Exploring the toxicity of the aged styrene-butadiene rubber microplastics to petroleum hydrocarbon-degrading bacteria under compound pollution system.

As a new pollutant, microplastics have increasingly drawn public attention to its toxic behavior in the environment. The aim was to investigate the effect of styrene-butadiene-rubber microplastics (mSBR) with different degrees of aging on petroleum hydrocarbon (PHC) degrading bacteria in an environment with simultaneously existing pollutants. A series of experiments were carried out to investigate the changes in the physical and chemical properties of mSBR with aging and to examine the influence of these changes on the inhibition of PHC-degrading bacteria by mSBR in the vicinity of coexisting pollutants. The results showed that in the early stage of ultraviolet aging (10d), the particle surface shows wrinkles, but the structure is intact. After reaching the late stage of aging (20d), nano-scale fragments were generated on the surface of mSBR, the average particle size decreased from 3.074 µm to 2.297 µm, and the zeta potential increased from - 25.1 mV to - 33.1 mV. The inhibitory effect of bacteria is greater. At the same time, these changes in the physicochemical properties increase the adsorption effect of Cd by 20%, and also improve the stability of mSBR in solution, whereby bacterial growth is inhibited by inhibiting the LPO activity and protein concentration of PHC degrading bacteria.

Evaluation of Rheum Turkestanicum in Hexachlorobutadien-Induced Renal Toxicity.

Hexachlorobutadien is nephrotoxic agent in rodents. The mechanism of toxicity includes generation of free radicals, depletion of thiol groups and production of toxic metabolites. Antioxidant compounds may reduce HCBD-nephrotoxicity. In this research we investigated the effect of Rheum turkeatanicum extract against HCBD-toxicity. The animals were divided to 4 groups which were including control (saline, 1 mL/kg), HCBD (100 mg/kg) and treatment groups which received extract at doses 100 and 200 mg/kg. The extract were administered as intraperitoneally (i.p.) 1 h before HCBD injection (i.p.). The animals were anesthetized by ether, 24 h after HCBD administration. The results showed elevation of serum creatinine, serum urea, urinary protein, urinary glucose, malondialdehyde levels in kidney and reduction of thiol in kidney by HCBD. The histopathological studies showed that there was apoptosis and necrosis in HCBD treated groups. Administration of R.turkestanicum reduced HCBD toxicity. The extract reduced hitopathological changes in kidney. It may be concluded that the nephroprotective effect of extract may be due to different mechanisms such as antioxidant activity or by decreasing the toxic metabolites of HCBD or inhibition of enzymes which are involved in the bioactivation of HCBD such as glutathione-S-transferase (GST) or cysteine-S-conjugate ß-lyase.

Preventive activity of olive oil phenolic compounds on alkene epoxides induced oxidative DNA damage on human peripheral blood mononuclear cells.

The aim of this study was to investigate the ability of epoxides of styrene (styrene-7,8-oxide; SO) and 1,3-butadiene (3,4-epoxy-1-butene; 1,2:3,4:-diepoxybutane) to cause oxidative stress and oxidative DNA damage on human peripheral blood mononuclear cells (PBMCs) and whether a complex mixture of olive oil phenols (OOPE) could prevent these effects. The DNA damage was measured by the single-cell gel electrophoresis (SCGE; comet assay). We found that the DNA damage induced by alkene epoxides could be prevented by N-acetyl-cysteine (10 mM) and catalase (100 U/ml). Alkene epoxides caused a significant (P < 0.05) increase of both peroxide concentration in extra- and intracellular environment and formamidopyrimidine DNA glycosylase (FPG)- and Endonuclease III (ENDO III)-sensitive sites in PBMCs, demonstrating the presence of oxidized bases. OOPE (1 µg of total phenols/ml) was able to prevent the alkene epoxide induced DNA damage both after 2 and 24 h of incubation. In addition, OOPE completely inhibited the SO-induced intracellular peroxide accumulation in PBMCs and prevented the oxidative DNA damage induced by SO, as evidenced by the disappearance of both FPG- and ENDO III-sensitive sites. This is the first study demonstrating the ability of OOPE to prevent the DNA damage induced by alkene epoxides providing additional information about the chemopreventive properties of olive oil.

The mammalian toxicological hazards of petroleum-derived substances: an overview of the petroleum industry response to the high production volume challenge program.

