Human and Experimental Toxicology

Fipronil, an insecticide of the phenylpyrazole class has been classified as a carcinogen by United States Environmental Protection Agency, yet very limited information is available about its genotoxic effects. Adult male and female animals were gavaged with various doses of fipronil (2.5, 12.5, and 25 mg/kg body weight (bw)) to evaluate micronucleus test (mice), chromosome aberration (CA), and comet assay (rats), respectively. Cyclophosphamide (40 mg/kg bw; intraperitoneal) was used as positive control. Another group of animals were pretreated with vitamin E orally (400 mg/kg bw) for 5 days prior to administration of fipronil (12.5 mg/kg). Fipronil exposure in both male and female mice caused significant increase in the frequency of micronuclei (MN) in polychromatic erythrocytes. Similarly, structural CAs in bone marrow cells and DNA damage in the lymphocytes was found to be significantly higher in the male and female rats exposed to fipronil as compared to their respective controls. The average degree of protection (male and female animals combined together) shown by pretreatment of vitamin E against fipronil-induced genotoxicity was 63.28%: CAs; 47.91%: MN formation; and 74.70%: DNA damage. Findings of this study demonstrate genotoxic nature of fipronil regardless of gender effect and documents protective role of vitamin E.

Due to the reduction of air change rates in low-energy houses, the contribution to indoor air quality of volatile organic compounds (VOCs) emitting from oriented strand boards (OSB) has become increasingly important. The aim of this study was to evaluate sensory irritations, pulmonary effects and odor annoyance of emissions from OSB in healthy human volunteers compared to clean air. Twenty-four healthy non-smokers were exposed to clean air and OSB emissions for 2 h under controlled conditions in a 48 m³ test chamber at three different time points: to fresh OSB panels and to the same panels after open storage for 2 and 8 weeks. Chemosensory irritation, exhaled nitric oxide (NO) concentration, eye blink frequency, lung function and subjective perception of irritation of eyes, nose and throat were examined before, during and after exposure. Additionally, olfactory perception was investigated. Total VOC exposure concentrations reached 8.9 ± 0.8 mg/m³ for the fresh OSB panels. Emissions consisted predominantly of α-pinene, ▵³-carene and hexanal. Two-hour exposure to high VOC concentrations revealed no irritating or pulmonary effects. All the subjective ratings of discomfort were at a low level and the medians did not exceed the expression ‘hardly at all.’ Only the ratings for smell of emissions increased significantly during exposure in comparison to clean air. In conclusion, exposure of healthy volunteers to OSB emissions did not elicit sensory irritations or pulmonary effects up to a VOC concentration of about 9 mg/m³. Sensory intensity of OSB emissions in the chamber air was rated as ‘neutral to pleasant.’

Paraoxonase 1 (PON1) has been proposed as an antioxidant enzyme. Although lead-inhibited PON1 activity has been demonstrated mostly based on in vitro experiments, it is uncertain whether this phenomenon is relevant in pathogenesis of lead-induced oxidative stress in the lead exposure. We examined associations of blood lead levels (BLL) and PON1 activity along with oxidative stress parameters in lead exposure workers. We determined malondialdehyde (MDA), conjugated diene (CD), total peroxides (TP), total antioxidant status (TAS), the oxidative stress index (OSI), and PON1 activity in earthenware factory workers ( n = 60) and control subjects ( n = 65). The lead-exposed group significantly increased lipid peroxidation parameters and OSI compared to the control group ( p < 0.001). The lead-exposed group had significantly decreased PON1 activity and TAS levels compared to the control group ( p < 0.001). Multiple linear regression analysis revealed that BLL were significantly correlated with decreased TAS ( r = −0.496) and PON1 activity ( r = −0.434), but with increased CD ( r = 0.694), TP ( r = 0.614), MDA ( r = 0.788), and OSI ( r = 0.722). Interestingly, BLL at 10 µg/dL significantly decreased PON1 activity and increased oxidative stress parameters with insignificant changes in other biochemical and hematological parameters. Altogether, the reduction of PON1 activity may associate in an imbalance in pro-oxidants and antioxidants, leading to oxidative damage in lead-exposed workers even at low BLL.

This study deals with the health effects within a child population, neighbouring a landfill. After detecting metals in soil and air samples collected in the surroundings of the landfill and in a control site, we have studied: (i) levels of lead (Pb) and exposure biomarkers in blood and urine, (ii) oxidative stress biomarkers and (iii) renal injury by applying a set of early effect biomarkers. Levels of Pb were higher in the exposed site (i.e. 1129 mg/kg and 640 ng/m³ in soil and air samples, respectively) versus those in the control site (i.e. 14.3 mg/kg and 9.3 ng/m³ in soil and air samples, respectively). Pb impregnation and levels of delta-aminolevulinic acid in urine were influenced by the living site that shows the prevailingly alarming situation in the Mbeubeuss landfill. Malondialdehyde changes indicated Pb-induced excessive production of reactive oxygen species. Lactate dehydrogenase activities and proteinuria were found to be higher in the children living in the exposed site. These evidences may reveal the usefulness of these two effect biomarkers to monitor the kidney injury entailed by relatively low-environmental exposure to Pb. Overall, these results show that the Mbeubeuss landfill constitutes a real source of environmental and health risk, be it living or working on site, of the surrounding population, predominantly for children.

