Distribution of carbon‐14 labeled C60 ([¹⁴C]C60) in the pregnant and in the lactating dam and the effect of C60 exposure on the biochemical profile of urine

Abstract

This study was conducted to determine the distribution of [(14)C]C60 in the pregnant rat and fetuses, and in the lactating rat and offspring. Pregnant rats were dosed on gestation day (gd) 15 and lactating rats were dosed on postnatal day (pnd) 8 via tail vein injection with a suspension of approximately 0.3 mg [(14)C]C60 kg(-1) body weight prepared in polyvinylpyrrolidone (PVP), or with PVP alone. Tissues were collected at 24 and 48 h after dosing. The largest portion of the administered dose was detected in the liver (approximately 43%, pregnant dam; approximately 35%, lactating dam) and lung (approximately 25%, lactating dam). Radioactivity (approximately 6%) was distributed to the reproductive tract, placenta and fetuses of the pregnant dam. Lactating rats had radioactivity distributed to the milk (3140 dpm g(-1) tissue, 24 h; 1620 dpm g(-1) tissue, 48 h), and to the pups' GI tract (2.8%, 24 h; 4.4% 48 h) and liver (<1%). Blood radioactivity was significant at 24 h (14-19%) and at 48 h (7%) after dosing; largely accounted for in the plasma fraction. Less that 4% of the dose was recovered in the maternal spleen, heart, brain, urine or feces. Metabolomics analysis of urine indicated that dams exposed to [(14)C]C60 had decreased metabolites derived from the Krebs cycle and increased metabolites derived from the urea cycle or glycolysis, as well as alterations in the levels of some sulfur-containing amino acids and purine/pyrimidine metabolites. This study demonstrated that [(14)C]C60 crosses the placenta and is transmitted to offspring via the dam's milk and subsequently systemically absorbed.

Exposure to zinc oxide nanoparticles affects reproductive development and biodistribution in offspring rats

“…Prenatal titanium dioxide exposure also results in alteration to the cerebral cortex, olfactory bulb and some regions intimately related to dopamine systems of offspring mice (Umezawa et al, 2012). Fullerene distributed to the placenta and fetuses of exposed pregnant dams and to the milk and pups of exposed lactating dams (Sumner et al, 2010) Yosida et al (2008 noted that carbon black nanoparticles adversely affect mouse spermatogenesis caused the consequent fluctuation of sperm testosterone levels. Moreover, researchers argue that nanomaterials found in many products affected poor fetal growth and low birth weight in unborn and newborn infants (Yamashita et al, 2011;Wang et al, 2010).…”

A perspective on the developmental toxicity of inhaled nanoparticles

“…Carbon based NP, systemically administered, are also able to distribute to the placenta and yolk sac and partly translocate to the fetus. This is true for fullerenes of different sizes, administered either before placentation is initiated [156], or later in gestation [60]. Interestingly, even at very high doses (0.8 mg/mouse), at which other NPs induce severe fetal effects, fullerenes were non-toxic [62].…”

“…By varying the day of administration relative to the conception the changes in particle transfer during gestation can be evaluated. In pregnant rats, the intravenous administration of 14 C(C60) fullerenes resulted in transfer into the placenta (2.21% of the injected dose) and fetuses (0.87% of the injected dose) [60]. When administered IV to lactating dams on postnatal day (PND) 9, the presence of 14 C in the GItract and liver of the pups (2.7-4.3% and 0.05-0.06% of the injected dose, respectively) demonstrated that 14 C(C60) fullerenes reached the pups via the milk.…”

Human health hazards of persistent inorganic and carbon nanoparticles

“…Potential effects on the lungs include damage to membranes, cytotoxicity, genotoxicity, apoptosis (induced programmed cell death), necrosis (cell death due to toxic interference with vital cell functions), inflammation, fibrosis, and cancer [1-3, and references therein]. Inhaled nanoparticles may penetrate the alveolar-capillary barrier between the respiratory and circulatory system, and thus be translocated from the lungs [2,3,[30][31][32][33][34][35][36][37][38][39][40][41][42], and references therein]. When the nanoparticles translocate to the circulatory system, other organs may also be affected [1-3, 15, 16, 30-32, 39-42].…”

“…Dependent on size and character of the particle surface, translocation of nanoparticles from the intestines to the cardiovascular system is a possibility [41,114,115]. For instance, C 60 nanoparticles (fullerenes) present in the milk of lactating rats were found to lead to systemic exposure of offspring to C 60 [41].…”