The role of regenerative cell proliferation in chloroform-induced cancer.
Chloroform produces cancer by a nongenotoxic-cytotoxic mode of action, with no increased cancer risk expected at noncytotoxic doses. The default risk assessment for inhaled chloroform relies on liver tumor incidence from a gavage study with female B6C3F1 mice and estimates a virtually safe dose (VSD) at an airborne concentration of 0.000008 ppm of chloroform. In contrast, a 1000-fold safety factor applied to the NOAEL for liver cytotoxicity from inhalation studies yields a VSD of 0.01 ppm. This estimate relies on inhalation data and is more consistent with the mode of action of chloroform.
Butterworth
B E
BE
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.
Templin
M V
MV
Borghoff
S J
SJ
Conolly
R B
RB
Kedderis
G L
GL
Wolf
D C
DC
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002725:Chloroform / Q000633:toxicity*; D004247:DNA / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced*; D051381:Rats; D018570:Risk Assessment
D002725:Chloroform; D004247:DNA