Petroleum-derived substances are complex and composed of aliphatic (normal-, iso-, and cycloparaffins), olefinic, and/or aromatic constituents. Approximately 400 of these complex substances were evaluated as part of the US Environmental Protection Agency voluntary High Production Volume (HPV) Challenge program. The substances were separated into 13 groups (categories), and all available data were assessed. Toxicology testing was conducted as necessary to fully address the end points encompassed by the HPV initiative. In a broad sense, volatile hydrocarbons may cause acute central nervous system effects, and those that are liquids at room temperature pose aspiration hazards if taken into the lungs as liquids and may also cause skin irritation. Higher boiling substances may contain polycyclic aromatic constituents (PACs) that can be mutagenic and carcinogenic and may also cause developmental effects. Substances containing PACs can also cause target organ and developmental effects. The effects of aliphatic constituents include liver enlargement and/or renal effects in male rats via an α-2u-globulin-mediated process and, in some cases, small but statistically significant reductions in hematological parameters. Crude oils may contain other constituents, particularly sulfur- and nitrogen-containing compounds, which are removed during refining. Aside from these more generic considerations, some specific petroleum substances may contain unusually toxic constituents including benzene, 1,3-butadiene, and/or n-hexane, which should also be taken into account if present at toxicologically relevant levels.

Protective effect of pomegranate seed oil on hexachlorobutadiene-induced nephrotoxicity in rat kidneys.

Hexachlorobutadiene (HCBD) is a potent nephrotoxin in rodents. Pharmacological studies have shown that pomegranate fruit preparations have antioxidant, anti-inflammatory chemopreventive effects. In this study, the effect of pomegranate seed oil (PSO) on HCBD-induced nephrotoxicity was investigated in adult male rats. Animals were divided into five groups. Group 1 was treated with corn oil (1 mL/kg, i.p.). Group 2 received a single dose of HCBD (50 mg/kg, i.p.). Groups 3-5 were treated with PSO (0.16, 0.32, and 0.64 mg/kg, i.p., respectively) 1 h before HCBD (50 mg/kg, i.p.) injection. A significant elevation of serum creatinine and urea (p < 0.001) levels as well as urine glucose and protein (p < 0.001) concentrations (as markers of acute renal failure) was observed 24 h after administration of HCBD as compared to control group. HCBD also caused a significant decrease in total thiol content (p < 0.001) and a significant increase in thiobarbituric acid reactive species (TBARS, as an index of lipid peroxidation) levels (p < 0.001) in kidney homogenate samples. PSO pretreatment resulted in a significant and dose-dependent decrease in serum creatinine (p < 0.001) and urea levels (p < 0.001) as well as urine glucose (p < 0.001) and protein concentrations (p < 0.001) when compared with HCBD treated alone. PSO also significantly reversed the HCBD-induced depletion in total thiol content (p < 0.001) and elevation in TBARS (p < 0.001) in kidney homogenate samples. The results of this study showed that PSO clearly attenuated HCBD-induced nephrotoxicity, but explanation and mechanism of this protection need further explorations.

Glutathione transferases and glutathionylated hemoglobin in workers exposed to low doses of 1,3-butadiene.

We evaluated glutathione transferase (GST) activities and the levels of glutathionylated hemoglobin in the RBC of 42 workers exposed to 1,3-butadiene in a petrochemical plant, using 43 workers not exposed to 1,3-butadiene and 82 foresters as internal and external controls, respectively. Median 1,3-butadiene exposure levels were 1.5, 0.4, and 0.1 microg/m3 in 1,3-butadiene-exposed workers, in workers not directly exposed to 1,3-butadiene, and in foresters, respectively. In addition, we determined in the peripheral blood lymphocytes of the same individuals the presence of GST polymorphic genes GSTT1 and GSTM1 and the distribution of GSTP1 allelic variants. Comparing the mean values observed in petrochemical workers with those of control foresters, we found a marked decrease of GST enzymatic activity and a significant increase of glutathionylated hemoglobin in the petrochemical workers. A weak but significant negative correlation was found between levels of 1,3-butadiene exposure and GST activity, whereas a positive correlation was found between 1,3-butadiene exposure and glutathionylated hemoglobin. A negative correlation was also observed between GST activity and glutathionylated hemoglobin. No influence of confounders was observed. Using a multiple linear regression model, up to 50.6% and 41.9% of the variability observed in glutathionylated hemoglobin and GST activity, respectively, were explained by 1,3-butadiene exposure, working setting, and GSTT1 genotype. These results indicate that occupational exposure to 1,3-butadiene induces an oxidative stress that impairs the GST balance in RBC, and suggest that GST activity and glutathionylated hemoglobin could be recommended as promising biomarkers of effect in petrochemical workers.

