Biological effects of molybdenum(IV) sulfide nanoparticles and microparticles in the rat after repeated intratracheal administration.

In this study, molybdenum(IV) sulfide (MoS2 ) nanoparticles (97 ± 32 nm) and microparticles (1.92 ± 0.64 µm) stabilized with poly (vinylpolypyrrolidone) (PVP) were administered intratracheally to male and female rats (dose of 1.5 or 5 mg/kg bw), every 14 days for 90 days (seven administrations in total). Blood parameters were assessed during and at the end of the study (hematology, biochemistry including glucose, albumins, uric acid, urea, high density lipoprotein HDL, total cholesterol, triglycerides, aspartate transaminase, and alanine transaminase ALT). Bronchoalveolar lavage fluid (BALF) analyses included cell viability, biochemistry (total protein concentration, lactate dehydrogenase, and glutathione peroxidase activity), and cytokine levels (tumor necrosis factor α, TNF-α, macrophage inflammatory protein 2-alpha, MIP-2, and cytokine-induced neutrophil chemoattractant-2, CINC-2). Tissues were subjected to routine histopathological and electron microscopy (STEM) examinations. No overt signs of chronic toxicity were observed. Differential cell counts in BALF revealed no significant differences between the animal groups. An increase in MIP-2 and a decrease in TNF-α were observed in BALF in the exposed males. The histopathological changes in the lung evaluated according to a developed classification system (based on severity of inflammation, range 0-4, with 4 indicating the most severe changes) showed average histopathological score of 1.33 for animals exposed to nanoparticles and microparticles at the lower dose, 1.72 after exposure to nanoparticles at the higher dose, and 2.83 for animals exposed to microparticles at the higher dose. In summary, it was shown that nanosized and microsized MoS2 can trigger dose-dependent inflammatory reactions in the lungs of rats after multiple intratracheal instillation irrespective of the animal sex. Some evidence indicates a higher lung pro-inflammatory potential of the microform.

Assessment of acute toxicological effects of molybdenum(IV) disulfide nano- and microparticles after single intratracheal administration in rats.

Despite growing applications of molybdenum(IV) sulfide (MoS2) nano- and microparticles in their capacity as lubricants, data available on their safety are scarce. In this study the effect of MoS2 nano- and microparticles after single intratracheal instillation in rats has been analyzed. MoS2 suspensions were administered at the dose of 1.5 or 5 mg MoS2/kg body weight. The analysis after 24 h and 7 days included: blood biochemical parameters, hematological parameters, bronchoalveolar lavage fluid (BALF) parameters with selected cytokines, a comet assay and histopathological examination. In the BALF cells isolated from animals exposed to both forms, numerous macrophages loaded with particles were observed. The hematological and biochemical parameters analyzed 24 h or 7 days after the exposure to both forms did not show any biologically meaningful changes. Comet assay results showed no genotoxic effect. The histopathological analysis of the lungs revealed inflammatory changes in the respiratory system of the treated animals, slightly stronger for the microsized form. The deposits of particles observed in the lung tissue up to 7 days after the instillation indicate their easy penetration through the epithelium and prolonged clearance. Concluding, no meaningful acute systemic effects were observed, however some pathological changes were noted in the lung tissue.

Embryolethal and teratogenic effects of carbendazim in rats.

This study was performed to evaluate the effects of prenatal development of rats. Females were exposed to carbendazim by gavage every day on days 6-15 of gestation at doses 8, 35, 160 mg/kg b.w. Carbendazim administered at doses of 35 and 160 mg/kg was associated with significant maternal toxicity, embryonal lethality, congenital defects, and retarded fetal development. It produced encephalocele, umbilical hernia, missing or shorter tail, and internal malformations of brain, kidneys, and skeletal malformations of ribs, arch, and vertebrae. NOEL for the dam and fetus in our study was 8 mg/kg/day.

Concentrations of anaesthetic gases in hospital operating theatres.

Occupational exposure to anaesthetic gases (halothane, forane and nitrous oxide) was assessed in hospitals located in Lódz and its satellite towns. Individual dosimetry and stationary sampling methods were employed. The samples of air from workplaces were analysed by gas chromatography with mass detection or flow ionisation (halothane, forane) and by infra-red spectroscopy method (nitrous oxide). The concentrations of halothane and accompanying substances (ethanol, isopropanol and diethyl ether) indicate that Polish OELs were met in the majority of the hospitals. As Polish hygiene standards for forane and nitrous oxide are no available, the concentration values were compared with Swedish and German OELs. The comparison revealed that forane concentrations did not exceed Swedish OEL but nitrous oxide did exceed German maximum allowable levels.

