Table 1.
Epidemiological evidence on organophosphorus flame retardants, 2000–2019.
| Author | Date | Country | Population | Exposure Assessment | Compounds of Interest | Health Outcome | Covariates | Human Health Findings |
|---|---|---|---|---|---|---|---|---|
| Doherty et al. [58] | 2019 | USA | 149 children of 36 months | Urine sample collected from mothers between 24- and 29-week gestation | DPHP, BDCIPP, IP-PPP, BCIPHIPP | Children’s cognitive function (Composite, Fine Motor, Visual Reception, Receptive Language, Expressive Language) was assessed using the Mullen Scales of Early Learning (MSEL) at age between 2 and 3 years | Maternal age, education, income, race/ethnicity, BMI, and child’s sex | Concentrations of IP-PPP (ng/mL) were associated with MSEL Cognitive Composite Score (β= −2.61; 95% CI: −5.69, 0.46), Fine Motor Scale (β= −3.08; 95% CI: −5.26, −0.91) and the Expressive Language Scale (β= −1.21; 95% CI: −2.91, 0.49) |
| 227 children of 36 months | Urine sample collected from mothers between 24- and 29-week gestation | DPHP, BDCIPP, IP-PPP, and BCIPHIPP | Children’s language (Vocabulary, Grammatical Complexity) was assessed using the MacArthur-Bates Communicative Development Inventories (MB-CDI) at age between 2 and 3 years | Maternal age, education, income, race/ethnicity, BMI, and child’s sex | Prenatal IP-PPP concentrations were inversely associated with age-standardized scores on the MB-CDI Vocabulary assessment (β= −1.19; 95% CI: −2.53, 0.16) | |||
| Ait Bamai et al. [59] | 2018 | Japan | 296 children | House dust samples collected at age 7 of children | TMP, TEP, TPP, TBP, TCIP | Eczema and wheeze were assessed in children aged 7 years using the International Study of Asthma and Allergies in Childhood questionnaire | Sex, household income, maternal smoking, and parental history of atopy. | Among children without any filaggrin mutations, TDCIPP was associated with wheeze (OR: 1.22, 95% CI: 1.00–1.48) |
| TCEP, TEHP, TBEP, TDCPP, TPhP, TCP | ||||||||
| Araki et al. [60] | 2018 | Japan | 128 elementary school-aged children | Multisurface dust | TMP, TEP, TPP, TNBP, | International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire | Sex, grade, annual income, and dampness index | Association between TDCIPP in house dust and eczema (OR:3.75; 95% CI: 1.39, 10.2) |
| TCIPP, TCEP, TEHP, TBEP, | ||||||||
| TDCPP, TPHP, TMPP | ||||||||
| 113 to 128 elementary school-aged children | Urine samples collected from children | 5-HO-EHDPHP, EHPHP, | International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire | Sex, grade, annual income, dampness index, and creatinine | Association between ΣuTCIPP and rhinoconjunctivitis (4th quartile vs. 1st quartile) (OR= 5.01; 95% CI: 1.53, 6.5; p = 0.008], TBEP-OH (>LOD vs. <LOD) and eczema (OR= 2.86; 95% CI: 1.04, 7.85; p = 0.041), BDCIPP (3rd tertile vs. 1st tertile) and at least one of the symptoms (wheeze, rhino-conjunctivitis, eczema) (OR= 3.91; 95% CI: 1.24, 12.3; p = 0.019] | |||
| BBOEP, 3-HO-TBEP, BBOEHEP, BCIPP, BCIPHIPP, DPHP, 4-HO-DPHP, | ||||||||
| 3-HO-TPHP, 4-HO-TPHP, BDCIPP, DNBP, uTCEP | ||||||||
| Carignan et al. [61] | 2018 | USA | 201 couples from the Environment and Reproductive Health (EARTH) | One or two spot urine samples per in vitro fertilization cycle | BCIP, BDCIPP, DPHP, IP-PPP, tb-PPP | Proportion of fertilized oocytes, number of best quality embryos, proportion of cycles resulting in implantation, clinical pregnancy and live birth | Year of IVF treatment cycle, primary infertility diagnosis, and maternal urinary PFR metabolites as well as paternal and maternal age, body mass index, and race/ethnicity. | Paternal urinary concentrations of BDCIPP were associated with fertilization (95% CI: 0.01, 0.12; p-trend = 0.06) |
