Fluoride and Children’s IQ Decrements: Risk Assessment for Reference Dose and Health-­‐Based Safe Drinking Water Level. Estimation of RfD (Reference Dose) and RfC (Reference Concentration), LOAEL, NOAEL, BMD, Benchmark Dose, from human epidemiological studies of fluoride and IQ. A large and statistically significant adverse association was found between fluoride exposure and IQ.

1. Fluoride
and
Children’s
I.Q.
Decrements
Risk
Assessment
for
Reference
Dose
and
Health-­‐Based
Safe
Drinking
Water
Level
Presented
by
J.
William
Hirzy,
Ph.D.
Summary
of
a
paper
submiJed
to
a
peer-­‐reviewed
journal
for
publicaMon

2. Some
DefiniMons:
• RfC
Reference
ConcentraMon.
The
concentraMon
in
water
of
a
contaminant
that
can
be
ingested
for
life
with
virtually
no
adverse
effect.
• RfD
Reference
Dose.
The
dose,
e.g.
milligrams
per
day,
that
can
be
ingested
for
life
with
virtually
no
adverse
effect

3. More
DefiniMons
• LOAEL
Lowest
Observed
Adverse
Effect
Level.
The
lowest
dose
that
results
in
an
observed
adverse
effect.
• NOAEL
No
Observed
Adverse
Effect
Level.
The
dose
below
which
no
adverse
effect
is
observed.

4. More
DefiniMons
• BMD
Benchmark
Dose.
The
dose
of
a
toxicant
that
causes
a
“benchmark”
response
(BMR)
level
of
adverse
effect.
We
use
a
BMR
of
loss
of
1
IQ
point.
• BMCL
Lower
95%
Confidence
Limit
on
the
concentraMon
of
a
toxicant
that
causes
the
BMR.

5. SMll
More
DefiniMons
• UF
Uncertainty
Factor.
A
factor
of
1
-­‐
10
used
to
account
for
uncertainMes
in
esMmaMng
an
RfD.
E.g.,
to
convert
a
LOAEL
to
a
NOAEL,
or
account
for
intra-­‐human
geneMc
diversity.
• MF
Modifing
Factor.
A
factor
of
1
-­‐
10
to
account
for,
e.g.
severity
of
an
adverse
effect.

6. Excerpt
from
Am.
Dental
Assoc.
LeJer
to
Congress
sent
Sept.
4,
2014
What
the
following
risk
assessment,
using
standard
EPA
methodology,
shows
is
a
refutaMon
of
the
libelous
ADA
leJer.
We
stand
ready,
indeed
we
are
eager,
to
confront
these
and
other
libels
from
ADA
and
its
supporters
before
a
Joint
Congressional
CommiJee
hearing,
where
all
parMes
must
give
sworn
tesMmony
subject
to
penalMes
for
perjury.

7. Primary
Drinking
Water
Standards
• Under
the
Safe
Drinking
Water
Act
(SDWA
2002)
the
enforceable
primary
standard,
Maximum
Contaminant
Level
(MCL)
is
set
as
close
as
technically
and
economically
feasible
to
the
non-­‐
enforceable,
health
based
standard,
Maximum
Contaminant
Level
Goal
(MCLG).
• The
MCLG
must
protect
the
enMre
populaMon
against
any
known
or
anMcipated
adverse
effect
on
health,
with
an
adequate
margin
of
safety.
Thus
the
MCLG
cannot
allow
any
more
than
the
RfD
to
be
ingested.

8. IQ
Loss
Risk
Assessment
• Our
assessment
is
based
primarily
on
the
work
of
Choi
et
al.
(2012)
–
a
meta-­‐analysis
showing
26
of
27
studies
of
fluoride
exposure
on
children’s
IQ
showed
loss
of
IQ
at
higher
vs
lower
exposures……
• along
with
the
work
of
Xiang
et
al.
(2003a,
2003b,
2013),
which
was
included
as
part
of
the
Choi
et
al.
2012
publicaMon.

