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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
132.6 mg/kg bw/day
Effect on fertility: via inhalation route
Dose descriptor:
NOAEC
187 mg/m³
Additional information

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

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

- Ethylene glycol dimethyl ether effected the fetal development in rats, rabbits and mice

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

It can therefore be concluded that Ethylene glycol dimethyl ether has to be labeled with R60 – May impair fertility; R61 – May cause harm to the unborn child; H360 – May damage fertility or the unborn child and that further testing is not scientifically necessary.

NOEL calculation:

 

- NOEC:

0.187 mg/L

- respiratory volume (male rat):

20.5 L/hour (according to Guidance on Information Requirements and Chemical Safety Assessment, Chapter R8, Appendix 8-2, Table 8-17, p. 70)

- exposure duration:

6 hours per day

- mean body weight:

173.5 g

NOEL:

=>    20.5 L/hour x 6 hours = 123 L per 6 hours equivalent to 123 L/d

=>    23 mg/rat/d (NOEL)

=>    132.6 mg/kg bw/d = NOEL (systemic)


Short description of key information:
Effects on male reproductive system
- NOEC (14 day inhalation toxicity study, male rats): 0.187 mg/L (corresponding to 132.6 mg/kg bw/d, calculation please see below)
- NOEC (14 day inhalation toxicity study, male rabbits): 0.187 mg/L
- NOAEC (14 day inhalation toxicity study, male rats): < 0.374 mg/L
- NOAEL (5 week oral toxicity study, male mice): < 250 mg/kg bw/d

Effects on developmental toxicity

Description of key information
NOAEC (developmental/maternal, inhalatory, rabbit): 0.06 mg/L (corresponding to 5.6 mg/kg bw/d)
NOEC (maternal, inhalatory, rat): 0.374 mg/L (corresponding to 183.3 mg/kg bw/d, highest dose tested)
NOEC (developmental, inhalatory, rat): 0.037 mg/L (corresponding to 18.2 mg/kg bw/d)
NOAEC (developmental, inhalatory, rat/rabbit): < 0.374 mg/L
NOAEL (maternal, oral, rat): 120 mg/kg bw/d
NOAEL (developmental, oral, rat): < 30 mg/kg bw/d
NOAEL (maternal/developmental, oral, mouse): < 2000 mg/kg bw/d
NOAEL (maternal, oral, mouse): 361 mg/kg bw/d
NOAEL (developmental, oral, mouse): < 361 mg/kg bw/d
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
5.6 mg/kg bw/day
Effect on developmental toxicity: via inhalation route
Dose descriptor:
NOAEC
60 mg/m³
Additional information

The developmental toxicity of Ethylene glycol dimethyl ether was evaluated in two inhalation studies in rabbits and rats according to OECD guideline 414 study and in several non-guideline oral studies in rats and mice. The lowest derived NOAEC from a rabbit teratogenicity study was 0.06 mg/L corresponding to a systemic concentration of 5.6 mg/kg bw/d (for calculations please see below). This NOAEC was based on slightly reduced food consumption of the dams and decreased vitality of the pups within the first 24 hours after parturition.
Therefore, it is concluded that Ethylene 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 with R60 – May impair fertility; R61 – May cause harm to the unborn child; H360 – May damage fertility or the unborn child (reproductive toxic, category 2).

 

NOAEL/NOEL-calculations:

 

1. Rabbit

- NOAEC (maternal/developmental):

0.06 mg/L

- respiratory volume:

94 L/kg bw/6 hours (according to Snipes, M.B.; long-term Retention and Clearance of Particles inhaled by mammalian Species; Crit. Rev. Toxicol. 20, 175-211, cited by the Federal Institute for occupational Safety and Health, 1998)

- exposure duration:

6 hours per day

 

=>    94 L respired volume/kg bw/d

=>    0.06 mg x 94 L =5.6 mg/kg bw/d = NOAEL(systemic)

 

2. Rat

- NOEC (maternal):

0.374 mg/L

- NOEC (developmental):

0.037 mg/L

- respiratory volume (female rat):

15.7 L/hour (according to Guidance on Information Requirements and Chemical Safety Assessment, Chapter R8, Appendix 8-2, Table 8-17, p. 70)

- exposure duration:

6 hours per day

- mean body weight:

192 g

maternal NOEL:

=>    15.7 L/hour x 6 hours = 94.2 L per 6 hours equivalent to 94.2 L/d

=>  35.2 mg/rat/d (maternal NOEL)

=>    183.3 mg/kg bw/d = NOEL(maternal, systemic)

developmental NOEL:

=>    15.7 L/hour x 6 hours = 94.2 L per 6 hours equivalent to 94.2 L/d

=>    3.5 mg/rat/d (developmental NOEL)

=>    18.3 mg/kg bw/d = NOEL (developmental, systemic)

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 of male test animals and the fetal toxicity of Ethylene 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 R60 – May impair fertility; R61 – May cause harm to the unborn child; H360 – May damage fertility or the unborn child

Furthermore the substance is found to be moderately 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.