Spermatotoxicity of dichloroacetic acid.
The testicular toxicity of dichloroacetic acid (DCA), a disinfection byproduct of drinking water, was evaluated in adult male rats given both single and multiple (up to 14 d) oral doses. Delayed spermiation and altered resorption of residual bodies were observed in rats given single doses of 1500 and 3000 mg/kg; these effects persisted to varying degrees on post-treatment days 2, 14, and 28. Delayed spermiation and formation of atypical residual bodies also were observed on days 2, 5, 9, and 14 in rats dosed daily with 1440, 480, 160, and 54 mg/kg. Distorted sperm heads and acrosomes were observed in step 15 spermatids after 14 doses of 480 and 1440 mg/kg. Decreases in the percentage of motile sperm occurred after 9 doses of 480 and 1440 mg/kg and 14 doses of 160 mg/kg. Increased numbers of fused epididymal sperm were observed on days 5, 9, and 14 in rats dosed with 1440, 480, and 160 mg/kg, respectively; other morphologic abnormalities occurred at 160 mg/kg and higher. On day 14, a significant decrease in epididymis weight was observed at 480 and 1440 mg/kg, and epididymal sperm count was decreased at 160 mg/kg and higher. These studies demonstrate that the testicular toxicity induced by DCA are similar to those produced by the analogue, dibromoacetic acid. However, the testicular toxicity of DCA is less severe at equal molar concentrations. Moreover, the DCA-induced testicular lesions occur with greater potency as the duration of dosing increases, indicating the importance of using low-dose subchronic exposures to assess the health risk of prevalent disinfection byproducts.
Linder
R E
RE
National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Klinefelter
G R
GR
Strader
L F
LF
Suarez
J D
JD
Roberts
N L
NL
D000085:Acetates / Q000633:toxicity*; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003999:Dichloroacetic Acid / Q000633:toxicity*; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects; D013076:Sperm Count / Q000187:drug effects; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects* / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D013739:Testosterone / Q000097:blood
D000085:Acetates; D013739:Testosterone; C088674:dibromoacetic acid; D003999:Dichloroacetic Acid