Behavioral effects in adult rats exposed to low doses of a phthalate mixture during the perinatal or adolescent period (original) (raw)
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Bis (2-ethylhexyl) phthalate (DEHP) is a typical environmental endocrine disruptor. Previous studies have shown that prenatal exposure to DEHP can disrupt neurobehavioral development in early life, adolescence and even adulthood. The goal of the current study was to investigate whether gestation exposure to DEHP impairs neurobehavior in the offspring of elderly mice. DEHP (200 mg/kg) was administered orally to pregnant mice during the second or last trimester of pregnancy. Exposure to gestational DEHP at the final stage but not at the intermediate stage increased anxiety and depression-like behavior during prolonged immobility in men during forced swimming tasks, reduced center stay time in open field tests, and reduced time to access the open arm elevated cross maze. No differences in depression and anxiety-like behavior were detected in the female offspring of the three groups. On the other hand, DEHP exposure in the middle but not the last stage of pregnancy resulted in impaired spatial memory, longer search time of learning platform in males, and shorter target quadrant distance in the water maze. In contrast, female offspring showed no significant differences in spatial memory and learning functions between the three groups. In summary, prenatal exposure to DEHP impairing neurobehavior in the offspring of elderly mice in a stage-dependent and sex-specific manner.
Environmental Health Perspectives, 2014
Background: There is concern over potential neurobehavioral effects of prenatal phthalate exposures, but available data are inconsistent. oBjectives: We examined associations between prenatal urinary concentrations of phthalate metabolites and neurobehavioral scores among children. Methods: We measured phthalate metabolite concentrations in urine samples from 153 pregnant participants in the Study for Future Families, a multicenter cohort study. Mothers completed the Child Behavior Checklist when the children were 6-10 years of age. We estimated overall and sexspecific associations between phthalate concentrations and behavior using adjusted multiple regression interaction models. results: In boys, concentrations of monoisobutyl phthalate were associated with higher scores for inattention (β = 0.27; 95% CI: 0.04, 0.50), rule-breaking behavior (β = 0.20; 95% CI: 0.01, 0.38), aggression (β = 0.34; 95% CI: 0.09, 0.59), and conduct problems (β = 0.39; 95% CI: 0.20, 0.58), whereas the molar sum of di(2-ethylhexyl) phthalate metabolites was associated with higher scores for somatic problems (β = 0.15; 95% CI: 0.03, 0.28). Higher monobenzyl phthalate concentrations were associated with higher scores for oppositional behavior (β = 0.16; 95% CI: 0.01, 0.32) and conduct problems (β = 0.21; 95% CI: 0.06, 0.37) in boys, but with reduced anxiety scores in girls (β =-0.20; 95% CI:-0.39,-0.01). In general, the associations reported above were close to the null among girls. Model coefficients represent the difference in the square root-transformed outcome score associated with a 1-unit increase in log-transformed metabolites. conclusions: Our results suggest associations between exposure to certain phthalates in late pregnancy and behavioral problems in boys. Given the few studies on this topic and methodological and population differences among studies, additional research is warranted.
Toxicological sciences : an official journal of the Society of Toxicology, 2018
Phthalate administration to male rats has been shown to negatively impact neural development while development of the female rat brain is less affected. Because a number of exogenous agents have been shown to interfere with dopamine function, we evaluated post-adolescent behavioral (operant conditioning for food reward and locomotor activity), histological (tyrosine hydroxylase; TH), and genetic (mRNA levels) outcomes of preadolescent (postnatal days [PND] 16-22) phthalate exposure. Male and female Long-Evans rats were administered 4 doses (0, 1, 10, or 20 mg/kg) of di-(2-ethylhexyl)phthalate (DEHP) i.p. from PND16 to 22. Rats were trained on an operant task to bar press for chocolate-flavored pellets from PND55-63 then euthanized on PND78. The 10 mg/kg DEHP dose was associated with elevated bar pressing for food reward during acquisition and extinction while the 20 mg/kg dose was associated with elevated locomotor activity in both males and females. Stereological analysis revealed ...
International Journal of Environmental Research and Public Health
Phthalates are well-known, ubiquitous environmental contaminants influencing children’s health and their neurodevelopment. However, results of the previously conducted studies are not entirely conclusive. The aim of this review is to present the current state of knowledge with respect to the association between the prenatal phthalate exposure and sex-specific child neurodevelopmental outcomes. A systematic search of the literature was carried out to identify the studies that analyse the sex-specific association between prenatal exposure to phthalates and cognitive, psychomotor outcomes and behavioural and emotional problems. The search was conducted in May 2021, and it was limited to the papers published in English between January 2015 and April 2021. The following databases were used: PubMed, Scopus and Elsevier. The selection process was carried out by two independent authors according to the inclusion criteria. Of a total of 7542 records, 17 epidemiological studies met the inclus...