Maternal and fetal toxicity of N-methylmorpholine by oral administration in rats.

N-methylmorpholine, which is used as a catalyst in polyurethane foams producing, in solvents, stabilizing agents, and corrosion inhibitors, was administered to female rats by gavage at 100, 200, 600, and 900 mg/kg during organogenesis. It did not exhibit selective toxicity toward the developing conceptus. This compound administered to pregnant females was fetotoxic and teratogenic in the presence of maternal toxicity. N-methylmorpholine induced anophthalmia, internal hydrocephalus, and hydronephrosis but only at one dose which was also maternotoxic. Teratogenesis Carcinog. Mutagen. 19:369-376, 1999.

Occupational exposure to ethylene oxide of hospital staff.

Occupational exposure to ethylene oxide was assessed among the workers remaining in direct contact with ethylene oxide or with ethylene oxide-sterilized instruments in 13 hospitals located in the city of Lódz and its suburbs. Individual dosimetry and stationary sampling methods were employed. The samples collected from the occupational environment were analysed by gas chromatography with mass detection. The analytical method enabled determination of low ethylene oxide concentrations in the presence of the accompanying chemicals, such as ethyl alcohol, isopropyl alcohol, ethyl ether and isoflurene. In total, 227 determinations were made, and ethylene oxide at concentrations above 0.01 mg/m3 (which was the detection limit of the method) was found to be present in 164 samples. The ethylene oxide levels were found to vary widely, from lower than 0.01 TLV to several hundred times the TLV value.

[Evaluation of reproductive disorders in men occupational exposed to lead]. / Ocena zaburzen plodnosci mezczyzn narazonych zawodowo na olów.

The objective of the study was to define the prevalence of reproductive disorders in men occupationally exposed to lead in concentrations occurring usually in the work environment. The period of time preceding the conception in couples in which men were occupationally exposed to lead was adopted as the measure of the disorder. A cross-section survey was performed. Men of selected plants of Upper Silesia and Glogów responded to questions included in the questionnaire regarding age, education, occupation, occupational exposure, health condition, addictions, the situation in the family as well as questions concerning the respondent's spouse (age, education, occupation, addictions, health condition). The blood lead concentrations in persons exposed to this metal in the period preceding the conception were defined on the basis of medical data stored by the plant occupational outpatient clinics. The control group consisted of workers of the metallurgic industry, living in Lódz or its vicinity, and non-occupationally exposed men living in Silesia. In total 341 exposed men and 510 non-exposed controls participated in the study. The investigated groups were rather homogeneous as to the age of those under study and their spouses, education, addictions and the number of children. The analysis of the survey results indicated that in 5% of couples in the control group the time before conception exceeded one year. A similar occurrence of reproductive disorders was found in couples in which man was occupationally exposed to lead. The proportion of couples with reproductive disorders in this group (regardless of the size of Pb exposure) was 6%. The stratification of the Pb-exposed groups, taking into account the exposure size in accordance with the WHO criteria (group 1-220 micrograms/l, that is below the accepted value above which the ZnPP level increases; group II-PbB 200-400 micrograms/l that is up to the level recommended as the highest level for the population occupationally exposed to lead; and group III-PbB above 400 micrograms/l) allowed the analysis of the frequency of reproductive disorders depending on the size of the exposure. The percentage of couples with delayed conception accounted for 4.5% in group I; 8.7% in group II, and in group III did not differ significantly from that in the control group. These results show that men's occupational exposure to lead below allowable concentration in the biological material (500 micrograms/Pb/l blood in Poland or 400 micrograms/Pbl recommended by WHO) does not pose the risk for prolonged period preceding the conception in their partners.

[Frequency of birth defects in newborns in four regions of Poland]. / Czestosc wad wrodzonych u noworodków w czterech regionach Polski.

