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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
other: Standard reliability rating not applicable: Non standard test (in-vitro bioaccessibility). Methodology and results are very well documented.

Data source

Reference
Reference Type:
publication
Title:
Short term serum pharmacokinetics of diammine silver fluoride after oral application
Author:
Vasquez, E. et al.
Year:
2012
Bibliographic source:
BMC Oral Health 12:60, 1 - 7

Materials and methods

Objective of study:
absorption
Principles of method if other than guideline:
This preliminary study determined the applied doses (3 teeth treated with test item), maximum serum concentrations, and time to maximum serum concentration for fluoride and silver in 6 adults over 4 hours. Fluoride was determined using the indirect diffusion method with a fluoride selective electrode, and silver was determined using inductively coupled plasma-mass spectrometry. A mean amount of 7.57 mg (6.04 μL) diammine silver fluoride solution was applied to 3 teeth of the participants.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: dissolution
Details on test material:
- Name of test material (as cited in study report): Diammine silver fluoride (DSF)(Saforide, Toyo Seiyaku Kasei Co. Ltd. Osaka, Japan)
- Molecular formula: Ag(NH3)2F
- Physical state: clear and colourless, with a weak odour of ammonia
- Composition of test material, percentage of components: The 38% solution contains 24.9 (w/v) silver (Ag), and 5.5% fluoride (F).
- Lot No.: 155060
- Specific gravity: 1.253 (25°C):

Test animals

Species:
human
Sex:
male/female
Details on test animals and environmental conditions:
Six healthy volunteers (4 females, mean age 36.2, range 23 -52 years) were recruited from staff members of the Universidad Católica de Santa María, Arequipa, Peru. Each had gingival recession exposing non-carious cementum. Participant were taking no medications and had most permanent teeth present.

Administration / exposure

Route of administration:
other: Three maxillary teeth (cuspid and premolars) in the same quadrant were treated with diammine silver fluoride.
Duration and frequency of treatment / exposure:
one application followed by a 4 hour observation period
Doses / concentrations
Remarks:
Doses / Concentrations:
The mean amount of DSF solution applied to the 3 teeth was 7.57 mg (6.04 µL).

Results and discussion

Main ADME results
Type:
absorption
Results:
Over the 4 hour observation period, the mean maximum serum concentrations were 1.86 µmol/L for fluoride and 206 nmol/L for silver. These maximums were reached 3.0 hours and 2.5 hours for fluoride and silver, resectively.

Applicant's summary and conclusion

Conclusions:
Over the 4 hour observation period, the mean maximum serum concentrations were 1.86 µmol/L for fluoride and 206 nmol/L for silver. These maximums were reached after 3.0 hours and 2.5 hours for fluoride and silver, resectively.
According to the authors, this preliminary study suggests that serum concentrations of fluoride and silver after topical application of DSF should pose little toxicity risk when used in adults.