Thyroid Function in Long-Term

and Occupational Exposures to

Perchlorate
Lewis E. Braverman, MD
NIS
 The Effect of 3mg CLO4 Ingestion on Thyroid
RAIU's

25
% Thyroid RAIU

20 *

15 *
8 Hour
10 24 Hour
5
0
Baseline 14 Day 28 Day
n=8 *p < 0.02 vs Baseline
 Effect of CLO4 on Thyroid RAIU

25
uptake (24h)

20
15
10
123

5
% I

0
Baseline CLO4 14d off CLO4 15d

35mg CLO4/d p<0.01 7mg CLO4/d p<0.01

1.4mg CLO4/d p<0.05 0.5mg CLO4/d NS

Greer et al (Exp’t Health Persp , 2002)

n = 13 .5
 24h Urine CLO4 Before, During and After Perchlorate
Administation

2500.0
ug ClO4 / 24hours

2000.0

1500.0

1000.0

500.0

0.0
placebo 0.5mg CLO4 3.0mg CLO4

Before During After

The ingestion of 0.5 or 3 mg perchlorate daily
for six months did not affect thyroid function
in euthyroid adults, suggesting that low
concentrations of perchlorate in drinking
water may not adversely affect thyroid
function.
High ClO4 absorption during three nights
work exposure decreased the 14-hour RAIU
by 38% in ClO4 production workers
compared to the RAIU after three days off.
However, serum TSH and Tg concentrations
and thyroid volume by ultrasound were not
affected by ClO4, suggesting that long-term,
intermittent, high exposure to ClO4 does not
introduce hypothyroidism or goiter in adults.
 Current U.S. Perchlorate
Recommendations
No Effect Level (RAIU) Safety Factor of 10 Water

N.A.S./EPA 7 ug/kg x 70 = 490 0.7 ug/kg x 70 = 49 24.5 ppb

ug/d ug/d

MASS 7 ug/kg x 70 = 490 1 ppb

ug/d

CA 7 ug/kg x 70 = 490 6 ppb

ug/d

Note: If infant nurses and breast milk contains 10 ug/L (maximum intake
1 L/d) and mean weight is 4 kg, baby would be exposed to 2.5 ug/kg, still
below no effect level of 7 ug/kg.
Gabe McIntosh
Perchlorate Collaborators
S.H. Lamm, M.D.
E.N. Pearce, M.D., M.Sc.
S. Pino, B.S.
J. Lawrence, M.D.
X. He, M.D.
J. Gibbs, M.D.
A. Firek, M.D.
B. Blount, Ph.D.
A.M. Leung, M.D.
Environmental Perchlorate
Exposure
Perchlorate in Groundwater
 Perchlorate Contamination
• April 1997: new analytical method
developed to detect low levels (4 μg/L)
• Subsequent surveys detected perchlorate
in ground waters in several states where
ClO4 was used
• Potential health risks: assessed variously
by the EPA, CA, MA, others
U.S. Perchlorate Releases as of 2003

EPA
Mean Perchlorate Levels in
U.S. Lettuce Samples
14
11.6 11.9
12 10.7
10
7.76
8
ppb
6
4
2
0
Green Leaf Iceberg Red Leaf Romaine

U.S. FDA, November 2004

 Applied Biosystems, Inc.
145.7

Apricots(Chili)
2.4
Bananas(Columbia)
Perchlorate Content in Various Foods

39.9
Raw Asparagus(Mexico)
463.5

Cantaloupes(Guatemala)
151.7

Cantaloupes(Costa
Rica)

10.0
Oranges(Cal)

19.3
Green Grapes(Cal)

23.1
Raspberries(Chili)

62.8
Tomatoes (Mexico)

0.3
Tomatoes (Florida)

200

150

100

50

0
Perchlorate(ug/kg)
 Dairy Milk Perchlorate in the US and
Japan

12
Median Perchlorate

Range 5.5-16.4

8
(ug/L)

