Table 9.
NMDRCs for EDCs identified in the epidemiology literature
| Chemicals by chemical class | Affected endpoint | NMDRC | Study subjects | Refs. |
|---|---|---|---|---|
| Insecticides | ||||
| Trans-nonachlor | Diabetes incidence | Highest risk in groups with intermediate exposures (quartile 2) | CARDIA participants, case-control study (n = 90 cases and n = 90 controls) | 833 |
| Telomere length in peripheral leukocytes | Increased length in intermediate exposures (quintile 4) | Adults aged 40+ (Korea, n = 84) | 591 | |
| p,p′-DDE | BMI, triglyceride levels, HDL cholesterol | Highest risk in groups with intermediate exposures (quartile 3) | CARDIA participants (n = 90 controls from nested case control study) | 590 |
| Risk of rapid infant weight gain | For infants born to women of normal weight prepregnancy, risk is highest with intermediate exposures. | Infants from Childhood and the Environment project, Spain (n = 374 from normal prepregnancy weight mothers; n = 144 from overweight mothers) | 834 | |
| Telomere length in peripheral leukocytes | Increased length with intermediate exposures (quintile 4) | Adults aged 40+ (Korea, n = 84) | 591 | |
| Oxychlordane | Bone mineral density of arm bones | With low exposures, fat mass had inverse associations with bone mineral density; with high exposures, fat mass had positive associations with bone mineral density. | NHANES 1999–2004 participants, aged 50+ (n = 679 women, n = 612 men) | 835 |
| Plastics | ||||
| Mono-methyl phthalate (MMP) | Atherosclerotic plaques | Increased risk in intermediate exposure groups (quintiles 2–4) | Adults aged 70, living in Sweden (n = 1016) | 836 |
| Perfluorinated compounds | ||||
| PFOA | Arthritis (self-reported) | Increased risk in intermediate exposure groups (quartile 2) | NHANES participants, aged 20+ (both sexes, n = 1006) | 837 |
| Fire retardants | ||||
| PBB-153 | Blood triglyceride levels | Increased risk in intermediate exposure groups (quartile 2) | NHANES participants, aged 12+ (n = 637) | 604 |
| PBDE-153 | Prevalence of diabetes, | Prevalence of diabetes highest in intermediate groups (quartiles 2–3 relative to individuals with undetectable levels) | NHANES participants, aged 12+ (n = 1367) | 604 |
| Prevalence of metabolic syndrome, levels of blood triglycerides | Prevalence of metabolic syndrome highest in intermediate exposure groups (quartile 2 relative to individuals with undetectable levels); blood triglycerides highest in low exposure groups (quartile 1 relative to individuals with undetectable levels) | NHANES participants, aged 12+ (n = 637) | 604 | |
| PCB | ||||
| PCB-74 | Triglyceride levels | Lowest levels are observed in intermediate groups (quartile 2) | CARDIA participants (n = 90 controls from nested case-control study) | 590 |
| PCB-126 | Bone mineral density in right arm | With low exposures, fat mass had inverse associations with bone mineral density; with high exposures, fat mass had positive associations with bone mineral density | NHANES participants, aged <50 (n = 710 women, n = 768 men) | 835 |
| PCB-138 | Bone mineral density in right arm | With low exposures, fat mass had inverse associations with bone mineral density; with high exposures, fat mass had positive associations with bone mineral density | NHANES participants, women aged 50+ (n = 679 women, n = 612 men) | 835 |
| PCB-153 | Telomere length in peripheral leukocytes | Increased length with intermediate exposure groups (quintile 4) | Adults aged 40+ (Korea, n = 84) | 591 |
| PCB-170 | Diabetes incidence | Highest risk in groups with intermediate exposures (quartile 2) | CARDIA participants, case-control study (n = 90 cases and n = 90 controls) | 833 |
| Endometriosis | Decreased risk in groups with intermediate exposures (quartile 3) | Participants from the Women at Risk of Endometriosis (WREN) study, 18–49 yr old, case-control study (n = 251 cases; n = 538 controls) | 838 | |
| PCB-172 | DNA hypomethylation (by Alu assay) | Highest levels of hypomethylation in groups with lowest and highest exposures | Adults aged 40+ (Korea, n = 86) | 839 |
| PCB-180a | BMI | Highest BMI with intermediate exposures (quartile 2) | CARDIA participants (n = 90 controls from nested case control study) | 590 |
| PCB-187a | HDL cholesterol levels | Lowest levels with intermediate exposures (quartile 2) | CARDIA participants (n = 90 controls from nested case control study) | 590 |
| PCB 196–203 | Diabetes incidence | Highest risk in groups with intermediate exposures (quartile 2) | CARDIA participants, case-control study (n = 90 cases and n = 90 controls) | 833 |
| PCB-196 | Endometriosis | Decreased risk in groups with intermediate exposures (quartile 3) | Participants from the Women at Risk of Endometriosis (WREN) study, 18–49 yr old, case-control study (n = 251 cases; n = 538 controls) | 838 |
