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Cherian et al.
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same risk profile, Adenosine was considered to be nonsensitizing
to the skin of guinea pigs. A 48-h patch test
performed using .2% Adenosine on 10 subjects yielded
negative results. Negative results were also observed in an
HRIPT performed on 205 subjects using the same test substance.
A trade name material consisting of15% mannitol and
15% Disodium Adenosine Triphosphate was used in different
aqueous dilutions in a Magnusson-Kligman maximization test
(.075% mannitol and .075% Disodium Adenosine Triphosphate
(intracutaneous induction); 1.5% mannitol, 1.5%
Disodium Adenosine Triphosphate (epicutaneous induction
and challenge)) and HRIPT (1.5% mannitol, 1.5% Disodium
Adenosine Triphosphate). No signs of sensitization were
observed in either study.
A phototoxicity and photosensitization study was performed
with a trade name mixture consisting of15% mannitol
and 15% Disodium Adenosine Triphosphate. The test substances
were applied at 10% (i.e., 1.5% mannitol, 1.5%
Disodium Adenosine Triphosphate and 2% (i.e., .3% mannitol,
.3% Disodium Adenosine Triphosphate) aqueous dilutions
in the phototoxicity and photosensitization studies,
respectively. No skin reactions were noted in either study.
Adenosine was predicted to be slightly irritating to the eyes
in a HET-CAM assay. It was considered to be non-irritating to
rabbit eyes in a different study.
The effect of inhaled Adenosine (.6 to 6.7 mg/mL) was
studied in 8 asthmatic subjects. Significant falls in SGaw from
a mean baseline of .124 ± .024 to .046 ± .008 and .066 ±
.012 s/cm/water were observed at 3 and 30 min, respectively.
Inhalation did not produce significant changes in levels of
histamine, neutrophil chemotactic factor, or cyclic adenosine
phosphate in the blood.
The effects of aerosolized Adenosine Triphosphate and
Adenosine Phosphate on dyspnea and airway caliber were
studied. The PD20 was 26.9 mg/mL and 39.6 mg/mL for
Adenosine Triphosphate and Adenosine Phosphate, respectively,
in responsive subjects. The perception of dyspnea
assessed by the Borg score increased from .1 to 3.3 and .2 to
2.5 after Adenosine Triphosphate and Adenosine Phosphate,
respectively, in patients with asthma. In a different study, 2 out
of 19 healthy patients coughed after inhalation of Adenosine
Phosphate, none reaching C5. Two out of 18 volunteers
coughed after administration ofAdenosine Triphosphate, with
15 reaching C5. Eight out of 20 chronic cough patients
coughed with Adenosine Phosphate, 2 reaching C5. Eighteen
of 19 chronic cough patients reached C5 after inhalation of
Adenosine Triphosphate.
Thirty-nine patients with various dermatoses were used in
a study evaluating histamine release from human cutaneous
mast cells following intracutaneous injection with 48/80
(1 mg/mL water), Adenosine Triphosphate (60 mg/mL
water), adenosine diphosphate (30 mg/mL water), or
Adenosine Phosphate (37 mg/mL water). In addition, 3
concentrations of histamine dihydrochloride were also injected
(1, 3, and 10 μg/mL), andusedtocompare the
responses elicited from the test substance. Injection of
Adenosine Triphosphate in the skin caused a response similar
to that of histamine, but only at high concentrations.
Adenosine Triphosphate released histamine at
concentrations >1 mg/mL, while 48/80 stimulated histamine
release in skin at concentrations >1 μg/mL.
The effect of orally ingested Adenosine Triphosphate
(400 mg/d) in resistance-trained athletes was evaluated over a 12wk
period. No significant changes in blood chemistry or hematology
were observed, and no adverse effects were reported.
Discussion
The Adenosine ingredients reviewed in this document are
naturally-occurring, ubiquitous chemicals. Because the noted,
safe use of these ingredients in therapeutics results in significantly
greater systemic exposures than could be possible
from cosmetic use, the concern for systemic toxicity is
mitigated. The Panel determined that the available human
sensitization data on Disodium Adenosine Triphosphate and
Adenosine can be used as read-across sources to mitigate any
concerns for the other ingredients lacking these data. The
safety of the ingredients included in this report was further
supported by low concentrations of use, sufficient impurities
data, negative animal oral toxicity assays, and human clinical
studies. In addition, The Panel noted the effects ofAdenosine
administered via a nebulizer in asthmatic patients and determined
that these effects would not be pertinent to cosmetic
exposure, as delivery of Adenosine via cosmetic products
would result in a much lower exposure than that ofa nebulizer.
The Panel discussed the issue of incidental inhalation
exposure from powders and hair sprays. The Council survey
results indicate that Adenosine is being used in face powders
at concentrations up to .1%. In addition, Adenosine is used in
spray moisturizing products at up to .041%, and Adenosine
Phosphate is used at up to .04% in hair sprays. The Panel noted
that in aerosol products, most droplets/particles would not be
respirable to any appreciable amount. Furthermore, droplets/
particles deposited in the nasopharyngeal or bronchial regions
ofthe respiratory tract present no toxicological concerns based
on the chemical and biological properties ofthese ingredients.
Coupled with the small actual exposure in the breathing zone
and the concentrations at which the ingredients are used, the
available information indicates that incidental inhalation
would not be a significant route ofexposure that might lead to
local respiratory or systemic effects. A detailed discussion and
summary of the Panel's approach to evaluating incidental
inhalation exposures to ingredients in cosmetic products is
available at https://www.cir-safety.org/cir-findings.
Conclusion
The Expert Panel for Cosmetic Ingredient Safety concluded that
Adenosine, Adenosine Phosphate, Adenosine Triphosphate,
Disodium Adenosine Phosphate, and Disodium Adenosine
https://www.cir-safety.org/cir-findings

IJT - CIR - February 2024

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IJT - CIR - February 2024 - Cover1
IJT - CIR - February 2024 - Cover2
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IJT - CIR - February 2024 - Contents
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IJT - CIR - February 2024 - Cover3
IJT - CIR - February 2024 - Cover4
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