Cl. Gaworski et al., Toxicologic evaluation of flavor ingredients added to cigarette tobacco: skin painting bioassay of cigarette smoke condensate in SENCAR mice, TOXICOLOGY, 139(1-2), 1999, pp. 1-17
Four comparative two-stage SENCAR mouse skin painting bioassays were conduc
ted with cigarette smoke condensate (CSC) preparations to evaluate the effe
ct of common American cigarette flavoring ingredients on tumor promotion. E
ach independent study employed a unique flavoring combination applied to to
bacco at exaggerated levels, and in total resulted in an evaluation of 150
ingredients. Groups of 30-50 female SENCAR mice each were initiated topical
ly with 50 mu g of 7,12-dimethylbenz(a)anthracene (DMBA), and promoted thri
ce weekly for 26 weeks with either 10 or 20 mg of CSC from test cigarettes
containing ingredient mixtures. For comparison, separate groups of mice rec
eived concurrent treatment with CSC from reference cigarettes prepared with
out added ingredients. Negative and positive controls were treated with ace
tone or 12-0-tetradecanoyl-phorbol-13-acetate (TPA) as a promoter, respecti
vely. CSC-only groups served as promotion controls. Tumors developed in >80
% of the TPA-treated mice by study week 11, with a <3% background tumor for
mation in the acetone treated controls at termination. Tumor incidence in C
SC-only promotion control groups was <20%, with no apparent difference betw
een reference and test CSC groups. Approximately 70% of the DMBA-initiated
mice promoted with 20 mg CSC developed tumors. Tumors first appeared around
week 9, with about five tumors/tumor bearing animal. Tumor incidence, late
ncy and multiplicity were CSC dose related, with a lower tumor incidence (a
pproximately 50%), longer latency (12 weeks), and reduced tumor burden (fou
r tumors/tumor bearing animal) at the 10 mg CSC dose level. While tumor inc
idence, latency and multiplicity data occasionally differed between test an
d comparative reference CSC groups, all effects appeared to be within norma
l variation for the model system. Furthermore, none of the changes appeared
to be substantial enough to conclude that the tumor promotion capacity of
CSC obtained from cigarettes containing tobacco with ingredients was discer
nibly different from the CSC obtained from reference cigarettes containing
tobacco processed without ingredients. (C) 1999 Elsevier Science Ireland Lt
d. All rights reserved.