Last data update: Sep 23, 2024. (Total: 47723 publications since 2009)
Records 1-4 (of 4 Records) |
Query Trace: McLanahan ED [original query] |
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Public health evaluation of PFAS exposures and breastfeeding: A systematic literature review
Hoadley L , Watters M , Rogers R , Siegmann Werner L , Markiewicz KV , Forrester T , McLanahan ED . Toxicol Sci 2023 194 (2) 121-137 Per- and polyfluoroalkyl substances (PFAS) are a class of man-made chemicals that are persistent in the environment. They can be transferred across the placenta to fetuses and through human milk to infants. The American Academy of Pediatrics advises that the benefits of breastfeeding infants outweigh the potential risks of harm from environmental chemicals in "nearly every circumstance." However, there are few chemical-specific summaries of the potential harms of exposure to PFAS during the neonatal period through breastfeeding. This systematic review explores whether exposure to PFAS through breastfeeding is associated with adverse health outcomes among infants and children using evidence from human and animal studies. Systematic searches identified 4,297 unique records from 7 databases. The review included 37 total articles, including 9 animal studies and 1 human study measuring the direct contribution of exposure of the infant or pup through milk for any health outcome. Animal studies provided evidence of associations between exposure to PFOA through breastfeeding and reduced early life body weight gain, mammary gland development and thyroid hormone levels. They also provided limited evidence of associations between PFOS exposure through breastfeeding with reduced early life body weight gain and cellular changes in the hippocampus. The direct relevance of any of these outcomes to human health is uncertain, and it is possible that many adverse health effects of exposure through breastfeeding have not yet been studied. This review documents the current state of science and highlights the need for future research to guide clinicians making recommendations on infant feeding. |
Incorporation of fetal and child PFOA dosimetry in the derivation of health-based toxicity values
Kieskamp KK , Worley RR , McLanahan ED , Verner MA . Environ Int 2017 111 260-267 BACKGROUND: Multiple agencies have developed health-based toxicity values for exposure to perfluorooctanoic acid (PFOA). Although PFOA exposure occurs in utero and through breastfeeding, current health-based toxicity values have not been derived using fetal or child dosimetry. Therefore, current values may underestimate the potential risks to fetuses and nursing infants. OBJECTIVE: Using fetal and child dosimetry, we aimed to calculate PFOA maternal human equivalent doses (HEDs), corresponding to a developmental mouse study lowest observed adverse effect level (LOAEL, 1mg/kg/day). Further, we investigated the impact of breastfeeding duration and PFOA half-life on the estimated HEDs. METHODS: First, a pharmacokinetic model of pregnancy and lactation in mice was used to estimate plasma PFOA levels in pups following a maternal exposure to 1mg PFOA/kg/day for gestational days 1-17. Four plasma PFOA concentration metrics were estimated in pups: i) average prenatal; ii) average postnatal; iii) average overall (prenatal and postnatal); and iv) maximum. Then, Monte Carlo simulations were performed using a pharmacokinetic model of pregnancy and lactation in humans to generate distributions of maternal HEDs that would result in fetal/child plasma levels equivalent to those estimated in pups using the mouse model. Median (HED50) and 1st percentile (HED01) of calculated HEDs were calculated. RESULTS: Estimated PFOA maternal HED50s ranged from 3.0x10(-4) to 1.1x10(-3)mg/kg/day and HED01s ranged from 4.7x10(-5) to 2.1x10(-4)mg/kg/day. All calculated HEDs were lower than the HED based on adult dosimetry derived by the Environmental Protection Agency (EPA) (5.3x10(-3)mg/kg/day). CONCLUSION: Our results suggest that fetal/child dosimetry should be considered when deriving health-based toxicity values for potential developmental toxicants. |
Dietary iodine sufficiency and moderate insufficiency in the lactating mother and nursing infant: A computational perspective
