IJT - CIR - February 2024 - 76S

76S
International Journal of Toxicology 43(Supplement 1)
examination, complete blood cell count, and chemistry panel
were unremarkable. The authors of the report did not disclose
if patch or skin prick tests were performed.
A 45-yr-old man developed acute generalized exanthematous
pustulosis on his limbs and face 48 h after starting an
oral GBE treatment for tinnitus.64 The patient had not previously
taken any GBEs before and was not taking any other
medication. The patient had no history of adverse drug reactions
or psoriasis. The rash cleared within 10 d of stopping
the GBE treatment. The patient refused a follow-up cutaneous
patch test.
In anecdotal accounts from Chinese medicine, consumption
of fresh Ginkgo biloba nuts may cause stomach ache,
nausea, diarrhea, convulsions, weak pulse, restlessness, difficulty
breathing, and shock.2 Death has been reported in
children following consumption of fresh nuts.
Other Clinical Reports
No adverse effects were reported in a clinical study of two
cosmetic formulations containing 1.5% GBE (glycolic extract
standardized by quercetin concentrations) and other antioxidants
in 45 volunteers (no further information provided on
adverse effect testing).65 One formulation contained sunscreen
and was applied during the day, while the other formulation
was without sunscreen and was applied at night. These formulations
were applied daily for 90 d.
In another clinical study, no adverse effects were reported
in 20 volunteers following use of a cosmetic formulation
containing .30% GBE twice daily for 28 d.66 No further details
regarding the GBE used or on adverse effect testing were
provided.
Numerous studies have investigated the efficacy and safety
ofGBEs in humans in the treatment ofvarious afflictions. In a
cross-matching review ofmuch ofthis published toxicological
and clinical data on GBEs (mainly the herbal supplement EGb
761®), the authors of the review evaluated the findings of 75
clinical studies with a total of7115 patients treated orally with
GBEs and found no specific or serious undesired reactions to
GBEs.54 Any adverse events observed frequently occurred at
the same frequency as placebo treatments. Based on crossmatching
data on the historic use by humans, large intake,
toxicological and clinical studies, the authors concluded that
GBEs are well tolerated and safe.
Summary
According to the Dictionary, most of the Ginkgo biloba-derived
ingredients detailed in this safety assessment are reported
to function as skin conditioning agents, while some are
reported to function as antioxidants in cosmetics. Investigations
into the efficacy of the leaf extract for use in herbal
medicines or dietary supplements are numerous and are
mainly based on oral administration. The available toxicity
data that correspond to specific use of these ingredients in
cosmetics are extremely limited. This safety assessment focuses
on data relevant to the use of Ginkgo biloba-derived
ingredients in cosmetics, with specific attention on dermal
application when available.
According to 2018 VCRP survey data, Ginkgo Biloba Leaf
Extract has the most reported uses in cosmetic products, with a
total of 712; the majority of the uses are in leave-on eye
makeup preparations and skin care products. Two other
Ginkgo-derived ingredients, Ginkgo Biloba Leaf Powder and
Ginkgo Biloba Nut Extract, are reported to be in use, with 27
or fewer uses reported in the VCRP. However, the results of
concentration of use surveys on these 10 ingredients conducted
by the Council indicate use for only Ginkgo Biloba
Leaf Extract; in 2014, a maximum rinse-off concentration of
.25% was reported in skin cleansing products and a maximum
leave-on concentration of .24% was reported in manicuring
preparations.
GBEs are used extensively as an herbal supplement for
anti-inflammatory, cognitive-promoting, antioxidant, and
vascular effects and are approved herbal medicines in Germany
for use for treatment of memory deficits, dementia, and
other organic brain syndromes when extracted with acetone/
water. GBEs may interact with pharmaceutical drugs. Nuts
from Ginkgo biloba are consumed as a delicacy in Japan and
China and are used in traditional Chinese medicine. Anecdotal
accounts report that consumption of the nuts may have acute
adverse effects.
In general, toxicokinetics data are not expected to be found
on botanical ingredients because each botanical ingredient is a
complex mixture of hundreds of constituents. However, there
have been many pharmacokinetics studies on GBEs, specifically
on some of the key constituents, which indicate GBEs
may be well absorbed after oral administration. The GBE
constituent, quercetin, was found to penetrate human dermatomed
skin; however, quercetin was not present in the
dermis or receptor fluid ofthis dermal penetration study. In an
oral ADME study in rats, at least 60% of a radiolabeled GBE
(flavonol glycosides and proanthocyanidins) was absorbed,
with the main site of absorption likely in the upper gastrointestinal
tract. Radioactivity was measured in exhalation and
elimination products. In a human plasma study, ginkgolide A,
ginkgolide B, and bilobalide were found to be bioavailable
after single oral dosing of 3 different Ginkgo biloba leaf
preparations.
The LD50 ofa standardized GBE (EGb 761®) administered
orally to mice was reported to be 7730 mg/kg, and the LD50
after intravenous administration with this standardized GBE
was 1100 mg/kg for both rats and mice. The lethal dose for
Ginkgo Biloba Meristem Cell was greater than 2000 mg/kg in
rats and the maximum tolerated dose for this ingredient was
greater than 1000 mg/kg in dogs.
In 3-mo studies by the NTP of a specific GBE at up to
2000 mg/kg/d in corn oil, increased liver weights, decreased
kidney weights, increased incidences of hepatocytic hypertrophy
and focal hepatocytic necrosis, and increased

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