Brominated Diphenyl Ethers

Extracts in hexane were analyzed for halogenated
flame retardants (Br/Cl-FRs), including fifty-one PBDEs, using gas
chromatography negative ion mass spectrometry (GC-ECNI-MS) (Table S1). The Br/Cl-FRs were determined using
HP-5MS (Agilent Technologies, Inc., U.S.A.) or RTX-1614 (Restek Corporation,
U.S.A.) capillary columns. Co-eluting congeners, including BDE-17/25,
BDE-28/33, and BDE-138/166 were quantified together. PBDEs were monitored
at m/z 79 and 81 and quantified
using external standard calibration. Other Br/Cl-FRs were monitored
by characteristic fragments (Table S1).
Gas chromatographic oven temperature and mass spectral conditions
are given in Table S2.

The CCLS is a population-based case-control study in 35 counties in California, including 17 counties in the San Francisco Bay area and 18 in the Central Valley [11 (link),26 (link)]. Between 1995 and 2012, cases ≤14 years old were ascertained within 72 h of diagnosis from nine major pediatric clinical centers in the study area. Using California birth certificate information, controls were matched to cases on the basis of date of birth, sex, Hispanic ethnicity, and maternal race. Parents of both case and control participants were initially interviewed to gather information about their child’s exposure to suspected leukemia risk factors. Families who had not moved since the child’s diagnosis date (reference date for controls) were eligible for a second interview (Tier 2), during which carpet dust samples were collected and information about pesticide use was obtained. The second interview and dust sampling were limited to cases and controls <8 years old (diagnosed December 1999 to June 2006) to ensure the samples reflected early-life chemical exposure of the child. Case-control matching was not maintained due to residential eligibility criteria and voluntary participation. There were 731 participants for the Tier 2 interviews (324 cases and 407 controls). Of these, 296 cases (91%) and 333 controls (82%) agreed to participate. Due to insufficient dust or interferences in the chemical analyses, some samples were not quantified, leading to a final 277 cases and 306 controls (n = 583) [13 (link)].
The dust samples were collected using either a high-volume small surface sampler (HVS3) or a household vacuum cleaner. As described previously [26 (link)], concentrations of 64 organic chemicals (ng/g dust) were measured using gas chromatography/mass spectrometry (GC/MS) in multiple ion-monitoring mode after extraction with three different extraction methods. Nine metals were measured using microwave-assisted acid digestion combined with inductively coupled plasma/mass spectrometry (ICP/MS).
Our analysis investigated the association of 67 chemicals with the risk of childhood leukemia. Out of the entire CCLS dataset, only chemical exposure variables with at least 20% non-missing observations were included, as past experience has shown that higher levels of missingness contribute negligible information on potential relations with an outcome. We organized exposures into seven chemical class indices: polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), insecticides, herbicides, metals, tobacco exposure markers of nicotine and cotinine, and polybrominated diphenyl ethers (PBDEs). The reason for these groupings was that the chemicals share a structural similarity (e.g., PCBs, PAHs, metals) or usage (e.g., herbicides, insecticides). Most missing data were the result of findings below a chemical’s detection limit. Additionally, there were missing data in the PBDE chemicals due to insufficient levels of house dust for analysis. Both types of missing observations were imputed with log-normal distributions, as previously described [15 (link)].
The interviewers took a global positioning system reading of the residence coordinates, which were linked to census data for the computation of the neighborhood deprivation index and used to evaluate spatial random effects for unexplained spatial heterogeneity in leukemia risk.