Prenatal Perfluorooctanoic Acid Exposure in CD-1 Mice: Low-Dose Developmental Effects and Internal Dosimetry

Abstract

Perfluorooctanoic acid (PFOA) is an environmental contaminant that causes adverse developmental effects in laboratory animals. To investigate the low-dose effects of PFOA on offspring, timed-pregnant CD-1 mice were gavage dosed with PFOA for all or half of gestation. In the full-gestation study, mice were administered 0, 0.3, 1.0, and 3.0 mg PFOA/kg body weight (BW)/day from gestation days (GD) 1-17. In the late-gestation study, mice were administered 0, 0.01, 0.1, and 1.0 mg PFOA/kg BW/day from GD 10-17. Exposure to PFOA significantly (p < 0.05) increased offspring relative liver weights in all treatment groups in the full-gestation study and in the 1.0 mg PFOA/kg group in the late-gestation study. In both studies, the offspring of all PFOA-treated dams exhibited significantly stunted mammary epithelial growth as assessed by developmental scoring. At postnatal day 21, mammary glands from the 1.0 mg/kg GD 10-17 group had significantly less longitudinal epithelial growth and fewer terminal end buds compared with controls (p < 0.05). Evaluation of internal dosimetry in offspring revealed that PFOA concentrations remained elevated in liver and serum for up to 6 weeks and that brain concentrations were low and undetectable after 4 weeks. These data indicate that PFOA-induced effects on mammary tissue (1) occur at lower doses than effects on liver weight in CD-1 mice, an observation that may be strain specific, and (2) persist until 12 weeks of age following full-gestational exposure. Due to the low-dose sensitivity of mammary glands to PFOA in CD-1 mice, a no observable adverse effect level for mammary developmental delays was not identified in these studies.

Per- and polyfluorinated substances (PFASs): Environmental challenges

“…In utero or early life exposure of rodents to PFOS, PFHxS or PFOA also caused developmental toxicities in adults, including pulmonary injuries [237], uterine and mammary gland development delays (or stimulation, depending on gender, strain and dose), sometimes at very low doses [26, 91,229,238,239]; glucose and lipid metabolic disorders [240];…”

“…Typical environmental exposures to and intakes of long-F-chain PFASs (PFOA and PFOS), along with some median lethal doses (LD 50 ), no-observed-adverse-effect-levels (NOAELs), lowest-observed-adverse-effect-levels (LOAELs), tolerable daily intakes (TDIs) and related data; logarithmic scales; data expressed as ng/g body weight (bw) or ng/mL (blood serum, milk, water) and ng/g bw /day, unless indicated otherwise. a: ng/g bw /day; b: up to 3 g/kg [86]; c: ng/g wet weight [13,35,87] [91]; bb: [103,104]; cc: serum level in pups [91]; dd: oral PFOS in a strain of mice [105]; ee: in serum [106][107][108]; ff: the C8 Health Project [108][109][110][111]; gg: [112]. …”

“…; d: [5, 16, 88]; e: [89]; f: reduced triiodothyronine (T3) level [89] ; g: PFOA gavage, ng/kg bw /day [26,90,91]; h: (TDIs, ng/g bw /day)[45]; i:[87]; j:[92]; k: ng/mL[93][94][95]; l:[14,47] m:[96]; n: [5, 41]; o: [5]; p: 40 g/kg bw intravenous (iv) emulsion[97], i.e. ~1.2 10 9 ng/mL serum (~65 mL blood/kg bw , Hct ~50%); q: liquid ventilation ~200 mL/kg bw over ~80 h[98]; r: 2.7 g C 8 F 17 Br/kg bw emulsion iv[97], or ~70 10 6 ng/mL serum (70 kg patient, 5 L blood, hematocrit 45%); s: F-octyl bromide, produced by telomerization, 99.9% pure; t: 7.7 g/kg bw , mice[99]; u: rodents[100]; v: ng/mL blood serum; w:[101]; x: [76, 102]; y: [87]; z: ng/g liver [52, 53]; aa: serum level gavage…”

Drinking Water in Germany: A Case Study of High Quality Drinking Water

“…18 mg per person per day, which is below 90 mg per person per day (or class III). Also recent reviews on low-dose compounds found effects at doses far below those related to the Cramer class III (Macon et al 2011 andAndrade et al 2006). Thus, a TTC of 0.15 mg per person per day has been determined as a 6 As the EU Drinking Water Directive (1998) noted, "for the purposes of the minimum requirements of this Directive, water intended for human consumption shall be wholesome and clean if it is free from any micro-organisms and parasites and from any substances which, in numbers or concentrations, constitute a potential danger to human health".…”

IR820 Nanoconjugates for Theranostic Applications

“…The initial concentration (concentration at injection) was estimated for an average 25-g mouse. The injected amount was approximately 6 µg dye based on the 0.24 mg/kg standardized dosage, with a mouse plasma volume of approximately 1.5 mL based on literature ratios of 58.5 mL plasma /kg body weight (Macon et al, 2011). This results in an initial concentration of approximately 4 µg dye/mL in plasma.…”