IJT - CIR - February 2024 - 74S

74S
International Journal of Toxicology 43(Supplement 1)
toxicity effects were described in the Toxicological Studies
section. In the micronucleus study, no significant alterations in
the percentages of PCEs were observed in females of either
genotype; however, a significant decrease in the percentage of
PCEs were observed in both genotypes in males, indicating
the studied GBE induced bone marrow toxicity in male mice.
In the comet assay, there was no significant difference in the
percent tail DNA in any of the GBE-treated groups in either
mouse genotype. Heavily damaged cells called " hedgehogs "
indicating cytotoxic effects were not detected in any animals.
The researchers performing these 3 assays concluded that the
studied GBE is not genotoxic.49
Ginkgo Biloba Meristem Cell. In a micronucleus test, no increase
in the frequency of micronucleated polychromatophilic
erythrocytes in bone marrow was observed in male mice
administered 500 to 2000 mg/kg/d Ginkgo Biloba Meristem
Cell.48 There was no significant difference in the ratio of
polychromatophilic erythrocytes in total red blood cells when
compared to the negative control. The positive control yielded
expected results. No further details were provided.
Carcinogenicity
The carcinogenic potential of a GBE administered orally was
studied by the NTP in male and female rats and mice.9 In the
study on mice, groups of 50 male and 50 female B6C3F1/N
mice received 200, 600, or 2000 mg/kg ofthis GBE in corn oil
5 d/wk for 104 wk via gavage. In the study on rats, groups of
50 F344/N male and 50 female rats received 100, 300, or
1000 mg/kg body weight of this GBE for 104 (males) or 105
(females) wk via gavage. Control groups received corn oil
(5 mL/kg in mice and 2.5 mL/kg in rats). In rats involved in
what was deemed a " special study, " groups of 10 male and
female rats received the same doses as in the main study; blood
was collected from these rats on day 22 and at week 14 for
thyroid hormone analyses and other analyses of the liver and
thyroid gland. All animals were observed twice daily. Body
weights were evaluated at study beginning and ending and at
different intervals during the course ofthe study. At the end of
the study period, tissues from over 40 sites were examined for
every animal, including ovaries and uteri in females and
prostate gland and testes with epididymis and seminal vesicles
in males.
In mice, mortality was significantly higher in the 600 and
2000 mg/kg males than in the vehicle controls, with the most
frequent cause of death being liver tumors. Survival in the
600 mg/kg females was significantly greater than that of the
vehicle controls. Mean body weights in the mid- and highdose
group male mice were less than (10% or more) those of
the vehicle controls after weeks 85 and 77, respectively. The
mean body weights of the high-dose females were generally
less than the vehicle controls between weeks 17 and 69 and
after week 93.
In rats, mortality in the 1000 mg/kg males was significantly
higher than that ofthe vehicle controls, with the most frequent
cause ofdeath being mononuclear cell leukemia. The survival
of the treated groups of female rats was comparable to the
vehicle control. In week 14, all dose group males and females
of the 1000 mg/kg group in the special study had increased
levels ofthyroid stimulating hormone compared to the vehicle
controls; the increase was dose-related in the male rats. Mean
body weights in the mid- and high-dose male and female rats
were less than (10% or more) those ofthe vehicle controls after
weeks 93 and 89, respectively.
Lesions in the liver, thyroid gland, and nose were observed
in all the studied GBE dose groups in mice and rats. These
lesions included hypertrophy in the liver and thyroid gland in
rats and mice, liver hyperplasia in male and female rats, and
hyperplasia and atrophy of the epithelium in the nose of male
and female rats. Inflammation, hyperplasia, hyperkeratosis,
and ulcers were also observed in the forestomach ofmale and
female mice. Additionally, increased incidences of cancers of
the thyroid gland were observed in male and female rats and
male mice and of liver cancers in male and female mice. The
study concluded that the studied GBE caused cancers of the
thyroid gland in male and female rats and male mice, and
cancers of the liver in male and female mice.9
In dietary carcinogenicity studies of a standardized GBE
(EGb 761®) in mice (at up to 200 mg/kg/d) or rats (at up to
100 mg/kg/d), no neoplastic or pre-neoplastic effects were
observed.54 The rodents received the test material for up to 85
wk. No changes in body weight gain were reported. No further
details are available.
The International Agency for Research on Cancer (IARC)
has determined that GBEs are possibly carcinogenic to humans
(group 2B) based on inadequate human carcinogenicity
evidence and sufficient evidence in experimental animals.55
The animal data used to reach this determination were from the
NTP studies that are described above that used a specific GBE.
IARC also reviewed the findings of a randomized control
study, 4 nested case-control epidemiological studies researching
the potential effects of the use of GBE dietary
supplements in elderly patients, and a population based casecontrol
epidemiological study in ovarian cancer patients.
IARC suggested that the mechanisms for carcinogenicity
associated with GBEs may be genotoxicity and/or topoisomerase
inhibition that could be related to the constituents:
quercetin, kaempferol, and/or rutin.
Other Relevant Studies
Immunotoxicity
In a popliteal lymph node assay (PLNA), the sensitization
potential ofa GBE was evaluated.13 Groups ofmale C57BL/6
mice received subplantar injections of 10 μl DMSO (induction)
followed by another injection of DMSO (negative
control group), a crude ethanolic-aqueous GBE, heptane

