Survival and infectivity of Toxoplasma gondii and Cryptosporidium parvum oocysts bioaccumulated by Dreissena polymorpha.

AIMS: The study was aimed to understand the depuration process of Cryptosporidium parvum and Toxoplasma gondii oocysts by zebra mussel (Dreissena polymorpha), to consider the use of the zebra mussel as a bioremediation tool. MATERIALS AND METHODS: Two experiments were performed: (i) individual exposure of mussel to investigate oocyst transfers between bivalves and water and (ii) in vivo exposure to assess the ability of the zebra mussel to degrade oocysts. RESULTS: (i) Our results highlighted a transfer of oocysts from the mussels to the water after 3 and 7 days of depuration; however, some oocysts were still bioaccumulated in mussel tissue. (ii) Between 7 days of exposure at 1000 or 10 000 oocysts/mussel/day and 7 days of depuration, the number of bioaccumulated oocysts did not vary but the number of infectious oocysts decreased. CONCLUSION: Results show that D. polymorpha can release oocysts in water via (pseudo)faeces in depuration period. Oocysts remain bioaccumulated and infectious oocyst number decreases during the depuration period in zebra mussel tissues. Results suggest a degradation of bioaccumulated C. parvum and T. gondii oocysts. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlighted the potential use of D. polymorpha as a bioremediation tool to mitigate of protozoan contamination in water resources.

Cytotoxic and genotoxic evaluation of different synthetic amorphous silica nanomaterials in the V79 cell line.

The nature of occupational risks and hazards in industries that produce or use synthetic amorphous silica (SAS) nanoparticles is still under discussion. Manufactured SAS occur in amorphous form and can be divided into two main types according to the production process, namely, pyrogenic silica (powder) and precipitated silica (powder, gel or colloid). The physical and chemical properties of SAS may vary in terms of particle size, surface area, agglomeration state or purity, and differences in their toxicity potential might therefore be expected. The aim of this study was to compare the cytotoxicity and genotoxicity of representative manufactured SAS samples in Chinese hamster lung fibroblasts (V79 cells). Five samples from industrial SAS producers were evaluated, that is, two pyrogenic SAS powders (with primary particle sizes of 20 nm and 25/70 nm), one precipitated SAS powder (20 nm) and two precipitated SAS colloids (15 and 40/80 nm). V79 cell cultures were treated with different concentrations of SAS pre-dispersed in bovine serum albumin -water medium. Pyr (pyrogenic) 20, Pre (precipitated) 20 and Col (colloid) 15 significantly decreased the cell viability after 24 h of exposure, whilst Pyr 25/70 and Col 40/80 had negligible effects. The cytotoxicity of Pyr 20, Pre 20 and Col 15 was revealed by the induction of apoptosis, and Pyr 20 and Col 15 also produced DNA damage. However, none of the SAS samples generated intracellular reactive oxidative species, micronuclei or genomic mutations in V79 cells after 24 h of exposure. Overall, the results of this study show that pyrogenic, precipitated and colloidal manufactured SAS of around 20 nm primary particle size can produce significant cytotoxic and genotoxic effects in V79 cells. In contrast, the coarser-grained pyrogenic and colloid SAS (approximately 50 nm) yielded negligible toxicity, despite having been manufactured by same processes as their finer-grained equivalents. To explain these differences, the influence of particle agglomeration and oxidative species formation is discussed.

Cytotoxicity and genotoxicity of panel of single- and multiwalled carbon nanotubes: in vitro effects on normal Syrian hamster embryo and immortalized v79 hamster lung cells.

Carbon nanotubes (CNTs) belong to a specific class of nanomaterials with unique properties. Because of their anticipated use in a wide range of industrial applications, their toxicity is of increasing concern. In order to determine whether specific physicochemical characteristics of CNTs are responsible for their toxicological effects, we investigated the cytotoxic and genotoxic effects of eight CNTs representative of each of the commonly encountered classes: single- SW-, double- DW-, and multiwalled (MW) CNTs, purified and raw. In addition, because most previous studies of CNT toxicity were conducted on immortalized cell lines, we decided to compare results obtained from V79 cells, an established cell line, with results from SHE (Syrian hamster embryo) cells, an easy-to-handle normal cell model. After 24 hours of treatment, MWCNTs were generally found to be more cytotoxic than SW- or DWCNTs. MWCNTs also provoked more genotoxic effects. No correlation could be found between CNT genotoxicity and metal impurities, length, surface area, or induction of cellular oxidative stress, but genotoxicity was seen to increase with CNT width. The toxicity observed for some CNTs leads us to suggest that they might also act by interfering with the cell cycle, but no significant differences were observed between normal and immortalized cells.

