It has been reported that @entity3636 administered to BDF1 @entity19 by inhalation for 2 years at concentrations of 5, 30 or 90 p.p.m. for 6 h/day, 5 days/week induced an @entity1358 in male but not female @entity19 exposed to the doses of 30 and 90 p.p.m. A small increase in @entity96 was statistically significant in the female @entity19 at 90 p.p.m. if the incidences of @entity189 and @entity652 were combined. Because @entity3636 is not a DNA reactive mutagen, a 13-week time-course and dose-response study was conducted under conditions of the original bioassay to examine whether regenerative cell proliferation was an underlying mechanism of @entity105 . @entity19 were given @entity1603 via infusion during the last 3.5 days prior to necropsy to label cells in S-phase. @entity3636 induced pathology and regenerative cell proliferation, measured as the @entity894 ( @entity894 , percentage of cells in S-phase), were assessed microscopically and immunohistochemically. Male @entity19 exposed to 30 and 90 p.p.m. exhibited a dose-dependent increase in regenerating tubules within the renal cortex and up to a 31-fold increase in @entity894 . No @entity8 or increased @entity894 were observed in females. Increased centrilobular to midzonal hepatocyte degeneration and vacuolation and a 7-fold increase over controls in the hepatocyte @entity894 were observed in the female @entity19 at 90 p.p.m. at 13 weeks. Males exhibited similar pathology, but the increase in @entity894 was not sustained. The observed correlations between cytolethality and regenerative cell proliferation with @entity5 formation supports extensive evidence that @entity3636 induces @entity5 via a non-genotoxic-cytotoxic mode of action. A concentration of 5 p.p.m. is the no-observed-adverse-effect level for nephrotoxicity, cell proliferation and @entity5 . An appropriate safety factor applied to this value is a straightforward approach to @entity5 risk assessment that is consistent with the mode of action of @entity3636 .

Patterns of XXXX -induced regenerative cell proliferation in BDF1 @entity19 correlate with organ specificity and dose-response of @entity5 formation.

@entity1603 :: ('MESH:D001973', 'Chemical') :: ['bromodeoxyuridine'] @entity8 :: ('MESH:D007674', 'Disease') :: ['renal lesions'] @entity894 :: ('MESH:C566784', 'Disease') :: ['labeling index', 'LI'] @entity96 :: ('MESH:D008113', 'Disease') :: ['liver tumors'] @entity19 :: ('10090', 'Species') :: ['mice', 'Mice'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity3636 :: ('MESH:D002725', 'Chemical') :: ['chloroform', 'Chloroform'] @entity189 :: ('MESH:D002277', 'Disease') :: ['carcinomas'] @entity1358 :: ('MESH:D002292', 'Disease') :: ['increase in renal cell tumors'] @entity652 :: ('MESH:D000236', 'Disease') :: ['adenomas'] @entity105 :: ('MESH:D063646', 'Disease') :: ['carcinogenesis']
@entity3636 :: (MESH:D002725,Chemical) :: ['chloroform']
