Developmental Toxicology Evaluation of 1-Pentanol,1-Hexanol,and 2-Ethyl-1-Hexanol Administered by Inhalation to Rats

Abstract

As part of a large study evaluating the developmental toxicology of industrial alcohols, groups of approximately 15 Sprague-Dawley rats were exposed for 7 h/day on gestation days 1–19 to one of three alcohols at the highest concentrations we could generate as a vapor. Since these concentrations were not sufficiently high to be toxic to the maternal rats, lower levels were not included. These concentrations were 14,000, 3500, and 850 mg/m³ 1-pentanol, 1-hexanol, and 2-ethyl-1-hexanol, respectively. Dams were weighed daily for the first week of exposure and weekly thereafter and were sacrificed on day 20. Fetuses were serially removed, blotted dry, examined for external malformations, sexed, weighed, fixed, and examined for visceral or skeletal defects. Pentanol reduced maternal feed intake and weight gain, but there were no significant decreases in fetal weights. Resorptions were slightly increased in the group exposed to 1-hexanol, and 2-ethyl-1-hexanol reduced maternal feed intake, but neither hexanol derivative produced malformations. Obviously, teratogenicity by other routes of exposure cannot be ruled out, particularly in view of the low volatility of these alcohols. However, the present studies indicate that inhalation of pentanol, hexanol, or 2-ethyl-1-hexanol at the stated concentrations can produce limited maternal toxicity, but none was teratogenic to rats.

References

1. Nelson, B.K. , Brightwell, W.S. , MacKenzie, D.R. , Khan, A. , Burg, J.R. , Weigel, W.W. , and Goad, P.T. (1985). Teratological assessment of methanol and ethanol at high inhalation levels in rats. Fundament. Appl. Toxicol. 5, 727–36.

2. Nelson, B.K. , Brightwell, W.S. , Mackenzie-Taylor, D.R. , Khan, A. , Burg, J.R. , Weigel, W.W. , and Goad, P.T. (1988). Teratogenicity of n-propanol and isopropanol at high inhalation concentrations to rats. Food Chem. Toxicol. 26, 247–54.

3. Nelson, B.K. , Brightwell, W.S. , Khan, A. , Burg, J.R. , and Goad, P.T. (1989). Lack of selective developmental toxicity of three butanol isomers administered by inhalation to rats. Fundam. Appl. Toxicol. 12, 469–479.

4. Von Oettingen, W.F. (1943). The Aliphatic Alcohols: Their Toxicity and Potential Dangers in Relation to Their Chemical Constitution and Their Fate in Metabolism. U.S. Public Health Bulletin No. 281. Washington, D.C.: U.S. Government Printing Office.

5. Nelson, B.K. , Brightwell, W.S. , and Burg, J.R. (1985). Comparison of behavioral teratogenic effects of ethanol and n-propanol administered by inhalation to rats. Neurobehav. Toxicol. Teratol. 7, 779–83.

6. Nelson, B.K. (1986). Behavioral teratology of industrial solvents. In: Riley, E.P. , and Vorhees, C.V. (eds.). Handbook of Behavioral Teratology. New York: Plenum, pp. 391–406.

7. Ritter, E.J. , Scott, W.J. , Jr., Randall, J.L. , and Ritter, J.M. (1987). Teratogenicity of di(2-ethylhexyl) phthalate, 2-ethylhexanol, 2-ethylhexanoic acid, and valproic acid, and potentiation by caffeine. Teratology 35, 41–6.

8. Peters, R. E. (1978). Higher aliphatic alcohols. In: Mark, H.F. , Othmer, D.F. , Overberger, C.G. , and Seaborg, G.T. (eds.). Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Vol. I. New York: John Wiley and Sons, pp. 716–39.

9. NIOSH (1974). National Occupational Hazard Survey. Dhhs Publication No. (NIOSH) 14–127.

10.

10. Eller, P.M. (ed.) (1984). NIOSH Manual of Analytical Methods, 3rd ed., Vol. I. DHHS (NIOSH) Publication No. 84–100.

11.

11. Wilson, J.G. (1965). Embryological considerations in teratology. In: Wilson, J.G. , and Warkany, J. (eds.). Teratology: Principles and Techniques. Chicago: University of Chicago Press, pp. 251–61.

12.

12. Nelson, B.K. , Setzer, J.V. , Brightwell, W.S. , Mathinos, P.R. , Kuczuk, M.H. , Weaver, T.E. , and Goad, P.T. (1984). Comparative inhalation teratogenicity of four glycol ether solvents and an amino derivative in rats. Environ. Health Perspect. 57, 261–71.

13.

***Address reprint requests to: B. K. Nelson Division of Biomedical and Behavioral Science NIOSH C-24 4676 Columbia Parkway Cincinnati, OH 45226–1998