IJT - CIR - February 2024 - 77S

Burnett et al.
77S
incidences hyaline droplet accumulation, atrophy and pigment
accumulation in macrophages in the olfactory epithelium were
observed in mice. In a similar NTP study ofthe same GBE test
material in rats, increased liver weights, increased incidences
of hepatocyte hypertrophy, increased incidences of thyroid
gland follicular cell hypertrophy, and increased incidences of
pigmentation in the olfactory epithelium of the nose were
observed. There was no evidence of organ damage or impairment
ofhepatic or renal function when a GBE (EGb 761®)
was administered orally over 27 wk to rats and mice at doses
ranging from 100 to 1600 mg/kg. In a 4-wk oral repeated dose
study, no adverse effects were observed in rats that received up
to 2000 mg/kg Ginkgo Biloba Meristem Cell. In the follow-up
13-wk oral study, the NOAEL in rats for Ginkgo Biloba
Meristem Cell was greater than 1000 mg/kg.
In an oral DART study in which mated female mice received
standardized GBE (EGb 761®) on gestation days 6
through 15, the NOEL for dams and fetuses was greater than
1225 mg/kg/d. No maternal toxicity and no embryotoxic
effects were observed. Another oral DART study investigated
the effects of standardized GBE (EGb 761®) in female mice
that received the test material during a 28-d period before
mating, on gestation days 1 through 7, or on gestation days 10
through 18. The standardized GBE produced adverse effects at
14.8 mg/kg/d, including effects on the estrous cycle, fertility,
reproductive performance, and hormone levels. The standardized
GBE may also cause adverse effects on ovarian
function as an antifertility agent. In an embryo-fetal development
study, no adverse effects were observed in maternal or
embryonic rats following dosing ofan aqueous GBE similar to
EGb 761® on gestation days 1 through 14, with doses up to
14 mg/kg/d.
The authors of a comparative review and analysis of
published and unpublished data of the GBE herbal supplement
EGb761® concluded that the positive findings in some
in vitro genotoxicity tests are linked to cytotoxic effects of
Ginkgo biloba extract and the use of very high test concentrations,
as compared to therapeutic use concentrations.
The GBE specifictoNTP studieswas mutagenicinanAmes
test at up to 10,000 μg/plate, and the same GBE (.2-1.2 mg/
ml) was mutagenic in mouse L5178Y cells. In a mouse
micronucleus test of the GBE used by the NTP at up to
2000 mg/kg/d, no increase in the frequency of micronucleated
erythrocytes was observed in male mice, but the
results were deemed equivocal in female mice. The same
GBE at up to 2000 mg/kg/d was not genotoxic in a reporter
gene mutation assay, a combined liver comet assay, or bone
marrow micronucleus assay in mice. Ginkgo Biloba Meristem
Cell wasnot mutagenicinanAmestestatupto
5000 μg/plate, nor did it induce chromosomal aberrations in
Chinese hamster lung cultured cells, with or without metabolic
activation. Ginkgo Biloba Meristem Cell did not increase
the frequency of micronucleated erythrocytes in male
mice at up to 2000 mg/kg/d.
In oral carcinogenicity studies of rats and mice conducted
by the NTP, lesions in the liver, thyroid gland and nose were
observed in all GBE dose groups (200-2000 mg/kg/d in corn
oil, by gavage). 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 ulcer were also observed in the forestomach
of male and female mice. Additionally, increased incidences
ofcancers ofthe thyroid gland were observed in male
and female rats and male mice, as were liver cancers in male
and female mice. 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) for up to 85 wk, no neoplastic or
pre-neoplastic effects were observed. IARC has determined
that GBEs are possibly carcinogenic to humans (group 2B)
based on data that included the NTP studies.
In a PLNA validation study, a GBE exposure yielded
statistically significant lymphoproliferative reactions in the
ipsilateral popliteal lymph node, which may have been caused
by ginkgolic acid.
No irritation was observed in a 24-h human patch test of
Ginkgo Biloba Leaf Extract (100%; ethanol:water:butylene
glycol extract).
In a guinea pig study, sensitization was observed to
ginkgolic acid at concentrations of .1% and 1%, but no
sensitization was observed to a GBE that contained ∼1000
ppm (∼.1%) ginkgolic acid. No dermal sensitization was
reported in HRIPTs of products containing up to .2% Ginkgo
Biloba Leaf Extract.
Guinea pig sensitization studies of crude Ginkgo biloba
fruit extract, the main aromatic components of the fruit, and
urushiol found no cross-reactions among the compounds. It
was also determined that ginkgolic acid was the main allergen
in Ginkgo biloba.
The results ofa phototoxicity and photosensitization study
on a lip product containing .0072% Ginkgo Biloba Leaf
Extract were negative.
An in vitro assay using an eye product containing .013%
Ginkgo Biloba Leaf Extract predicted no ocular irritation.
Reports ofcontact dermatitis have been reported following
exposure to the fruit pulp of Ginkgo biloba. Patients have
reported erythematous reactions and generalized exanthematous
pustulosis following ingestion of certain GBE supplements.
No adverse effects were reported in clinical studies of
cosmetic formulations containing up to 1.5% GBEs (glycolic
extract standardized by quercetin concentrations). In anecdotal
accounts from Chinese medicine, consumption of fresh
Ginkgo biloba nuts may cause stomachache, nausea, diarrhea,
convulsions, weak pulse, restlessness, difficulty breathing,
and shock. Death has been reported in children following
consumption of fresh nuts. A cross-matching review of
multiple clinical studies found no specific or serious undesired
reactions to GBEs (mainly EGb 761®).

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