Skip to main content
. 2021 Mar 8;19(3):e06421. doi: 10.2903/j.efsa.2021.6421

Table 11.

Summary of epidemiological studies on HBCDDs

Reference Recruitment year
Country Study design
Follow‐up (years) N
Population group (age) (years)
Gender (% males) Compound
Tissue analysed
Method (LOD/LOQ) Levels of Exposure (ng/g lipid)a Endpoint health category Effect estimate (95% CI), p‐value
Ongono et al. (2019) 1990
France Cohort
19 71,415
Adults (52.87 ± 6.66)
0% ΣHBCDDs
Food samples
LC‐MS/MS 0.22 ng/kg bw per dayb Diabetes type 2 1.18 (1.06–1.30) NS; 1.28 (1.15–1.42 NS; 1.35 (1.20–1.51) NS; 1.47 (1.29–1.67) NSc
Meijer et al. (2012) 2001–2002
The Netherlands Birth cohort
0.25, 1.5 34
Infants (0.25, 1.5)
100% ΣHBCDDs
Maternal serum
LC‐MS/MS (NR) 0.7 (ND–7.4) Free testosterone –0.31 (NR) NSd
Ruel et al. (2019) 2001–2002
The Netherlands Birth cohort
1.5 59
Children (1.5)
63% ΣHBCDDs
Maternal serum
LC‐MS/MS (NR) 0.82 (0.47–1.26) BSID‐II‐NL −0.133 (NR) NSd
MDI 0.004 (NR) NSd
Roze et al. (2009) 2001–2002
The Netherlands Birth cohort
5–6 62
Toddlers (5–6)
61% ΣHBCDDs
Maternal serum
LC‐MS/MS (NR) 0.8 (0.3–7.5) Coordination 0.29 (NR) NSd
Total intelligence (WISC‐III‐NL) 0.39 (NR) < 0.05d
Verbal intelligence (WISC‐III‐NL) 0.48 (NR) < 0.01d
Motor performance and behavioure NR (NR) NSd
Berghuis et al. (2018) 2001–2002
The Netherlands Birth cohort
13–15 31
Adolescents (13–15)
100% ΣHBCDDs
Maternal serum
LC‐MS/MS (NR) 0.79 (0.46–1.31) Performance intelligence (WISC‐III‐NL) −0.352d (−6.525, 0.029) 0.052f
Total intelligence (WISC‐III‐NL) −0.355d (−5.854, −0.001) 0.050f
Sustained auditory attention (‘Score!’, TEA‐Ch‐NL) −0.301d (−13.739, 0.913) 0.084f
Neurodevelopmentf NR (NR) NSd
Reproductive developmentg NR (NR) NR
Koual et al. (2019) 2013–2017
France Cross‐sectional
NA 91
Adults (64.0, 51.0–73.0)
0% α‐HBCDDh
Adipose tissue
LC‐MS/MS (NR) 1.62 (0.97–1.95) Breast cancer metastasis NR (NR) 0.18
Ploteau et al. (2017), Matta et al. (2020) 2013–2015
France Cross‐sectional
NA 99
Adults (18‐45)
0% α‐HBCDD
Adipose tissue
LC‐MS/MS (NR) Controls; 0.70, IQR (0.43–1.39) Severe endometriosisi NR (NR) NSj
74
Adults (18‐45)
0% α‐HBCDD
Serum
LC‐MS/MS (NR) NA Severe endometriosis i NR (NR) NSj
den Hond et al. (2015) NR
Belgium Cross‐sectional
NA 120
Adults (34.1, 30.0‐–38.5)
100% Total HBCDDs
Serum
GC‐ECNI‐MS (NR) %> LOQ, cases 10 (11.8%), controls 5 (5.3%) Subfertility 0.65 (0.14–2.92) 0.57j
Kim and Oh (2014) NR
South Korea Cross‐sectional
NA 38
Infants (23–37)
NR α‐HBCDD
β‐HBCDD
γ‐HBCDD
Serum (Children)
LC‐MS/MS (0.036) 1.84 (< MDL–16.6); 0.46 (< MDL–1.3); 14.05 (< MDL–147.8) Congenital Hypothyroidism (children) NR (NR) NS
β‐HBCDD
γ‐HBCDD
Maternal Serum
LC‐MS/MS (0.036) 0.46 (< MDL–1.88); 8.86 (< MDL–91.1) Congenital Hypothyroidism (mothers) NR (NR) NS
α‐HBCDD
Maternal Serum
LC‐MS/MS (0.036) 2.57 (< MDL–13.8) Congenital Hypothyroidism (mothers) NR (NR) 0.004
Li et al. (2014) 2009
China Cross‐sectional
NA 80
Adults (42, 30–50)
40% α‐HBCDD
β‐HBCDD
γ‐HBCDD
ΣHBCDD
Serum
LC‐MS (20, 20, 10) 5.9 (ND–2,702.5) Thyroid hormones NR (NR) NSd
Johnson et al. (2013) 2002–2003
USA Cross‐sectional
NA 62
Adults (18–54)
100% Total HBCDDs
Dust
GC‐ECNI‐MS 197 (IQR, 107–391) Free androgen index 0.46 (NR) 0.004d
Sex hormone binding globulin –0.35 (NR) 0.03d
Hormonesk NR (NR) NSd
Kicinski et al. (2012) 2008–2011
Belgium Cross‐sectional
NA 515
Adolescents (14.9 (0.7))
53% Total HBCDDs
Serum
GC‐MS (30 ng/L) < LOQ, (ND–234) NES‐CPT, Reaction Timen −3.53 (−18.72–11.67) NSj
NES‐CPT, Errors of Omissionn 27.80% (−17.5%–97.9%) NSl
NES‐CPT, Errors of Commissionn 21.80% (−2.5% to 52.2%) NSl
NES, System, Digit‐Symbol testn −0.44 (−6.59 to 5.72) NSj
NES, Digit Span testn 0.13 (−0.22 to 0.49) NSj
Eggesbø et al. (2011) 2003
Norway Cross‐sectional
NA 193
Neonates (3 days)
46% Total HBCDDs
Breast milk
GC–ECNI‐MS (NR) 0.54 (0.10–31) TSH 0.00 (‐0.02, 0.02) NSj
Weiss et al. (2006) 2000
Sweden Cross‐sectional
NA 50 (25)m
Adults (62, 52–81)
0% ΣHBCDD
α‐HBCDD
β‐HBCDD
γ‐HBCDD
Serum
LC‐MS/MS (0.12 pg/g; diastereomers 0.03, 0.06, 0.03) 0.46 (< 0.24–3.4) Bone mineral density NR (NR) NS
Stapleton et al. (2011) 2008–2010
USA Cross‐sectional
NA 140
Adults (< 20: 23%)0% ΣHBCDD
α‐HBCDD
β‐HBCDD
γ‐HBCDD
Serum
LC‐MS/MS (NR) NA (no detected) TSH, TT3, fT3, TT4, fT4 NA (NA) NA
Müller et al. (2016) 2012
Tanzania Cross‐sectional
NA 150
Neonates (0)
0% Total HBCDDs
Breast milk
GC‐ECNI‐MS (NR) NA (1 sample above LOQ) Birth weight
Birth length NA (NA) NA

