Sex-dependent difference in the hepatic and pulmonary toxicological effects in mice administrated 7-chlorinated benz[<i>a</i>]anthracene

Abstract

Chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs) have recently been found in the environment at relatively high concentrations. However, their toxicological information has not been well documented. In this study, a 24 hr in vivo experiment was conducted to evaluate the sex-dependent difference of the acute toxicological effects of 7-chlorinated benz[a]anthracene (7-ClBaA) as a model Cl-PAH. 7-ClBaA or its parent chemical, BaA, was once orally administered to male or female ICR mice at concentrations of 1, 10, and 100 mg/kg body weight. The relative liver weights of the males were significantly increased at the highest dose of both chemicals compared to the vehicle controls, but the weights were comparable among all groups in the females. The plasma 7-ClBaA level was similar in both sexes, but significantly higher than that of BaA. 7-ClBaA dose-dependently induced expression of the genes Cyp1a1, 1a2, and 1b1 in the liver and lung, and these stimulations were significantly higher in both organs and genders at a dose of 100 mg/kg 7-ClBaA compared with an equivalent amount of BaA, except in the case of hepatic Cyp1a2 and 1b1 and pulmonary Cyp1a2 in the female mice. The results suggest that acute toxicity of 7-ClBaA is gender-and organ-specific, and female mice might be less sensitive to acute toxicity of both 7-ClBaA and BaA than the males.

Parent and Halogenated Polycyclic Aromatic Hydrocarbons in the Serum of Coal-Fired Power Plant Workers: Levels, Sex Differences, Accumulation Trends, and Risks

“…Although there was little difference in the serum concentrations of ∑ 8 HPAHs between males and females, male workers exhibited higher prevalence and risk according to the physical examination results, suggesting that lung and liver toxicity may be sex-specific. These findings are in alignment with the reported sex differences in HPAHs in acute toxicological studies, 17 in which male mice appear to be more susceptible to HPAHs than female mice. Future case− control studies are warranted to explore the specific health effects on humans.…”

“…Surprisingly, 1-ClPyr was also significantly positively correlated with fasting blood glucose levels in females. In toxicological studies on HPAHs, only hepatotoxicities of 7-ClBaA and 6-ClBaP have been evaluated and are reportedly higher than those of their PPAHs. , Due to the small number of workers with hepatic dysfunction in this study, it was difficult to draw a statistically significant conclusion, although the workers with hepatic dysfunction showed high levels of serum PAHs and HPAHs.…”

“…Exposure to HPAHs is of increasing public health concern because HPAHs are more toxic than their PPAHs and show different toxicological effects. , Although toxicological studies on HPAHs are still limited, their toxicity is thought to be mainly related to aromatic hydrocarbon receptor (AhR)-mediated toxicity, carcinogenicity, and DNA damage, ,− including their effect on the expression of cytochrome P-450 (CYP) genes . They also stimulate the metabolic pathways of chemicals other than the AhR-mediated metabolism .…”

“…12,13 Although toxicological studies on HPAHs are still limited, their toxicity is thought to be mainly related to aromatic hydrocarbon receptor (AhR)mediated toxicity, carcinogenicity, and DNA damage, 12,14−16 including their effect on the expression of cytochrome P-450 (CYP) genes. 17 chemicals other than the AhR-mediated metabolism. 11 Just as PAHs can produce excessive reactive oxygen species and induce a significant increase in lipid peroxidation and a prominent decrease in antioxidant enzymes after being metabolized, 18,19 exposure to 6-chlorobenzo[a]pyrene at certain concentrations can cause strong oxidative stress and a strong inhibition effect on cell viability.…”

Determination of Particle-Associated PAH Derivatives (ClPAHs, NPAHs, OPAHs) in Ambient Air and Automobile Exhaust by Gas Chromatography/Mass Spectrometry with Negative Chemical Ionization

“…Oxygenated PAHs (OPAHs), nitrated PAHs (NPAHs), and chlorinated PAHs (ClPAHs) make up of a class of PAH derivatives that pose a threat to human health because of their toxicity (9)(10)(11)(12). These compounds are present in ambient air particles emitted by combustion processes or formed in the atmosphere via gaseous or heterogeneous reactions (13)(14)(15).…”