Range 1.5-11.3

0
N=104 N=54
U.S Japan
(FDA, 2004) (Dyke et al, 2006)
 Perchlorate in Multivitamins
• Perchlorate detected in 20
of 31 OTC multivitamin
preparations tested
– Detectable concentrations
10 - 2420 ng/g (dose 0.03 -
18 µg/day)
– Highest dose found in a
prenatal multivitamin

Snyder SA et al. Analytica Chimica Acta in press

Geometric Means and 95% Confidence Intervals
for Urinary Perchlorate, NHANES 2001-2002
Adjusted* urinary perchlorate geometric mean

n = 2820
(mcg/L)

*Adjusted for
race/ethnicity, sex,
age, fasting, and
urine creatinine

Blount BC et al J Expo Sci Environ Epidemiol epub Oct 2006

Perchlorate Content of U.S. Cows’ Milk and
Breast Milk Samples

n = 50 n = 36

Kirk et al. Environ Sci & Technol 2005

Correlation between Breast Milk Perchlorate and
Iodine Concentration

n = 6 samples
containing
>10 mcg/L
perchlorate

Kirk et al. Environ Sci & Technol 2005

 Projected Perchlorate Intake of Breastfed
Infants as a Function of Age

Based on milk samples from 10 lactating US women

Kirk AB et al Environ Health Perspect Epub Nov 2006

 Mean Breast Milk Iodine by Quartiles in 57
Boston-Area Women
500

400

300

Mean Breast Milk

Iodine (mcg/L) 200

100
AI

0
0 1 2 3 4 5

Quartile

27 of the 57 samples (47%) did not contain sufficient iodine to

meet infants’ Adequate Intake (AI) of 110 – 130 mcg/day *
* Institute of Medicine recommendation
 Urine, Breast Milk and Infant
Formulae Perchlorate in Boston
Median Perchlorate (ug/L)

12
Range 1.3-411

4 Range 0.4-127
Range 0.2-4.1

0
N=56 N=49 N=17
Urine Breast Milk Infant Formulae

Pearce et al, JCEM 2007

 Relation of Breast Milk
Iodine and Perchlorate Concentrations
2500

n = 49, r2 = 0.05, p = 0.11

2000

1500

1000
Breast Milk
Iodine 500
(mcg/L)
0

0 100 200 300 400 500

Breast Milk Perchlorate (mcg/L)

Pearce et al JCEM 2007;92:1673-7
 Relation of Breast Milk Iodine and
Perchlorate Concentrations ≥10 mcg/L
2500

n = 23, r2 = 0.002, p = 0.84

2000

1500

Breast Milk 1000

Iodine
(mcg/L)
500

0 100 200 300 400 500

Breast Milk Perchlorate (mcg/L)

Pearce et al JCEM 2007;92:1673-7
 Predicted Change in Serum T4 and TSH Levels
with Changes in Urinary Perchlorate.
1135 Women with Urinary Iodine <100 mcg/L, NHANES 2001-2002

Increase in TSH (mU/L)

Increase in Urine Decrease in
Initial TSH Initial TSH
Perchlorate T4 (mcg/dl)
1.40 mU/L 3.11 mU/L
(50th %ile) (90th %ile)
to 1.6 mcg/L
0.83 0.42 0.93
(25th percentile)
to 2.9 mcg/L
1.06 0.56 1.24
(50th percentile)
to 5.2 mcg/L
1.28 0.70 1.56
(75th percentile)

Blount BC et al Environ Health Perspect 2006;114:1865-71

 Median Urine Iodine in Pregnant Women
in the US, Wales, Italy, and Ireland
150
Median Iodine (ug/L)

100

50

0
N=348 N=396 N=311 N=82

US Cardiff, Turin, Dublin,

(Caldwell et al Wales Italy Ireland
Thyroid 2005)
 Urine Perchlorate in Pregnant Women in
the US ,Wales, Italy and Ireland
Median Perchlorate (ug/L)