BSID: Bayley Scales of Infant Development; CI: confidence interval. FU: follow‐up; GC‐ECNI‐MS: Gas chromatography‐electron capture negative ion‐mass spectrometry; HBCDD: hexabromocyclododecane; IQR: interquartile range; LC‐MS‐MS: liquid chromatography‐random mass spectrometry; LOD: limit of detection; LOQ: limit of quantification; MDI: mental development index; NA: not applicable; ND: not detected; NES‐CPT: Neurobehavioral Evaluation System‐Continuous Performance test; NS: not statistically significant.

a

Median (range).

b

Calculated as: Σ[food consumption (g/day) × food contamination (ng/g of food)]/bw (kg); food consumption over the previous year estimated through a validated 208‐item semi‐quantitative dietary questionnaire sent in 1993; food contamination data extracted from the 2nd Anses French Total Diet Study (TDS2) in 2011.

c

HR for Quintile 2 vs. Quintile 1, Quintile 3 vs. Quintile 1, Quintile 4 vs. Quintile 1, Quintile 5 vs. Quintile 1, respectively.

d

rho.

e

Including motor performance (coordination, fine motor skills), cognition (intelligence, visual perception, visuomotor integration, inhibitory control, verbal memory and attention) and behaviour.

f

Including verbal intelligence (WISC‐III‐NL); auditory‐verbal memory (AVLT); selective visual attention (‘Sky Search’,TEA‐Ch‐NL); motor outcome (Movement‐ABC).

g

Including testosterone, sex hormone‐binding globulin (SHBG); LH, FSH, estradiol (E2), free E2 (FE2) and inhibin B (InhB)], testes volume, penile length were also assessed.

h

β‐HBCDD and γ‐HBCDD detection rates were lower than 75% and were excluded by the authors from the statistical analysis.

i

Ovarian Endometrioma.

j

OR or beta.

k

Including follicle stimulating hormone (FSH), serum luteinising hormone (LH), estradiol, prolactin, free T4, total T3 and thyrotropin (TSH), inhibin B, testosterone; sex hormone binding globulin (SHBG), free androgen index (FAI), free unbound testosterone.

l

% change.

m

The PBDE/HBCDD extracts were later pooled (n = 25, 125 mL/pool) for stereoisomer determination.

n

The Neurobehavioral Evaluation System (NES) is a computerised battery of tests developed to study neurobehavioural effects in humans. The Neurobehavioral Evaluation System‐Continuous Performance Test (NES‐CPT) evaluates sustained attention. The Neurobehavioral Evaluation System‐Digit‐Symbol Test evaluates a range of cognitive operations. The Neurobehavioral Evaluation System‐Digit Span Test evaluates the working memory and the ability to hold and manipulate information. The Neurobehavioral Evaluation System‐Finger Tapping Test evaluates the motor speed and coordination.