Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

Testing proposal made for TEGME with the results to be used to predict the toxicity of TEGBE in conjuntion with new OECD422 screening studies used to bridge data gaps.

Effects on developmental toxicity

Description of key information

Study

Result

Comment

TEGBE

Chernoff Kavlock reproductive and developmental toxicity oral screening study

NOAEL (devtox): 1000mg/kgbw/day

No statistically significant effects at maximum tested dose

Similar results also seen with TEGME and TEGEE.

Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no adverse effect observed
Additional information

There is data from available from a developmental toxicity screening test on TEGBE supplied as supporting evidence for this end point. Whilst this does not meet the requirements for this end point on its own, it has value as a bridging study to the developmental toxicity studies of the source substances. In this screening study, Wistar derived rats were exposed GD7-16 to TEGBE (250, 1000 mg/kg, plus negative and positive controls (latter methoxyethanol at 50 and 250 mg/kg). 10 animals were used per dose level and in concurrent controls. The criteria for evaluation were that for a substance to pass the screen and show no potential for reprotoxicity, there should be:

  • No effect on litter size, pup weight, survival or pup weight gain.
  • No reduction in litter size (mean less than 8) or reduced post natal survival (screening criteria for teratogenicity)
  • No reduction on post natal weight gain (<30%) with no reduction in survival (screening criteria for foetal toxicity)

TEGBE was also evaluated using the zebrafish embryotoxicity test (ZET). 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. At 72 hpf, the embryos were evaluated for dead or alive. At 96 hpf, the embryos and larvae were evaluated for a wide series of normal or anomalous developmental characteristics. TEGBE was found to cause some delay in hatching in 25% of embryos. Although this was significantly lower than the delays seen in the concurrent controls, it was within the range of controls used throughout this study which examined 10 substances in total. The positive controls (ethanol and methoxyacetic acid) used exhibited a wider range of developmental effects (growth retardation and malformations). This result is considered unclear.

2-(2 -(2-butoxyethoxy)ethoxy)acetic acid (TEGBEAA) was evaluated using the zebrafish embryotoxicity test (ZET). TEGBEAA was evaluated as this assay does not have metabolic capacity and TEGBEAA is the main metabolite of 2 -(2 -(2 -butoxyethoxy)ethoxy)ethanol, the subject of this dossier. 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. At 72 hpf, the embryos were evaluated for dead or alive. At 96 hpf, the embryos and larvae were evaluated for a wide series of normal or anomalous developmental characteristics. TEGBEAA was considered as positive by the study authors in the embryonic zebrafish screening test.  Only two end points were affected, one associated with embryotoxicity (pericardial edema) and the other with teratogenicity (malformations of the chorda/spine).  Neither of these effects was seen in the negative control.  The former is seen extensively with methoxyacetic acid but the latter only with 2% ethanol. The NOAEL was 2.5mM (550mg/L).

A testing proposal for an OECD414 study in rats has been submitted for this substance.

Justification for classification or non-classification

Whilst there is limited data avaible for the developmental toxicity of this substance, No signficant adverse effects are seen on reproductive parameters at doses <1000mg/kgbw/day from the available data. On this basis, there is no data to suggest that the substance meets the criteria for classification either as a developmental or reprotoxic substance. Whilst the results from the ZET are equivocal and could even be considered positive for the acid metabolite of TEGBE, this assay is not sufficient on which to base a classification decision. Further data will be generated for these endpoints.