Temporal Evaluation of Polybrominated Diphenyl ... - ACS Publications

Mar 17, 2017 - Cancer Prevention Institute of California, Berkeley, California 94704, ... of Epidemiology, School of Medicine, University of Californi...
0 downloads 0 Views 597KB Size
Subscriber access provided by University of Newcastle, Australia

Article

Temporal Evaluation of Polybrominated Diphenyl Ether (PBDE) Serum Levels in Middle-aged and Older California Women, 2011-2015. Susan Hurley, Debbie Goldberg, David O Nelson, Weihong Guo, Yunzhu Wang, Hyoung-Gee Baek, Junesoo Park, Myrto Petreas, Leslie Bernstein, Hoda Anton-Culver, and Peggy Reynolds Environ. Sci. Technol., Just Accepted Manuscript • DOI: 10.1021/acs.est.7b00565 • Publication Date (Web): 17 Mar 2017 Downloaded from http://pubs.acs.org on March 21, 2017

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

Environmental Science & Technology is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 25

Environmental Science & Technology

1

TITLE: Temporal Evaluation of Polybrominated Diphenyl Ether (PBDE) Serum Levels in

2

Middle-aged and Older California Women, 2011-2015.

3

AUTHORS: Susan Hurley1*, Debbie Goldberg1, David O. Nelson1, Weihong Guo2,3, Yunzhu

4

Wang2, Hyoung-Gee Baek2, June-Soo Park2, Myrto Petreas2, Leslie Bernstein4, Hoda Anton-

5

Culver5, Peggy Reynolds1, 6

6 7 8 9 10 11 12 13 14 15

1

Cancer Prevention Institute of California, Berkeley, CA, USA;

2

Environmental Chemistry Laboratory, Department of Toxic Substances Control, Berkeley, CA,

USA; 3

Food and Drug Laboratory Branch, California Department of Public Health, Richmond, CA

USA; 4

Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte,

CA, USA; 5

Department of Epidemiology, School of Medicine, University of California Irvine, Irvine, CA, USA; 6

Stanford University School of Medicine, Department of Health Research and Policy, Stanford,

16

CA, USA;

17

Corresponding Author:

18

Susan Hurley,

19

Cancer Prevention Institute of California

20

2001 Center Street, Suite 700

21

Berkeley, CA 94704

1 ACS Paragon Plus Environment

Environmental Science & Technology

22

[email protected]

23

Office phone: (510) 608-5189

24

MANUSCRIPT WORD COUNT: 4391 text + 4 small tables & 1 small figure at 300 each =

25

5,891 TOTAL

26

ABSTRACT:

27

Fax: (510) 666-0693

In response to health concerns and widespread human exposures, two widely-used

28

commercial formulations of polybrominated diphenyl ethers (PBDEs) were banned in the United

29

States in 2005. Initial biomonitoring data have provided early indications of reduced human

30

exposures since these bans took effect. Our objective was to evaluate temporal trends in PBDE

31

serum levels among a population of older California women during a four-year period, beginning

32

approximately five years after these formulations were banned. Automated solid phase

33

extraction and gas chromatography/high resolution mass spectrometry were used to measure

34

PBDE levels in blood collected during 2011-2015 among 1,253 women (ages 40-94)

35

participating in the California Teachers Study. Only congeners with detection frequencies (DF) >

36

75% were included in the present analysis: BDE-47 (DF=88%); BDE-100 (DF=78%); and BDE-

37

153 (DF=80%). Results from age- and race/ethnicity-adjusted linear regression analyses

38

indicated modest, but statistically significant, average annual percent increases in the serum

39

concentrations of all three PBDEs over the four-year study period. While not without limitations,

40

these results, in the context of other biomonitoring data, suggest that earlier reported declines in

41

PBDE levels may have plateaued and may now be starting to increase. Further biomonitoring to

42

ascertain current trends and determinants of population exposures is warranted.

