Windows of sensitivity to toxic chemicals in the development of the endocrine system: an analysis of ATSDR's toxicological profile database.

This review utilizes the robust database of literature contained in toxicological profiles developed by the Agency for Toxic Substances and Disease Registry. The aim was to use this database to identify developmental toxicity studies reporting alterations in hormone levels in the developing fetus and offspring and identify windows of sensitivity. We identified 74 oral exposure studies in rats that provided relevant information on 30 chemicals from 21 profiles. Most studies located provided information on thyroid hormones, with fewer studies on anterior pituitary, adrenal medulla, ovaries, and testes. No studies pertaining to hormones of the posterior pituitary, pancreas, or adrenal cortex were located. The results demonstrate that development of the endocrine system may be affected by exposure to environmental contaminants at many different points, including gestational and/or lactational exposure. Moreover, this review demonstrates the need for more developmental toxicity studies focused on the endocrine system and specifically alterations in hormone levels.

Per- and polyfluoroalkyl mixtures toxicity assessment "Proof-of-Concept" illustration for the hazard index approach.

The 2018 ATSDR mixture framework recommends three approaches including the hazard index (HI) for environmental mixture toxicity assessment. Per- and polyfluoroalkyls (PFAS) are found in our environment and general populations. Recent experimental mixture toxicity studies of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) and an assessment of 17 PFAS indicate the use of additivity for their joint toxicity assessment. The aim of this investigation was to detail the stepwise procedures and examine the extent and use of the HI approach for PFAS mixture assessment. Using estimated general public lifetime exposures (high, medium, and low), binary mixtures of PFOS and PFOA yielded, respectively, hazard indices (HIs) of 30.67, 8.33, and 3.63 for developmental toxicity; 10.67, 5.04, and 2.34 for immunological toxicity; 3.57, 1.68, and 0.78 for endocrine toxicity; 4.51, 1.73, and 0.79 for hepatic toxicity; and 15.08, 2.29, and 0.88 for reproductive toxicity. A heterogeneous mixture of PFOA, PFAS, dioxin (CDD), and polybrominated compounds (PBDE) for high exposure scenario yielded HIs of 30.99 for developmental, 10.77 for immunological, 3.64 for endocrine, 4.61 for hepatic, and 17.36 for reproductive effects. The HI values are used as a screening tool; the potential concern for exposures rises as HI values increase. For HI values >1, a follow-up including further analysis of specific exposures, use of internal dosimetry, and uncertainty factors is conducted before recommending appropriate actions. The HI approach appears suitable to address present-day PFAS public health concerns for initial assessment of multiple health effects, until further insights are gained into their mechanistic toxicology.The findings and conclusions in this article are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry.

Windows of Sensitivity to Toxic Chemicals in the Development of Cleft Palates.

Cleft lip and cleft palate are among the most common birth defects worldwide. There is a genetic component to the development of these malformations, as well as evidence that environmental exposures and prescription drug use may exacerbate or even produce these manifestations. Thus, it is important to understand the underlying mechanisms and when these exposures affect development of the growing fetus. The purpose of this investigation was to critically review the available literature related to orofacial cleft formation following chemical exposure and identify specific time frames for windows of sensitivity. Further, an aim was to evaluate the potential for predicting effects in humans based on animal studies. Evidence indicates that chemical causes of cleft palate development are due to dose and timing of exposure, susceptibility of the species (i.e., the genetic makeup), and mechanism of action. Several studies demonstrated that dose is a crucial factor; however, some investigators argued that even more important than dose was timing of exposure. Data show that the window of sensitivity to environmental teratogens in the development of cleft palates is quite narrow and follows closely the window of palatogenesis in the fetus of any given species.

Blood cadmium and depressive symptoms in young adults (aged 20-39 years).

BACKGROUND: Genetic and environmental factors contribute to the risk of depression and several studies have noted an association between tobacco smoke and depression. Cadmium is a neurotoxicant and the main source of non-occupational exposure is tobacco smoke. METHOD: We conducted a cross-sectional analysis of data from 2892 young adult (aged 20-39 years) participants of the National Health and Nutrition Examination Survey (NHANES) 2007-2010. Multivariate logistic regressions, adjusted for age, sex, race/ethnicity, education, poverty income ratio (PIR), obesity, alcohol intake, blood lead (BPb) and smoking status, were used to analyze the association between blood cadmium (BCd) and depressive symptoms, as determined by the score on the nine-item Patient Health Questionnaire (PHQ-9). RESULTS: Individuals in the highest BCd quartile had higher odds of having depressive symptoms [odds ratio (OR) 2.79, 95% confidence interval (CI) 1.84-4.25] than those in the lowest BCd quartile. Smoking status, but not BPb, was statistically significantly associated with depressive symptoms. Stratification by smoking status found that BCd was significantly associated with depressive symptoms in both non-smokers (OR 2.91, 95% CI 1.12-7.58) and current smokers (OR 2.69, 95% CI 1.13-6.42). CONCLUSIONS: This is the first study to report an association between BCd levels and depressive symptoms using a nationally representative sample. The association of cadmium with depressive symptoms was independent of smoking status. If this association is further confirmed, the continued efforts at reducing cadmium exposures, mainly through tobacco smoking cessation programs, may decrease the incidence of depression.