STAKEHOLDER PANEL ON INFANT FORMULA
& ADULT NUTRITIONALS (SPIFAN)
Standard Method Performance
Requirement Approval (SMPR)
FLUORIDE
Christopher Blake, Nestlé
Gaithersburg, Maryland, USA
March 18, 2014
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1
Element
CAS Number
Atomic Mass
(Number)
Classification
group
Year of
Discovery
Ist IP (EV)
Fluoride (F)
16984-48-8
18.9984 (9)
Halogen
1886
17.4 EV
Fluorine (F)
has 18
known
isotopes
from 14F to
31F
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Only one stable isotope: 19F
18F
is the longest-lived radioisotope, with a half-life of 110 minutes.
All other isotopes have very short half-lives: s or ms.
The least stable isotope is 15F, whose half-life is 4.1 x 10−22 seconds
Only 14F has an unknown half-life.
2
•
•
•
•
•
•
•
1529, The word "fluorine" derives from the Latin stem of the main source mineral,
fluorite, first mentioned by Georgius Agricola, the "father of mineralogy".
1700s, hydrofluoric acid was discovered.
1810, André-Marie Ampère suggested that hydrofluoric acid was a compound of
hydrogen with an unknown element, analogous to chlorine.
Several 19th century experimenters, the "fluorine martyrs", were killed or blinded,
trying to isolate fluorine.
1886, the French chemist Henri Moissan, isolated elemental fluorine.
1906, two months before his death, Moissan received the Nobel Prize in chemistry.
2012, first source of naturally occurring fluorine gas was found in fluorite mines in
Bavaria, Germany
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3
•
In the 19th century, research on fluoride and its occurrence in teeth and bones
began.
•
The total fluoride content of the human body is 2-5 g, and depends on age and
exposure to fluoride. The skeleton of a newborn contains only about 5-50 mg of
fluoride.
•
1916, first evidence of brown mottling of teeth was reported in the USA, and was
eventually found to be caused by fluorides in water.
•
1945, the idea gained ground that if infants ingested fluoride during the formative
years, the tooth would develop ‘stronger,’ with a more cavity-resistant enamel.
•
Over the past 50 years, much controversy has occurred around the use of fluoridated
drinking water related to health and safety.
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•
The American Dental Association recommends that infant formula should be
prepared with unfluoridated water.
•
In many European countries fluoridated salt (200-250 mg fluoride/kg of salt), is used in
place of fluoridated water.
•
Fluoride has no known essential function in human growth and development and
no signs of fluoride deficiency have been identified (EFSA, 2013).
•
Further reading:
European Food Safety Authority (EFSA), Parma, Italy, published «Scientific Opinion
on Dietary Reference Values for fluoride. EFSA Journal 2013;11(8):3332.
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Element
Sources
Benefits
Fluoride (F)
Fluoridated water,
fluoridated salt, tooth
paste, tea . Some fish
and shrimp.
Prevention of dental
caries, bone
formation.
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Risks
No signs of fluoride deficiency
have been identified in
humans. Overdose (fluorosis)
may lead to mottled teeth
(see pictures below).
6
Severe enamel fluorosis involves brownish defects to the tooth enamel
which may also be pitted.
Normal dental enamel
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Moderate white
streaks
Severe mottling of
teeth
7
Life stage
Age
F (mg/day)
Infants
0‐6 months
0.01
Infants
7‐12 months
0.5
Children
1‐3 years
0.7
Children
4‐8 years
1.0
Children
9‐13 years
2.0
Children
14‐18 years
3.0
Adolescents – Adults (M)
Adolescents – Adults (F)
19‐50 years
4.0
3.0
Adults (M)
Adults (F)
51-70 years
4.0
3.0
Pregnancy
14 - 50 years
3.0
Mothers Breast Feeding
14 -50 years
3.0
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Legislation
Infant formula
Codex Alimentarius
Commission
FAO/WHO (2007).
Codex Standard 721981 Revised section A
Follow-on formula
Formulae for special
medical purposes
FAO/WHO (1987)
Codex Standard 156
FAO/WHO (2007). Codex
Standard 72-1981
Revised section B
Not applicable
FDA. Infant Formula Act.
21 CFR 107
EU (2013) Council
directive 609/2013
/EC
EU (2013) Council
directive 609/2013 /EC
USA
FDA. Infant Formula
Act. 21 CFR 107
EU
EU (2006) Commission
directive 2006/141/EC
Australia and New
Zealand
Food Standards Australia and New Zealand Standard 2.9.1a
China
GB 10765-2010 (Infant formula and Follow-on Formula)
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Regulating body
Units
Australia/New Zealand
Minimum
Maximum
See next slide
China
-
-
-
Codex Standard 72- 1981
µg/100 kcal
(rtf)
-
100 *
EU: 2006/141/EC (infant formula)
µg/100 kcal
(rtf)
-
100
EU: 609/2013/EC (medical foods)
-
-
-**
-
-
USA, FDA CFR 21 Part 107
* Codex states that fluoride must not be added to infant formula
** 609/2013/EU permits NaF and KF to be added to medical foods
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Statement on dental fluorosis
(1) An infant formula product must comply with subclause (2) where it contains –
–
(a) more than 17 μg of fluoride per 100 kJ prior to reconstitution, in the case of
– powdered or concentrated infant formula product; or
– (b) more than 0.15 mg of fluoride per 100 mL, in the case of ‘ready to drink’ formula.