Lead (Pb) is a developmental neurotoxicant found in industrial activities, many of them already prohibited worldwide. This study aimed to evaluate current blood Pb (PbB) levels in children in Cordoba, Argentina, and to compare these with similar studies performed before Pb was banned in gasoline in 1996. We also sought to identify mechanistically relevant biomarkers by measuring δ-aminolevulinic acid dehydratase (δ-ALAD), superoxide dismutase (SOD), and catalase (CAT) activities. We finally aimed to determine whether sociodemographic characteristics are associated with Pb toxicity. Blood samples collected from 161 healthy children between September 2009 and February 2010 revealed mean PbB levels of 2.58 ± 0.30 µg/dl. Enzymatic δ-ALAD, CAT, and SOD activities showed no significant variations when plotted against PbB levels. Finally, children living in the suburbs have higher PbB levels than their city counterparts, while low socioeconomic status increased δ-ALAD inhibition compared with that of middle-income children. Overall, these results evidenced a substantial reduction in exposure to Pb in this pediatric population over a decade after Pb was restricted in gasoline and reveal the importance of pursuing novel biomarkers of toxicity along with the sociodemographic profile to complement Pb diagnosis.

To explore lead-induced oxidative stress among urban adolescents, the present study, the first from India, was designed to determine the proportion of urban adolescents with blood lead > 10 μg/dL and its impact on selected oxidative stress parameters and delta-aminolevulinic acid dehydratase (δ-ALAD) inhibition, which could be used as biomarkers of lead intoxication. A total of 39, urban, male adolescents, drawn from Lucknow and adjoining areas, were recruited to determine lead, d-ALAD, malondialdehyde (MDA) and glutathione (GSH) in blood and catalase (CAT) in RBCs. Mean level of blood lead was 9.96 ± 3.63 μg/dL (4.62 - 18.64); 43% of adolescents crossed the Centre for Disease Control (CDC) intervention level of 10 mg/dL blood lead. On the basis of blood lead levels (BLLs), adolescents were categorized into two groups: Group I and Group II had a blood lead < 10 μg/dL (7.40 ± 1.62) and < 10 μg/dL (13.27 ± 2.67), respectively, with significantly different mean values (P < 0.001). Age, sex, body mass index (BMI), Hb level (malnutrition), and area of living as confounders of lead exposure and toxicity were not statistically different between the two groups. However, d-ALAD activity was significantly lower (P < 0.001), while CAT activity was higher in Group II than in Group I (P < 0.01). MDA level was also significantly higher in Group II compared to Group I (P < 0.001). There were significant negative correlation of BLL with d-ALAD (r = -0.592, P < 0.001), and positive correlations with CAT (r= -0.485, P < 0.01) and MDA (r = -0.717, P < 0.001). Interestingly, d-ALAD, in turn, had significant negative correlations with CAT (r = -0.456, P <0.01) and MDA (r = -0.507, P < 0.01). Results of the present pilot study provide clues to the possible low level of lead-induced oxidative stress in urban adolescents, suggesting that lead-induced d-ALAD inhibition can also be an indicator of oxidative stress. The potential of oxidative stress parameters to be used as biomarkers of lead toxicity warranted further investigation.

The purpose of this study was to characterize the zinc oxide nanoparticles (ZnO-NPs) and their bulk counterpart in suspensions and to access the impact of their acute oral toxicity at doses of 300 and 2000 mg/kg in healthy female Wistar rats. The hematological, biochemical, and urine parameters were accessed at 24 and 48 h and 14 days posttreatment. The histopathological evaluations of tissues were also performed. The distribution of zinc content in liver, kidney, spleen, plasma, and excretory materials (feces and urine) at 24 and 48 h and 14 days posttreatment were accessed after a single exposure at dose of 2000 mg/kg body weight. The elevated level of alanine amino transferase, alkaline phosphatase, lactate dehydrogenase, and creatinine were observed in ZnO-NPs at a dose of 2000 mg/kg at all time points. There was a decrease in iron levels in all the treated groups at 24 h posttreatment as compared to control groups but returned to their normal level at 14 days posttreatment. The hematological parameters red blood cells, hemoglobin, hematocrit, platelets, and haptoglobin were reduced at 48 h posttreatment at a dose of 2000 mg/kg ZnO-NPs and showed hemolytic condition. All the treated groups were comparable to control group at the end of 14 days posttreatment. The zinc concentration in the kidney, liver, plasma, feces, and urine showed a significant increase in both groups as compared to control. This study explained that ZnO-NPs produced more toxicological effect as compared to their bulk particles as evidenced through alteration in some hemato-biochemical parameters and with few histopathological lesions in liver and kidney tissues.

