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Table 16. Spleen weights and histology for pups in a two-generation study of reproductive toxicity
in rats exposed to zoxamide
Generation Finding Dietary concentration (ppm)
F 1a
F 1b
F 2a
F 2b
0 1000 5000 20 000
Males
Absolute spleen weight (g) 0.283 0.223* 0.236* 0.205*
Relative spleen weight (%) 0.473 0.415* 0.420* 0.394*
Reduced extramedullary haematopoiesis 0/24 6/26* 7/24* 9/26*
(No. affected/No. examined)
Females
Absolute spleen weight (g) 0.286 0.248* 0.226* 0.208*
Relative spleen weight (%) 0.489 0.461 0.424* 0.408*
Reduced extramedullary haematopoiesis
(No. affected/No. examined)
1/24 5/25 12/25* 15/27*
Males
Absolute spleen weight (g) 0.263 0.242 0.220* 0.203*
Relative spleen weight (%) 0.442 0.431 0.404 0.385*
Females
Absolute spleen weight (g) 0.267 0.235 0.216* 0.199*
Relative spleen weight (%) 0.457 0.442 0.419 0.395*
Males
Absolute spleen weight (g) 0.253 0.229 0.217* 0.172*
Relative spleen weight (%) 0.439 0.425 0.425 0.354*
Reduced extramedullary haematopoiesis 1/23 5/24 6/24 13/22*
Females
Absolute spleen weight (g) 0.267 0.234 0.211* 0.184*
Relative spleen weight (%) 0.479 0.460 0.429* 0.380*
Reduced extramedullary haematopoiesis 0/23 5/24 12/23* 12/22*
Males (dams and pups dosed by gavage)
Absolute spleen weight (g) 0.269 0.280 0.270 0.252
Relative spleen weight (%) 0.457 0.534 0.481 0.448
Reduced extramedullary haematopoiesis 0/10 — — 0/11
Females (dams and pups dosed by gavage)
Absolute spleen weight (g) 0.251 0.265 0.273 0.258
Relative spleen weight (%) 0.453 0.455 0.483 0.481
Reduced extramedullary haematopoiesis (n=) 0/9 — — 0/10
Males (dams only dosed by gavage)
Absolute spleen weight (g) 0.290 0.295 0.282 0.285
Relative spleen weight (%) 0.474 0.484 0.468 0.478
Reduced extramedullary haematopoiesis (n=) 0/10 — — 1/11
Females (dams only dosed by gavage)
Absolute spleen weight (g) 0.286 0.266 0.283 0.267
Relative spleen weight (%) 0.483 0.485 0.510 0.476
Reduced extramedullary haematopoiesis (n=) 0/9 — — 0/11
From O’Hara et al. (1998)
* Significant difference from controls (p < 0.05);
ZOXAMIDE 487–522 JMPR 2007