6
In US, Geometric mean was 3.5ug/L (n=2,800). Blount et al, 2006

Range 1.8 - 5.4

0.04 -107.6
3
0.05 -368
0.08 -174.5

0
N=115 N=396 N=311 N=82
US Cardiff, Turin, Dublin,
Wales Italy Ireland
(He et al, 2007)
 Perchlorate and Free T4 Values in Individuals
with Urinary Iodine Concentrations <100 mcg/L:
Cardiff, Wales

R2 = 0.002

Perchlorate
mcg/L

Free T4
 Perchlorate and TSH Values in Individuals
with Urinary Iodine Concentrations <100 mcg/L:
Cardiff, Wales
100.00 Iodine < 100

R2 = 0.00005
80.00

Perchlorate 60.00

(mcg/L)
40.00

20.00

R Sq Linear = 5.306E-4

0.00
-0.10

10.00

100.00

TSH (mIU/L)
 Perchlorate and Free T4 Values in Individuals
with Urinary Iodine Concentrations <100 mcg/L:
Turin, Italy

R2 = 0.003

Perchlorate
mcg/L

Free T4
 Perchlorate and TSH Values in Individuals
with Urinary Iodine Concentrations <100 mcg/L:
Turin, Italy

R2 = 0.024

Perchlorate
(mcg/L)

TSH (mIU/L)
 Predicted Change in Serum T4 and TSH Levels
with Changes in Urinary Perchlorate.
1135 Women with Urinary Iodine <100 mcg/L, NHANES 2001-2002

Increase in TSH (mU/L)

Increase in Urine Decrease in
Initial TSH Initial TSH
Perchlorate T4 (mcg/dl)
1.40 mU/L 3.11 mU/L
(50th %ile) (90th %ile)
to 1.6 mcg/L
0.83 0.42 0.93
(25th percentile)
to 2.9 mcg/L
1.06 0.56 1.24
(50th percentile)
to 5.2 mcg/L
1.28 0.70 1.56
(75th percentile)

Blount BC et al Environ Health Perspect 2006;114:1865-71

 Median Urine Iodine in Pregnant Women
in the US, Wales, Italy, and Ireland
150
Median Iodine (ug/L)

100

50

0
N=348 N=396 N=311 N=82

US Cardiff, Turin, Dublin,

(Caldwell et al Wales Italy Ireland
Thyroid 2005)
 Urine Perchlorate in Pregnant Women in
the US ,Wales, Italy and Ireland
Median Perchlorate (ug/L)

6
In US, Geometric mean was 3.5ug/L (n=2,800). Blount et al, 2006

Range 1.8 - 5.4

0.04 -107.6
3
0.05 -368
0.08 -174.5

0
N=115 N=396 N=311 N=82
US Cardiff, Turin, Dublin,
Wales Italy Ireland
(He et al, 2007)
 Perchlorate and Free T4 Values in Individuals
with Urinary Iodine Concentrations <100 mcg/L:
Cardiff, Wales

R2 = 0.002

Perchlorate
mcg/L

Free T4
 Perchlorate and TSH Values in Individuals
with Urinary Iodine Concentrations <100 mcg/L:
Cardiff, Wales
100.00 Iodine < 100

R2 = 0.00005
80.00

Perchlorate 60.00

(mcg/L)
40.00

20.00

R Sq Linear = 5.306E-4

0.00
-0.10

10.00

100.00

TSH (mIU/L)
 Perchlorate and Free T4 Values in Individuals
with Urinary Iodine Concentrations <100 mcg/L:
Turin, Italy

R2 = 0.003

Perchlorate
mcg/L

Free T4
 Perchlorate and TSH Values in Individuals
with Urinary Iodine Concentrations <100 mcg/L:
Turin, Italy

R2 = 0.024

Perchlorate
(mcg/L)

TSH (mIU/L)