Records of births from registry offices in seven provinces (Walbrzych, Piotrków Trybunalski, Suwalki, Krosno, Rzeszów, Przemysl, Tarnobrzeg) making four regions (south-western, central, north-eastern and south-eastern) were used for the analysis of the geographical distribution of congenital malformations. This area is inhabited by approximately 10% of the whole population with annual number of briths equal to 9% of the total number in Poland. The incidence of congenital malformations was analysed in 21.167 newborns taking into consideration such variables as smoking and other habits and occupational of parents, maternal age, and environmental pollution. In the cohort under study the incidence of malformations was different and it was as follows: Walbrzych-1.92%, Rzeszów-1.42%, Tarnobrzeg-1.37%, Suwalki-1.23%, Krosno-1.16%, Piotrków Trybunalski-1.12% and Przemysl-0.7%. The incidence of birth defects in infants born to young mothers (< 20 years) was 1.8% and to older ones (> 35) 1.9%. A comprehensive analysis of the environmental pollution revealed its highest level in the south-western region (the Walbrzych province) in comparison with other study areas.

[Environmental factors which impair male fertility]. / Czynniki srodowiska uposledzajace plodnosc mezczyzn.

Introduction of new technologies involving many chemicals does not remain free from the effect on the human health. Occupational acute poisoning is rare now-a-days, but we often face many problems arising out of the late sequel to exposures, such as mutations, neoplasms or reproduction disorders. Numerous research institutes of occupational medicine are involved in the evaluation of the effect of environmental factors on the workers' health. Many recent publications emphasise that the quality of the human semen is gradually decreasing which is manifested by the lower number of spermatozoons (1 cm3) semen, a higher proportion of morphologically impaired spermatozoons and a higher per cent of motile spermatozoons. The quality of the semen is affected not only by the hazards present in the general environment, but also by the factors occurring in the work environment. Occupational exposure induces sometimes infertility of couples but more often impairs the reproduction, and this is one of important issues which be addressed by occupational medicine.

[Comparative evaluation of the frequency of congenital defects in newborns from the provinces of Walbrzych, Piotrkow Trybunalski and Suwalki]. / Porównawcza ocena czestosci wad wrodzonych u noworodków z województw Walbrzyskiego, Piotrkowskiego i Suwalskiego.

The aim of the study was the assessment of congenital defect frequency in 11,869 neonates born between December 1994 and July 1995 in three provinces of Poland: Walbrzych, Piotrków Trybunalski and Suwalki. The percentage of neonates with congenital defects ranged from 1.9% in a typically industrial area (Walbrzych) to 1.2% in a mainly rural area (Suwalki), and 1.1% in a rather industrial area (Piotrków Trybunalski). The majority of single defects consisted of anomalies of limbs and musculoskeletal deformities. Smoking habits and professional activities of mothers did not exert a clear influence on the frequency of birth defects. Only among newborns from the province of Piotrków Trybunalski who were born by young mothers (< 20 years of age) we observed a higher frequency of congenital defects in comparison with older mothers of 20-34 years old group.

[Occupational exposure of medical personnel to chemical factors affecting fertility]. / Zawodowe narazenie personelu medycznego na czynniki chemiczne mogace zaburzac plodnosc.

Exposure to factors present in the working environment may exert an adverse effect on both those directly and on their progeny. Together with large populations exposed to harmful factors in different branches of industry (chemical, metallurgical, textile etc.), health service workers should be also taken into account as another significant group exposed. Factors affecting fertility, health service workers are mostly exposed to, are as follows: cytostatic drugs, chemicals used in sterilization, gases for general anaesthesia and enormous number of factors the health service workers are in contact with in laboratories. The authors reviewed the world literature and presented kinds of harmful factors and their effect on fertility in persons employed in health services and exposed to them.

[Disturbances of prenatal development in rats exposed to fenitrothion]. / Zaburzenia rozwoju prenatalnego szczurów narazanych na fenitrotion.

