A comparison of the effects of the three isomers of dinitrobenzene on the testis in the rat.
Sexually mature Alpk/AP (Wistar derived) rats were killed 5 days after a single oral dose of 50 mg/kg of the 1,2-, 1,3-, or 1,4-isomers of dinitrobenzene. Testis weight reductions accompanied by testicular lesions were observed in the animals dosed with 1,3-dinitrobenzene (1,3-DNB) while the 1,2- and 1,4-isomers were without effect on the testis. However, 1,4-dinitrobenzene, but not 1,2-dinitrobenzene, was of a potency similar to that of 1,3-DNB in producing cyanosis and splenic enlargement in these animals, indicating that different mechanisms are probably responsible for these two toxic effects. In a subsequent study the pathogenesis of the testicular damage resulting from a single oral dose of 5, 10, 15, or 25 mg 1,3-DNB/kg was studied in sexually mature rats. Animals were killed 6, 12, 24, 48, and 96 hr after dosing and a detailed histopathological examination of the testes and selected tissues was made. At 12 hr after a single oral dose of 25 mg/kg, 1,3-DNB produced testicular lesions limited to Stages VIII to XI of the spermatogenic cycle. By 24 hr widespread Sertoli cell damage was evident and in some tubules was associated with degeneration of primary spermatocytes. Ultrastructural examination at this time confirmed that there were effects on Sertoli cells in the absence of germ cell damage. Similar effects were seen 48 hr after a single oral dose of 15 mg 1,3-DNB/kg. Doses of 5 or 10 mg 1,3-DNB/kg were without effect on the testis. The Sertoli cell is implicated as the prime target for the toxic action of 1,3-DNB with germ cell damage a secondary event.
Blackburn
D M
DM
Pathology Section, Imperial Chemical Industries plc, Cheshires, United Kingdom.
Gray
A J
AJ
Lloyd
S C
SC
Sheard
C M
CM
Foster
P M
PM
D000284:Administration, Oral; D000818:Animals; D004136:Dinitrobenzenes / Q000633:toxicity*; D008297:Male; D009578:Nitrobenzenes / Q000633:toxicity*; D051381:Rats; D012671:Seminiferous Tubules / Q000187:drug effects / Q000473:pathology; D013154:Spleen / Q000187:drug effects; D013329:Structure-Activity Relationship; D013737:Testis / Q000187:drug effects* / Q000473:pathology
D004136:Dinitrobenzenes; D009578:Nitrobenzenes; C040234:1,2-dinitrobenzene; C053052:1,4-dinitrobenzene; C017906:3-dinitrobenzene