Induction of sulfadiazine resistance in vitro in Toxoplasma gondii.

We induced sulfadiazine resistance in two sulfadiazine sensitive strains of Toxoplasma gondii, RH (Type I) and ME-49 (Type II) in vitro by using drug pressure. At first, sulfadiazine susceptibility of the two sensitive strains and two naturally resistant strains of T. gondii was evaluated on Vero cells using an enzyme-linked immunosorbent assay (ELISA). The IC(50) values of sulfadiazine were 77 µg/mL for RH, 51 µg/mL for ME-49 and higher than 1000 µg/mL for the two natural resistant strains. Secondly, induced resistance of the strains by gradually increase sulfadiazine concentration was verified by this test, which resulted IC(50) values at higher than 1000 µg/mL. In conclusion we developed in vitro two sulfadiazine resistant strains called RH-R(SDZ) and ME-49-R(SDZ). These strains resistant to sulfadiazine would be useful to characterize resistance mechanisms to sulfadiazine.

In vitro cytotoxicity and transforming potential of industrial carbon dust (fibers and particles) in syrian hamster embryo (SHE) cells.

Carbon fibers have many applications, mainly in high-tech industries such as the aviation industry. Eleven carbon samples (fibers and particles) coming from an aeronautic group were tested for their cytotoxicity and carcinogenic potential using in vitro short-term assays in Syrian hamster embryo cells. These samples were taken during each important step of the process, i.e. from the initial heating of polyacrylonitrile fibers to pure carbon fibers. They were compared to an asbestos fiber, an amorphous silica, and two commercial graphite powders. Their physical-chemical characteristics and their capacity to release reactive oxygen species (ROS) were determined. This study showed that none of the carbon samples was able to generate ROS as measured by Electron Paramagnetic Resonance analysis, and in our biological assays, they demonstrated no morphological transformation potential and low cytotoxicity compared to positive control (chrysotile asbestos).

Q2 dependence of the neutron spin structure function g2(n) at low Q2.

We present the first measurement of the Q2 dependence of the neutron spin structure function g2(n) at five kinematic points covering 0.57 (GeV/c)2 < or = Q2 < or = 1.34 (GeV/c)2 at x approximately = 0.2. Though the naive quark-parton model predicts g2 = 0, nonzero values occur in more realistic models of the nucleon which include quark-gluon correlations, finite quark masses, or orbital angular momentum. When scattering from a noninteracting quark, g2(n) can be predicted using next-to-leading order fits to world data for g1(n). Deviations from this prediction provide an opportunity to examine QCD dynamics in nucleon structure. Our results show a positive deviation from this prediction at lower Q2, indicating that contributions such as quark-gluon interactions may be important. Precision data obtained for g1(n) are consistent with next-to-leading order fits to world data.

Precision measurement of the neutron spin asymmetryA(n)(1) and spin-flavor decomposition in the valence quark region.

We have measured the neutron spin asymmetry A(n)(1) with high precision at three kinematics in the deep inelastic region at x=0.33, 0.47, and 0.60, and Q(2)=2.7, 3.5, and 4.8 (GeV/c)(2), respectively. Our results unambiguously show, for the first time, that A(n)(1) crosses zero around x=0.47 and becomes significantly positive at x=0.60. Combined with the world proton data, polarized quark distributions were extracted. Our results, in general, agree with relativistic constituent quark models and with perturbative quantum chromodynamics (PQCD) analyses based on the earlier data. However they deviate from PQCD predictions based on hadron helicity conservation.

Man-made mineral fiber hazardous properties assessment using transgenic rodents: example of glass fiber testing.