Fisher W , Wang J , George NI , Gearhart JM , McLanahan ED . PLoS One 2016 11 (3) e0149300 The Institute of Medicine recommends that lactating women ingest 290 mug iodide/d and a nursing infant, less than two years of age, 110 mug/d. The World Health Organization, United Nations Children's Fund, and International Council for the Control of Iodine Deficiency Disorders recommend population maternal and infant urinary iodide concentrations ≥ 100 mug/L to ensure iodide sufficiency. For breast milk, researchers have proposed an iodide concentration range of 150-180 mug/L indicates iodide sufficiency for the mother and infant, however no national or international guidelines exist for breast milk iodine concentration. For the first time, a lactating woman and nursing infant biologically based model, from delivery to 90 days postpartum, was constructed to predict maternal and infant urinary iodide concentration, breast milk iodide concentration, the amount of iodide transferred in breast milk to the nursing infant each day and maternal and infant serum thyroid hormone kinetics. The maternal and infant models each consisted of three sub-models, iodide, thyroxine (T4), and triiodothyronine (T3). Using our model to simulate a maternal intake of 290 mug iodide/d, the average daily amount of iodide ingested by the nursing infant, after 4 days of life, gradually increased from 50 to 101 mug/day over 90 days postpartum. The predicted average lactating mother and infant urinary iodide concentrations were both in excess of 100 mug/L and the predicted average breast milk iodide concentration, 157 mug/L. The predicted serum thyroid hormones (T4, free T4 (fT4), and T3) in both the nursing infant and lactating mother were indicative of euthyroidism. The model was calibrated using serum thyroid hormone concentrations for lactating women from the United States and was successful in predicting serum T4 and fT4 levels (within a factor of two) for lactating women in other countries. T3 levels were adequately predicted. Infant serum thyroid hormone levels were adequately predicted for most data. For moderate iodide deficient conditions, where dietary iodide intake may range from 50 to 150 mug/d for the lactating mother, the model satisfactorily described the iodide measurements, although with some variation, in urine and breast milk. Predictions of serum thyroid hormones in moderately iodide deficient lactating women (50 mug/d) and nursing infants did not closely agree with mean reported serum thyroid hormone levels, however, predictions were usually within a factor of two. Excellent agreement between prediction and observation was obtained for a recent moderate iodide deficiency study in lactating women. Measurements included iodide levels in urine of infant and mother, iodide in breast milk, and serum thyroid hormone levels in infant and mother. A maternal iodide intake of 50 mug/d resulted in a predicted 29-32% reduction in serum T4 and fT4 in nursing infants, however the reduced serum levels of T4 and fT4 were within most of the published reference intervals for infant. This biologically based model is an important first step at integrating the rapid changes that occur in the thyroid system of the nursing newborn in order to predict adverse outcomes from exposure to thyroid acting chemicals, drugs, radioactive materials or iodine deficiency. |
Marginal iodide deficiency and thyroid function: dose-response analysis for quantitative pharmacokinetic modeling
Gilbert ME , McLanahan ED , Hedge J , Crofton KM , Fisher JW , Valentin-Blasini L , Blount BC . Toxicology 2011 283 (1) 41-8 Severe iodine deficiency (ID) results in adverse health outcomes and remains a benchmark for understanding the effects of developmental hypothyroidism. The implications of marginal ID, however, remain less well known. The current study examined the relationship between graded levels of ID in rats and serum thyroid hormones, thyroid iodine content, and urinary iodide excretion. The goals of this study were to provide parametric and dose-response information for development of a quantitative model of the thyroid axis. Female Long Evans rats were fed casein-based diets containing varying iodine (I) concentrations for 8 weeks. Diets were created by adding 975, 200, 125, 25, or 0 mcg/kg I to the base diet ( approximately 25 mcg I/kg chow) to produce 5 nominal I levels, ranging from excess (basal+added I, Treatment 1: 1000 mcg I/kg chow) to deficient (Treatment 5: 25 mcg I/kg chow). Food intake and body weight were monitored throughout and on 2 consecutive days each week over the 8-week exposure period, animals were placed in metabolism cages to capture urine. Food, water intake, and body weight gain did not differ among treatment groups. Serum T4 was dose-dependently reduced relative to Treatment 1 with significant declines (19 and 48%) at the two lowest I groups, and no significant changes in serum T3 or TSH were detected. Increases in thyroid weight and decreases in thyroidal and urinary iodide content were observed as a function of decreasing I in the diet. Data were compared with predictions from a recently published biologically based dose-response (BBDR) model for ID. Relative to model predictions, female Long Evans rats under the conditions of this study appeared more resilient to low I intake. These results challenge existing models and provide essential information for development of quantitative BBDR models for ID during pregnancy and lactation. |
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