IJT - CIR - February 2024 - 56S

56S
International Journal of Toxicology 43(Supplement 1)
an ingested pellet targeted at release in the proximal or distal
small intestine, or via a naso-duodenal tube.30 BloodAdenosine
Triphosphate and metabolite concentrations were monitored by
high performance liquid chromatography (HPLC) 4.5 h (nasoduodenal
tube) or 7 h (pellets) post-administration. Adenosine
Triphosphate concentrations in the blood did not increase after
supplementation ofAdenosine Triphosphate via pellets or nasoduodenal
tube. Concentrations of uric acid were significantly
increased compared to placebo by approximately 50% after
administration via proximal-release pellets and naso-duodenal
tube, but not after administration via distal-release pellets. The
mean time to peak uric acid concentration was shorter for nasoduodenal
tube administration (75 to 195 min) as compared to
the pellet administration (150-390 min).
Toxicological Studies
Acute Toxicity Studies
Oral
Adenosine. An LD50 of >2000 mg/kg bw was established
for mice given Adenosine orally.33 No other details regarding
this study were provided.
An acute oral toxicity study on Adenosine was performed on
female Wistar rats (3 rats/group) according to Organization for
Economic Cooperation and Development (OECD) Test
Guideline (TG) 423.2 In both groups, the test substance
(Adenosine in methylcellulose) was given at a dose of2000 mg/
kg bw. Animals were observed for 14 d following treatment and
killed on day 15. All rats survived treatment and no treatmentrelated
clinical symptoms were observed. Necropsy revealed
pale kidneys in two animals ofgroup 1 and all animals ofgroup
2. The LD50 was reported to be >2000 mg/kg bw.
Adenosine Triphosphate. The oral LD50 of Adenosine Triphosphate
was reported to be >2000 mg/kg in rats.34 No other
details regarding this study were provided. In a different study,
groups of 5 male anesthetized New Zealand White rabbits
were given 2 or 20 mg/kg Adenosine Triphosphate via a
gastric cannula.35 The test substance did not have an effect on
diastolic aortic pressure, heart rate, central venous pressure,
iliac venous blood flow, lung resistance, or the arterial partial
pressure of oxygen (PaO2).
Disodium Adenosine Triphosphate. An oral LD50
of >2000 mg/kg was reported for both mice and rats treated
with Disodium Adenosine Triphosphate.36 No other details
regarding these studies were provided.
Short-Term Toxicity Studies
Oral
Adenosine and Adenosine Triphosphate. New Zealand White
rabbits were given doses ofeither 3 mg/kg/d (n = 4) or 20 mg/
kg/d (n = 12) Adenosine Triphosphate mixed with cellulose, or
Developmental and Reproductive
Toxicity Studies
Intraperitoneal
Adenosine. Adenosine (50, 100, and 150 mg/kg) was administered
intraperitoneally to mice and rats once a day for
5d.33 Decreased spermatogenesis and increased numbers of
abnormal sperm were noted. No other details regarding this
study were provided.
Genotoxicity
In Vitro
Adenosine. The potential mutagenicity of Adenosine (up to
333 μg/plate, vehicle not stated), was evaluated in Salmonella
typhimurium (TA98, TA100) in an Ames assay performed
without metabolic activation.37 The test material was considered
to be non-genotoxic. Similarly, negative results were obtained in
an Ames assay performed with and without metabolic activation
on Adenosine in dimethyl sulfoxide (DMSO; up to 5000 μg/
plate) using S typhimurium (TA97, TA98, TA100, TA1535,
TA1537, TA1538) and Escherichia coli (WP2 uvrA).2
The genotoxicity of Adenosine was also evaluated in a
Chinese hamster ovary cell/hypoxanthine-guanine
phosphoribosyl-transferase (CHO/HGPRT) assay.38 Adenosine
in DMSO was not genotoxic when tested at up to
2000 μg/mL, with and without metabolic activation.
Carcinogenicity Studies
No data regarding the carcinogenicity of these ingredients
were found in the published literature, and unpublished data
were not submitted.
20 mg/kg/d adenosine hemisulfate salt (n = 4) for 14 d.35
Adenosine Triphosphate and adenosine hemisulfate, dissolved
in saline, were administered daily via gastric cannula. Control
rabbits received a corresponding amount of saline. No
modification of electrocardiogram morphology or heart rate
was detected in treated animals compared to controls. Central
venous and arterial pressures were comparable in all groups.
After treatment with 3 and 20 mg/kg/d, increases of 30 and
50% in the intervillous vein blood flow (IVBF) were observed,
respectively. The left ventricular work index (LVWI) was
significantly increased by 10% in animals given 20 mg/kg/d
Adenosine Triphosphate. In addition, treatment with the
higher dose level led to a 12.5% decrease of the spontaneous
respiratory frequency. A 26% 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.
Similar results were noticed in rabbits treated with
adenosine hemisulfate; however, lung resistance and PaO2
levels remained unchanged.

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