Transgenic BigBlue rats were exposed to CM 44 glass fibers (6.3 mg/m3) by nose only, 6 h/day for 5 days. Two endpoints were examined 1, 3, 14, 28, and 90 days following exposure: fiber biopersistence and mutations in lung DNA. The half-time of the fibers >20 microm was 12.8 days, and mutant frequencies of control and exposed rats were similar across all time points. The mutation spectra of both series were similar after 28 days of fixation time. These results showed that a glass fiber with a high clearance in the lung seems to not present any significant effect on mutagenesis on lung DNA and are in marked contrast to results for asbestos, which caused a twofold mutant frequency increase as described in a previous study.

Development and validation of a new bitumen fume generation system which generates polycyclic aromatic hydrocarbon concentrations proportional to fume concentrations.

Bitumen fumes emitted during road paving and roofing contain polycyclic aromatic compounds (PACs) of potential health concern. Little information is available for an experimental device devoted to inhalation experiments with animals exposed to bitumen fumes, and in all studies the systems were never validated for a range of fume concentrations, which prohibited their use for toxicological concentration-effect studies. Therefore, the purpose of this study was to validate a new experimental device able to generate bitumen fumes at different total particulate matter (TPM) concentrations with a linear correlation between TPM and the concentrations of different PACs, thus allowing toxicological dose-response studies with fumes representative of those in the field. Atmosphere samples collected from an animal exposure chamber allowed the determination of TPM, toluene soluble matter, polycyclic aromatic hydrocarbons (PAHs) and semi-volatiles. The particulate size distributions were determined in order to assess the deposition pattern in the respiratory tract. The temperature of 170 degrees C was chosen by analogy with the upper range of the temperature used during paving operations. The temperature of the air passing over the fume emission area was regulated to 20 degrees C and stirring of the heated bitumen was restricted to 90 r.p.m. The data show that the objective of developing a static fume generation system that reproducibly produces fumes in the inhalation chamber for specified target concentrations (TPM) were successful. The within-day variation coefficients for TPM were between 2.5 and 6.1%. The day-to-day variations for TPM concentration were between 4.1 and 5.8%. The concentrations of the 4-5 ring PAHs and the polycyclic aromatic sulphur heterocycles were proportional to the TPM concentration. The 2 and 3 ring PAH concentrations showed a deviation from proportionality with the TPM, probably due to their re-evaporation during sampling. The mass median aerodynamic diameter of airborne particles varied from 1.4 micro m at a fume concentration of 5 mg/m(3) to 3.2 micro m at 100 mg/m(3). In conclusion, this equipment was suitable for nose-only inhalation studies in the 5-100 mg/m(3) range of TPM. Bitumen fumes were generated with a good reproducibility under well-controlled conditions. Finally, the PAH profiles from atmospheric samples were in good agreement with those measured during road paving.

A spectrophotometric method for the determination of organic soluble matter in bitumen fumes.

A UV spectrophotometric procedure was validated for the determination of organic soluble matter in bitumen fumes collected by filtration technique. Ultrasonic extraction was carried out with toluene, an efficient extraction solvent for polycyclic aromatic hydrocarbons, followed by UV absorbance measurements at 320 nm. A calibration curve is plotted from the same set of samples determined by classical weighing method. Further determinations can also be made using the slope factor of the calibration curve. The procedure presents obvious simplicity and rapidity advantages and is less prone to losses than the measurements of weight. Inter-method comparisons of samples collected from experimental laboratory-generated penetration bitumen fumes commonly used in road paving showed that the three available procedures-weighing, infrared, and UV--described for the determination of organic soluble matter yield equivalent results.

Bitumen fumes: review of work on the potential risk to workers and the present knowledge on its origin.