Female rats were given fenitrothion by gavage every other day from days 6-15 of gestation at daily doses 3, 15, 30, 45 mg/kg (0.3%, 1.7%, 3.4%, 5.2% LD50). Assessment of general toxicity of pregnant dams (death rate, body weight gain, food and water consumption, relative and absolute organs weight, hematocrit and hemoglobin level), embryotoxicity, fetotoxicity and teratogenicity of fenitrothion was performed. Death rate in female rats exposed at doses 45 mg/kg and 30 mg/kg was 88% and 39% respectively. The toxic activity of fenitrothion at dose 30 mg/kg was reflected in significant decreased body weight gain, food consumption, also hemoglobin and hematocrit values and decreased of absolute weight of liver and kidneys, increased relative weight of adrenal and ovaries. The toxic activity at dose 15 mg/kg/day was reflected in significant decreased of relative weight of liver. At the dose 30 mg/kg of fenitrothion exhibited embryotoxic effect producing significant increase in the frequency of early resorption per litter and postimplantation losses. Fetotoxic effect manifested by increased of frequency fetuses and litters with enlarged cerebral ventricles was observed at doses 15 mg/kg and 30 mg/kg. Furthermore, at dose 30 mg/kg fenitrothion produced delayed ossification of sternum and cranium, and decrease fetal body weight and length. Fenitrothion at doses 3-30 mg/kg did not induced teratogenic effects. The NOAEL for developmental toxicity was 3 mg/kg/day (0.3 LD50) and the LOAEL 15 mg/kg/day (1.7 LD50).

Effect of oral Sulfenamide TS administration on prenatal development in rats.

Sulfenamide TS (N-cyclohexyl-2-benzothiazolesulfenamide), accelerator of rubber vulcanization, was administered to female rats by gavage at doses of 50, 150, and 450 mg/kg (1%, 3%, and 8% of LD50) during organogenesis. The maternal toxicity of Sulfenamide TS was found at the highest dose of 450 mg/kg. Oral administration of this compound to female rats during organogenesis induced fetotoxic effects at doses of 50 mg/kg and higher. The dose-dependent increase in the frequency of fetuses/ litters with internal hydrocephalus was observed.

Evaluation of oral exposure to Polnoks R for female rats in developmental toxicity studies.

This study was performed to evaluate the effects of prenatal development of rats exposed to Polnoks R, an antioxidant in elastomer processing. Pregnant female rats were exposed to Polnoks R by gavage every day on days 6-15 of gestation at doses of 170, 340, and 670 mg/kg body weight (b,w) (6%, 13%, and 25% LD50). Clinical observations, maternal body weights, and food and water consumption were recorded throughout gestation. At scheduled necropsy on 20 day of gestation maternal animals were evaluated for body weight, liver, spleen, ovarjan kidney, and adrenal weights, number of ovarian corpora lutea, and status of uterine implantation sites. Fetuses were counted, weighed, and examined for external, skeletal, and visceral alterations. Maternal weight gain was reduced in the group receiving Polnoks R at the 670 mg/ kg dose. In all groups the daily food and water consumptions were similar to controls. The relative weights of the adrenals, ovaries, spleen, and liver of the females intoxicated with the highest dose of Polnoks R were significantly higher than control organs. Polnoks R is an embryotoxic and fetotoxic agent. It produced a significant increase in the average number of postimplantation losses and a decrease in both the weight and body length of the fetuses from the pregnant female rats exposed to the highest dose. This chemical also produced birth defects-absent or short tail, cleft palate, and internal hydrocephalus-but only at doses toxic to the mother.

[Frequency of birth defects in four different regions in Poland]. / Wstepna analiza czestosci wad wrodzonych u noworodków w wybranych rejonach Polski.

The aim of this paper is preliminary assessment of birth defect in different regions of Poland with various environmental pollution. During the first 3 month of registration among 7253 newborns were 91 (1,3%) birth defect (0,8%-1,6% in different regions).

[Mortality of workers in the dye industry. I. Analysis of general mortality]. / Umieralnosc pracowników przemyslu barwnikarskiego. I. Analiza umieralnosci ogólnej.

A mortality study was carried out among workers employed in a plant producing different kinds of dyes using benzidine. The cohort comprised 8,523 males and 2,006 females whose vital status was recorded between Jan 1, 1945 and Dec 31, 1991. They had worked in this plant for, at least, 3 months between Jan 1, 1945 and Dec 31, 1974. The cohort was divided into 4 subcohorts: I. those exposed only to benzidine; II. those exposed to benzidine and to other occupational hazards; III. those involved directly in the dyes production but not exposed to benzidine, and IV. those not involved directly in the dye production-mainly administrative staff. Death risk was estimated on the basis of standardized mortality ratio (SMR), determined by means of the person-years method. The general population of Poland was taken as a reference group. The observed number of deaths in the cohort and each subcohort was compared with expected deaths. The comparison was based on the national rates by adjustment for age, gender and calendar time. An excessive mortality due to mental disorders (SMR = 2.37) was found in the male cohort, and due to atherosclerosis in both cohorts--male (SMR = 1.25) and female (SMR = 1.37). An analysis of mortality in subcohorts showed similar but not the same relationship. Mortality because of malignant neoplasms will be presented in the next paper.