9. Basis
for
our
Assessment
• We
assumed
that
there
is
probably
a
fluoride
exposure
Level
below
which
the
Adverse
Effect
of
IQ
decrease
is
Not
Observed,
called
NOAEL.
• We
used
two
sets
of
fluoride
exposures
that
caused
loss
of
IQ,
viz.,
3
ppm
from
the
Choi
et
al.
study,
called
LOAEL.
And
the
data
set
from
Xiang
et
al.
2003a.

10. Findings
•
Safe*
levels
of
fluoride
in
drinking
water
(MCLG):
• From
Choi
et
al.
data:
0.018a
ppm
• From
Xiang
et
al.
data
0.013bppm
• Current
EPA
standard
4
ppm
• Likely
new
EPA
standard
~
2
ppm
• a
Using
LOAEL/NOAEL
=
uncertainty
factors
• b
Benchmark
Dose
Method
• *
Levels
before
accounMng
for
other
fluoride
exposure
• ppm
=
milligrams/Liter,
mg/L

12. Work
of
Xiang
et
al.
2003a,b,
2013
• Children
in
villages
of
Wamiao
(hi
F-­‐)
and
Xinhuai
(lo
F-­‐)
were
studied
• IQs,
arsenic
and
fluoride
in
drinking
water,
blood-­‐lead
levels,
and
urinary
iodine
were
measured.
No
staMsMcally
significant
differences
in
As,
Pb,
I
levels
between
groups.

13. Graphical
presentaMon
of
these
data
follow
on
the
next
two
slides

14. y
=
-­‐5.5685x
+
104.61
75
80
85
90
95
100
105
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
IQ,
m
ean
Water
F,
mean
(mg/L)
IQ
vs
Water
F
(for
"high
F"
village
Waimao,
grouped
by
water
F
category)
Impact
Significant
for
Individual
Children

15. y
=
10.1x
-­‐
8.088
0
10
20
30
40
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
IQ<80
(
%)
Water
F,
mean
(mg/L)
Figure
2
Percent
IQ<80
vs
Water
F
(for
"high
F"
village
Waimao,
grouped
by
water
F
category)
Impact
Significant
at
the
NaMonal
Level

16. Impact
of
5
Point
Loss
of
IQ
Throughout
a
PopulaMon
of
260,000,000

17. Benchmark
Dose
Modeling
of
Xiang
2003a
Data
–
EPA
BMD
Sorware
Lower
Confidence
Level
on
Benchmark
ConcentraMon
(BMCL
)for
Loss
of
1
IQ
Point:
0.22
mg/L

18. RfC/RfD
CalculaMon
from
BMD
Modeling
• 0.22
mg/L
x
0.60
L/day
(H2O
intake*)
=
0.13
mg/day
•
• RfD
=
BMDL**
÷
[(UF)x(MF)]
•
• RfD
=
0.13
mg/day
÷
[10
x
1]
=
0.013
mg/day
•
• We
use
UH
human
variability
factor
of
10,
and
MF
of
1
to
account
for
severity
of
effect
(EPA
1998)
*For
Choi
et
al.
children:
1.5
x
mean
H2O
intake
of
U.S.
Children
(EPA
2010)
**
From
the
95%
Lower
Confidence
Limit,
BMCL,
of
0.22
mg/L

19. MCLG
CalculaMon
MCLG
=
0.013
mg/day
÷
1.04
L/day*
=
0.013
mg/L
*
95th
percenMle
U.S.
children
water
intake
(Table
5-­‐3
EPA
2010)
• Human
breast
milk
fluoride
level
ca.
0.004
mg/L
(Ekstrand
1981)

20. LOAEL/NOAEL
CalculaMons
Summary
• We
calculated
a
daily
dose
that
caused
the
IQ
loss,
then
applied
standard
uncertainty
factors
(EPA
2002)
to
reach
a
dose
that
should
not
cause
that
effect.
3.0
mg/L
x
0.60
L/day
=
1.8
mg/day
• 1.8
mg/day÷
10
(UL)
x
10
(UH)
=
0.018
mg/day
• That
is
the
reference
dose,
RfD
• We
used
the
95
percenMle
of
U.S.
childrens
H2O
intake
(Table
5-­‐3
EPA
2010)
to
reach
a
Maximum
Contaminant
Level
Goal.
• 0.018
mg/day
÷
1.04
L/day
=
0.017
mg/L
UL
converts
LOAEL
to
NOAEL;
UH
accounts
for
intra-­‐human
variability