Bitumens fumes contain polycyclic aromatic compounds (PAC). There is a possibility of long-term health effects following chronic exposure by inhalation or skin contamination in asphalt road pavers and highway maintenance workers. Epidemiological and experimental studies on this topic are reviewed and the possible causes of cancer discussed with a primary focus on heterocyclic polyaromatic compounds. In 2001, the results of the IARC epidemiological study confirmed an excess of lung cancer despite a lower cancer mortality. In vitro genotoxicity and mechanistic studies demonstrated a mutagenic effect of bitumen fume condensates (BFC) and some data suggested that the polycyclic aromatic hydrocarbons (PAH) analysed were not the major genotoxic compounds in bitumen fume condensates. Other compounds such as nitrogen-, sulfur- and/or oxygen-containing PAH or their alkyl substituted analogues, mutagenic in the Ames mutation assay, may be involved in the genotoxic effect of BFC. After skin painting with BFC, DNA adducts were found in skin, lung and lymphocytes of all the treated animals. Differences in the adduct patterns were also observed, but a more polar adduct was common to the three tissues and not observed in those from rats treated with coal-tar fume condensates (CTFC). Rat inhalation experiments with bitumen fumes confirmed the presence of a DNA-adduct in the lungs with the same Rf as the previous polar adduct. This adduct therefore merits further investigation as a potential biomarker in lymphocyte DNA to follow exposed workers. All the analytical data and the mechanistic data are complementary and suggest the potential role of thiophenes in the genotoxicity of bitumen fumes. Some thiophenes have lower mutagenic activity than their isosteric PAH, whereas others are very potent carcinogens. Generally, the sulfur analogues of PAH (SPAH) in bitumen fumes have a higher concentration than the PAH of similar molecular weight, whereas the SPAH in coal-tar fumes have a much lower concentration than the corresponding PAH. This may explain why the more polar adducts have been detected only in animals exposed to bitumen fume. In a skin carcinogenicity study of condensed asphalt roofing fumes, it has been demonstrated that the most active fractions were those containing a variety of aromatic SPAH. In conclusion to this review, there is an interest in determining the chemical identity of the major DNA adducts induced by BFC. This would allow experimental studies on the carcinogenic potency of these compounds and their validation as potential biomarkers. These compounds could thus merit further analytical investigation in preference to the PAH included in the list of the US Environmental Protection Agency that are currently being analysed by the industry in field studies.

Differential gene expression in mesothelioma.

To investigate the molecular events controlling malignant transformation of human pleural cells, we compared constitutive gene expression of mesothelioma cells to that of pleural cells. Using cDNA microarray and high-density filter array, we assessed expression levels of > 6500 genes. Most of the highly expressed transcripts were common to both cell lines and included genes associated with stress response and DNA repair, outcomes consistent with the radio- and chemo-resistance of mesothelioma. Interestingly, of the fewer than 300 genes that differed between cell lines, most functioned in (i) macromolecule stability, (ii) cell adhesion and recognition, (iii) cell migration (invasiveness), and (iv) extended cell division. Expression levels of several of these genes were confirmed by RT-PCR and could be useful as diagnostic markers of human mesothelioma.

Inhaled crocidolite mutagenicity in lung DNA.

We used transgenic mice carrying the lacI reporter gene to study the mutagenesis potential of asbestos crocidolite. The animals were exposed by nose-only inhalation to an aerosol containing 5.75 mg/m(3) crocidolite dust for 6 hr/day and 5 consecutive days. After 1, 4, and 12 weeks, we examined four end points: the cytology of bronchoalveolar lavage, the lung load of crocidolite, the hydrophobic DNA adducts, and the mutations in the lacI reporter gene. Twelve weeks after exposure, nearly 10% of the inhaled fibers remained in the lung (227 +/- 103 ng/mg lung). There was evidence of a typical inflammatory response consisting of multinucleate macrophages at weeks 4 and 12, whereas immediately after the exposure, we observed numerous polymorphonuclear neutrophils. The mutant frequency significatively increased during the fourth week after the exposure: 13.5 [time] 10(-5) in the exposed group versus 6. 9 10(-5) in the control group. The induction factor, defined by the ratio of checked mutants of exposed mice to checked mutants of control mice, was 1.96. The mutation spectrum of control lung DNA and exposed lung DNA was similar, suggesting the possible involvement of a DNA repair decrease in crocidolite-treated animals. We used the (32)P-postlabeling method and did not detect any increase of either 5 mC or bulky adduct in treated mice. This is the first study that demonstrates asbestos mutagenicity in vivo after a nose-only inhalation.

Effects of nickel sulfate on pulmonary natural immunity in Wistar rats.

