A comparison of male-mediated effects in rats and mice exposed to 1,3-butadiene

Male-mediated developmental toxicity

“…By using this type of study design, we have examined the following compounds using chronic and acute exposure: cyclophosphamide, 1,3-butadiene and urethane (ethyl carbamate) ( Table 1). [42][43][44][45][46][47][48][49] Cyclophosphamide was positive for all endpoints in the rat after chronic gavage exposure. 43,44 This effect has also been shown by others 45 and led to the belief that chronic exposure might be a more realistic model than acute exposure, as man is chronically exposed in the workplace and environmentally.…”

“…[102][103][104] Ethnicities and the associated different dietary and cultural habits can affect congenital anomaly rates. 105 The large animal studies of the 1980s and 1990s demonstrated that damage could be transmitted through the father to both the first [42][43][44][46][47][48][49] and second generation. 50 It was originally assumed that this transmission was limited to genetically-based inheritance.…”

“…46 In the rat, no dominant lethality was observed. 48 However, for urethane, there were negative results for dominant lethality and congenital malformations after subchronic exposure in the drinking water, although an increase in tumors in males was observed after acute intraperitoneal treatment. 49 A Japanese study in ICR mice after acute intraperitoneal treatment also reported negative results for dominant lethal mutations, confirming results by other workers, but demonstrated an increase in congenital malformations, tumors in the F1 generation and transmitted tumors in the F2 and F3 generations.…”

“…They can be measured and scored in the same way as teratogenic defects after in utero exposure of females. [42][43][44][46][47][48][49] A1b: If delayed effects in the offspring are considered as childhood cancers, cognitive developmental defects, growth disorders and the like, then in humans after radiation it was thought that exposed fathers had given rise to leukemia in their children. 63,64 However, the case was thrown out of court because it foundered on 'the balance of probabilities' .…”

Induction of DNA Damage and G2 Cell Cycle Arrest by Diepoxybutane through the Activation of the Chk1-Dependent Pathway in Mouse Germ Cells

“…32 Meanwhile, the testicular genotoxicity of BD and its metabolites has been assessed for a long time, and there was evidence of congenital malformations and dominant lethal mutations in male mice after BD exposure but not in rats. 33 Clastogenic data of BD's epoxy metabolites, especially that of DEB, were also available in germinal cells in both mice and rats from spermatid micronucleus tests and heritable translocation assays. 34,35 These results indicated that male reproductive genotoxicity of BD may still depend on the production of potent metabolites.…”