| USA | 211 women from the Environment and Reproductive Health (EARTH) | One or two urine samples per IVF cycle | BCIP, BDCIPP, DPHP, IP-PPP, tb-PPP | Proportion of fertilized oocytes, number of best quality embryos, proportion of cycles resulting in implantation, clinical pregnancy and live birth | Maternal age, body mass index, race/ethnicity, year of IVF treatment cycle, and primary Society for Assisted Reproductive Technology (SART) infertility diagnosis at study entry | Association between the levels of two individual metabolites (DPHP and tb-PPP) and of total metabolites, and reduced probability of successful fertilization, implantation, clinical pregnancy, and live birth | ||
| Deziel et al. [62] | 2018 | USA | 200 women (100 papillary thyroid cancer cases and 100 controls) | Single spot urine samples | BCIPP, BCIHPP, BDCIPP | Age, BMI, education level, family history of thyroid cancer, previous benign thyroid disease, and alcohol consumption | No association between BCIPHIPP, BCIPP, DPHP, BDCIPP, IP-PPP, tb-PPP and papillary thyroid cancer (PTC) | |
| IP-PPP, DPHP and tb-PPP | ||||||||
| Hoffman et al. [63] | 2018 | USA | 248 pairs women–child | Urine samples collected between 24–30 weeks gestation | BDCIPP, DPHP, IP-PPP, | Gestational age in days (combination of last menstrual period and earliest-ultrasounds data) and birthweight | Maternal age, race, education, parity, prepregnancy BMI and season of urine sample collection | Among female infants, IP-PPP was associated with birth (β = −1.00 week; 95% CI: −1.85, −0.15 weeks; p= 0.02). Among male infants, DPHP was associated with gestational duration (β = 0.75 weeks; 95% CI: 0.01, 1.50 weeks; p = 0.05) |
| BCIPHIPP, BCIPP, tb-PPP | ||||||||
| Preterm birth (defined as <37 weeks gestation) | Maternal age, race, education, parity, prepregnancy BMI and season of urine sample collection | Among females infants, preterm birth was associated with IP-PPP (OR: 4.58; 95% CI: 1.23, 17.06) and BDCIPP (OR: 3.99; CI: 1.08, 14.78). Among male infants maternal urinary IP-PPP concentrations were associated with preterm birth (OR: 0.21; 95% CI: 0.06, 0.68). | ||||||
| Castorina et al. [64] | 2017 | USA | 248 to 249 pairs women–child | Urine samples collected during the 2nd prenatal study visit | BDCIPP, DPHP, IP-PPP, tb-PPP | Children’s cognitive abilities was assessed by a single bilingual psychometrician at age 7 using the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV) (Full-Scale IQ, Working memory, Perceptual reasoning, Verbal comprehension, Processing speed) | Maternal education, PPVT scores, CES-D scores, country of birth and prenatal urinary DAP metabolite levels, HOME z-score, language of WISC testing, child sex and age at assessment, and household poverty | Association between DPHP and Full-Scale IQ (β: −2.9; 95% CI: −6.3, 0.5), DPHP and Working memory (WISC-IV scale) (β: −3.9; 95% CI: −7.3, −0.5), ΣPFR metabolites and Working memory (WISC-IV scale) (β: −4.6, 95% CI: −8.9, −0.3). |
| Urine samples collected during the 2nd prenatal study visit | BDCIPP, DPHP, IP-PPP, tb-PPP | Children’s behavior was assessed by maternal and teacher report at age 7 using the Behavior Assessment System for Children 2 (BASC-2) (ADHD Index, Inattention DSM-IV, Hyperactive/Impulsive DSM-IV, total subscale DSM-IV) and the Conners’ ADHD/DSM-IV Scales (CADS) (Hyperactivity scale, Attention problems scale) | Sex, age at assessment, maternal country of birth, HOME score at 7-years, prenatal DAPs, and maternal depression and education | Association between IP-PPP and Hyperactivity scale (BASC-2—Maternal Report (T-score) (β: 2.4; 95% CI: 0.1, 4.7), BDCIPP and Attention problems scale (BASC-2—Teacher Report (T-score) (β: 1.1; 95% CI: −0.1,2.3; p- < 0.1) | ||||
