Methods for NCI studies in Nonhuman Primates
The NCI Laboratory of Chemical Pathology conducted
a 36-year project (1961-1997) on lifetime carcinogenesis studies in
cynomolgus and rhesus monkeys. The CPDB includes lifetable analyses
on 25 chemicals.
Some of the inclusion rules of the CPDB have been
relaxed in order to include these monkey experiments. The following
methodology has been adopted:
- An experiment with fewer than 5 animals is considered
inadequate and is not included in the CPDB. To obtain at least 5
animals per group in these studies, results have been combined for
both sexes of cynomolgus and separately for both sexes of rhesus
- Although experiments with surgical intervention are generally
excluded from the CPDB, in these monkey tests, laparoscopic
examination of the liver was performed every 3-6 months, followed
by wedge or needle biopsies of observed liver lesions.
- A few positive experiments are included that are shorter than
one-half the standard 20-year life span, even though such tests are
generally excluded from the CPDB.
- Experiments on sodium arsenate and sterigmatocystin are
included even though monkeys were put on test as adults, at 4 years
- Control monkeys are from the colony at NCI, which included
breeders, offspring, and a small number of feral monkeys. The age
of control animals ranged from neonate to greater than 25 years at
a given time. Control monkeys were included only if they lived to
be older than 8 months, the age of the first tumor in any group.
Concurrent, vehicle controls were used only for IQ.
- The dose rate for a group is calculated as the mean of the
dose-rate of individual monkeys. To obtain the daily dose rate for
each monkey, the cumulative dose in mg/kg reported by NCI, was
divided by the number of days of its life. Dosing schedules ranged
across chemicals from once every 4 weeks to 5 times per week; for
most experiments the chemicals were administered in a vitamin
sandwich 5 times per week.
- TD50 values are estimated using lifetable data and
are reported for every site at which a tumor occurred, benign or
malignant, in dosed animals.
- In experiments with multiple target sites, a composite
TD50 value is reported for all animals with tumors at
any of the target sites (“MXB,MXB” in “All
Experiments and Citations in CPDB,” as with NCI/NTP bioassays
- Adamson, R. H., and Sieber, S. M. Chemical carcinogenesis
studies in nonhuman primates. In: Organ and Species Specificity
in Chemical Carcinogenesis. (R. Langenbach S. Nesnow, and J. M.
Rice, Eds.), Plenum Press, New York and London, 1982, pp.
- Adamson, R. H., Takayama, S., Sugimura, T., and Thorgeirsson,
U. P. Induction of hepatocellular carcinoma in nonhuman primates by
food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline.
Environ. Health Perspect. 102: 190-193(1994).
- Dalgard, D. W. Induction, Biological Markers and Therapy of
Tumors in Primates. National Cancer Institute Final Report of
Contract No. N01-CP-40510, Vienna, VA, Corning Hazelton Laboratory
Study No. 421-166, Reporting period: July 1, 1994-March 31,
- Thorgeirsson, U. P., Dalgard, D. W., Reeves, J., and Adamson,
R. H. Tumor incidence in a chemical carcinogenesis study in
nonhuman primates. Regul. Toxicol. Pharmacol. 19:
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