[Mortality among the dye industry workers. II. An analysis of malignant neoplasm mortality]. / Umieralnosc pracowników przemyslu barwnikarskiego. II. Analiza umieralnosci z powodu nowotworów zlosliwych.

A mortality study was carried out among workers employed in a plant producing different kinds of dyes, including benzidine. The cohort comprised 8,523 males and 2,006 females whose vital status was recorded between Jan 1, 1945 and Dec. 31, 1991. They had worked in this plant for, at least, 3 months between Jan. 1, 1945 and Dec 31, 1974. The cohort was divided into 4 subcohorts: I. those exposed only to benzidine: II. those exposed to benzidine and other occupational hazards; III. those involved directly in the dye production but not exposed to benzidine, and IV. those not involved directly in the dye production-mainly administrative staff. Death risk was estimated on the basis of standardized mortality ratio (SMR) determined by means of the person-years method. The general population of Poland was taken as a reference group. The observed number of deaths in the cohort and each subcohort was compared with expected deaths. The comparison was based on national rates by adjustment for age, gender and calendar time. Significant excessive mortality due to cancer of urinary bladder was observed in the male subcohort I (SMR = 14.69), II (SMR = 16.34) and III (SMR = 3.17); due to malignant neoplasm of pancreas in the male subcohort II (SMR = 3.26); due to malignant neoplasm of testis in the male subcohort III (SMR = 3.17); due to malignant neoplasm of pancreas in the male subcohort II (SMR = 3.26); due to malignant neoplasm of testis in the male subcohort III (SMR = 3.23). Significant excessive mortality due to malignant neoplasm of liver and intrahepatic bile ducts was found in the female subcohort IV (SMR = = 2.36).

Assessment of the effect of n-butanol given to female rats in drinking water on fertility and prenatal development of their offspring.

Female rats were given aqueous solutions of n-butanol containing 0.24, 0.8 and 4% n-butanol (0.3; 1.0 and 5.0 g/kg/day) for 8 weeks before and during gestation. The control animals received tap water. The experiment was performed in two stages. The first comprised of the assessment of the oestrous cycle before exposure and then during 4-5 and 7-8 weeks of exposure, and the second stage of the fertility of female rats and their foetal development. The duration of the cycle and its individual stages in the control and the exposed females were similar. It was found that n-butanol alcohol is a foetotoxic agent and produces developmental anomalies in a foetus's skeleton and central nervous system.

[Intracellular receptors of polyaromatic hydrocarbons]. / Wewnatrzkomórkowe receptory wielopierscieniowych weglowodorów aromatycznych.

Molecular aspects of the expression of genes responsible for coding the proteins which participate in the oxidative metabolism of polyaromatic hydrocarbons (PAH) have been discussed. Particular attention has been paid to the expression of the gene for the intracellular PAH-binding AHR protein receptor. Possible relationship between genetically-conditioned polymorphism of PAH oxidative metabolism and individual susceptibility to lung cancer has been presented. Methods for assessment of the affinity of AHR protein to PAH which make it possible to assess human susceptibility to carcinogens have been reviewed.

The effect of maternal exposure to dioxolane on prenatal and postnatal development in rats.

Female rats were given by gavage every other day from days 8-20 of gestation an aqueous solution of dioxolane at daily doses equal to 0.025, 0.1 and 0.2 LD50 (first series--prenatal development) or from days 2-20 of gestation at daily doses equal to 0.025, 0.075 and 0.15 LD50 (second series--postnatal development). At doses toxic or subtoxic to maternal rats (0.1 and 0.2 LD50) dioxolane did not cause increased embryo or fetus intrauterine death rates or congenital defects, it did cause, however, dose-related delays in fetal development. Dioxolane does not cause impairment of physical development or behavioral disturbances. Exposure to higher doses of the compound (0.2 LD50) leads to increased perinatal death rates in the offspring, without causing, however, disturbances in the maternal instinct. The exposure of pregnant rats to dioxolane decreased haemoglobin levels in 5-week-old offspring. At a dose 1.15 g/kg (0.2 LD50) the chemical significantly increased exploratory motor activity of female offspring at the age of 8 weeks, but did not affect significantly locomotor activity of males and the active avoidance acquisition of adult offspring.