Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
Please refer to "Effects on fertility" and "Developmental toxicity"
Effect on fertility: via oral route
Dose descriptor:
NOAEL
175 mg/kg bw/day
Additional information

In accordance with Section 1.2 of REACH Annex IX, there is sufficient information from several studies leading to the conclusion that Triethylene glycol dimethyl ether has to be classified as reprotoxic category 2, R61 and reprotoxic category 3, R62, because

- Triethylene glycol dimethyl ether caused changes in testes epididymides and spermatogenesis of rats and a decreased fertility in female mice via oral route,

- Triethylene glycol dimethyl ether effected the fetal development in rabbits and mice

- There is strong evidence that 2-Methoxyethanol which is known as a very potent reproduction toxicant is a metabolite of Triethylene glycol dimethyl.

 

It can therefore be concluded that Triethylene glycol dimethyl ether has to be labeled with R61 – May cause harm to the unborn child and R62 – Possible risk of impaired fertility; H360 – May damage fertility or the unborn child and that further testing is not scientifically necessary.


Short description of key information:
Effects on male reproductive system
- NOAEL (29 day oral toxicity study, rats): 250 mg/kg bw/d
- NOAEL (146 day oral toxicity study, mouse): 175 mg/kg bw/d

Effects on developmental toxicity

Description of key information
NOEL (developmental, oral, rabbit): 75 mg/kg bw/d
NOEL (maternal, oral, rabbit): 125 mg/kg bw/d
NOEL (developmental, oral, mouse): 250 mg/kg bw/d
NOAEL (maternal, oral, mouse): 1000 mg/kg bw/d
NOEAL (developmental, oral, mouse): < 3500 mg/kg bw/d
NOAEL (maternal, oral, mouse): < 3500 mg/kg bw/d
NOEL (maternal/developmental, oral, mouse): 713 mg/kg bw/d (highest dose tested)
NOAEL (reproductive, oral, mouse): 87.5 mg/kg bw/d
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
75 mg/kg bw/day
Additional information

The developmental toxicity of Triethylene 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 NOAEL from a rabbit teratogenicity study was 75 mg/kg bw/d (developmental). This NOAEL was based on embryotoxic effects (decrease in preimplatation loss, resorptions and number of dead fetuses).
Therefore, it is concluded that Triethylene glycol dimethyl ether is subject to classification and labelling according to Directive 67/548/
EECand Regulation 1272/2008/EC regarding reproductive toxicity. Ethylene glycol dimethyl ether has to be labeled withR61 – May cause harm to the unborn child and R62 – Possible risk of impaired fertility; H360 – May damage fertility or the unborn child.

Toxicity to reproduction: other studies

Additional information

Please refer to "Effects on fertility" and "Developmental toxicity"

Justification for classification or non-classification

Due to the observed effects on testes, epididymides and spermatogenesis of male test animals and the fetal toxicity of Triethylene glycol dimethyl ether a classification for reproductive toxicity is appropriate. It is concluded that the substance is subject to classification and labeling according to Directive 67/548/EECand Regulation 1272/2008/EC regarding reproductive toxicity/teratogenicity. Ethylene glycol dimethyl ether has to be labeled with R61 (reprotoxic categrory 2) – May cause harm to the unborn child and R62 (reprotoxic categrory 3) – Possible risk of impaired fertility; H360 – May damage fertility or the unborn child.

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