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Letter pubs.acs.org/journal/estlcu
Temporal Trends in Exposure to Organophosphate Flame Retardants in the United States Kate Hoffman,† Craig M. Butt,† Thomas F. Webster,‡ Emma V. Preston,‡ Stephanie C. Hammel,† Colleen Makey,‡ Amelia M. Lorenzo,† Ellen M. Cooper,† Courtney Carignan,§ John D. Meeker,∥ Russ Hauser,§ Adelheid Soubry,⊥ Susan K. Murphy,#,@ Thomas M. Price,@ Cathrine Hoyo,∇ Emma Mendelsohn,† Johanna Congleton,● Julie L. Daniels,$ and Heather M. Stapleton*,† †
Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, United States Boston University School of Public Heath, Boston, Massachusetts 02118, United States § Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115, United States ∥ University of Michigan School of Public Health, Ann Arbor, Michigan 48109, United States ⊥ Epidemiology Research Group, Department of Public Health and Primary Care, KU Leuven-University, B-3000 Leuven, Belgium # Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, North Carolina 27710, United States @ Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Duke University Medical Center, Durham, North Carolina 27710, United States ∇ Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, United States ● Environmental Working Group, Washington, D.C. 20009, United States $ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States ‡
S Supporting Information *
ABSTRACT: During the past decade, use of organophosphate compounds as flame retardants and plasticizers has increased. Numerous studies investigating biomarkers (i.e., urinary metabolites) demonstrate ubiquitous human exposure and suggest that human exposure may be increasing. To formally assess temporal trends, we combined data from 14 U.S. epidemiologic studies for which our laboratory group previously assessed exposure to two commonly used organophosphate compounds, tris(1,3-dichloro-2propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP). Using individual-level data and samples collected between 2002 and 2015, we assessed temporal and seasonal trends in urinary bis(1,3dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), the metabolites of TDCIPP and TPHP, respectively. Data suggest that BDCIPP concentrations have increased dramatically since 2002. Samples collected in 2014 and 2015 had BDCIPP concentrations that were more than 15 times higher than those collected in 2002 and 2003 (10β = 16.5; 95% confidence interval from 9.64 to 28.3). Our results also demonstrate significant increases in DPHP levels; however, increases were much smaller than for BDCIPP. Additionally, results suggest that exposure varies seasonally, with significantly higher levels of exposure in summer for both TDCIPP and TPHP. Given these increases, more research is needed to determine whether the levels of exposure experienced by the general population are related to adverse health outcomes.
■
INTRODUCTION Polybrominated diphenyl ethers (PBDEs) were once among the most widely used flame retardant chemicals applied to consumer products; however, concern over their persistence and toxicity led to their phase-out beginning in the early 2000s. Since then, the chemical flame retardant industry has moved toward replacements.1−5 One class of alternatives consists of the organophosphate flame retardants (PFRs), which include chlorinated alkyl phosphates [e.g., tris(1,3-dichloro-2-propyl) © 2017 American Chemical Society
phosphate (TDCIPP)] and nonhalogenated aryl phosphates [e.g., triphenyl phosphate (TPHP)]. Data suggest that PFR use increased after the PBDE phase-out, and they are now among the most commonly detected flame retardants in furniture and Received: Revised: Accepted: Published: 112
December 27, 2016 January 26, 2017 January 27, 2017 February 8, 2017 DOI: 10.1021/acs.estlett.6b00475 Environ. Sci. Technol. Lett. 2017, 4, 112−118
113
North Carolina (40) combined (116) Massachusetts (14) New Jersey (26) North Carolina (43) California (33)
combined (741) North Carolina (347)a Massachusetts (45) Massachusetts (29) North Carolina (9) Massachusetts (46)c North Carolina (8) North Carolina (64) New Hampshire (11) North Carolina (69) New Jersey (18) North Carolina (27) California (28)
state (n)
2.9
3.0 3.2
2.9 2.0
2.4
1.2
1.9 1.7
1.7
7.1
1.8
1.9
1.7
10.9
5.6 7.3
6.1 1.0
4.7
3.3
2.4 1.3
2.3
0.7
0.8
1.3
0.5
0.4
0.4
1.8b 3.0