| Hoffman et al. [65] | 2017 | USA | 70 cases and 70 controls | Dust samples from homes | TCEP, TCIPP, TDCPP and TPHP | Diagnostic of papillary thyroid cancer (PTC) | Indicator of tumor aggressiveness for FR exposure above the median | Higher levels of TCEP associated with increased odds of PTC (OR: 2.42; 95% CI: (1.10, 5.33) |
| Lipscomb et al. [66] | 2017 | USA | 72 children aged 3–5 years | Passive wristband samplers worn continuously for 7 days | TPP, TCIPP, TCEP, TDCPP | Children’s social behaviors were assessed using the Social Skills Improvement System-Rating Scales (SSIS-RS) by their teacher in the preschools they were attending (seven subscales representing positive behaviors: Communication, Cooperation, Assertion, Responsibility, Empathy, Engagement, and Self-Control; four subscales representing behavior problem domains: Externalizing, Bullying, Hyperactivity/Inattention, and Internalizing) | Gender, age, family context, and child’s exposure to adverse experiences | lnΣOPFR levels were associated with responsibility (β = −0.25, p < 0.001) and externalizing problems (β = 0.31, p < 0.05) |
| Preston et al. [67] | 2017 | USA | 51 adults | 133 urine samples collected at months 1,6 and 12 | DPHP | Free thyroxine (fT4), total thyroxine (TT4), total triiodothyronine (TT3), and thyroid stimulating hormone (TSH) in serum samples | Sampling round, time of sample collection, specific gravity-corrected iodine and BDE-47 and sex | DPHP was associated with a 0.43 μg/dL (95% CI: 0.47, 1.36) increase in mean TT4 levels |
| 25 women | 61 urine samples collected at months 1,6 and 12 | DPHP | Free thyroxine (fT4), total thyroxine (TT4), total triiodothyronine (TT3), and thyroid stimulating hormone (TSH) in serum samples | Sampling round, time of sample collection, specific gravity-corrected iodine and BDE-47 | DPHP was associated with a 0.91 μg/dL (95% CI: 0.47, 1.36) increase in mean TT4 levels | |||
| 26 men | 61 urine samples collected at months 1,6 and 12 | DPHP | Free thyroxine (fT4), total thyroxine (TT4), total triiodothyronine (TT3), and thyroid stimulating hormone (TSH) in serum samples | Sampling round, time of sample collection, specific gravity-corrected iodine and BDE-47 | No significant association between DPHP and TT4, fT4, TT3, TSH | |||
| Soubry et al. [68] | 2017 | USA | 67 men | Urines samples | BCIP, BDCIPP, DPHP, IP-PPP, tb-PPP | DNA extracted from sperm samples | Age, obesity-status and multiple testing, exposure to monoisopropylphenyl | Association between BDCIPP, DPHP, IP-PPP and hyper- or hypomethylation of different genes specific to the metabolites |
| diphenyl phosphate | ||||||||
| Canbaz et al. [69] | 2016 | Sweden | 110 children who developed asthma at 4 or at 8 years, matched with 110 controls from a large perspective study | Dust collected from the mother’s mattress two months after childbirth | TCEP, TCIPP, TDCPP, TBEP, TPhP, EHDPHP, mmp-TMPP | Asthma at 4 or 8 years was defined based on at least two of the following three criteria: (i) >1 episode of wheeze in the last 12 months; (ii) a doctor’s diagnosis of asthma; (iii) asthma medicine prescribed occasionally or regularly over the last 12 months | No association between PEFRs concentrations and development of childhood asthma | |
