What's in a Name?

Kathryn Rosica of the Chemical Manufacturers Association raised an interesting point in her letter (EHP, vol. 102, p. 1006). Neither the term "glycol ethers" nor the term "ethylene glycol ethers" strictly identifies a class of chemicals whose members all share a common distinctive toxicological profile. As Rosica correctly noted, "Higher molecular weight ethylene glycol monoethers that have been tested have not been associated with significant adverse developmental and reproductive effects." For these compounds, the most sensitive toxic endpoint is usually the destruction of red blood cells.

However, Rosica's carefully limited language may have created a misimpression of its own. The class of "higher molecular weight ethylene glycol monoethers that have been tested" is limited, so far as I am aware, to just four chemicals: ethylene glycol propyl ether, ethylene glycol butyl ether, ethylene glycol hexyl ether, and ethylene glycol phenyl ether. Most glycol ethers are excluded by this careful description. Many of the excluded compounds have been shown to cause fetal malformations, embryofetal death, and testicular atrophy, by the same mechanisms and in some cases with the same potency as the more notorious ethylene glycol methyl ether (EGME) and ethylene glycol ethyl ether (EGEE). These similarly toxic but less frequently discussed glycol ethers include ethylene glycol dimethyl ether (1-6), ethylene glycol diethyl ether (3,7), diethylene glycol methyl ether (3,8), diethylene glycol dimethyl ether (3-5,9-13), diethylene glycol diethyl ether (3,4), and triethylene glycol dimethyl ether (3,4,10,14,15). In fact, most of the ethylene glycol ether derivatives tested do share a common toxicological profile. Nor is the teratogenicity of the glycol ethers limited solely to ethylene glycol ether derivatives; the beta isomer of propylene glycol methyl ether is also a powerful teratogen (16,17).

Clear terminology is always desirable. To be strictly accurate, one might properly use the phrase "the teratogenic, embryolethal, and spermatotoxic glycol ethers," to differentiate these compounds from other glycol ethers such as the highly hematotoxic ethylene glycol butyl ether. However, as a practical matter, most ethylene glycol ethers are teratogens and testicular toxins. The fact that research and discussion have focused heavily on EGME and EGEE, the toxicological archetypes of the series, may have fostered an erroneous belief on the part of chemical manufacturers, users, and product formulators that the less frequently cited compounds are "safe" substitutes. Clearly, many of them are not. To continue that narrow focus and to suggest that glycol ethers other than the "classic" EGME and EGEE and their acetates do not share a similar toxicological profile would be a great disservice to those people who may be exposed to these compounds.

Will Forest
Hazard Evaluation System and Information Service, California Department of Health Services/Department of Industrial Relations, Berkeley, California

References

1. Uemura K. The teratogenic effects of ethylene glycol dimethyl ether on mouse [in Japanese] . Acta Obstet Gynaecol Japan 32:113-121 (1980).

2. Nagano K, Nakayama E, Oobayashi H, Nishizawa T, Okuda H, Yamazaki K. Experimental studies on toxicity of ethylene glycol alkyl ethers in Japan. Environ Health Perspect 57:75-84 (1984).

3. Schuler RL, Hardin BD, Niemeier RW, Booth G, Hazelden K, Piccirillo V, Smith K. Results of testing fifteen glycol ethers in a short-term in vivo reproductive toxicity assay. Environ Health Perspect 57:141-146 (1984).

4. Plasterer MR, Bradshaw WS, Booth GM, Carter MW, Schuler RL, Hardin BD. Developmental toxicity of nine selected compounds following prenatal exposure in the mouse: naphthalene, p-nitrophenol, sodium selenite, dimethyl phthalate, ethylenethiourea, and four glycol ether derivatives. J Toxicol Environ Health 15:25-38 (1985).

5. Hardin BD, Eisenmann CJ. Relative potency of four ethylene glycol ethers for induction of paw malformations in the CD-1 mouse. Teratology 35:321-328 (1987).

6. Leonhardt DE, Coleman LW, Bradshaw WS. Perinatal toxicity of ethylene glycol dimethyl ether in the rat. Reprod Toxicol 5:157-162 (1991).

7. George JD, Price CJ, Marr MC, Kimmel CA, Schwetz BA, Morrissey RE. The developmental toxicity of ethylene glycol diethyl ether in mice and rabbits. Fundam Appl Toxicol 19:15-25 (1992).

8. Hardin BD, Goad PT, Burg JR. Developmental toxicity of diethylene glycol monomethyl ether (DiEGME). Fundam Appl Toxicol 6:430-439 (1986).