43

2 ACS Paragon Plus Environment

Page 2 of 25

Page 3 of 25

44

Environmental Science & Technology

TOC/ABSTRACT ART:

45 46

KEYWORDS: PBDEs, human exposure, temporal trends, serum

47

INTRODUCTION:

48

Polybrominated diphenyl ethers (PBDEs) are a class of over 200 congeners introduced in the

49

late 1970s as flame retardant additives to a wide variety of consumer products and building

50

materials.1 Their use skyrocketed over the ensuing three decades and reports began to emerge

51

during the 1990s of rapidly rising body burden levels of PBDEs in human tissues, worldwide and

52

within the United States.2-9 These observations, coupled with laboratory evidence of potentially

53

associated adverse health effects, including neurodevelopmental toxicity, immunotoxicity,

54

endocrine disruption, and carcinogenicity, resulted in the restriction and ban in the production

55

and use of PBDEs, both internationally and in the United States.7, 10-12

56

PBDEs historically have been used in three primary commercial formulations, containing

57

mixtures of compounds; these are named by the average number of bromine atoms of the

58

chemical compounds they contain. The Penta- formulation (primarily composed of BDE-99,

59

BDE-47, BDE-100, BDE-153,and BDE-154)13 was predominately used to treat polyurethane

60

foam cushioning in furniture and carpet padding. The Octa- formulation (primarily composed of

61

BDE-183, BDE-207, BDE-203, BDE-209, and BDE-197)13 was used to treat hard plastic casings 3 ACS Paragon Plus Environment

Environmental Science & Technology

62

in computers and other electronic appliances and equipment. The Deca- formulation, almost

63

entirely composed of BDE-209,13 was also used in hard plastic casings, as well as in textiles,

64

adhesives, and wire insulation.6, 10, 12 In the United States, regulatory and voluntary measures

65

resulted in the discontinuation of the production, use, and sale of the Penta- and Octa-

66

formulations by the end of 2004 and the Deca-formulation by the end of 2013.10

67

In Europe, where PBDEs were phased-out a few years earlier than in the United States, there

68

is evidence, although somewhat mixed, that PBDE levels in environmental matrices, wildlife and

69

human tissue have been declining.14 In the United States comparatively few data are available to

70

evaluate the success of the PBDE phase-outs. Two small biomonitoring studies in California

71

have indicated secular decreases in PBDE levels in breast milk15 and blood.16 A larger study of

72

newborn blood spots in New York has also suggested secular decreases in body burden levels

73

since the 2005 phase-out of the Penta- and Octa- formulations.17 In contrast, although not

74

specifically designed to evaluate temporal trends, a pair of small breast milk biomonitoring

75

studies in Texas indicated no declines in PBDE levels from 2003 through 2007.18

76

The objective of the current analysis was to add to the limited data available to help inform

77

the degree to which the phase-out of PBDEs in this country has reduced human exposures.

78

Capitalizing on the availability of serum specimens collected from over 1,000 middle-aged and

79

older California women participating in an on-going cohort study, we conducted a temporal

80

analysis of PBDE serum levels in blood specimens collected from 2011 through 2015.

81

MATERIALS AND METHODS:

82

Study Population

4 ACS Paragon Plus Environment

Page 4 of 25

Page 5 of 25

83

Environmental Science & Technology

The study population consisted of 1,253 participants drawn from the California Teachers

84

Study (CTS), a prospective cohort study that recruited 133,479 female professional public school

85

employees in 1995-1996 primarily to study breast cancer. A full description of the cohort is

86

available elsewhere.19 Women included in the current analysis were serving as controls in an on-

87

going breast cancer case-control study nested within the CTS or were recruited separately in a

88

convenience sample of breast cancer-free CTS participants which targeted non-whites to enhance

89

racial/ethnic diversity. Controls in the case-control study were drawn from a probability sample

90

of at-risk cohort members frequency matched to breast cancer cases by age, race/ethnicity and

91

broad geographic region (corresponding to the three CTS field collection study sites). The

92

convenience sample of breast-cancer free participants was drawn from a probability sample of

93

CTS members under the age of 80 years who self-reported as either White, Black, Hispanic or

94

Asian/Pacific Islander and were geographically distributed so as to provide approximately equal

95

representation of urban and rural residence. Furthermore all participants included in the current

96

analysis lived in California and completed a supplementary interviewer-administered

97

questionnaire when their blood was drawn between 2011 and 2015. Participants’ ages were

98

ascertained by the questionnaire and dates of blood collection were recorded by the interviewer

99

at the time blood was collected. Study participants reported their race/ethnicity at recruitment

100

into the study on the baseline CTS questionnaire. The use of human subjects was reviewed and

101

approved by the California Health and Human Services Agency, Committee for the Protection of

102

Human Subjects and all participating centers’ Institutional Review Boards.