Evaluation of cancer tests of 1,3-butadiene using internal dose, genotoxic potency, and a multiplicative risk model.

In cancer tests with 1,3-butadiene (BD), the mouse is much more sensitive than the rat. This is considered to be related to the metabolism of BD to the epoxide metabolites, 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane, and 1,2-epoxy-3,4-butanediol. This study evaluates whether the large difference in outcome in cancer tests with BD could be predicted quantitatively on the basis of the concentration over time in blood (AUC) of the epoxide metabolites, their mutagenic potency, and a multiplicative cancer risk model, which has earlier been used for ionizing radiation. Published data on hemoglobin adduct levels from inhalation experiments with BD were used for the estimation of the AUC of the epoxide metabolites in the cancer tests. The estimated AUC of the epoxides were then weighed together to a total genotoxic dose, by using the relative genotoxic potency of the respective epoxide inferred from in vitro hprt mutation assays using EB as standard. The tumor incidences predicted with the risk model on the basis of the total genotoxic dose correlated well with the earlier observed tumor incidences in the cancer tests. The total genotoxic dose that leads to a doubling of the tumor incidences was estimated to be the same in both species, 9 to 10 mmol/Lxh EB-equivalents. The study validates the applicability of the multiplicative cancer risk model to genotoxic chemicals. Furthermore, according to this evaluation, different epoxide metabolites are predominating cancer-initiating agents in the cancer tests with BD, the diepoxide in the mouse, and the monoepoxides in the rat.

Regucalcin down-regulation in rat kidney tissue after treatment with nephrotoxicants.

Gene expression of regucalcin (Rgn), a calcium-binding protein, was investigated in kidney of male Wistar rats treated with proximal tubule segment-specific nephrotoxicants, namely hexachloro-1:3-butadiene (HCBD), specific for S(3) segment (pars recta) and potassium dichromate (chromate) specific for S(1)-S(2) segments (pars convoluta), according to age of animals and dose of chemicals. In the age-dependent study, male Wistar rats were treated with a single injection of HCBD (100mg/kg b.w. i.p.) or chromate (25 mg/kg b.w. s.c.) at 5 weeks or 12 weeks of age; in dose-response study, rats were treated with a single injection of three doses of HCBD (25, 50, and 100 mg/kg b.w. i.p.) or chromate (8, 12.5, and 25mg/kg b.w. s.c.) at 8 weeks of age. Forty-eight hours after treatment, Rgn and glutamine synthetase (GS) activity in kidney cortex, blood urea nitrogen (BUN) and plasma creatinine were measured; light microscopy was performed also. The results show that young rats are less susceptible to chromate (severe necrosis is evident only in adult rats), whereas age does not influence HCBD nephrotoxicity. Rgn is down regulated by HCBD at both age points, but not by chromate at 5 weeks of age. In addition, HCBD causes down-regulation of Rgn from the low dose in 8-week-old rats, whereas chromate causes the same effect at the high dose only. GS activity in kidney cortex shows a similar behavior, even if sensitive to low doses of chromate also, whereas BUN and creatinine increase after the high dose of both chemicals only. Accordingly, light microscopy shows a segment-specific, dose-dependent increase of severity of damage caused by the chemicals. Rgn gene expression appears a sensitive genomic marker to evaluate the renal impairment caused by chemicals and its down-regulation seems to be related to damage, early or already established, to S(3) segment of the proximal tubule.

Safety evaluation of a triterpenoid-rich extract from bamboo shavings.

Triterpenoids, which may have significant application to the development of natural medicines and functional foods as biological active components, are widely distributed throughout the plant kingdom. This paper evaluated the safety of a triterpenoid-rich extract of bamboo shavings (EBS) systematically. (i) Acute toxicity test: The oral maximum tolerated dose of EBS was more than 10 g/kg body weight both in rats and in mice, due to the absence of toxicity according to the criteria of acute toxic classifications. (ii) Mutagenicity test: It had no mutagenicity judged by negative experimental results of Ames test, mouse bone marrow cell micronucleus test and mouse sperm abnormality test. (iii) 30 days feeding study: No abnormal symptoms and clinical signs or deaths had been found in rats in each group during the test. No significant difference had been found in body weight, food consumption and food availability of rats in each test group (P>0.05). In addition, no significant differences were found in each hematology value, clinical chemistry value and organ/body weight ratio, either (P>0.05). No abnormality of any organ was found during histopathological examination. It can be concluded that the extract of bamboo shavings is of low toxicity and support the use of EBS for various foods.