This study was designed to investigate the in vivo effect of nickel sulfate on the pulmonary non-specific immune defences. Groups of four male Wistar rats were treated with a single intratracheal instillation of NiSO(4) at different doses: 1, 2, 4 and 8 micromol of NiSO(4) per rat. Control rats received a corresponding instillation of the saline vehicle. The effect of NiSO(4) on the cytotoxic activity of the pulmonary natural killer (NK) cells and alveolar macrophages (AM), as well as the pulmonary production of cytokines such as alpha-tumor necrosis factor (TNF-alpha) and gamma-interferon (IFN-gamma), were examined 1, 2 and 7 days later. Spontaneous NK-cytotoxicity towards mouse-derived tumor cell line, Yac-1 was suppressed 1 day after treatment at doses of 2 micromol/rat and above with only one result significant (P<0.05); 2 days after treatment the suppression was increased with all results significant at the same doses; 1 week after treatment NK activity restoration was observed except for the highest dose, 8 micromol/rat. AM-mediated cytotoxicity towards mouse-derived tumor cell line, 3T12, did not show any significant difference in treated and untreated animals. In contrast, whereas moderate levels of TNF-alpha were detected in the broncho-alveolar lavage (BAL) fluid supernatants of controls, the NiSO(4) treatment highly suppressed TNF-alpha production with a maximum observed after 2 days. TNF-alpha suppression was found to be transient, at least with the lowest NiSO(4) dose, with levels returning to normal after 7 days. A non-significant increase in IFN-gamma was observed in the BAL fluids of treated animals at each time of examination. Taken together, these results indicate that NK cell activity and TNF-alpha secretion are sensitive targets for instilled NiSO(4) in Wistar rats.

Inhalation study on exposure to bitumen fumes. Part 1: Development and validation of the equipment.

Bitumen fumes emitted during road paving or roofing contain polycyclic aromatic hydrocarbons (PAHs). Experimental studies have been previously performed to test the carcinogenic potency of bitumen fumes. Some of them have been criticised either on the grounds that the fume condensates were not representative of fumes to which humans are exposed or because the fumes were never characterised in terms of particle size and poorly in terms of composition and concentration in the chambers. For a nose-only inhalation study, we have evaluated the ability of a new fume generation system to deliver stable and reproducible atmospheres of bitumen fumes to an inhalation chamber and investigated the representativity of the fumes generated at a concentration level of 5 mg/m3. The fume generator comprises: (1) an insulated 20 l heated kettle (200 degrees C for bitumen); (2) an insulated inlet pipe with a needle valve to adjust the flow of the test compound from the kettle; (3) a fume generation chamber equipped with a series of interchangeable channels of different width. The fume concentration in the exposure chamber can be controlled by changing the channel width or by restricting the evaporation surface with aluminium foil, and/or by changing the flow rate. Samples of the atmosphere in the chamber were collected and analysed for quantitative determination of total particulate matter (TPM), soluble matter, benzo[a]pyrene (B[a]P) content of the fumes and other PAHs, and evaluation of the particle size distribution. The representativeness of the fumes has been tested by comparison with fumes generated in the Shell small-scale fume rig, which was previously validated against field fumes collected during paving operations. Evaporative losses from the filters during sampling, transport and storage have been also assessed. At 5 mg/m3 TPM, the agreement between laboratories was quite good for the TPM analyses and was good for the soluble matter and B[a]P. Evaporative losses may lead to underestimation of the true exposure level in the inhalation chambers but the use of an XAD-2 cartridge backup is one approach to partially recover losses which occur on the filter. The particle size distributions are somewhat different from those reported for fumes associated with roofing and indoor mastic laying works, in that we found more than 85% of particles to be smaller than 1 micron, compared with 40% particles in the previous analyses. In conclusion, this equipment allows reproducible generation of fumes at the 5 mg/m3 TPM that are fairly representative of those produced in the field with the same bitumen.

Inhalation study on exposure to bitumen fumes. Part 2: Analytical results at two exposure levels.

