ObjectiveThe genotoxicity of zinc oxide nanoparticles （ZnO NPs） in rats was determined by Pig⁃a mutation assay in vivo. MethodsCombined with 28-day oral toxicity test， male SD rats were given ZnO NPs by oral administration for 28 days， at doses of 0， 14， 70 and 350 mg‧kg^-1 （maximum concentration of nanoscale dispersion state）. Rats in control groups received 350 mg‧kg^-1 of normal size ZnO， 40 mg‧kg^-1 N-ethyl-N⁃nitrosourea（ENU）or 0 mg·kg^-1 ZnO NPs（solvent control group） Changes of body weight were recorded. At 0， 15， 28 d and 28 d of recovery observation period， 200 μL of tail venous blood was collected from each group， which was labeled by APC mouse anti-rat erythroid cells and FITC mouse anti-rat CD59. The information of 1×10⁶ red blood cells（RBC） from each sample were collected by flow cytometry， and the mutation rate of RBC^CD59- was calculated. ResultsCompared with the solvent control group， after 15 days of intragastric administration， the mutation rate of RBC ^CD59- in peripheral blood of in 350 mg‧kg^-1 ZnO NPs group and 40 mg‧kg^-1 ENU group was significantly increased while that of in 70 mg‧kg^-1 ZnO NPs group was also significantly increased after 28 days of intragastric administration.with time-response and dose-response relationship. All groups except 40 mg‧kg^-1 ENU group showed no significant difference in the mutation rate of RBC^CD59- in peripheral blood in comparison with the solvent control group after 28-days recovery observation. Conclusion70 and 350 mg‧kg^-1 ZnO NPs can increase the mutation rate of Pig⁃a gene in peripheral blood of SD rats.

Background The respiratory toxicity of inhaled polyhexamethylene guanidine (PHMG) has been extensively studied since the humidifier disinfectant incident. However, the impacts of inhalation of PHMG on the immune system are not comprehensively studied yet. Objective To explore the effects of inhalation of PHMG disinfectant aerosol on major immune organs and immune cells in mice. Methods Thirty male C57BL/6J mice (6-8 weeks old) were randomly divided into three groups: control, low-dose (0.1 mg·m⁻³ PHMG), and high-dose (1.0 mg·m⁻³ PHMG), with ten mice in each group. The mice were administered by oral-nasal inhalation of PHMG aerosol for 4 h per day, 5 d per week for 4 weeks consecutively. After designed treatment, venous blood was collected from the inner canthus of the eyes of mice and peripheral hematological indicators were measured with a blood analyzer. Then the mice were sacrificed by cervical dislocation and the lung, thymus, spleen, and femur were isolated. Lung, thymus, and spleen were weighed and organ coefficients were calculated, and single cell suspensions of thymus, spleen, and bone marrow were prepared to analyze lymphocytes phenotypes and proportions by flow cytometry. Results The body weight of mice in the high-dose group was lower than that of mice in the control group (P<0.01) from the 7th day of inhalation, and decreased by 15.74% compared with that of mice in the control group at the end of inhalation (P<0.01). The lung coefficients of both the low-dose and high-dose groups were higher than that of the control group (P<0.01), the thymus coefficient of mice in the high-dose group was lower than that of the control group (P<0.05), but the spleen coefficient did not change significantly (P>0.05). Leukocyte count [(1.49±0.22)×10⁹·L⁻¹], lymphocyte count [(0.96±0.36)×10⁹·L⁻¹] and its proportion [(63.13±14.96)%] in the peripheral blood of mice in the high-dose group were lower than those in the control group [(2.69±0.25)×10⁹·L⁻¹, (2.33±0.28)×10⁹·L⁻¹, and (86.23±3.40)%, respectively] (P<0.01), whereas red blood cell count [(12.32±0.46)×10¹²·L⁻¹], hemoglobin count [(175.25±4.65) g·L⁻¹], and hematocrit [(53.55±0.70)%] in the peripheral blood of mice in the high-dose group were higher than those in the control group [(11.11±0.37)×10¹²·L⁻¹, (160.67±4.04) g·L⁻¹, and (45.10±9.75)%, respectively] (P<0.05). Compared with the control group, the proportion of CD4+ CD8+ double-positive T cells decreased (P<0.05), the proportions of CD4+ T cells and CD8+ T cells increased (P<0.05), and the amounts of CD8+, CD4+ CD8+, CD4+, and CD4- CD8- cells decreased (P<0.05) in the thymus of mice of the high-dose group, the proportion of CD4+ T cells in the spleen of the high-dose group increased (P<0.05), the proportions and amounts of T cells, CD4+ T cells, and CD8+ T cells in the bone marrow of the high-dose group increased (P<0.05). Conclusion Inhalation of PHMG may cause thymic atrophy, disrupt T-lymphocyte development, and lead to an imbalance in the number of immune cells in the bone marrow, peripheral blood, and spleen, suggesting that inhalation of PHMG induces immune dysfunction.