0.1
1.3 1.8
SG-corrected GM BDCIPP (ng/mL)
0.3
1.5 1.4
SG-corrected GM DPHP (ng/mL)
46.9
42.6 (12.6)e
3.7 (1.5)
3.2 (0.9) 0.7 (0.4)
g
2.8 (2.2) 6.3 (2.2)
29.8 (8.5)
53.1
47.8 63.8
53.4 50.0
37.5
0.0
0.0 3.7
39.7 (5.0)f 22.3 (3.2) 37.2 (3.8)
100.0
25.9 (5.1)
0.0
0.0
−d
20.1 (1.1)
55.3
44.4
17.2
100.0
26.3 0.0
percent male
39.8 (12.1)
34.9 (7.4)
46.1 (13.9)
36.6 (4.3)
32.3 (9.3) 29.6 (5.1)
mean age (standard deviation)
09/2015
01/2014 03/2014 04/2015 11/2015
− − − − −
11/2015
0.0
0.0
03/2014 04/2014 03/2015
03/2014
− 0.0 0.0
01/2013
07/2013
12/2012
01/2014
03/2011
07/2012
09/2015 10/2015 01/2016 11/2011
analysis date
0.0
0.0
100.0
4.8
0.0
0.0
−
48.0 100.0
percent females pregnant
enzyme digestion, SPE, isotope dilution, LC−ESI-MS/MS
SPE, isotope dilution, LC−ESI-MS/MS SPE, isotope dilution, LC−APCI-MS/MS
SPE, isotope dilution, LC−APCI-MS/MS
enzyme digestion, SPE, isotope dilution, LC−ESI-MS/MS enzyme digestion, SPE, isotope dilution, LC−ESI-MS/MS
SPE, isotope dilution, LC−ESI-MS/MS SPE, isotope dilution, LC−ESI-MS/MS
SPE, isotope dilution, LC−ESI-MS/MS
SPE, isotope dilution, LC−APCI-MS/MS
SPE, isotope dilution, LC−APCI-MS/MS
SPE, isotope dilution, LC−APCI-MS/MS
SPE, isotope dilution, LC−APCI-MS/MS
SPE, isotope dilution, LC−APCI-MS/MS
SPE, isotope dilution, LC−APCI-MS/MS
enzyme digestion, SPE, isotope dilution, LC−ESI-MS/MS SPE, isotope dilution, LC−APCI-MS/MS
analysis method
15
14 16
29
24
15
14 6
23
22
19
18
29
11
21
20
17
ref
Two participants from the original cohort (n = 349) who were
Letter pubs.acs.org/journal/estlcu
Temporal Trends in Exposure to Organophosphate Flame Retardants in the United States Kate Hoffman,† Craig M. Butt,† Thomas F. Webster,‡ Emma V. Preston,‡ Stephanie C. Hammel,† Colleen Makey,‡ Amelia M. Lorenzo,† Ellen M. Cooper,† Courtney Carignan,§ John D. Meeker,∥ Russ Hauser,§ Adelheid Soubry,⊥ Susan K. Murphy,#,@ Thomas M. Price,@ Cathrine Hoyo,∇ Emma Mendelsohn,† Johanna Congleton,● Julie L. Daniels,$ and Heather M. Stapleton*,† †
Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, United States Boston University School of Public Heath, Boston, Massachusetts 02118, United States § Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115, United States ∥ University of Michigan School of Public Health, Ann Arbor, Michigan 48109, United States ⊥ Epidemiology Research Group, Department of Public Health and Primary Care, KU Leuven-University, B-3000 Leuven, Belgium # Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, North Carolina 27710, United States @ Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Duke University Medical Center, Durham, North Carolina 27710, United States ∇ Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, United States ● Environmental Working Group, Washington, D.C. 20009, United States $ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States ‡
S Supporting Information *
ABSTRACT: During the past decade, use of organophosphate compounds as flame retardants and plasticizers has increased. Numerous studies investigating biomarkers (i.e., urinary metabolites) demonstrate ubiquitous human exposure and suggest that human exposure may be increasing. To formally assess temporal trends, we combined data from 14 U.S. epidemiologic studies for which our laboratory group previously assessed exposure to two commonly used organophosphate compounds, tris(1,3-dichloro-2propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP). Using individual-level data and samples collected between 2002 and 2015, we assessed temporal and seasonal trends in urinary bis(1,3dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), the metabolites of TDCIPP and TPHP, respectively. Data suggest that BDCIPP concentrations have increased dramatically since 2002. Samples collected in 2014 and 2015 had BDCIPP concentrations that were more than 15 times higher than those collected in 2002 and 2003 (10β = 16.5; 95% confidence interval from 9.64 to 28.3). Our results also demonstrate significant increases in DPHP levels; however, increases were much smaller than for BDCIPP. Additionally, results suggest that exposure varies seasonally, with significantly higher levels of exposure in summer for both TDCIPP and TPHP. Given these increases, more research is needed to determine whether the levels of exposure experienced by the general population are related to adverse health outcomes.
