Table 5:

Developmental PFAS exposure and cardiovascular health

Exposure details	Window of exposure	Model	Epigenetic/molecular effect	Phenotype	Sex specificity	Reference
PFOA at dose of 2 mg/kg egg weight injected into eggs	Embryonic days 0–10	Chicken	Not investigated	Altered cardiomyocyte size, increased intracellular calcium	Not reported	[148]
PFOA at doses of 0, 0.5, 1, and 2 mg/kg of egg weight injected into eggs	Embryonic days 0–19	Chicken	Not investigated	Thinning of the right ventricular wall in 1 and 2 mg/kg dose groups relative to vehicle control in 19-day embryo hearts; changes in ventricular wall thickness, increased left ventricular mass, and increased heart rate in 1-day-old hatchling hearts	Not reported	[149]
PFOA (2 mg/kg) or HFPO-DA (1, 2, 4, and 8 mg/kg) injected into eggs	Embryonic days 0–21	Chicken	Not investigated	Thinning of the right ventricular wall and elevated heart rates with PFOA or HFPO-DA treatment	Not reported	[150]
PFuDA, PFDA, PFNA, and PFOA in doses 10 μM to 2 mM	Embryonic days 0–10	Xenopus	Not investigated	Pericardial edema at embryonic stage 26, heart malformations (enlarged atrium, loss of atrial septum, and thinner atrial and ventricular walls) in animals exposed to 130 μM PFDA or PFuDA	Not reported	[151]
PFOS at doses of 0.1, 0.6, and 2.0 mg/kg/day by oral gavage	Gestational days 2–21	Rat	Not investigated	Dose-dependent increase in apoptosis in heart at post-natal day 21	Not reported	[152]
PFOA 1, 10, and 20 mg/kg via intraperitoneal injection	Gestational days 5–9	Mouse	Not investigated	Cardiac mitochondrial swelling and reactive oxygen species at day 15 gestation	Not reported	[153]
1, 25, 50, and 100 μg/l PFOA in culture medium	2–30 h post-fertilization	Zebrafish	Not investigated	Reduced heart rate at 48 h post-fertilization for 25, 50, and 100 μg/l PFOA; increased apoptosis in heart at all doses at 72 h post-fertilization	Not reported	[154]
HFPO-DA at 1–125 mg/kg/day or 10–250 mg/kg/day via oral gavage	Gestational days 16–20 for 1–125 mg/kg/day and gestational days 8 until post-natal day 2 for 10–250 mg/kg/day	Rat	Not investigated	Elevated offspring triglycerides and cholesterol at highest doses for gestational day 8 to post-natal day 2 exposure	Not reported	[155]
PFOA at 0, 0.01, 0.1, 0.3, 1, 3, or 5 mg PFOA/kg body weight via oral gavage	Gestational days 1–17	Mouse	Not investigated	Increase in body weights in low dose exposed females at 20–29 weeks of age; increased serum insulin and leptin at lower doses at 21–33 weeks of age	Only data from females were reported in this manuscript	[156]
Six PFAS (Me-PFOSA-AcOH, PFDA, PFNA, PFOS, PFOA, and PFHxS) in maternal serum during third trimester	Late gestation	Human	Not investigated	Positive association between several PFAS and total cholesterol and triglycerides in pregnant women	This study investigated pregnant women	[157]
Levels of 10 PFAS (PFOS, PFOA, PFNA, PFDA, PFUnDA, PFHxS, PFDoA, PFBS, PFHpA, and PFOSA) in maternal blood during early pregnancy	Early gestation	Human	Not investigated	Increased risk of gestational diabetes with PFBS, PFOS, and PFHpA; positive correlation between PFOS, PFNA, PFDA, PFHxS, and PFHpA and glucose levels in oral glucose tolerance test; PFAS mixtures associated with abnormal glucose homeostasis	This study investigated pregnant women	[158]
PFHxS, PFOS, and PFOA), PFNA, and PFDA in maternal serum	Early gestation	Human	Not investigated	PFAS exposures (except PFHxS) associated with higher systolic and diastolic blood pressures (not all associations significant)	This study investigated pregnant women	[159]
First trimester maternal plasma levels of PFOA, PFOS, and PFHxS	Early gestation	Human	Not investigated	Increased risk of preeclampsia with PFHxS in women carrying female fetuses; increased risk of hypertension with PFOS and PFHxS in women carrying male fetuses	This study investigated pregnant women; associations differed based on fetal sex	[160]
Levels of 27 PFAS in maternal blood and cord blood plasma before and during delivery	Late gestation	Human	Not investigated	Increased odds of septal defects with exposure to 6 m-PFOS or PFDA in maternal blood; increased odds of conotruncal defects with exposure to PFOS or PFDoA in maternal blood	Not reported	[165]
Estimated serum PFOA concentration during pregnancy	Gestation	Human	Not investigated	Weak association between maternal serum PFOA concentrations and congenital heart defects	Not reported	[166]
Estimated serum PFOA concentration during pregnancy	Gestation	Human	Not investigated	No significant association between maternal serum PFOA concentrations and congenital heart defects	Not reported	[167]
PFOA exposure, assessed by Little Hocking Water Association service category	Gestation	Human	Not investigated	No significant association between maternal PFOA exposure and congenital defects of any kind	Not reported	[168]
