- Click here for explanation of classification scheme.

To estimate the total exposure and hazard risk of fluoride in infants and children in the US based on estimates from previous studies of various exposure pathways.

Not described.

Drew on US governmental agency data on reference dose. Drew on previous research to estimate exposure via different pathways.

Not described. 

Selection of Studies

Not described

Design

Combined estimates of exposure from prior research to develop two models of exposure: A central measure of exposure and a high measure of exposure.

Blinding used

Not applicable

Intervention

None

Statistical Analysis

No inferential statistics used. Estimates based on epidemiological exposure model used by the US Environmental Protection Agency.

Timing of Measurements

Not applicable

Dependent Variables

• Exposure to fluoride in infants (less than one year)
• Exposure to fluoride in children three to five years.

Independent Variables

• Pathway
• Fluoride concentration
• Exposure frequency
• Exposure duration (years)
• Absorption factor
• Conversion factor
• Body weight
• Average time (365 days).
   

Control Variables

• Fluoridated vs. non-fluoridated drinking (tap) water
• Age.

• Initial N: Not applicable
• Attrition (final N):
• Age:
  • Infants (less than one year)
  • Children (three to five years)
• Ethnicity: Not applicable
• Other relevant demographics: Living in fluoridated vs. non-fluoridated areas
• Location: US.

Calculating Estimated Daily Intake

First, the authors used the following formula to calculate the estimated daily intake from each separate ingestion “pathway” (that is, the manner in which children and infants are exposed to fluoride via ingestion). The following formula was used to calculate estimated daily intake (EDI):

[Concentration x Intake rate x Exposure frequency x Exposure duration x Absorption factor x Conversion factor] / [Body weight x Average time]

Absorption and conversion were assigned a value of one since fluoride is readily absorbed through the gastrointestinal tract.

Identifying Pathways

Authors calculated two levels of EDI for each pathway: Central tendency exposure (what the “average” person in the age group is [CTE]); and the Reasonable maximum exposure (an estimate of the “upper level” of possible exposure [RME]. They examined eight different pathways.

Infants (<12 months)

Pathway	Concentration (range)	Central Measure (recommended intake)	CTE Estimated Daily Intake (mg/kg per day)	Reasonable Maximum (90th percentile of recommended intake)	RME Estimated Daily Intake (mg/kg per day)
Drinking water	1mg/L (mean 1.01±0.15mg/L)	Fluoridated area: 0.34L per day Non-fluoridated area: 0	Fluoridated area: 0.04	Fluoridated area: 0.88L per day Non-fluoridated area: 0	Fluoridated area: 0.1 Non-fluoridated area:0
Soft drinks and fruit juice	0.76mg/L (0.1 to 6.7mg/L)	19 grams per day	0.0017	23.75mg per day	0.021
Infant formula	0.65mg/kg (means for different types range from 0.23mg/kg for ready-to-use formula to 1.13mg/kg for concentrate)	198ml/feeding, 4.4 feedings per day	0.067	214ml per feeding, 4.8 feedings per day	0.079
Cow's milk	0.041mg/kg (0.007-0.086mg/kg)	61 grams per day	0.0003	76.25 grams per day	0.00037
Food	0.262mg/kg (wide range depending on type of foods eaten)	223.6 grams per day	0.0052	612.7 grams per day	0.014
Incidental ingestion of soil	Not applicable	Not applicable	Not applicable	Not applicable	Not applicable
Fluoride supplements	Not applicable	Six to 12 months: 0.25mg per day NaF	0.0074	Six months to three years: 0.25mg per day NaF	0.015
Toothpaste	1,000mg/kg	Not applicable	Not applicable	Not applicable	Not applicable
Cumulative Intake			Fluoridated area: 0.11 Non-fluoridated area: 0.08		Fluoridated area: 0.20 Non-fluoridated area: 0.11

 

 

Children three to five years

 

Pathway	Concentration	Central Measure (recommended intake)	CTE Estimated Daily Intake (mg/kg per day)	Reasonable Maximum (90th percentile of recommended intake)	RME Estimated Daily Intake (mg/kg per day)
Drinking water	1mg/L (mean 1.01±0.15mg/L)	Fluoridated area: 0.4L per day Non-fluoridated area:0	Fluoridated area: 0.04 Non-fluoridated area: 0	Fluoridated area: 0.9L per day  Non-fluoridated area: 0	Fluoridated area: 0.1 Non-fluoridated area: 0
Soft drinks and fruit juice	0.76mg/L (0.1 to 6.7mg/L	269 grams per day	0.0017	336.25mg per day	0.021
Infant formula	Not applicable	Not applicable	Not applicable	Not applicable	Not applicable
Cow's milk	0.041mg/kg (0.007-0.086mg/kg)	335g per day	0.0003	418.75 grams per day	0.00037
Food	0.262mg/kg (wide range depending on type of foods eaten)	691.9 grams per day	0.0052	1,312.5 grams per day	0.014
Incidental ingestion of soil	430mg/kg (10-37,000mg/kg)	0.1 gram per day	Not applicable	0.4 grams per day	Not applicable
Fluoride supplements	Not applicable	0.5mg per day NaF	0.0074	0.5mg per day NaF	0.015
Toothpaste	1,000mg/kg	0.26g per brushing, one brushing per day	Not applicable	0.77 grams per brushing, three brushings per day	Not applicable
Cumulative Intake			Fluoridated area: 0.06 Non-fluoridated area: 0.06		Fluoridated area: 0.23 Non-fluoridated area: 0.21

                                                                                 

  Estimating Hazard

The authors then added CTE and RME exposure for all pathways for the different populations and divided this number by the “reference dose” which is the dose below which there is unlikely to be any deleterious effects (based on US Environmental Protection Agency toxicity values of 0.06mg/kg per day). This provides an index (“hazard index”) of the possible levels of exposure by population. A hazard index is higher than one means that the population is at risk for exposure above the reference dose (0.06mg per day). The reference dose is different than the “tolerable upper limit” set by the US Institutes of Medicine, which is 0.1mg per day.

Uncertainty

The authors acknowledge that the estimates are fraught with uncertainty. While the ranges for some pathways are fairly narrow (e.g., fluoridation in tap water), others tend to be highly variable (e.g., fluoride in soil or from foods). Also, as bottled water (not currently fluoridated) is used in place of tap water in some families, this can lower the cumulative estimated amount of fluoride ingested per day. Overall, the authors characterize the level of uncertainty of their estimates as “medium” at best and most likely “medium to high.”

While the central measure (CTE) of cumulative intake is within the optimum range (0.06mg per day for children, 0.08mg per day for infants) for children in both fluoridated and non-fluoridated areas and infants in non-fluoridated areas, it is estimated to be higher than optimal for infants in fluoridated areas, due in large measure to using fluoridated water for infant formula.

All children and infants in both fluoridated and non-fluoridated areas are over the optimal range when the higher measure of exposure (RME) is used. The authors say that this is due to the fluoride present in infant formula and from exposure to fluoride in toothpaste in children.

 

The research "raises questions about the continued need for fluoridation in the US municipal water supply to protect against the risk of fluorosis. However, given the uncertainties inherent in this analysis, it is not possible to be conclusive."

Other:

Not reported

Strengths

• Combined estimates from various pathways to come up with an overall exposure risk
• Provided both a central measure of exposure as well as a reasonable maximum exposure
• Identified the fact that there is a high level of uncertainty about the estimates due to wide variation in many of the parameters.

Weaknesses

• Provide no indication of how studies of particular exposure pathways were identified
• Provide no detail on the quality of the studies used to provide pathway estimates.