■
INTRODUCTION Polybrominated diphenyl ethers (PBDEs) were once among the most widely used flame retardant chemicals applied to consumer products; however, concern over their persistence and toxicity led to their phase-out beginning in the early 2000s. Since then, the chemical flame retardant industry has moved toward replacements.1−5 One class of alternatives consists of the organophosphate flame retardants (PFRs), which include chlorinated alkyl phosphates [e.g., tris(1,3-dichloro-2-propyl) © 2017 American Chemical Society
phosphate (TDCIPP)] and nonhalogenated aryl phosphates [e.g., triphenyl phosphate (TPHP)]. Data suggest that PFR use increased after the PBDE phase-out, and they are now among the most commonly detected flame retardants in furniture and Received: Revised: Accepted: Published: 112
December 27, 2016 January 26, 2017 January 27, 2017 February 8, 2017 DOI: 10.1021/acs.estlett.6b00475 Environ. Sci. Technol. Lett. 2017, 4, 112−118
113
North Carolina (40) combined (116) Massachusetts (14) New Jersey (26) North Carolina (43) California (33)
combined (741) North Carolina (347)a Massachusetts (45) Massachusetts (29) North Carolina (9) Massachusetts (46)c North Carolina (8) North Carolina (64) New Hampshire (11) North Carolina (69) New Jersey (18) North Carolina (27) California (28)
state (n)
2.9
3.0 3.2
2.9 2.0
2.4
1.2
1.9 1.7
1.7
7.1
1.8
1.9
1.7
10.9
5.6 7.3
6.1 1.0
4.7
3.3
2.4 1.3
2.3
0.7
0.8
1.3
0.5
0.4
0.4
1.8b 3.0
0.1
1.3 1.8
SG-corrected GM BDCIPP (ng/mL)
0.3
1.5 1.4
SG-corrected GM DPHP (ng/mL)
46.9
42.6 (12.6)e
3.7 (1.5)
3.2 (0.9) 0.7 (0.4)
g
2.8 (2.2) 6.3 (2.2)
29.8 (8.5)
53.1
47.8 63.8
53.4 50.0
37.5
0.0
0.0 3.7
39.7 (5.0)f 22.3 (3.2) 37.2 (3.8)
100.0
25.9 (5.1)
0.0
0.0
−d
20.1 (1.1)
55.3
44.4
17.2
100.0
26.3 0.0
percent male
39.8 (12.1)
34.9 (7.4)
46.1 (13.9)
36.6 (4.3)
32.3 (9.3) 29.6 (5.1)
mean age (standard deviation)
09/2015
01/2014 03/2014 04/2015 11/2015
− − − − −
11/2015
0.0
0.0
03/2014 04/2014 03/2015
03/2014
− 0.0 0.0
01/2013
07/2013
12/2012
01/2014
03/2011
07/2012
09/2015 10/2015 01/2016 11/2011
analysis date
0.0
0.0
100.0
4.8
0.0
0.0
−
48.0 100.0
percent females pregnant
enzyme digestion, SPE, isotope dilution, LC−ESI-MS/MS
SPE, isotope dilution, LC−ESI-MS/MS SPE, isotope dilution, LC−APCI-MS/MS
SPE, isotope dilution, LC−APCI-MS/MS
enzyme digestion, SPE, isotope dilution, LC−ESI-MS/MS enzyme digestion, SPE, isotope dilution, LC−ESI-MS/MS
SPE, isotope dilution, LC−ESI-MS/MS SPE, isotope dilution, LC−ESI-MS/MS
SPE, isotope dilution, LC−ESI-MS/MS
SPE, isotope dilution, LC−APCI-MS/MS
SPE, isotope dilution, LC−APCI-MS/MS
SPE, isotope dilution, LC−APCI-MS/MS
SPE, isotope dilution, LC−APCI-MS/MS
SPE, isotope dilution, LC−APCI-MS/MS
SPE, isotope dilution, LC−APCI-MS/MS
enzyme digestion, SPE, isotope dilution, LC−ESI-MS/MS SPE, isotope dilution, LC−APCI-MS/MS
analysis method
15
14 16
29
24
15
14 6
23
22
19
18
29
11
21
20
17
ref
Two participants from the original cohort (n = 349) who were