During the hot application of bitumen-containing materials, e.g. in road paving or roofing, fumes are emitted that contain traces of polycyclic aromatic compounds (PACs). Although worker's exposure to these fumes is low, it might lead to health problems. For studying DNA adduct formation as a consequence of inhalation of bitumen fumes we developed and validated an inhalation system (a dynamic fume generator plus a nose only inhalation chamber). This paper presents and discusses the analytical results from the different laboratories involved in this study on the fumes sampled in the inhalation chamber during three series of experiments where the animals were exposed to fumes at the 5 mg/m3 and 50 mg/m3 level, coming from bitumen heated at 200 degrees C and, as a positive control, fumes from coal tar, heated to 110 degrees C at the 5 mg/m3 level. The following parameters were controlled: temperatures at different key places in the generator; humidity of the chamber; the bitumen or coal tar flow rate; and Total Particulate Matter (TPM). Analyses were performed for Benzene Soluble Matter (BSM), the EPA polycyclic aromatic hydrocarbon (PAH) mixture and for a number of heteroatom-containing PACs. The data show that the coal tar fumes produced at 110 degrees C were very volatile and that most of the differences in particulate matter found between the laboratories can be attributed to evaporative losses. The bitumen fumes boil 25-50 degrees C higher and contain higher boiling compounds. A comparison is made between the PAC exposure profiles for bitumen experiments aimed at 5 and 50 mg/m3. Although the same molecules are found in both fumes their proportion is dramatically different. This effect is largest with the 2- and 3-ring PACs, the ratio of the concentrations found in the 50 mg/m3 TPM concentration to that in the 5 mg/m3 experiment gradually declines from 5500 for acenaphthene to 500 for pyrene, for the 5-ring PACs this ratio is 20-30. As function of their vapour pressure, the ratios of the concentrations of the hetero PACs follow the same trend as that of the 16 EPA PAHs and are of the same order of magnitude. In conclusion, for the compounds investigated, the equipment delivers a fume atmosphere in a reproducible manner. The 50 mg/m3 bitumen fumes are not representatives of field fumes. The reason for these quantitative differences is unclear and further work would be needed to clarify this. Nevertheless it was felt that these fumes at 50 mg/m3 might be a useful tool for qualitative detection of DNA adducts in an animal exposure study.

Evaluation of rat hepatic 2E1 activity in function of age, sex and inducers: choice of an experimental model capable of testing the hepatotoxicity of low molecular weight compounds.

The aim of this work on rat hepatic P450 2E1 activity was to seek the most suitable experimental model to study the role of cytochrome P450 2E1 in the metabolism of industrial chemicals. Two sets of experiments were devoted to selecting the age and sex of animals and to estimating the response of male and female rats to different inducers. In the first set, the effect of three inducers (fasting; ethanol; acetone) was studied in male rats aged 5, 7 and 9 weeks. In the second set, the effect of different inducers, namely beta-naphthoflavone (BNF), phenobarbital (PB), ethanol, acetone and pyridine, on PNP and chlorzoxazone (CLZO) hydroxylase activities was studied in 7 week old male and female rats. The results demonstrate firstly that microsomal p-nitrophenol (PNP) hydroxylase activity significantly decreases in control male rats in inverse function of age, and secondly that induction by ethanol decreases with age. The PNP hydroxylase activity level of controls and the significant increases in PNP hydroxylase activity observed in 7 week old male rats show that this is the most suitable age for the second set of experiments. In this second set, it was shown that P450 1A (induced by BNF) is involved in CLZO hydroxylase activity only. PB increased the hydroxylase activities in male and female rats by about 1.5 and 1.7 times those of the controls, respectively. The effects of P450 2E1 inducers in function of sex show that male rats exhibited more significant increases in PNP and CLZO hydroxylase activities than female. The specificity of these two substrates is discussed. Neither of these two reactions was specifically catalysed by P450 2E1, but PNP may be considered as the most specific and the least sensitive substrate. In addition, the linear relationship observed between the two substrates (PNP and CLZO) showed a good correlation between their activities (r = 0.90, P < 0.001). In conclusion, these results suggest the use of the 7 week old male rat as the experimental model to study the role of cytochrome P450 2E1 in the hepatotoxicity of low molecular weight industrial chemicals.

Occupational cancer in France: epidemiology, toxicology, prevention, and compensation.