21. UL
to
convert
LOAEL
to
NOAEL
UH
Intra-­‐human
variability
Summary
of
Results
From
LOAEL/NOAEL
+
Uncertainty
Factors
and
BMD
Methods
The
MCLG
(SDWA
2002)
shown
above
has
not
taken
into
account
other
fluoride
exposures,
and
these
exposures
exceed
the
RfD’s
shown
in
Table
3
on
which
the
MCLGs
are
based.
See
next
slide.

22. Non-­‐H20
Fluoride
Exposure
Data
from
Table
2-­‐9
(NRC
2006);
Body
Mass
Data
from
EPA
2011
These
data
show
that
children
receive
from
NON-­‐WATER
sources
more
fluoride
than
even
our
highest
MCLG/RfD

23. Conclusion
There
is
no
safe
level
of
fluoride
in
drinking
water,
and
the
MCLG
should
be
set
at
zero.

24. RecommendaMons
• Since
current
fluoride
exposures
exceed
the
RfD
values,
steps
to
reduce
fluoride
exposures
should
be
taken.
• AddiMon
of
fluoride
to
drinking
water
should
cease.
• Fluoride
supplement
tablets
should
be
banned.
• Fluoridated
tooth
paste
use
by
children
should
be
by
prescripMon
for
children
at
special
risk.

25. EPA
2010
Fluoride:
Dose-­‐response
analysis
for
non-­‐cancer
effects.
Health
and
Ecological
Effects
Division,
Office
of
Water.
December
2010.
Availabe
at:
www.hJp://water.epa.gov/acMon/advisories/drinking/upload/
Fluoride_dose_response.pdf
Accessed
September
2,
2014

26. Added:
EPA
1998.
TRAC
5/28-­‐29/98
TOPIC:
FQPA
SAFETY
FACTOR
(10X).
Staff
Paper
#
2.
Available
at:
www.epa.gov/oppfead1/trac/10xiss.htm.
(accessed
April
29,
2014).
:
EPA
1998.
TRAC
5/28-­‐29/98
TOPIC:
FQPA
SAFETY
FACTOR
(10X).
Staff
Paper
#
2.
Available
at:
www.epa.gov/oppfead1/trac/
10xiss.htm.
(accessed
April
29,
2014).

28. GOOD TEETH AND FLUORIDATION
0.0
20.0
40.0
60.0
80.0
100.0
1 5 9 13 17 21 25 29 33 37 41 45 49
50 STATES
Ranked, % Whole Population Fluoridated
%
.
% Whole
Population
Fluoridated
% High income
children
reporting
good/excellent
teeth
% Low income
children
reporting
good/excellent
teeth
Linear (% High
income
children
reporting
good/excellent
teeth)
Linear (% Low
income
children
reporting
good/excellent
teeth)
RANKING 50 STATES
FLUORIDATION DOES NOT IMPROVE TEETH
http://mchb.hrsa.gov/oralhealth/portrait/1cct.htm National Survey of Children's Health.
U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Bureau.
The National Survey of Children's Health 2003. Rockville, Maryland: U.S. Department of Health and Human Services, 2005
http://www.cdc.gov/oralhealth/waterfluoridation/fact_sheets/states_stats2002.htm http://pubs.usgs.gov/circ/2004/circ1268/htdocs/table05.ht
•
Higher
Income
=
BeJer
Teeth
•
No
significant
common
cause
For
the
Rich
Or
the
Poor
GOOD TEETH AND FLUORIDATION
0.0
10.0
20.0
30.0
40.0
50.0
60.0
70.0
80.0
90.0
100.0
1 7 13 19 25 31 37 43 49
50 STATES
%
% Whole
Population
Fluoridated
% High income
children
reporting
good/excellent
teeth
% Low income
children
reporting
good/excellent
teeth
Linear (% High
income
children
reporting
good/excellent
teeth)
Linear (% Low
income
children
reporting
good/excellent
teeth)