Acute testicular toxicity of 1,3-dinitrobenzene and ethylene glycol monomethyl ether in the rat: evaluation of biochemical effect markers and hormonal responses.
The studies described in this paper were undertaken to evaluate the use of plasma enzymes of testicular origin and plasma hormones as markers of acute testicular toxicity. Rats were dosed by gavage with a single dose of either 1,3-dinitrobenzene (1,3-DNB) or ethylene glycol monomethyl ether (EGME). Two experimental designs were used: a dose response and a time-dose response course. Lactate dehydrogenase isozyme C4 (LDH-C4) and sorbitol dehydrogenase (SDH) were used as germ cell markers and leucine aminotransferase (LAT) and androgen binding protein (ABP) were used as Sertoli cell markers. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were also monitored. Histopathology confirmed the known testicular toxicity of 1,3-DNB and EGME. 1,3-DNB induced Sertoli cell damage with associated degenerative changes in late pachytene spermatocytes. The effects of EGME were mainly on early and late pachytene and dividing spermatocytes. No changes in either testicular or plasma SDH or LAT were found. Similarly no effects were observed for plasma LH or testosterone. However testicular LDH-C4 and testosterone, plasma LDH-C4, ABP, and FSH did show compound related effects. LDH-C4 was reduced in testis and increased in plasma with both compounds and plasma LDH-C4 remained elevated up to 14 days after dosing. ABP levels in plasma were increased with 1,3-DNB and EGME. A reduction in testicular testosterone levels was recorded and plasma FSH concentrations were elevated after EGME treatment. It is concluded that plasma LDH-C4 activity and ABP may be of diagnostic value in acute testicular toxicity. Increases in plasma LDH-C4 precede noticeable histological findings.
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ICI plc., Central Toxicology Laboratory, Cheshire, United Kingdom.
Shingles
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Stonard
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D000727:Androgen-Binding Protein / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D004136:Dinitrobenzenes / Q000633:toxicity*; D005026:Ethylene Glycols / Q000633:toxicity*; D005640:Follicle Stimulating Hormone / Q000097:blood; D006728:Hormones / Q000097:blood*; D007064:L-Iditol 2-Dehydrogenase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051276:Leucine Transaminase; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism; D013733:Testicular Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000473:pathology; D013739:Testosterone / Q000097:blood; D000637:Transaminases / Q000378:metabolism
D000727:Androgen-Binding Protein; D015415:Biomarkers; D004136:Dinitrobenzenes; D005026:Ethylene Glycols; D006728:Hormones; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C017906:3-dinitrobenzene; D007064:L-Iditol 2-Dehydrogenase; D007770:L-Lactate Dehydrogenase; D000637:Transaminases; D051276:Leucine Transaminase; C005219:methyl cellosolve