| PCB-199a | Triglyceride levels | Highest risk in groups with intermediate exposures (quartiles 2–3) | CARDIA participants (n = 90 controls from nested case control study) | 590 |
| PCB-201 | Endometriosis | Decreased risk in groups with intermediate exposures (quartiles 2–3) | Participants from the Women at Risk of Endometriosis (WREN) study, 18–49 yr old, case-control study (n = 251 cases, n = 538 controls) | 838 |
| Heavy metals | ||||
| Selenium | Fasting glucose levels (by modeled exposure) | Intermediate exposures have highest fasting glucose levels | NHANES 2003- 2004 participants, aged 40+ (n = 917) | 840 |
| Glycosylated hemoglobin (by modeled exposure) | Intermediate exposures have highest % glycosylated hemoglobin | NHANES 2003- 2004 participants, aged 40+ (n = 917) | 840 | |
| Diabetes incidence (by modeled exposure) | Intermediate exposures have highest risk for diabetes | NHANES 2003- 2004 participants, aged 40+ (n = 917) | 840 | |
| Blood triglyceride levels | Intermediate exposures have highest triglyceride levels | NHANES participants, aged 40+ (n = 1159) | 841 | |
| Arsenic | Cytokines in umbilical cord blood | Lower inflammatory markers at intermediate exposures (quartile 2) | Pregnant women in Bangladesh (n = 130) | 842 |
| Manganese | Mental development scores in infants and toddlers | Intermediate exposures had highest mental development scores at 12 months of age; association lost in older toddlers | 12-month-old infants, Mexico (n = 301) | 843 |
| Sperm count, motility and morphology | Intermediate doses had lowest sperm counts and motility; intermediate doses also had the worst sperm morphologies | Men aged 18–55 (infertility clinic patients, n = 200) | 844 | |
| Mixtures | ||||
| 31 POP | Diabetes incidence | Highest incidence in intermediate groups (sextiles 2–3) | CARDIA participants, case-control study (n = 90 cases and n = 90 controls) | 833 |
| 16 POP | Diabetes incidence | Highest incidence in intermediate groups (sextiles 2–3) | CARDIA participants, case-control study (n = 90 cases and n = 90 controls) | 833 |
| Non-dioxin-like PCB (mix) | Metabolic syndrome | Highest incidence in intermediate groups (quartile 3) | NHANES 1999–2002 participants, aged 20+ (n = 721) | 845 |
| Dioxin-like PCB (mix) | Triacylglycerol levels by quartile of exposure | Highest levels in intermediate groups (quartile 3) | NHANES 1999–2002 participants, aged 20+ (n = 721) | 845 |
| Additional supportive evidence for NMDRC in the epidemiology literature | ||||
| Insecticides | ||||
| Heptachlor epoxide | Prevalence of newly diagnosed hypertension | Highest risk in intermediate groups (quartile 2); other endpoints do not have NMDRC | NHANES participants, women aged 40+, cross-sectional (n = 51 cases, n = 278 total) | 26 |
| β-Hexachlorocyclohexane | Triacylglycerol levels by quartile of exposure | Highest risk in intermediate group (quartile 2) | NHANES participants, aged 20+ (n = 896 men, 175 with metabolic syndrome) | 845 |
| Plastics | ||||
| Mono-N-butyl phthalate (MBP) | BMI, age-specific effects | Effects seen only in elderly participants (age 60–80); risk is lowest in quartile 3 | NHANES male participants (n = 365; age 60–80) | 470 |
| Mono-benzyl phthalate (MBzP) | BMI, age-specific effects | Effects seen only in young participants (age 6–11); risk is highest in quartiles 2–3 | NHANES participants (both sexes, n = 329 males; n = 327 females) | 470 |
| Flame retardants | ||||
| PFOA | Thyroid disease (self-reported) | Lowest risk in intermediate groups (quartile 3) | NHANES 1999–2000, 2003–2006 participants, males aged 20+ (n = 3974) | 837 |
| Dioxin and related compounds | ||||
| TCDD | Age at natural menopause | Highest for intermediate exposure group (quintile 4) | Highly exposed women; Seveso Women's Health Study participants (n = 616) | 468 |
| HCDD | Bone mineral density in right arm by quintile of fat mass | With low exposures, fat mass had inverse associations with bone mineral density; with high exposures, fat mass had positive associations with bone mineral density | NHANES participants, women aged 50+ (n = 679 women, n = 612 men) | 835 |
| Heavy metals | ||||
| Selenium | Prevalence of peripheral artery disease | Disease prevalence decreased in intermediate doses, then increased gradually with higher doses | NHANES participants, aged 40+ (n = 2062) | 469 |
BMI, Body mass index; HCDD, hexachloro-dibenzo-p-dioxin; HDL, high-density lipoprotein; PCB, polychlorinated biphenyls; PFOA, perfluorooctanoic acid; PBB, polybrominated biphenyl; PBDE, polybrominated diphenyl ethers; POP, persistent organic pollutants.
a
In many cases, multiple chemicals in the same class had similar effects. A few chemicals were selected to illustrate the observed effect. This list is not comprehensive.