Developmental and heritable genetic defects induced in mice by municipal landfill leachate.

Environmental pollution by solid waste leachate is a serious environmental and public health concern. Leachate contamination and pollution of environmental matrices have been reported, but no report of embryotoxic and developmental defects, and heritable transfer of leachate-induced toxicity in mice. We investigated the ability of Aba-Eku landfill leachate to induce embryonic malformations, developmental toxicity, and germline and somatic DNA damage in the F1 of exposed pregnant mice. Pregnant mice (n = 100) were randomly distributed into 5 experimental groups of 20 animals/group and exposed to 0.2 mL of 5-75% concentrations of the leachate (v/v; Aba-Eku landfill leachate: distilled water) by daily gavage from gestational day (GD) zero to postnatal day (PND) 21. A similar treatment was given to pregnant female mice administered with distilled water (negative control). At GD 18, ten dams from the treatment and control groups were sacrificed by cervical dislocation after which the embryos were collected from the uterus for analyses of fetal morphometric and skeletal metamers respectively. We then monitored the developmental conditions of F1 mice from the remaining ten dams until they were weaned at PND 21 and sacrificed at PND 56 and PND 98 for bone marrow micronucleus and spermiogram analyses respectively. We also analyzed the leachate for inorganic and organic pollutants and calculated the Leachate Pollution Index (LPI). The leachate reduced maternal and fetal birth weight and increased fetal mortality and postnatal appearance of physiological markers in the F1 mice. There was a significant increase (p < 0.05) in the frequency of fetal skeletal malformations, micronucleated polychromatic erythrocytes, and apparent decline of epididymal sperm parameters. The concentrations of the inorganic and organic pollutants, and the LPI exceeded standard limits. Exposure of pregnant female mice to Aba-Eku landfill leachate caused embryonic defects and heritable DNA damage in subsequent generations.

The first-line antituberculosis drugs, and their fixed-dose combination induced abnormal sperm morphology and histological lesions in the testicular cells of male mice.

Rifampicin (RIF), Isoniazid (INH), Ethambutol (EMB), Pyrazinamide (PZA), and/or their fixed-dose combination (FDC) are extensively prescribed in the cure of Tuberculosis (TB) globally. In spite of the beneficial effect, these drugs are capable of inducing cellular toxicity. Existing information on the genotoxic effects of the first-line anti-TB drugs is limited and contentious. Herein, we evaluated the reproductive genotoxicity of RIF, INH, EMB, PZA, and their FDC utilizing the mouse sperm morphology assay. Histological examination of the testes of exposed mice was also performed. Male Swiss albino mice (11-13 weeks old) were intraperitoneally exposed for 5 consecutive days to each of the anti-TB drugs at four different doses of 6.25, 12.5, 25, and 50 mg/kg bw of PZA; 2.5, 5.0, 10, and 20 mg/kg bw of RIF; 1.25, 2.5, 5.0 and 10 mg/kg bw of INH; 3.75, 7.5, 15 and 30 mg/kg bw of EMB; and 7, 14, 28 and 56 mg/kg bw of FDC corresponding respectively to ×0.25, ×0.5, ×1 and ×2.0 of the standard daily dose. In comparison with the negative control (normal saline), there was no significant difference in the testicular weight and organo-somatic index of exposed mice. There was an increase (p > 0.05) in the frequency of abnormal spermatozoa at most of the tested doses of each drug and a dose-dependent decrease with the FDC. Each of the anti-TB drugs except the FDC induced pathological lesions in the testes. These findings suggest that the individual first-line anti-TB drug unlike the FDC has the potential to provoke testicular anomalies in male mice.

Experimental modeling of the acute toxicity and cytogenotoxic fate of composite mixtures of chromate, copper and arsenate oxides associated with CCA preservative using Clarias gariepinus (Burchell 1822).

Concurrent occurrence of chromium (Cr), copper (Cu) and arsenic (As) from chromated copper arsenate (CCA) wood preservative in aquatic ecosystems demands that their joint-actions in eliciting toxic effects be assessed for adequate understanding of the health risk they may pose to biota. Clarias gariepinus was exposed to As2O3 , CrO3 and CuO and their composite mixtures (1:1 and 1:1:1) at various concentrations (0 - 600 mg/L) for 96-h to determine the acute toxicity using OECD (1992) protocol. C. gariepinus was then exposed to sub-lethal concentrations corresponding to 6.25, 12.5, 25.0, 50.0 and 100% of the 96-h LC50 for 7 days to assess the cytogenotoxic effects using piscine micronucleus (MN) test. The 96-h LC50 showed that the metals/metalloid demonstrated differential interactions in a concentration dependent pattern. The 96-h LC50 showed that Cr was the most toxic while Cu and As:Cu were indeterminate (Cr > Cr:Cu > As:Cr > As > As:Cr:Cu > Cu = As:Cu indeterminate). Isobologram and synergistic ratio (SR) models predicted antagonistic interaction between Cu:Cr and As:Cr and synergism between As:Cu in the causation of morbidity and mortality of C. gariepinus. Interaction factor model predicted antagonism as common interactive mechanism among the metal/metalloid mixtures in the induction of MN and abnormal nuclear erythrocytes in C. gariepinus. Predicted interactions among the three metals/ metalloid were largely antagonism and synergism towards the induction of acute toxicity and cytogenotoxicity. The models employed herein may be useful in establishing environmental safe limits for mixtures of metals/metalloids against the induction of acute toxicity and DNA damage in lower aquatic vertebrates.