Bis(2-methoxyethyl) ether

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Description of key information

In accordance with Section 1.2 of REACH Annex IX, there is sufficient information from several studies leading to the conclusion that Diethylene glycol dimethyl ether has to be classified as reprotoxic category 2, because

- Diethylene glycol dimethyl ether caused severe toxic effects in testes and spermatogenesis of test animals (rats, mice) via oral and inhalatory route,

- Diethylene glycol dimethyl ether affected the fetal development in rabbits and mice

- There is a strong evidence in literature that Diethylene glycol dimethyl ether is metabolised to 2-Methoxyethanol which is known as a very potent reproduction toxicant.

It can therefore be concluded that Diethylene glycol dimethyl ether has to be labeled with H360FD – May damage fertility or the unborn child and that further testing is not scientifically necessary.

Effects on male reproductive system
- NOAEC (2 weeks inhalation toxicity study, male rats): 110 ppm (corresponding to 175.1 mg/kg bw/d)
- NOEC (5 day inhalation toxicity study, male mouse): 250 ppm (not assignable)
- NOEC (2 weeks inhalation toxicity study, male rats): < 110 ppm (not reliable)
- NOAEL (20 days oral toxicity study, male rat): < 684 mg/kg bw/d

Effect on fertility: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEL

684 mg/kg bw/day

Study duration:

subacute

Effect on fertility: via inhalation route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEC

110 ppm

Study duration:

subacute

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Effects on developmental toxicity

Description of key information

Several studies have been perfromed showing a reproduction toxicity of Diethylenglycoldimethylether on prenatal development without implications by maternal toxicity. Obtained threshold limits are listed below.

Developmental studies
- NOAEL (developmental/maternal, oral, mouse): < 3000 mg/kg bw/d)
- NOAEL (maternal, oral, rabbit): 50 mg/kg bw/d
- NOAEL (developmental, oral, rabbit): 25 mg/kg bw/d
- NOAEL (developmental, oral, mouse): 62.5 mg/kg bw/d
- NOAEL (maternal, oral, mouse): 500 mg/kg bw/d (highest dose tested)
- NOAEL (developmental, oral, mouse): < 537 mg/kg bw/d
- NOAEL (maternal, oral, mouse): 537 mg/kg bw/d (highest dose tested)

Effect on developmental toxicity: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

25 mg/kg bw/day

Study duration:

subacute

Species:

rabbit

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

The developmental toxicity of Diethylene glycol dimethyl ether was evaluated in two oral studies in rabbits and mice equivalent to OECD guideline 414 and in several non-guideline oral studies in mice. The lowest derived NO(A)ELs from a rabbit teratogenicity study were 25 mg/kg bw/d (developmental) and 50 mg/kg bw/d (maternal). These NO(A)ELs were based on adverse effects on prenatal growth, viability and morphological development (NOEL developmental) and increased maternal mortality.

Therefore, it is concluded that Diethylene glycol dimethyl ether is subject to classification and labelling according to  Regulation 1272/2008/EC regarding reproductive toxicity. Ethylene glycol dimethyl ether has to be labeled with H360FD – May damage fertility or the unborn child (reproductive toxic, category 1B).

Justification for classification or non-classification

Due to the observed effects on testes of male test animals and the fetal toxicity of Diethylene glycol dimethyl ether a classification for reproductive toxicity is appropriate. It is concluded that the substance is subject to classification and labeling according to Regulation 1272/2008/EC regarding reproductive toxicity/teratogenicity. Ethylene glycol dimethyl ether has to be labeled with H360FD – May damage fertility or the unborn child.

 

 

Furthermore the substance is found to be not irritating and it is unlikely that higher amounts than tested in the inhalation reproductive/developmental toxicity studies will be systemically available via the skin barrier.No systemic adverse effects other than observed via inhalatory or oral route are expected to occur. Therefore, toxicity testing via dermal route is not scientifically necessary.