Ethoxyquin - harmful?

[Rikko]

Hi all,

(I posted this in the general reef forum and was pointed here. Guess I'm a little obscure. :P)

Has anyone done any experimentation with ethoxyquin-containing fish foods in a reef? The fact that it is in *all* dry fish foods (that I've seen) and has been banned for use in human food makes me wonder if it can have any adverse effects on any more sensitive tank fauna.

Safety (MSDS) data for ethoxyquin (http://physchem.ox.ac.uk/MSDS/ET/ethoxyquin.html)

ETHOXYQUIN - FRIEND OR FOE (http://siriusdog.com/articles/article78.htm)

No solid links have been found, though the EU has banned its use for most foods from what I've read. What makes me uneasy are the reports (anecdotal and testimonial - the greatest scientific endeavors!) of birth defects etc. in dogs.

I'm a little leery. Has any serious investigation been done into it?

[Randy Holmes-Farley]

It is toxic at high enough doses, but I'm not sure how much is typically in foods compared to how much is necessary to reach significant toxicity.

Here is database listing of known studies of its tocxicity:

http://www.pesticideinfo.org/List_AquireAll.jsp?Rec_Id=PC35089

some recent articles:

Induction of chromosome aberrations in cultured human lymphocytes treated with ethoxyquin. Blaszczyk, A.; Osiecka, R.; Skolimowski, J. Department of Cytogenetics and Plant Molecular Biology, University of Lodz, Lodz, Pol. Mutation Research (2003), 542(1-2), 117-128.
Abstract

The chromosomal aberration test was employed to investigate the effect in vitro of a known antioxidant and food preservative, ethoxyquin (EQ, 1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline) on human chromosomes. The studies were undertaken because there are no published in vitro data on genotoxicity of EQ in mammalian cells and there are many reports pointing out that it may be harmful to animals and human beings. Lymphocytes obtained from three healthy donors were incubated with EQ (0.01-0.5 mM) both with and without metabolic activation. Stability studies performed by HPLC anal. showed that EQ was stable under the conditions of the lymphocyte cultures. The results of the chromosome aberration assay showed that EQ induces chromosome aberrations: gaps and breaks as well as dicentrics and atypical translocation chromosomes.

Differences in ethoxyquin nephrotoxicity between male and female F344 rats. Neal, G. E.; Judah, D. J.; Hard, G. G.; Ito, N. MRC Toxicology Unit, University of Leicester, Leicester, UK. Food and Chemical Toxicology (2003), 41(2), 193-200.

Abstract

Dose-response studies have shown a sharp threshold for the renal papillary toxic effect in male rats between 0.25% and 0.5% ethoxyquin (Eto) in the diet over 6 mo. Although similar elevated urinary protein (albumin) levels resulted from dietary Eto (0.5%) in both males and females, papillary necrosis was male specific. Following [14C]Eto administration, radiolabel was assocd. with urinary albumin but not alpha 2 globulin (a2m-g). Autoradiog. studies indicated that the sex differences in nephrotoxicity do not involve differences in distribution or retention of Eto. Fecal and urinary metabolic profiles were also similar in the two sexes. The sharp threshold of toxicity in the male rat could indicate a fine balance between toxifying/detoxifying metab. of Eto.

Effects of ethoxyquin on the blood composition of turbot, Scophthalmus maximus. Saxena, T. B.; Zachariassen, K. E.; Jorgensen, L. Department of Zoology, Laboratory of Ecophysiology and Toxicology, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. Comparative Biochemistry and Physiology, Part C: Toxicology & Pharmacology (2000), 127C(1), 1-9.

Abstract

Ethoxyquin (6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline (EQ)) is a synthetic antioxidant used for preventing rancidity in animal foodstuffs. Three groups of ten fish were given a diet contg. resp. 75 (control group with the com. food), 200 and 400 ppm EQ for 16 days. The control group had a plasma osmolality and chloride concn. within the normal range of marine teleosts, but sodium concns. of only about 110 mM, indicating the presence in the plasma of substantial amts. of another cation. Fish given food with 400 ppm EQ displayed a 70 mM increase in the plasma concn. of sodium. This indicates that EQ has disturbed the iono-regulatory mechanisms, probably by reducing the ATP prodn. or inhibiting directly the Na/K-ATPase in the gills. The large increase in plasma sodium concn. was not accompanied by any significant increase in plasma osmolality, indicating that at least a part of the sodium added to the plasma is made osmotically inactive. In spite of the elevated plasma sodium concn., the sodium content of erythrocytes of the 400-ppm EQ fish was reduced to half, while the content of calcium was unaffected. The transmembrane energy gradient of sodium in the EQ exposed turbot obviously increased, allowing them to use a sodium coupled antiport system to keep the cellular calcium content low when the Ca-ATPases blocked. A mechanism of this kind is also likely to be important to turbot that experience hypoxia under natural conditions. The 400-ppm group also displayed a substantial increase in liver wt., but the physiol. significance of this effect is not clear. The leukocyte counts indicated the absence of obvious immunol. effects.