Prenatal Phthalate Exposure Is Associated with Childhood Behavior and Executive Functioning
Environmental Health Perspectives, 2010
Biomonitoring of phthalate metabolites has identified virtually ubiquitous human expo sure internationally and for all age groups (Centers for Disease Control and Prevention 2005). Phthalate metabolites have been detected in many body tissues including urine, blood, semen, amniotic fluid, and breast milk (National Research Council 2008). Despite the relatively rapid clearance of phthalate metabolites, urine phthalate biomarker meas urements are relatively stable over periods of days to months (Adibi et al. 2008; Hauser et al. 2004; Teitelbaum et al. 2008), probably because exposure sources and patterns of usage of phthalatecontaining products are com mon and fairly consistent (Hauser et al. 2004; Teitelbaum et al. 2008). At least 10 different phthalates are used commercially as plasticizers, solvents, anti foam agents, or alcohol denaturants. High molecularweight phthalates (HMWP) [e.g., di(2ethylhexyl) phthalate (DEHP)] can be found in tubing, vinyl flooring, and wall covering. Lowmolecularweight phthalates (LMWP) (e.g., diethyl phthalate) more com monly can be present in personal care prod ucts (fragrances, shampoo, cosmetics, and nail polish). Phthalates are also found as both inert and active ingredients in some pesticide formulations. Human exposure to phthalates
Behavioral Effects of Exposure to Phthalates in Female Rodents: Evidence for Endocrine Disruption?
International Journal of Molecular Sciences, 2022
Phthalates have been widely studied for their reprotoxic effects in male rodents and in particular on testosterone production, for which reference doses were established. The female rodent brain can also represent a target for exposure to these environmental endocrine disruptors. Indeed, a large range of behaviors including reproductive behaviors, mood-related behaviors, and learning and memory are regulated by sex steroid hormones. Here we review the experimental studies addressing the effects and mechanisms of phthalate exposure on these behaviors in female rodents, paying particular attention to the experimental conditions (period of exposure, doses, estrous stage of analyses etc.). The objective of this review is to provide a clear picture of the consistent effects that can occur in female rodents and the gaps that still need to be filled in terms of effects and mode(s) of action for a better risk assessment for human health.
Prenatal Exposure to Phthalates and Neurodevelopment in the CHAMACOS Cohort
Environmental Health Perspectives, 2019
BACKGROUND: Previous studies suggest that prenatal exposure to phthalates, ubiquitous synthetic chemicals, may adversely affect neurodevelopment. However, data are limited on how phthalates affect cognition, executive function, and behavioral function into adolescence. OBJECTIVE: We aimed to investigate associations of prenatal phthalate exposure with neurodevelopment in childhood and adolescence in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study. METHODS: We examined associations between maternal urinary phthalate metabolite concentrations measured twice during pregnancy and a range of neurodevelopmental outcomes from ages 7 through 16 y in the CHAMACOS birth cohort (n = 334). We used age-specific linear regression models and generalized estimating equation models to assess longitudinal effects and examined differences by sex. RESULTS: Phthalate metabolites were detected in 88%-100% of samples, depending on the metabolite. Associations of phthalates with neurodevelopmental outcomes were largely null with some noteworthy patterns. Higher prenatal concentrations of metabolites of low-molecular weight phthalates (RLMW) were associated with more self-reported hyperactivity [b = 0:8, 95% confidence interval (CI): 0.1, 1.4 per 2-fold increase in RLMW phthalates], attention problems (b = 1:5, 95% CI: 0.7, 2.2), and anxiety (b = 0:9, 95% CI: 0.0, 1.8) at age 16. We observed sex-specific differences for the sums of high-molecular-weight and di(2-ethylhexyl) metabolites and cognitive outcomes (e.g., b for Full-Scale IQ for boys =
Perinatal Exposure to Phthalates: From Endocrine to Neurodevelopment Effects
International Journal of Molecular Sciences, 2021
Phthalates, as other endocrine disrupting chemicals (EDCs), may alter the homeostasis and the action of hormones and signaling molecules, causing adverse health outcomes. This is true especially for infants, who are both more exposed and sensitive to their effects. Phthalates are particularly harmful when the exposure occurs during certain critical temporal windows of the development, such as the prenatal and the early postnatal phases. Phthalates may also interfere with the neuroendocrine systems (e.g., thyroid hormone signaling or metabolism), causing disruption of neuronal differentiation and maturation, increasing the risk of behavioral and cognitive disorders (ADHD and autistic behaviors, reduced mental, psychomotor, and IQ development, and emotional problems). Despite more studies being needed to better understand the role of these substances, plenty of evidence suggests the impact of phthalates on the neuroendocrine system development and function. This review aims to update ...
Associations of Prenatal Exposure to Phthalates with Measures of Cognition in 4.5-Month-Old Infants
International Journal of Environmental Research and Public Health, 2021
The association of prenatal phthalate exposure with physical reasoning was assessed in 159 (78 female; 81 male) 4.5-month-old infants from a prospective cohort. Phthalate metabolites were quantified in urine from 16–18 gestational weeks and a pool of five urines from across pregnancy. Infants’ looking times to physically impossible and possible events were recorded via infrared eye-tracking. Infants that recognize that one of the events is impossible will look at that event longer. Associations of phthalate biomarkers with looking time differences (impossible–possible) were adjusted for maternal age, infant sex, and order of event presentation, and effect modification by infant sex was assessed. Each interquartile range (IQR) increase of monoethyl phthalate in the pooled sample was associated with females’ increased looking time (β = 1.0; 95%CI = 0.3, 1.7 s) to the impossible event. However, for males, an IQR increase in monoethyl phthalate at 16–18 weeks (β = −2.5; 95%CI = −4.4,−0....