IJT - CIR - February 2024

Table of Contents for the Digital Edition of IJT - CIR - February 2024

Contents
IJT - CIR - February 2024 - Cover1
IJT - CIR - February 2024 - Cover2
IJT - CIR - February 2024 - 1S
IJT - CIR - February 2024 - 2S
IJT - CIR - February 2024 - Contents
IJT - CIR - February 2024 - 4S
IJT - CIR - February 2024 - 5S
IJT - CIR - February 2024 - 6S
IJT - CIR - February 2024 - 7S
IJT - CIR - February 2024 - 8S
IJT - CIR - February 2024 - 9S
IJT - CIR - February 2024 - 10S
IJT - CIR - February 2024 - 11S
IJT - CIR - February 2024 - 12S
IJT - CIR - February 2024 - 13S
IJT - CIR - February 2024 - 14S
IJT - CIR - February 2024 - 15S
IJT - CIR - February 2024 - 16S
IJT - CIR - February 2024 - 17S
IJT - CIR - February 2024 - 18S
IJT - CIR - February 2024 - 19S
IJT - CIR - February 2024 - 20S
IJT - CIR - February 2024 - 21S
IJT - CIR - February 2024 - 22S
IJT - CIR - February 2024 - 23S
IJT - CIR - February 2024 - 24S
IJT - CIR - February 2024 - 25S
IJT - CIR - February 2024 - 26S
IJT - CIR - February 2024 - 27S
IJT - CIR - February 2024 - 28S
IJT - CIR - February 2024 - 29S
IJT - CIR - February 2024 - 30S
IJT - CIR - February 2024 - 31S
IJT - CIR - February 2024 - 32S
IJT - CIR - February 2024 - 33S
IJT - CIR - February 2024 - 34S
IJT - CIR - February 2024 - 35S
IJT - CIR - February 2024 - 36S
IJT - CIR - February 2024 - 37S
IJT - CIR - February 2024 - 38S
IJT - CIR - February 2024 - 39S
IJT - CIR - February 2024 - 40S
IJT - CIR - February 2024 - 41S
IJT - CIR - February 2024 - 42S
IJT - CIR - February 2024 - 43S
IJT - CIR - February 2024 - 44S
IJT - CIR - February 2024 - 45S
IJT - CIR - February 2024 - 46S
IJT - CIR - February 2024 - 47S
IJT - CIR - February 2024 - 48S
IJT - CIR - February 2024 - 49S
IJT - CIR - February 2024 - 50S
IJT - CIR - February 2024 - 51S
IJT - CIR - February 2024 - 52S
IJT - CIR - February 2024 - 53S
IJT - CIR - February 2024 - 54S
IJT - CIR - February 2024 - 55S
IJT - CIR - February 2024 - 56S
IJT - CIR - February 2024 - 57S
IJT - CIR - February 2024 - 58S
IJT - CIR - February 2024 - 59S
IJT - CIR - February 2024 - 60S
IJT - CIR - February 2024 - 61S
IJT - CIR - February 2024 - 62S
IJT - CIR - February 2024 - 63S
IJT - CIR - February 2024 - 64S
IJT - CIR - February 2024 - 65S
IJT - CIR - February 2024 - 66S
IJT - CIR - February 2024 - 67S
IJT - CIR - February 2024 - 68S
IJT - CIR - February 2024 - 69S
IJT - CIR - February 2024 - 70S
IJT - CIR - February 2024 - 71S
IJT - CIR - February 2024 - 72S
IJT - CIR - February 2024 - 73S
IJT - CIR - February 2024 - 74S
IJT - CIR - February 2024 - 75S
IJT - CIR - February 2024 - 76S
IJT - CIR - February 2024 - 77S
IJT - CIR - February 2024 - 78S
IJT - CIR - February 2024 - 79S
IJT - CIR - February 2024 - 80S
IJT - CIR - February 2024 - 81S
IJT - CIR - February 2024 - 82S
IJT - CIR - February 2024 - 83S
IJT - CIR - February 2024 - 84S
IJT - CIR - February 2024 - 85S
IJT - CIR - February 2024 - 86S
IJT - CIR - February 2024 - 87S
IJT - CIR - February 2024 - 88S
IJT - CIR - February 2024 - 89S
IJT - CIR - February 2024 - 90S
IJT - CIR - February 2024 - 91S
IJT - CIR - February 2024 - 92S
IJT - CIR - February 2024 - 93S
IJT - CIR - February 2024 - 94S
IJT - CIR - February 2024 - 95S
IJT - CIR - February 2024 - 96S
IJT - CIR - February 2024 - 97S
IJT - CIR - February 2024 - 98S
IJT - CIR - February 2024 - 99S
IJT - CIR - February 2024 - 100S
IJT - CIR - February 2024 - 101S
IJT - CIR - February 2024 - 102S
IJT - CIR - February 2024 - 103S
IJT - CIR - February 2024 - 104S
IJT - CIR - February 2024 - 105S
IJT - CIR - February 2024 - 106S
IJT - CIR - February 2024 - 107S
IJT - CIR - February 2024 - 108S
IJT - CIR - February 2024 - 109S
IJT - CIR - February 2024 - 110S
IJT - CIR - February 2024 - 111S
IJT - CIR - February 2024 - 112S
IJT - CIR - February 2024 - 113S
IJT - CIR - February 2024 - 114S
IJT - CIR - February 2024 - 115S
IJT - CIR - February 2024 - 116S
IJT - CIR - February 2024 - 117S
IJT - CIR - February 2024 - 118S
IJT - CIR - February 2024 - Cover3
IJT - CIR - February 2024 - Cover4
https://www.nxtbookmedia.com