9. Price CJ, Kimmel CA, George JD, Marr MC. The developmental toxicity of diethylene glycol dimethyl ether in mice. Fundam Appl Toxicol 8:115-126 (1987).

10. Schwetz BA, Price CJ, George JD, Kimmel CA, Morrissey RE, Marr MC. The developmental toxicity of diethylene and triethylene glycol dimethyl ethers in rabbits. Fundam Appl Toxicol 19:238-245 (1992).

11. Cheever KL, Richards DE, Weigel WW, Lal JB, Dinsmore AM, Daniel FB. Metabolism of bis(2-methoxyethyl) ether in the adult male rat: evaluation of the principal metabolite as a testicular toxicant. Toxicol Appl Pharmacol 94:150-159 (1988).

12. Cheever KL, Weigel WW, Richards DE, Lal JB, Plotnick HB. Testicular effects of bis (2-methoxyethyl) ether in the adult male rat. Toxicol Ind Health 5:1099-1109 (1989).

13. Lee KP, Kinney LA, Valentine R. Comparative testicular toxicity of bis(2-methoxyethyl) ether and 2-methoxyethanol in rats. Toxicology 59:239-258 (1989).

14. George JD, Price CJ, Kimmel CA, Marr MC. The developmental toxicity of triethylene glycol dimethyl ether in mice. Fundam Appl Toxicol 9:173-181 (1987).

15. Bossert NL, Reel JR, Lawton AD, George JD, Lamb JC. Reproductive toxicity of triethylene glycol and its diacetate and dimethyl ether derivatives in a continuous breeding protocol in Swiss CD-1 Mice. Fundam Appl Toxicol 18:602-608 (1992).

16. Merkle J, Klimisch H-J, Jackh R. Prenatal toxicity of 2- methoxypropylacetate-1 in rats and rabbits. Fundam Appl Toxicol 8:71-79 (1987).

17. Jackh R, Hellwig J, Klimisch H-J. Prenatal toxicity of inhalation exposure to 2-methoxypropanol-1 in rabbits. Fundam Appl Toxicol 23:608-613.

I was delighted to read "An ECO-LOGICal Way to Dispose of Waste" in the September Innovations (EHP vol. 103, pp. 808-810). For many years I have been concerned about the human health effects from minute doses of persistent synthetic chemicals. It seemed that there was no way to get them out of our environment. Now the organic compounds can be changed back into harmless substances and can be separated out, contained, and then perhaps reused.

One doctor who would have been glad to know of any elimination of man-made chemicals was Theron G. Randolph, who died September 29, 1995, at age 89. In the 1950s he discovered that many of his patients were made ill by minute doses of chemicals; for example, the pesticides on food. He was honored for his discoveries that benefited so many patients. Dr. Randolph continued in practice until last year.

Again, thank you for the excellent article on an innovation that can reduce exposure to man-made toxins.

Marjorie Fisher
NOHA (Nutrition for Optimal Health Association) News, Winnetka, Illinois

In regard to the article, "Potential Impact of Global Climate Change on Malaria Risk," by Martens et al. in the May issue of EHP (vol. 103, pp. 458-464), I do not pretend to discuss the matter of climate change and malaria and the approaches used by Martens and colleagues. I am not convinced there is a real risk of the hypothetical global climate change on the spread of malaria. In my opinion, there are many other important factors to take into account, mainly concerning the so-called Third World.

What I cannot accept is the cover photograph of a mosquito species that has nothing to do with the Anopheles genus. It looks much more like an Aedes. I felt compelled to bring this to your attention in the hope it will contribute to the improvement of EHP.

Oswaldo Paulo Forattini
Universidade de Sao Paulo, Sao Paulo, Brazil

Erratum

We apologize for our error in identifying the mosquito on the cover of the May issue as Anopheles stephensi. Dr. Forattini is correct: the mosquito is of the genus Aedes. The photograph came to us from the World Health Organization. Following is an excerpt from the letter from WHO correctly identifying the mosquito.

Dear Dr. Hook:
As you will have seen from the data sheet that was sent with the [mosquito] image, it was supplied to the TDR Image Library [of WHO] by the Medical Illustration department of the Liverpool School of Tropical Medicine as part of a group depicting Anopheles stephensi.
I have now checked with the department concerned. They apologise for the mix up and do, indeed, confirm that the picture is of an Aedes species.
I echo the apology over the misidentification, and I sincerely hope this has not caused too great a problem.

Andy Crump, TDR Image Library Coordinator, World Health Organization

Last Update: November 27, 1995