Synthesis and evaluation of a series of 1,4-diarylbutadienes for anticoccidial activity.

During the course of a collaborative screening program, a set of 1-phenyl-4-pyridyl-butadienes was found to exhibit in vitro activity against Eimeria tenella in a cell-based assay. Activity was dependent on the chain length and degree of unsaturation of the linker between the two aryl groups as well as substitution of the pyridine moiety. Structure-activity relationship studies were subsequently conducted over a larger range of 1,4-diarylbutadienes in order to determine the scope of active compounds, to identify structural patterns governing activity and to enhance in vitro potency against E. tenella. In addition, the efficacy of many compounds for treating coccidiosis in chickens was measured by testing the ability of the compound to prevent or reduce intestinal and cecal lesions when administered by oral gavage. A few compounds in the series were identified that exhibited a moderate degree of in vitro and in vivo activity.

An analysis of the risk of B-lymphocyte malignancies in industrial cohorts.

Among numerous studies of occupational groups with varied chemical exposures (e.g., farmers, petroleum workers, and rubber workers), some have reported excess risk for non-Hodgkin's lymphoma (NHL), multiple myeloma, and other cancers of the B-lymphocyte cell line. While not conclusive, these studies raise questions about the effects of chemical exposures on the lymphocytic versus myeloid cell lines. Almost 70 occupational cohort studies were identified that addressed B-cell cancer risks in 9 major industrial categories, in order to look for common patterns across industries. This effort was substantially limited by the inconsistent nature of lymphohematopoietic (LH) classification schemes across studies and over time, and the relative paucity of B-cell-specific results in studies for any given industry. Taking these limitations into consideration, a descriptive, graphical analysis suggested a pattern of B-cell cancer elevations in the rubber and "general chemical" industries, but no consistent patterns in petroleum production/distribution or petrochemical production. The limited data sources, which lack detail about differences in hazard and exposure for different types of products/chemicals, did not allow a comprehensive look at possible common exposures associated with B-cell cancer elevations across industries. This study suggests that evaluation of possible associations between specific chemical exposures and B-cell malignancies would require additional studies with clear and common definitions of B-cell outcomes. The article concludes by giving an example of a possible common framework for categorizing NHL, the diseases for which most classification issues arise.

Significance of 1,3-butadiene to the US air toxics regulatory effort.

Because of its prevalence, particularly as a combustion by-product, 1,3-butadiene is a particularly important air toxic. It plays a significant role in all air toxics regulatory efforts in the US. The various requirements of the Federal Clean Air Act (CAA) dealing with air toxics are reviewed and the significance of 1,3-butadiene in each area is discussed in light of what is known about its emissions and health effects. The impacts of the changes in the understanding of 1,3-butadiene cancer potency over the past 15 years demonstrates the possible impact of such benchmarks and the importance of using the best science in understanding public health risks.

A mortality, morbidity, and hematology study of petrochemical employees potentially exposed to 1,3-butadiene monomer.

This three-part study is an update of a previous report that examined the mortality, morbidity, and hematological data of employees from a petrochemical facility in Texas who had potential exposure to 1,3-butadiene monomer. The first part describes the updated cause-specific mortality of 614 workers. Vital status for each cohort member was ascertained through 1998, a 9-year extension of the previous study. The second part is an examination of the morbidity experience of cohort members who were still working during 1992-1998, including 289 of the 614 mortality cohort members. The third part is an evaluation of the hematological results from routine health surveillance and/or medical examinations. Approximately 430 of the 614 employees who had complete blood count (CBC) data as of December 1999 were included in the hematological evaluations. The most recent examination containing CBC data was used and compared with similar data for over 2600 other employees from this facility. Overall mortality during the follow-up period, 1948-1998, was significantly lower than for the local comparison population (standardized mortality ratio (SMR) of 0.55 with a 95% confidence interval (CI) of 0.42-0.70). Mortality for all cancer was also significantly lower (SMR, 0.57; 95% CI, 0.32-0.92). Mortality for all lymphohematopoietic cancer was about the same as the comparison population (SMR, 1.06; 95% CI, 0.22-3.11). None of the cause-specific morbidity was in excess compared with an internal comparison group. There were no differences in the distribution or mean values of hematological variables (e.g. white blood cells, red blood cells, hemoglobin, platelets, mean corpuscular volume) between the butadiene cohort and the comparison group, or between a subgroup of workers in jobs with the highest potential for butadiene exposure (i.e. shipping) and the rest of the butadiene cohort. The findings of this study suggest that the butadiene exposure at this facility in the last 20 years does not pose a health hazard to employees.