| Zhao et al. [70] | 2016 | China | 154 men and 101 women | One blood sample | TCIPP, TBEP, TPHP, TEP, TNBP, EHDPP | Blood samples | Negative association between EHDPP, TPHP, and TNBP levels and sphingosine 1-phosphate concentration | Association between levels of the six PEFRs and increased sphingomyelin concentration (p < 0.001 for all OPFRs). The S1P level in the highest quartile of EHDPP was 36% lower (95% CI: −39%, −33%; p < 0.001) than that in the lowest quartile, 16% lower (95% CI: −19%, −14%; p < 0.001) than that in the highest TPHP quartile, and 36% lower (95% CI: −38%, −33%; p < 0.001) than that in the highest TNBP quartile |
| Araki et al. [71] | 2014 | Japan | 516 inhabitants (adults and children) in 156 different homes | Floor dust | TMP, TEP, TPP, TNBP, TCIPP, TCEP, TEHP, TBEP, TDCPP, T PHP, TMPP | All inhabitants of each home were asked to complete a self-administered questionnaire participants who reported having received medical treatment for bronchial asthma, atopic dermatitis, allergic rhinitis, and/or allergic conjunctivitis at any time during the preceding 2 years were classified as positive | Gender, age, tobacco smoke, ETS exposure, | Association between TNBP in multi-surface dust and asthma (OR: 5.34; 95% CI: 1.45, 19.7), TNBP in multi-surface dust and allergic rhinitis (OR: 2.55; 95% CI: 1.29, 45.01) |
| recent renovations, wall-to-wall carpeting, dampness | ||||||||
| index, hair/fur-bearing pets in the dwelling, | ||||||||
| mechanical ventilation equipment usage, and total | ||||||||
| fungi | ||||||||
| Meeker et al. [72] | 2013 | USA | 33 men | Urine samples | BDCIPP, DPHP | Blood and semen samples | Age, BMI, and time of sample collection, abstinence period | Association between BDCIPP levels and decreases in sperm quality parameters, and concentrations of total T3 (% change: 6.6; 95% CI: 1.6,12,8, p = 0.02) and TSH in serum (% change: 40.3; 95% IC: 11.4, 77.1, p = 0.006). DPHP was |
| associated with a 57% (95% CI: −77.8, −18.8, p = 0.01) decrease in sperm concentration and a 20% (95% CI: –41.1, 0.5) decrease in sperm motility | ||||||||
| Hutter et al. [32] | 2013 | Austria | 436 children | Air | TCEP, TDCPP | The cognitive evaluation was accomplished by a neurodevelopment test | Social status, gender and region (urban/rural) | Significant correlations of TCEP in PM10 and PM2.5 and school dust samples with cognitive performance. Cognitive performance decreased with increasing concentrations of TCEP |
| Bergh et al. [40] | 2011 | Sweden | Adults (men and women) | Air | TEP, TiPrP, TPrP, TiBP, TBP, TCEP, TCIPP, TPeP, THP, TDCPP, TPP, DPEHP, TEHP, TToP, d27-TBP cis | No association between OPFRs levels and reported Sick Building Syndrome symptoms | ||
| Kanazawa et al. [73] | 2010 | Japan | 134 adults (70 women and 64 men) | Floor dust | TBP, TBEP, TDCPP | Age (ordinal variable in increments of 10 years), gender, history of allergy, time spent | Association between TBP and mucosal symptoms of Sick Building Syndrome (OR: 15, 95% CI: 2.7–80), TBOEP (OR: 0.3, 95% CI: 0.1–0.7), TDCIPP (OR: 2.2, 95% CI: 1.0–4.6) | |
| at home (h/day; ≤12, >12), and condensation and moldy odor | ||||||||
| Meeker et al. [74] | 2009 | USA | 38 men | House dust | TDCPP, TPP | Serum and semen samples: hormones (Free T4, Total T3, TSH, FSH, LH, Inhibin B, Testosterone, SHBG, FAI, estradiol, Prolactin, Sperm concentration, sperm mobility, sperm morphology) | Age, BMI | Association between TDCIPP and Free T4 (β: −2.8; 95% CI: −4.6, −1.0; p: 0.004), TDCPP and prolactin (β:17.3; 95% CI: 4.1–32.2; p: 0.008), TPP and prolactin (β: 9.7; 95% CI: 2.3,18.9; p: 0.02) |
| 50 men | Age, BMI and abstinence period | Association between TPP and sperm concentration (β: −18.8; 95% CI: −30.1, −4.5; p: 0.01) |
Bold: Key elements of the table.