1,3-dichloro-2-propanol is a food-borne contaminant reported to cause liver injury. In this study, we evaluated the protective influence of caffeic acid on 1,3-dichloro-2-propanol-induced hepatotoxicity in rats. Rats were randomized into five groups (A–E). Rats received distilled water or caffeic acid (10 or 20 mg/kg body weight) for 7 days. In addition, rats were challenged with 1,3-dichloro-2-propanol on day 7. Caffeic acid prevented 1,3-dichloro-2-propanol-mediated alterations in alkaline phosphatase, alanine and aspartate aminotransferases, albumin and total bilirubin in the serum of rats. Furthermore, caffeic acid lowered superoxide ion, hydrogen peroxide and cytochrome P2E1 while increasing the activities of superoxide dismutase, catalase and glutathione S-transferase in the liver of 1,3-dichloro-2-propanol-treated rats. Caffeic acid raised the levels of nuclear erythroid-related factor 2 (Nrf-2), protein kinase A and phosphoinositide 3-kinase. Caffeic acid pretreatment annulled 1,3-dichloro-2-propanol-mediated alterations in the oxidative stress biomarkers; caspase-3, glutathione, malondialdehyde, protein carbonyl and fragmented DNA, in the liver of rats. Contrastingly, caffeic acid lowered 1,3-dichloro-2-propanol-mediated increase in the levels of nuclear factor-kappa B (NF-κB), tumour necrosis factor-α, interleukin-1β (IL-1β) and IL-6. In addition, caffeic acid preserved the morphological features of 1,3-dichloro-2-propanol-treated rats. Results from this study revealed that caffeic acid protects against 1,3-dichloro-2-propanol-induced hepatotoxicity by enhancing the cytoprotective enzymes through Nrf-2 while lowering inflammation through NF-κB.

Background: Deliberate self-poisoning (DSP) is a major health problem with increasing incidence mainly among young people. Objective: To examine the clinical and toxicological characteristics of DSP, it is compared to unintentional (non-DSP) exposures and those characteristics which might be associated with increased toxicological risk are identified. Methods: Two-year retrospective poison centre chart review. Statistics: χ² analysis. Results: 3802 DSP cases were reported. Most calls (95%) were made by physicians compared to 51%) in non-DSP exposures, P <0.0001. There were almost twice as many females as males, contrary to unintentional exposures (P <0.001). Peak frequency involvement was at the age of 15-20 years for females and older for males. Only 19.8%) of DSP calls were made within the first hour of exposure compared to 46%) of the non-DSP calls (P <0.001). Younger patients tended to present earlier. The vast majority of exposures occurred by ingestion and at home. Pharmaceuticals and chemicals were involved in 86% and 12% of DSP cases, respectively (compared to 29% and 44% in non-DSP exposures, respectively, P <0.001). Psychiatric drugs were more commonly used in older age groups and analgesics among the younger. Insecticides, sodium hypochlorite and rodenticides were the most frequently used chemicals. Neurological involvement was observed in 48.2% of DSP patients compared to 16.9% in non-DSP exposures. DSP was associated with greater severity than non-DSP exposures (21% and 10% had moderate to severe toxicity, respectively, P <0.001). Severity was greater among males, aged older than 45 years, with time from exposure to consultation 8 hours or longer and with exposure to chemicals, psychiatric drugs or combinations. Conclusions: Most DSP patients were females, aged 15-20 years, used pharmaceuticals and had neurological involvement. Males, aged over 45 years, with longer time to toxicology consult and the use of chemicals were associated with increased severity. These parameters should alert the treating physician to the possibility of a poor course and hence to a more aggressive therapeutic approach.

It is known that pesticides cross the placental barrier and can cause alterations in the development of placental structures resulting in adverse effects in reproduction. The objectives of this study were to investigate the effects of pesticide exposure during pregnancy on placental maturity and to evaluate the relationship between placental maturity, gestational age and birth weight. We collected the placentas from singleton pregnancies from women exposed (n = 9) and non-exposed (n = 45 full-term and n = 31 preterm) to pesticides as evaluated geographically, by questionnaire and by acetylcholinesterase levels. Placental morphometry from the central and peripheral regions was examined by microscopy and staining with hematoxylin and eosin. The placental maturity index (PMI) was estimated by dividing the number of epithelial plates in terminal villi to their thickness in 1 mm² of the placental parenchyma. Gestational age, birth weight and the following characteristics of the mother were also recorded: pre-pregnancy body mass index, weight gain during pregnancy and hemoglobin concentrations. Birth weight and the gestational age were correlated with PMI (r = .54 and r = .44, respectively; p < .01). Pesticide exposure was associated with a higher PMI (beta = 7.38, p = .01) after adjusting by variables related to placental maturity. In conclusion, the results suggest a relationship between prenatal exposure to pesticides and placental maturity and may potentially affect the nutrient transport from the mother to the fetus.