ToxSci Advance Access originally published online on June 1, 2007
Toxicological Sciences 2007 99(1):224-233; doi:10.1093/toxsci/kfm141
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Published by Oxford University Press 2007.
Toxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in the Developing Male Wistar(Han) Rat. II: Chronic Dosing Causes Developmental Delay
* School of Biology, University of Nottingham, University Park, Nottingham, NG7 2RD, UK
Covance Laboratories Ltd, Otley Road, Harrogate, North Yorkshire, HG3 1PY UK
National Institute of Environmental Health Sciences, PO Box 12233 (MD E1-06), 111 TW Alexander Drive, Research Triangle Park, North Carolina 27709
Health and Safety Laboratory, Harpur Hill, Buxton, Derbyshire, SK17 9JN, UK
¶ Central Science Laboratory, Environment, Food and Health, Sand Hutton, York, YO41 1LZ, UK
|| Institute of Occupational Medicine, Research Park North, Riccarton, Edinburgh, EH14 4AP, UK
1 To whom correspondence should be addressed. Fax: +44-115-9513251. E-mail: david.bell{at}nottingham.ac.uk.
Received March 16, 2007; accepted May 25, 2007
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Abstract |
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We have investigated whether fetal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes defects in the male reproductive system of the rat using chronically exposed rats to ensure continuous exposure of the fetus. Five- to six-week-old rats were exposed to control diet, or diet containing TCDD, to attain an average dose of 2.4, 8, and 46 ng TCDD/kg/day for 12 weeks, whereupon the rats were mated and allowed to litter; rats were switched to control diet after parturition. Male offsprings were allowed to develop until kills on PND70 (25 per group) or PND120 (all remaining animals). Offspring from the high-dose group showed an increase in total litter loss, and the number of animals alive on postnatal day (PND)4 in the high-dose group was 
26% less than control. The high and medium dose offsprings showed decreased weights at various ages. Balano-preputial separation (BPS) was significantly delayed in all three dose groups compared to control. There were no significant effects of maternal treatment when the offsprings were subjected to a functional observational battery or learning tests, with the exception that the high-dose group showed a deficit in motor activity. Twenty rats per group were mated to females, and there were no significant effects of maternal treatment on the fertility of these rats or on the F1 or F2 sex ratio. Sperm parameters at PND70 and 120 showed no significant effect of maternal treatment, with the exception that there was an increase in the proportion of abnormal sperm in the high-dose group at PND70; this is associated with the developmental delay in puberty in this dose group. There were no remarkable findings of maternal treatment on organ weights, with the exception that testis weights were reduced by 10% at PND70 (but not PND120), and although the experiment was sufficiently powered to detect small changes, ventral prostate weight was not reduced. There were no significant effects of maternal treatment upon histopathological comparison of high-dose and control group organs. These data confirm that developmental exposure to TCDD shows no potent effect on adult sperm parameters or accessory sexual organs, but show that delay in BPS occurs after exposure to low doses of TCDD, and this is dependent upon whether TCDD is administered acutely or chronically.
Key Words: dioxin; sperm; developmental toxicity.
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