Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no study available (further information necessary)
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

There is no data on the toxicity to reproduction for the substance 2 -(2 -(2-methoxyethoxy)ethoxy)ethanol and therefore a testing proposal has been submitted.

Effects on developmental toxicity

Description of key information

RAT (all in mg/kg bw/day)

NOEL (maternal) 625 (developmental) 625 (LOEL)=1250

NOEL (maternal) 1000 (developmental) 1000

NOEL (developmental) >1000

RABBIT

NOEL (maternal) 250, (devtox) 1000.

Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Additional information

In a guideline and GLP study, the developmental toxicity of triethylene glycol methyl ether (TEGME ) was evaluated in rabbits following oral (gavage) administration at dosages up to 1,500 mg/kg bw/day on Days 6-18 of gestation. Dosages of 500 mg/kg/day and higher caused increased body weight gain and feed consumption during the postdosage period, a common phenomenon seen in developmental toxicity studies after the termination of dosing. The 1500 mg/kg/day dosage of TEGME (and possibly the 1000 mg/kg/day dosage) caused death. The 1500 mg/kg/day dosage also produced abortions, clinical and necropsy observations, reduced maternal body weight, and feed consumption, compared to the study controls. Based on the data in this study, the maternal NOEL for TEGME is considered to be 250 mg/kg/day, and 500 mg/kg/day is considered the NOAEL for maternal toxicity. The 1500 mg/kg/day dosage significantly increased the fetal and/or litter incidences of two common skeletal variations. This maternally toxic dosage significantly increased (P<0.01) only the litter and/or fetal incidences of variations in fetal ossification (angulated hyoid alae and reversible delays in ossification of the xiphoid). Thus, TEGME should not be classified as a developmental toxicant since it does not present a unique hazard to the development of rabbit conceptuses. Based on these findings the NOEL for developmental toxicity is considered to be 1000 mg/kg/day, and the NOAEL for developmental toxicity is considered to be 1500 mg/kg/day.

 

In a guideline (TSCA) and GLP study, the developmental toxicity of TEGME was evaluated in rats following oral (gavage) administration at dosages up to 5,000 mg/kg bw/day on Days 6-15 of gestation. The 1250 mg/kg/day dose level slightly reduced relative feed consumption during the dosing period, but the absolute feed consumption at this level and the average maternal body weights and body weight gains at the 1250 and 2500 mg/kg/day levels were not affected by treatment with TEGME. Thus, 1250 mg/kg/day is considered a NOAEL, and 625 mg/kg/day is considered a NOEL for maternal toxicity. There were no increases in the incidence of external, internal soft tissue, or skeletal malformations or in the incidences of external or internal soft tissue variations at doses as high as 5000 mg/kg/day of TEGME. Reversible delays in fetal ossification and slightly lower fetal body weight (not statistically different from the control weight) occurred in the 1250 mg/kg/day dosage group. Thus, 1250 mg/kg/day is considered very near the NOAEL for TEGME developmental toxicity, and 625 mg/kg/day is considered the NOEL for developmental toxicity.

2-(2 -(2 -methoxyethoxy)ethoxy) ethanol (TEGME) and its main metabolite (2 -(2 -methoxyethoxy)ethoxy) acetic acid (TEGMEA) were evaluated using the zebrafish embryotoxicity test (ZET) ,which is used as a screening test for reproductive toxicity. The morphological characteristics of each embryo were assessed at 72 and 96 hours post fertilization (hpf) following exposure to the test substance at various concentrations up to a maximum tolerated dose ascertained by a dose range finder study. Both substances were considered as negative for developmental toxicity in this screening assay by the study authors.

  

Other studies are available that support the conclusion of a NOEL for developmental effects of 1000mg/kg bw/day.

Toxicity to reproduction: other studies

Additional information

In an oral developmental neurotoxicity study in rats using the substance triethylene glycol monomethyl ether (reported in chapter 7.9.1), a no observable effect level (NOEL) for developmental toxicity of 300 mg/kg/day was established, based on decreased postnatal weight gains at 1,650 and 3,000 mg/kg/day. The maternal NOAEL is 1,650 mg/kg/day (based on increased maternal kidney weights at 3,000 mg/kg/day).

Justification for classification or non-classification

There is no indication of fertility effects at a dose of 1000mg/kg bw or below. There is no indication of developmental toxicity effects at a dose of 1000mg/kg bw or below or effects that occur below the level where maternal toxicity is also observed. There is no indication that reproductive toxicity is a characteristic of this substance and that classification is warranted for this end point.