 14-day recovery period, or after 42 and 84 days of recovery (males only). Parameters investigated included in-life observations and body weights, clinical pathology, and histopathology with organ weights.

Exposure to Diglyme produced a variety of concentration-related changes. The most striking effect produced in all test groups was cellular injury involving the testes, seminal vesicles, epididymides and prostate. Although these effects were more severe at the higher concentrations tested, partial or complete recovery was seen by 84 days post-exposure. Changes in the haematopoetic system occurred in both sexes and involved the bone marrow, spleen, thymus, leucocytes and erythrocytes. The testicular effects of Diglyme were somewhat less pronounced than those seen with 2-Methoxyethanol. The NOEC for repeated inhalation exposure to Diglyme in female rats is 370 ppm (corresponding to 589 mg/kg bw/d). For males, the NOAEC was derived at 110 ppm (corresponding to 175.1 mg/kg bw/d).

Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: thymus; urogenital: testes

Justification for classification or non-classification

Since no severe changes in pathology and histopathology of organs occurred in the subacute oral study in rats with Triethylene glycol dimethyl ether and in the subacute inhalation study with its structural analog Diethylene glycol dimethyl ether in rats exposed to the test substance at a concentration up to 1000 mg/kg bw/d (changes in male reproductive organs at 1000 mg/kg bw/d) and thymus atrophy was observed at dose levels 250 mg/kg bw/d, Triethylene glycol dimethyl ether does not have to be classified regarding systemic and target organ toxicity after repeated exposure according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).


It can reasonably be deduced that the only severe effects caused by Triethylene glycol dimethyl ether are restricted to the male reproductive system (reduced testes and epididymides weight, changes in spermatogenesis etc.) and the fetal development/viability. The substance is already classified accordingly (R61 – May cause harm to the unborn child; H360 – May damage fertility or the unborn child; R62 – Possible risk of impaired fertility). No other severe systemic effects were observed after repeated applications to test animals.

Furthermore the substance is found to be not irritating to the skin and it is unlikely that higher amounts than tested in the repeated dose toxicity study will be systemically available via the skin barrier. Therefore, toxicity testing via dermal route is not scientifically necessary.

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