Spermatogenesis and mutagenicity of environmental hazards: extrapolation of genetic risk from mouse to man.

To perform germ cell mutagenicity studies it is mandatory to know the duration of the different stages of spermatogenesis. The timing of male germ cell development determines the test protocols. Chemical mutagens are characterized by their differential spermatogenic responses, e.g. different chemicals induce mutations in different germ cell stages. Knowledge of the sensitive germ cell stages for a test agent is essential for the evaluation of the genetic hazard, i.e. stem cell effects present permanent genetic hazards and post-stem cell effects present transient hazards. A variety of assays are available to determine germ cell mutagenicity in treated animals or in the progeny of treated animals. Germ cell cytogenetics in differentiating spermatogonia and the dominant lethal assay are used for genetic hazard identification. Their results allow categorization of chemicals as germ cell mutagens (Maximale Arbeitsplatz Konzentration categories for germ cell mutagens). Gene mutations or reciprocal chromosome translocations induced in germ cells are assessed by observation of mutant offspring of treated males. These results are applicable to the quantification of genetic hazards for chemical exposures which cannot be avoided, i.e. for occupational exposures to chemicals such as butadiene.

A study on reference standard for cytotoxicity assay of biomaterials.

The objective of the present study was to find a standard substance for use as a reference in the cytotoxicity assay of biomaterials, as an alternative to animal experiments in recent years. Eight kinds of rubber were made in a plate shape to keep their surface area at 1 cm2 against 10 ml of extract volume. They were extracted by the following three extraction methods (a) dynamic extraction at 200 rpm gyration on alumina balls at 37 degrees C for 24 h; (b) static extraction at 37 degrees C for 24 h and (c) extraction by heating in an autoclave at 121 degrees C for 60 min. At the end of each period each extract was examined for cell viability based on an evaluation by neutral red uptake. These methods were repeated up to seven times. Two kinds of chemicals were also tested. The extracts obtained were used to treat human gingival fibroblasts that have been cultured with DMEM supplemented with 5% fetal bovine serum into a 96 well tissue culture plate by 1 x 10(5) cells/ml, in an incubator aerated with 5% CO2, and 95% humidified air at 37 degrees C for 48 h. The extracts of ethylene-propylene, butyl, nitrile rubbers, and two kinds of chemicals yielded strong cytotoxicity in all three kinds of extraction methods, while chloroprene, fluorine-contained, isoprene, India, and silicone rubbers showed little cytotoxicity. The results obtained by the three kinds of extraction methods revealed no differences in the order of cytotoxicity of the materials tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Dangerous and cancer-causing properties of products and chemicals in the oil refining and petrochemical industry--Part II: Carcinogenicity, mutagenicity, and developmental toxicity of 1,3-butadiene.

1,3-butadiene (BD) is present in synthetic rubber and motor fuels (gasoline). BD is shown to cause lymphocytic lymphomas, heart hemangiosarcomas, lung alveolar bronchiolar cancers, forestomach-squamous cell cancers, harderian gland neoplasms, preputial gland adenoma or carcinoma, liver-hepatocellular cancers, mammary gland acinar cell carcinomas, ovary-glanulosa cell carcinoma, brain cancers, pancreas adenoma and carcinoma, testis-Leydig cell tumors, thyroid follicular adenoma and carcinoma, and zymbal gland carcinoma in rodents and to date no exposure level has been established at which this chemical does not cause cancers. In humans BD causes increase in lymphomas, leukemias, and other cancers of hematopoietic systems and organs. BD is also a potent alkylating agent, directly toxic to developing embryos and damages progeny after parental exposure.

[Occupational exposure to butadiene and various parameters of cellular immunity in workers in petrochemical plants]. / Zawodowa ekspozycja na butadien a niektóre parametry odpornosci komórkowej u pracowników petrochemii.

In 32 workers of Butadiene Division of the Mazovian Refining and Petrochemical Plant cellular immunity parameters were examined. The proposed parameters allowed to select those with defected immunity and monitor the effects of occupational exposure to some xenobiotics on human immune system.