(2) The label on a package of infant formula product referred to in subclause (1) must
contain statements –
–
(a) indicating that consumption of the formula has the potential to cause dental
– fluorosis; and
– (b) recommending that the risk of dental fluorosis should be discussed with a medical
practitioner or other health professional.
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References 1-5 are
listed in slide 18
Country
Infant
formula, Avg
(mg/kg)
Infant formula,
Avg
RTF (µg/100g)
Soya products
Range
(mg/kg)
Soya products
Range
RTF (µg/100g)
Australia 1
0.49
6.1
1.08 - 2.80
13.5 – 35.0
Canada 2
0.23
2.9
1.73
21.6
Poland 4
0.29
3.6
Japan 5
0.41
5.1
USA 1
0.9*
11.2
Iran
3
Cows milk: 0.7- 35 µg/100mL of F (various studies)
Breast milk: 0.4 – 2 µg/100ml of F (various studies)
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– Micro-diffusion
– Simple extractions: precipitation of milk proteins with citrate,
trichloroacetic acid, amido black, etc..
– Distillation
– Dry ashing with calcium hydroxide as fixative
– Oxygen ashing (Schöniger combustion flask)
– Headspace single-drop micro-extraction
– Microwave digestion
Procedures are available for measuring total and free forms of fluoride in
milk.
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• Fluoride Ion selective electrode (most common)
• Colorimetry
• Tiration against thorium nitrate
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• Graphite furnace - AAS
• High Resolution - Continuum Source-ETAAS
• Ion chromatography, conductivity detection or postcolumn reaction with UV/VIS detector
• Headspace Gas Chromatography
• Polarography
14
AOAC
– AOAC 961.16 Microchemical determination of fluorine
– AOAC 944.08 Fluorine in food.
These methods are not suitable for determining low levels of fluoride in
infant formula and adult nutritional products.
– Dabeka, R. W., McKenzie, A. D. J. AOAC., 64, (4): 1021-1026,1981.
Microdiffusion and fluoride-specific electrode determination of fluoride in infant foods:
collaborative study. Results from collaborative study were not accepted by AOAC.
Method not published .
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German Official Method
Amtliche Sammlung von Untersuchungsverfahren, nach Paragraph 35 LMBG.
(L 49.00-7): 2pp., 2000
Analysis of foods. Determination of fluoride in dietetic foods with an ion-sensitive
electrode.
-
This official German method was only validated on two dietetic products.
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• The method should be able to determine accurately and precisely fluoride in
infant formula and adult nutritionals, in the range from 0.1 to 130 µg/100 g
(RTF)
• Matrix Scope: Formulas made from any combination of milk, soy, rice,
hydrolyzed proteins and amino acids
• Targeted LOQ of the Method = 0.1 µg/100 g RTF
• Method accuracy should be verifiable
• The method must be robust enough to be used by different laboratories
world wide.
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• Method Name: Determination of Fluoride in Infant and Adult/Pediatric
Nutritional Formula
• Approved by: Stakeholder panel Infant Formula and Adult Nutritionals
• Final version date:
• Effective date:
• Intended Use: Reference method for dispute resolution.
• Applicability: Determination of chloride in all forms of infant, adult, and/or
pediatric formula (powders, ready‐to‐feed liquids, and liquid concentrates).
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Analytical Range
Limit of Quantification (LOQ)
0.1 - 130*
≤ 0.1*
Accuracy
± 5%
Repeatability (RSDr)
≤ 7%
Reproducibility (RSDR)
≤ 10%
Target Measurement Uncertainty
≤ 13.5%
Concentrations apply to: a) ‘ready-to-feed” liquids “as is”; b) re-constituted powders
(25 g into 200 g of water); and c) liquid concentrates diluted 1:1 by weight.
* µg /100 g reconstituted final product.
System suitability tests and/or analytical quality control
Reference Material(s): ?
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QUESTIONS??
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References:
1. Clifford H., Olszowy H. , Young M.,
Hegarty, J. Cross, M. “Fluoride content of
powdered infant formula meets Australian Food Safety Standards”. Australian & New
Zealand J. Public Health. 33(6):573-6, 2009.
2. Dabeka, R. W., McKenzie, A. D. «Lead, cadmium, and fluoride levels in market milk
and infant formulas in Canada”. JAOAC 70, (4): 754-757, 1987.
3. Mahvi, A. H., Ghanbarian, M., Ghanbarian, M., Khosravi, A., Ghanbarian, M.
“Determination of fluoride concentration in powdered milk in Iran 2010”. British J. of
Nutr. 107, (7): 1077-1079, 2012.
4. Opydo-Szymaczek, J.,“Dietary fluoride intake from infant and toddler formulas in
Poland”. J. Fd. Chem. Toxicol. 49, (8): 1759-1763, 2011.
5. Nohno, K., Zohoori, F. V., Maguire, A. “ Fluoride intake of Japanese infants from
infant milk formula”. Caries Research. 45, (5): 486-493, 2011
6. Dabeka, R. W., McKenzie, A. D. “ Lead, cadmium, and fluoride levels in market milk
and infant formulas in Canada”. JAOAC, 70, (4): 754-757, 1987.
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