Gasoline additives ethyl tert butyl ether (ETBE) and tertiary amyl methyl
ether (TAME) are used world wide, but the consequence of developmental exposure
to these hydrophilic chemicals is unknown for aquatic vertebrates. The effect of
ETBE and TAME on zebrafish embryos was determined following OCED 212 guidelines,
and their toxicity was compared to structurally related methyl tert-butyl ether
(MTBE), which is known to target developing vasculature. LC50s for ETBE and TAME
were 14 mM [95% CI = 10 to 20] and 10 mM [CI = 8 to 12.5], respectively. Both
chemicals caused dose dependent developmental lesions (0.625 to 10 mM), which
included pericardial edema, abnormal vascular development, whole body edema, and
craniofacial abnormalities. The lesions were suggestive of a dysregulation of
WNT ligands and matrix metalloproteinase (MMP) protein families based on their
roles in development. Exposure to 5 mM ETBE significantly (p ≤ 0.05)
decreased relative mRNA transcript levels of mmp-9 and
wnt3a, while 2.5 and 5 mM TAME significantly decreased
wnt3a, wnt5a, and wnt8a. TAME also
significantly decreased mmp-2 and -9 mRNA
levels at 5 mM. ETBE and TAME were less effective in altering the expression of
vascular endothelial growth factor-a and
-c, which were the only genes tested that were
significantly decreased by MTBE. This is the first study to characterize the
aquatic developmental toxicity following embryonic exposure to ETBE and TAME.
Unlike MTBE, which specifically targets angiogenesis, ETBE and TAME disrupt
multiple organ systems and significantly alter the mRNA transcript levels of
genes required for general development.