This article is a description of the current situation in France with regard to occupational cancer: research, prevention, and occupation. Toxicologic experiments are carried out using (italic)in vitro(/italic) and (italic)in vivo(/italic) tests, particularly using transgenic mice. Several epidemiologic studies have been conducted over the last decades: population-based case-control studies; mortality studies and cancer incidence studies carried out in historical cohorts of workers employed in the industry; and case-control studies nested in occupational cohorts. French ethical aspects of toxicologic and epidemiologic studies are described. The results thus obtained are used to establish regulations for the prevention and the compensation of cancers attributable to occupational exposure. This French regulation for prevention of occupational cancer involves several partners: (italic)a(/italic)) the states authorities, including labor inspectors, responsible for preparing and implementing the labor legislation and for supervising its application, particularly in the fields of occupational health and safety and working conditions; (italic)b(/italic)) the Social Security Organisation for the analysis of present or potential occupational risks based on tests, visits in plants, complaints or requests from various sources, and statistics. These activities are performed within the framework of the general French policy for the prevention of occupational cancer. This organization includes the National Institute for Research and Safety, particularly involved in research in the various fields of occupational risks--animal toxicology, biologic monitoring, exposure measurements epidemiology, psychology, ergonomy, electronic systems and machineries, exposure to chemicals, noise, heat, vibration, and lighting; and (italic)c(/italic)) companies where the regulation defines the role of the plant manager, the occupational physician, and the Health, Safety and Working Conditions Committee (comprising the manager, employees' representatives, the occupational physician, and the safety department) in dealing with any problem regarding safety, occupational hygiene, and working conditions. These organizations along with medical practitioners are involved with the compensation of occupational cancers. The regulation for compensation includes the tables of occupational cancer, the possibility of recognition of a cancer case when the requirements of the tables are not met, and the postprofessional follow-up of workers exposed to a carcinogenic agent.

Cutaneous sensitization to some polyisocyanate prepolymers in guinea pigs.

Isocyanates are used extensively in the polyurethane industry. Pulmonary and dermal sensitization resulting from exposure to diisocyanates has frequently been reported, but the potential effects of polyisocyanates on health are less well known. Thus, since 1978, occupational exposure limits have been established for diisocyanates only. Nevertheless, respiratory diseases and dermatitis have been reported in the polyurethane industry after accidental isocyanate contact during spills or splashes. The aim of this experimental work was to assess the dermal hypersensitivity of guinea pigs to some polyisocyanate prepolymers by means of a well-conducted standard predictive Buehler test. Our results showed that dicyclohexylmethane 4,4'-diisocyanate (HMDI), toluylene 2,4-diisocyanate (TDI), TDI adduct triol, TDI isocyanurate, 1,6-hexamethylene diisocyanate (HDI), HDI isocyanurate, HDI biuret and isophorone diisocyanate (IPDI) induced dermal sensitization while IPDI isocyanurate did not. In conclusion, the dermal hypersensitivity of guinea pigs to some polyisocyanates was similar to those of their corresponding monomers except for IPDI isocyanurate, suggesting that the results from diisocyanate monomers could not be a valuable approach for the detection of the sensitization potency of the corresponding prepolymers.

Histopathological study in B6C3F1 mice chronically exposed by inhalation to glutaraldehyde.

Glutaraldehyde vapors are irritating for the skin, eyes, nose and lungs; respiratory symptoms and headaches have been described among workers exposed to low concentrations of glutaraldehyde far below to 190 ppb. This study was initiated to determine the chronic effects in mice of inhaled glutaraldehyde vapors. B6C3F1 mice were exposed using whole-body inhalation chambers, 6 h/day, 5 days/week, for 52 and 78 weeks to 100 ppb, or to filtered air (controls). In nasal passages at the level of the vestibule, hyperplasia of the squamous epithelium lining of the dorsal wall and lateral aspect of the atrioturbinate was observed in a greater number of exposed females than in controls. Epidermal erosion and ulceration as well as squamous and inflammatory exfoliation were also seen in the nasal lumens. All these changes were dependent on the length of glutaraldehyde exposure. The present data suggest that glutaraldehyde long term exposure only led to changes in nasal passages of female mice but did not induce mortality and/or tumors in nasal passages, in all mice. These results, along with the previous subchronic inhalation study of Gross et al., 1994, demonstrates that in a long term study, chronic glutaraldehyde exposure close to the current threshold limit values induced lesions at the more anterior part of the nasal passages in mice and that they likely result from an irritation mechanism (antero-posterior gradient).