ToxSci Advance Access published online on December 2, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfg251
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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1 Environmental Health Science Bureau, Health Canada, Ottawa, Canada
* To whom correspondence should be addressed. E-mail: raymond_poon{at}hc-sc.gc.ca.
Pentyl ether (PE) and two newly synthesized polyoxy ethers, 1,4-diethoxybutane (DEB)2 and 1,6-dimethoxyhexane (DMH), have been proposed as candidate diesel fuel additives. To characterize and compare their toxicity and to provide information for risk assessment, a 4-week oral study was conducted on these compounds. Male Sprague Dawley rats (288 ± 20 g) were divided into groups of 7 animals each and were administered by gavage, low (2 mg/kg BW), medium (20 mg/kg BW) or high (200 mg/kg BW) doses of PE, DEB or DMH, respectively, 5 days per week for 4 weeks. Animals in the control group received the vehicle (corn oil, 1 ml/100 g BW) only. At the end of the exposure period, relative testis and thymus weights were reduced by 30% and 46%, respectively in animals treated with high dose DMH. Significant reduction in serum lactate dehydrogenase (LDH), serum uric acid and blood platelet counts was also observed in the high dose DMH. Serum corticosterone was significantly depressed in the high dose PE and DEB, and low dose DMH. Serum thiobarbituric acid reactive substances (TBARS) were decreased (p<0.05) in all DMH treatment groups and in the medium and high dose PE and DEB groups, while liver TBARS were unaffected by treatment. In the liver, increased glutathione (GSH) level and glutathione-S-transfereases activity were detected in the high dose DMH group. Urinary ascorbic acid levels were markedly increased in animals receiving the high dose PE, DEB and DMH. Urinary formic acid was increased by 13 times in the high dose PE and DEB groups. Testes of all animals receiving the high dose DMH showed a moderate to markedly degree of degeneration of the seminiferous tubules including a mild degree of vacuolation. At the same time, the epididymis of these animals had substantially reduced sperm density with prominent presence of spermatid giant cells. Mild histological changes were seen in the liver at all dose levels for all three chemicals. Thyroid effects were also observed in the high dose PE and DEB groups and in the medium and high dose DMH group. It was concluded that DMH is the most toxic of the three ethers tested, with testicular, epidiymal, and thymic effects being the most prominent at 200 mg/kg. Other significant changes included depressed platelet counts, and serum biochemical changes. Increased production of formic acid, an ocular toxin, from PE and DEB treatment may also be of toxicological concern.
© 2003 Society of Toxicology
Risk Assessment
Short-Term Oral Toxicity of Pentyl Ether, 1,4-Diethoxybutane and 1,6-Dimethoxyhexane in Male Rats
2 College of Veterinary Medicine, University of Illinois, Illinois, U.S.A.
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