Serum levels of 12 PFAS in children between 12 and 20 years of age	Adolescence	Human	Not investigated	Strong positive association between PFOS and diastolic blood pressure in males in linear model, but no significant association in non-linear model	Yes—Effects in males but not females	[48]
Serum levels of PFOA, PFOS, PFHxS, and PFNA in obese children 8–12 years of age	Pre-adolescence	Human	Not investigated	Risk of elevated systolic blood pressure and LDL/total cholesterol with PFNA; elevated LDL cholesterol with PFOA and PFOS; elevated total cholesterol with PFOA	No	[169]
Serum concentrations of 18 PFAS in adolescents aged 15–19 years	Adolescence	Human	Not investigated	Positive association between PFOS, PFNA, PFDA, PFUnDA, and apolipoprotein B, total- and LDL cholesterol; positive association between total PFAS, PFOS, PFNA, PFDA, PFUnDA, and risk of dyslipidemia; positive association between total PFAS, PFHxS, PFOS, PFOA, and hypertension; positive association between PFHpS and PFHxS and risk of obesity	Not reported	[170]
Levels of PFHxS, PFOS, PFOA, and PFNA in first trimester maternal plasma	Early gestation	Human	Not investigated	Positive association between prenatal PFHxS and triglycerides; positive association between PFNA and cardiometabolic risk score at 4 years of age	No	[171]
Serum concentrations of 12 PFAS in adolescents aged 14–19 years or children aged 8–11 years	Childhood and adolescence	Human	Not investigated	Increased total and LDL cholesterol with all PFAS in adolescents; increased total, LDL and HDL, cholesterol with PFOS and PFNA in children; increased HDL cholesterol with PFOA and PFHxS in children; lower BMI z-score with higher concentrations of PFAS	Yes—Stronger associations observed in girls	[172]
Levels of 5 PFAS in cord blood in World Trade Center birth cohort	Gestation	Human	Not investigated	Higher total cord blood lipids with PFOS, PFOA, and PFHxS levels; higher total cholesterol and lower triglycerides with PFDS; higher triglycerides with PFOA and PFHxS exposure	Not reported	[173]
Blood PFOS, PFHxS, and PFOA levels in children 8–14 years of age	Childhood–adolescence	Human	Not investigated	Increased blood glucose (2 h oral glucose tolerance test) with PFOA and PFHxS, or increased glucose area under the curve for PFHxS; significant alterations in lipids and amino acids with PFAS exposure	No	[174]
PFAS levels in maternal plasma (median 9.7 weeks gestation) and in children (median 7.7 years of age)	Early gestation and childhood	Human	Not investigated	Higher levels of PFOS, PFOA, PFDeA associated with higher total cholesterol and/or LDL cholesterol among girls; higher HDL cholesterol with PFAS among boys and girls	Yes	[175]
Levels of PFAS (PFOS, PFOA, PFNA, PFDA, and PFHxS) in 9-year-old children from the European Youth Heart Study	Childhood	Human	Not investigated	Inverse correlation between PFOA, PFDA, PFHxS, and leptin; positive and negative associations between adiponectin and PFOA or PFHxS, respectively, in boys	Yes	[176]
Maternal serum PFOA levels at gestational week 30	Late gestation	Human	Not investigated	Increased risk of overweight or obesity, larger waist circumference, serum insulin, and leptin with PFOA exposure in girls at 20 years of age	Yes	[177]
Maternal PFOA and PFOS levels in serum at gestational age 24 ± 10 weeks	Mid-gestation	Human	Not investigated	Increased risk of waist to height ratio > 0.5 with PFOA or PFOS at 5–9 years of age, with the PFOS association slightly greater in Greenlandic girls than boys	Yes	[178]
Levels of PFOS and PFOA in newborn dried blood spots	Late gestation	Human	Not investigated	Lower BMI with PFOA and PFOS, with stronger associations observed for girls	Yes	[179]
Levels of PFOS and PFOA in maternal plasma during 1st and 2nd trimester, and cord blood	Gestation	Human	Not investigated	Inverse association between maternal PFOA, PFOS, and children’s weight and body mass index in first year of life in boys, with no association observed in girls	Yes	[180]
Levels of PFOA and four other long-chain PFAS in maternal serum during 3rd trimester	Late gestation	Human	Not investigated	Inverse association between PFNA, PFDeA, PFUnDA, PFDoDA, and birth weight in girls; increased odds of small for gestational age with PFDeA, PFUnDA in girls; lower average height z-score with PFDeA, PFUnDA, PFDoDA; reduced childhood height in boys with PFNA, PFDoDA exposure	Yes	[181]
Maternal plasma levels of PFOS and PFOA during 1st and 2nd trimester	Early gestation	Human	Not investigated	No significant associations between maternal PFOS, PFOA and body mass index, risk of overweight, and waist circumference at 7 years of age	Not reported	[182]
Levels of PFOS, PFOA, and PFHxS in maternal serum, median gestational age 15 weeks	Early-mid gestation	Human	Not investigated	Inverse relationship between PFAS and birth weight; positive relationship between PFOA and body weight at 20 months of age	Only females were evaluated	[183]