103

Serum Collection

104 105

Blood was collected from participants between May 9, 2011 and August 24, 2015 by licensed phlebotomists, usually in the participants’ homes. Blood was collected into a 10 mL 5 ACS Paragon Plus Environment

Environmental Science & Technology

106

BD® tube (catalog#367985, Becton Dickinson, Franklin Lakes, NJ) with clot activator, double

107

gel for transport, and silicone coated interior using standard phlebotomy techniques. Prior to

108

field processing, specimens were kept on cool packs for at least 30 minutes. Within several hours

109

of collection, phlebotomists spun down the clotted blood samples in the field using portable

110

centrifuges to separate the serum portion. Processed samples were then frozen and stored at -20

111

°C for 4-6 weeks until transported either via local courier (on cool-packs) or overnight (on dry-

112

ice via FedEx) to the laboratory for chemical analysis. Samples remained frozen during this

113

transportation process. Upon receipt at the laboratory, specimens were stored at -20 °C until

114

analysis.

115

PBDE Analysis

116

Serum samples were analyzed for 19 PBDE congeners by the Environmental Chemistry

117

Laboratory at the California Department of Toxic Substances Control (Berkeley, CA). Samples

118

were thawed and aliquoted for PBDE and lipid measurements. Automated solid phase extraction

119

(SPE; Biotage, Uppsala, Sweden) and gas chromatography/high resolution mass spectrometry

120

(GC-HRMS, DFS, ThermoFisher, Bremen, Germany) were used for the analysis of PBDEs.20

121

Briefly, thawed serum samples (2 mL) were fortified with a panel of 13C12 labeled surrogate

122

standards and mixed well. Equal volumes (4 mL) of formic acid and water were added into each

123

sample before loading on the SPE modules. Oasis HLB cartridges (3 cc, 500 mg, Waters Co.,

124

Milford, MA, USA) and acidified silica (500 oC pre-baked, manually packed, 3 cc) were used for

125

the sample extraction and clean-up, respectively. The collected final eluates in hexane:

126

dichlomethane (1:1) were concentrated in TurboVap (Biotage, Charlotte, NC, USA), and spiked

127

with recovery standards. Standard reference material (SRM 1958, National Institute of Standards

128

and Technology, Gaithersburg, MD, USA) and bovine serum pre-spiked with known amounts of 6 ACS Paragon Plus Environment

Page 6 of 25

Page 7 of 25

Environmental Science & Technology

129

target analytes were used as QA/QC samples. The laboratory is proficient in the analysis of

130

PBDEs as demonstrated by its regular participation in the performance evaluation system

131

managed by the Arctic Monitoring & Assessment Program (AMAP).

132

A small volume of sera from each sample was sent to Boston Children’s Hospital for

133

measurement of total cholesterol and triglycerides by enzymatic methods.21, 22 Cholesterol and

134

triglycerides were used to calculate the lipid content based on Phillips’ formula.23 PBDE levels

135

were then normalized for lipids to produce values with units of ng/g lipid. To be consistent with

136

national biomonitoring data,24 we replaced concentrations below the laboratory limit of

137

detections (LODs) with LOD/√2 before lipid adjustment.

138

In order to minimize potential biases associated with imputing high frequency of non-

139

detectable levels, only the three congeners with detection frequencies (DF) of 75% or more were

140

included in the current analysis. These included: 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47),

141

with an average LOD of 0.032 ng/mL and DF=88%; 2,2',4,4',6-Pentabromodiphenyl ether (BDE-

142

100), with an average LOD of 0.007 ng/mL and DF=78%; and 2,2',4,4',5,5'-hexabromodiphenyl

143

ether (BDE-153), with an average LOD of 0.015 ng/mL and DF=80%.

144

Data analyses

145

Summary statistics (including means, medians, minimum and maximum values) were

146

generated for the lipid-normalized concentration of each congener. Initial evaluations of

147

temporal trends were evaluated by plotting the concentration of each PBDE congener versus the

148

date of sample collection. Linear models were used to regress the log10-transformed serum

149

concentration of each PBDE congener on serum collection date. (Serum concentrations were

150

log10-transformed to symmetrize the skewed distributions before using them in regressions). To

151

determine appropriate covariates, we conducted backward stepwise regressions, considering age 7 ACS Paragon Plus Environment

Environmental Science & Technology

152

at blood draw (continuous years – considered both as a linear and a quadratic term), and

153

race/ethnicity (categorical: White, Black, Hispanic, Asian/Pacific Islander, Other/unknown).

154

Regression models were built separately for each PBDE congener and only the factors that were

155

significant at p