Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females. Notably, proliferative changes with altered cell foci and focal inflammation were observed around bile ducts in the liver of all BPA-dosed groups in males, which achieved statistical significance from 0.5 mg/kg (ANOVA, Dunnett’s test, p<0.05). Toxicokinetic analysis revealed that systemic exposure to BPA was greater at early age (e.g., 210-fold in Cmax, and 26-fold in AUC at 50 mg/kg in male on day 1 over day 90) and in females (e.g., 4-fold in Cmax and 1.6-fold in AUC at 50 mg/kg vs. male on day 1), which might have stemmed from either age- or gender-dependent differences in metabolic capacity. These results may serve as evidence for the association between risk of cancer and exposure to low-dose BPA, especially in young children, as well as for varying toxicity of xenobiotics in different age and gender groups.

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Phthalates widely used in the manufacture of plastics have deeply penetrated into our everyday lives. Recently, a concern over the toxicity of phthalates on thyroid, has been raised but in most of cases, the doses employed were unrealistically high. To investigate the effects of phthalates on thyroid, we investigated the effects of the repeated oral exposure to low to high doses (0.3, 3, 30 and 150 mg/kg) di-2-ethylhexylphthalate (DEHP) from weaning to maturity for 90 days in juvenile rats on the thyroid. The histological examination revealed that DEHP significantly induced hyperplasia in the thyroid from the doses of 30 mg/kg, which was confirmed with Ki67 staining. In line with this finding, increased mRNA expression of thyrotropin releasing hormone (Trh) was observed in the thyroid of female at 0.3 mg/kg and 150 mg/kg as determined by RNAseq analysis. Moreover, significantly increased expression of parathyroid hormone (Pth) in the female at 0.3 mg/kg, and thyroglobulin (Tg) and thyroid hormone responsive (Thrsp) in the male at 0.3 mg/kg were noted in the blood, of which changes were substantially attenuated at 150 m/kg, alluding the meaningful effects of low dose DEHP on the thyroid hormone regulation. Urinary excretion of mono-2-ethylhexyl-phthalate (MEHP), a major metabolite of DEHP was determined to be 4.10 and 12.26 ppb in male, 6.65 and 324 ppb in female at 0.3 and 30 mg/kg DEHP, respectively, which fell within reported human urine levels. Collectively, these results suggest a potential adverse effects of low dose phthalates on the thyroid.

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Purpose: To analyze the relationship between prognosis and the severity of associated injuries in traumatic isolated 3rd, 4th and 6th cranial nerve palsies. Methods: The records of 39 patients (39 eyes) who were diagnosed with isolated 3rd, 4th or 6th cranial nerve palsy following trauma were reviewed retrospectively to analyze the etiology of trauma, the degree of associated injuries, the degree of paralysis, and the prognosis. Results: The 4th cranial nerve was affected most frequently (19 patients, 48.7%), followed by the 6th nerve (12 patients, 30.8%) and the 3rd nerve (8 patients, 20.5%). Traffic accidents were the most frequent etiology of traumatic cranial nerve palsies. Loss of consciousness, intracranial hemorrhage, craniofacial fracture, c-spine injury, and optic nerve injury were among the most common accompanying conditions. The 3rd cranial nerve was the most severely paralyzed and showed the highest number of associated injuries. The recovery rate of the all cranial nerve palsies was 46.2%. By nerve, the 3rd cranial nerve palsy showed the lowest recovery rate of 25%, followed by the 4th nerve at 47.4%, and the 6th nerve at 58.3%. Conclusions: The prognosis was worse in patients with intracranial hemorrhage, compared with those without intracranial hemorrhage. There was a higher average number of associated injuries and the degree of paralysis was more severe in 3rd nerve palsies.