IJT - CIR - February 2024 - 70S

70S
International Journal of Toxicology 43(Supplement 1)
Dermal Penetration
The ability of the GBE constituent, quercetin, to penetrate the
skin while in a cosmetic formulation was studied in vitro with
human dermatomed skin.44 The cosmetic formulation used in
the study was an emulsion containing trilaureth-4 phosphate,
ammonium acryloyldimethyltaurate/VP copolymer and
emollients, sclerotium gum, humectants, preservatives, and
water that was prepared and supplemented with 6.0% (w/w)
tritiated Ginkgo biloba glycolic leafextract. An analysis ofthe
GBE used in this study showed it contained .12% quercetin.
The test formulation (10 mg/cm2) was applied to the skin
samples (n = 6) that were mounted on Franz diffusion cells
for 24 h. Samples of the receptor fluid (citrate buffer with
.5% polysorbate 20; pH 5.5) were taken after 6 h and 24 h
exposures and quantified with high performance liquid
chromatography (HPLC). The skin cells were washed at the
end of the exposure time and the stratum corneum was
removed by tape stripping. The stratum corneum and viable
epidermis contained .17 +.002 μg/cm2 (24% of the applied
dose) and .23 +.04 μg/cm2 (33% of the applied dose)
quercetin, respectively. Quercetin in the dermis and the
receptor fluid was below limits of quantification or below
limits of detection. Approximately 40% quercetin was
measured in the washing solution. The total recovery of
quercetin was approximately 97%.
Absorption, Distribution, Metabolism, and
Excretion (ADME)
Animal. The absorption, distribution, and elimination of a
radiolabeled GBE were studied in male and female SpragueDawley
rats.9,45 The rats received a single oral suspended dose
(20 μCi; 380 mg/kg) of a radiolabeled GBE. The test material
was obtained from Ginkgo biloba grown under a supply of
[14C]acetate. Analysis showed that the flavonol glycosides
and proanthocyanidins bore the radiolabel; no radioactivity
was detected in the terpenes or the main sugars after the
hydrolysis of glycosides. The pharmacokinetic results, based
on blood specific activity data versus time course, were
characteristic of a two-compartment model with an apparent
first order phase and a half-life of approximately 4.5 h. Expired
[14C]CO2 represented 16% of the administered dose 3 h
post-treatment. After 72 h, 38% of the radioactivity was
excreted via exhalation, while 21% was determined to be
excreted in the urine and 29% was excreted in the feces. The
researchers of this study concluded that at least 60% of the
radiolabeled GBE was absorbed. The site of absorption was
likely the upper gastrointestinal tract.
Human. The bioavailability and pharmacokinetics of Ginkgo
biloba L. in human plasma were investigated using 3 different
preparations.46 The preparations were a tincture of fresh
Ginkgo biloba leaves (extracted with 65% v/v ethanol; 1 mL
contains 920 mg Ginkgo biloba leaves as active ingredient),
Ginkgo biloba fresh plant extract tablets (extracted with 67%
v/v ethanol; one 250 mg tablet contains 90 mg fresh plant
extract), and Ginkgo biloba extract EGb 761® tablets
(extracted with 60% m/m acetone; one tablet contains 40 mg
purified dried extract). The study was performed on 24 healthy
volunteers (6 males and 18 females): each volunteer received a
single oral dose of the maximum registered daily dosage of
either the tincture (90 drops or 2.73 mL), the fresh plant extract
(4 tablets), or EGb 761® (3 tablets) with 100 mL water. Prior to
dosing, each preparation was analyzed for concentrations of
bilobalide (646.93 μg, 1974.96 μg, and 3672.39 μg for the
tincture, fresh plant extract, and EGb 761®, respectively),
ginkgolide A (298.14 μg, 881.52 μg, and 1571.37 μg for the
tincture, fresh plant extract, and EGb 761®, respectively), and
ginkgolide B (147.45 μg, 524.56 μg, and 836.46 μg for the
tincture, fresh plant extract, and EGb 761®, respectively) prior
to the plasma study with liquid chromatography-mass spectrometry
(LC-MS).
Blood samples (36 mL) were taken 30 min prior to administration
and 15, 30, 45, 60, and 360 min after administration.
The samples were centrifuged to separate the plasma
and plasma was analyzed by LC-MS. The resulting maximum
concentrations (median) of bilobalide, ginkgolide A and
ginkgolide B in plasma after administration of the maximum
daily dose of the different Ginkgo biloba products were as
follows: 3.53, 3.62, and 1.38 ng/ml, respectively, after administration
of the tincture; 11.68, 7.36, and 4.18 ng/ml, respectively,
after administration of the fresh plant extract
tablets; and 26.85, 16.44, 9.99 ng/ml, respectively, after administration
of EGb 761® tablets. The authors of study
concluded that ginkgolide A and B and bilobalide are bioavailable
after oral dosing of 3 different Ginkgo biloba
preparations.46
Toxicological Studies
Acute Toxicity Studies
Oral
Ginkgo Biloba LeafExtract. The LD50 ofa standardized GBE
(EGb 761®) administered orally to mice was reported to be
7730 mg/kg.47
Ginkgo Biloba Meristem Cell. In a toxicity test to determine
lethal dose, a single oral dose of 0 or 2000 mg/kg Ginkgo
Biloba Meristem Cell was administered to 5 male and female
Sprague-Dawley rats in each group (written as provided, no
further details).48 After a 14-d observation period, the animals
were killed and underwent necropsy. No unscheduled deaths
or treatment-related effects were observed during the observation
period or at necropsy. The lethal dose for Ginkgo
Biloba Meristem Cell was greater than 2000 mg/kg in this rat
study.
In a single dose oral volume increase toxicity test, 2 male
and female Beagle dogs (written as provided, no further

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