IJT - CIR - February 2024 - 60S

60S
International Journal of Toxicology 43(Supplement 1)
were evaluated on weeks 0, 4, 8, and 12 to assess the chronic
effects of the test substance. Twenty-four males were randomly
assigned to receive either 400 mg/d of Adenosine
Triphosphate or maltodextrin (placebo), consumed orally via a
two-piece gelatin capsule 30 minutes prior to resistance
training sessions. On non-training days, participants were
instructed to consume one dose on an empty stomach prior to
breakfast. No statistically or clinically significant changes in
blood chemistry or hematology were observed. No adverse
effects were reported in this study.
Summary
The safety of Adenosine, Adenosine Phosphate, Adenosine
Triphosphate, Disodium Adenosine Phosphate, and Disodium
Adenosine Triphosphate as used in cosmetics is reviewed in
this safety assessment. According to the Dictionary, these
ingredients are reported to function in cosmetics as skinconditioning
agents - miscellaneous.
According to 2020 VCRP survey data, Adenosine,
Adenosine Phosphate, Adenosine Triphosphate, and Disodium
Adenosine Triphosphate are reported to be used in 905,
96, 42, and 116 formulations, respectively. The results of the
concentration ofuse survey conducted by the Council indicate
that Adenosine has the highest concentration of use; it is used
at up to 1% in body and hand products. Disodium Adenosine
Phosphate is not reported to be in use.
The penetration ability of Adenosine in different vehicles
was evaluated in human skin. The observed optimal Kpsof
Adenosine from a binary vehicle (propionic and hexanoic
acid), propionic acid solution, and hexanoic acid solution were
.004, .012, and .016 cm/min, respectively.
Wistar rats were given 10 mg/kg [14C]Adenosine Phosphate
dissolved in 9% aqueous sodium chloride via gavage.Within 72 h
ofadministration, 28% ofthe injected activity was excreted in the
urine and 6% was recovered in the feces. Eight volunteers were
given singles doses of 5000 mg Adenosine Triphosphate or
placebo via an ingested pellet targeted at release in the proximal or
distal small intestine, or via a naso-duodenal tube. Concentrations
ofuric acid were significantly increased compared to placebo after
administration via proximal-release pellets and naso-duodenal
tube, but not after administration via distal-release pellets.
No treatment-related symptoms were observed when
Wistar rats were orally given 2000 mg/kg bw Adenosine in
methylcellulose, however, pale kidneys were observed in all
females in one group given 2000 mg/kg Adenosine. In a
different study, the reported oral LD50 of Adenosine in mice
was >2000 mg/kg. The acute oral LD50 of Adenosine Triphosphate
was reported to be >2000 mg/kg in rats. No changes
in diastolic aortic pressure, heart rate, central venous pressure,
IVBF, lung resistance, or PaO2 were observed in New Zealand
White rabbits given a single dose ofup to 20 mg/kg Adenosine
Triphosphate orally. An oral LD50 of >2000 mg/kg was reported
for both mice and rats for Disodium Adenosine Triphosphate
in two different studies.
In a short-term toxicity study, New Zealand White rabbits
were given doses of either 3 mg/kg/d or 20 mg/kg/d Adenosine
Triphosphate mixed with cellulose, or 20 mg/kg/d
adenosine hemisulfate salt, for 14 d. Administrations occurred
via gastric cannula. The LVWI was significantly increased
by 10% in animals given 20 mg/kg/d Adenosine
Triphosphate. In addition, treatment with the highest dose
level led to a 12.5% decrease of the spontaneous respiratory
frequency. A26% reduction oflung resistance was noted in all
Adenosine Triphosphate -treated groups. Increases of 22 and
23% of PaO2 were observed in rabbits treated with 3 mg/kg/d
and 20 mg/kg/d Adenosine Triphosphate, respectively.
In a reproductive study, Adenosine (50, 100, and 150 mg/kg)
administered intraperitoneally in mice and rats for 5 d caused
decreased spermatogenesis and an increased number of abnormal
sperm.
Adenosine was non-genotoxic in Ames assays performed
with and without metabolic activation on S typhimurium and E
coli at up to 5000 μg/plate. Adenosine was also non-genotoxic
in a CHO/HGRPT assay at up to 2000 μg/mL, with and
without metabolic activation.
The cytotoxic effects of Adenosine in Swiss albino mouse
embryo 3T3 and 3T6 and in HeLa cells cultured with and
without adenosine deaminase were studied. Cells were exposed
to Adenosine at concentrations of0, .002, .005, .01, .02,
.20, 1.0, and 2.0 mM. When Adenosine was added to cell
cultures in a medium containing horse serum (does not contain
adenosine deaminase), it was found to be toxic at low concentrations.
Cell inhibition in calf serum was observed when
Adenosine was used at concentrations of 1.0 mM and higher.
The effect ofAdenosine on DNA synthesis and cell growth
in human HT-29, T84, HRT-18, and Colo320HSR and mouse
MCA-38 cell lines was studied. Adenosine was added with
methyl-[3H]thymidine (final concentrations, 1 μCi/mL, 1 μM).
DNA synthesis and cell proliferation were stimulated in all
cell lines tested, with an EC50 of 2.8-30 μM, and a maximum
stimulation was reached at 10-100 μM.
The effects of intradermal injections of Adenosine Phosphate
and Adenosine Triphosphate compared to intradermal
injections of histamine were evaluated. The backs of volunteers
were injected with 50 μL isosmotic phosphate buffered
saline containing Adenosine Triphosphate, Adenosine Phosphate,
histamine, compound 48/80, or saline. Adenosine
Triphosphate produced wheals in 5 out of 7 subjects injected
with 180 nmol, and in all subjects at higher doses, in a dosedependent
manner. Wheals that resulted from 1080 nmol
Adenosine Triphosphate were approximately equal to wheals
due to histamine (1.63 nmol). Injections of Adenosine Triphosphate
at high doses produced sensations ofpersistent pain
which was not observed with injection of saline or histamine.
Adenosine (10 mg) was considered to be non-irritating in
an in vitro skin irritation study performed using reconstructed
human epidermis, according to OECDTG 439. According to a
risk profile from the NFSA, Adenosine was non-irritating to
animal skin in multiple conventional tests. According to the

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