Fetal aortic valvuloplasty for critical aortic stenosis: single-center retrospective study focusing on postnatal outcome.

OBJECTIVE: We aimed to report our experience on fetal aortic valvuloplasty (FAV) for critical aortic stenosis (AS) focusing on the postnatal evolution of the patients. METHODS: This retrospective study was approved by our local Institutional Review Board (n°2002-0128143827). All fetuses with critical AS who underwent FAV in a single center between 01/2011 and 06/2022 were included. FAV were performed under ultrasound guidance. Technical success was based upon balloon inflation across the aortic valve and improvement of the anterograde aortic flow across the aortic valve. At birth, biventricular circulation (BVC) strategy was decided assuming the left ventricle (LV) systolic and diastolic functions would ensure the systemic circulation. RESULTS: Sixty-three FAV were performed on 58 fetuses at 24.6[21.4-32.4] weeks of gestation. The procedure was successful in 52/58(89.6%) fetuses. There were 11/58(19%) in utero demises and 9/58(15.5%) terminations of pregnancy. There were no liveborn patients after the unsuccessful procedures. 38/58(65.5%) infants were delivered at a median gestational age of 38.1[29-40.6] weeks and 21/38(55.3%) of them required prostaglandin. 28/38(73.7%) [28/58(48.3%)] children entered the BVC path at birth. Among them, 20 required an aortic valvuloplasty at birth (11 percutaneous, 9 surgical) and 8 did not require any treatment at birth but of those, 5/8 underwent a surgical valvuloplasty between day 26 and day 1200 of life. 11/28(39.3%) infants with BVC at birth required a second intervention and four of them required a third intervention. Two infants who entered the BVC at birth underwent a conversion to UVC. None of the surviving children with BVC developed pulmonary hypertension. The global survival rate in case of BVC was 22/28(78.6%) at 23.3[8-112] months of life. 10 patients had UVC at birth. Among them, 6 received comfort care from birth and only 4 underwent surgery. 3/10 patients were still alive at the latest assessment (48[22-102] months). CONCLUSION: FAV for critical aortic stenosis led to anterograde aortic flow in 89.6% of the fetuses, with BVC being achieved in 48.3% (73.7% of the live born). Among patients with BVC at birth, the rate of reintervention is high but long-term survival is satisfactory. This article is protected by copyright. All rights reserved.

Cost-effectiveness of Artificial Intelligence for Proximal Caries Detection.

Artificial intelligence (AI) can assist dentists in image assessment, for example, caries detection. The wider health and cost impact of employing AI for dental diagnostics has not yet been evaluated. We compared the cost-effectiveness of proximal caries detection on bitewing radiographs with versus without AI. U-Net, a fully convolutional neural network, had been trained, validated, and tested on 3,293, 252, and 141 bitewing radiographs, respectively, on which 4 experienced dentists had marked carious lesions (reference test). Lesions were stratified for initial lesions (E1/E2/D1, presumed noncavitated, receiving caries infiltration if detected) and advanced lesions (D2/D3, presumed cavitated, receiving restorative care if detected). A Markov model was used to simulate the consequences of true- and false-positive and true- and false-negative detections, as well as the subsequent decisions over the lifetime of patients. A German mixed-payers perspective was adopted. Our health outcome was tooth retention years. Costs were measured in 2020 euro. Monte-Carlo microsimulations and univariate and probabilistic sensitivity analyses were conducted. The incremental cost-effectiveness ratio (ICER) and the cost-effectiveness acceptability at different willingness-to-pay thresholds were quantified. AI showed an accuracy of 0.80; dentists' mean accuracy was significantly lower at 0.71 (minimum-maximum: 0.61-0.78, P < 0.05). AI was significantly more sensitive than dentists (0.75 vs. 0.36 [0.19-0.65]; P = 0.006), while its specificity was not significantly lower (0.83 vs. 0.91 [0.69-0.98]; P > 0.05). In the base-case scenario, AI was more effective (tooth retention for a mean 64 [2.5%-97.5%: 61-65] y) and less costly (298 [244-367] euro) than assessment without AI (62 [59-64] y; 322 [257-394] euro). The ICER was -13.9 euro/y (i.e., AI saved money at higher effectiveness). In the majority (>77%) of all cases, AI was less costly and more effective. Applying AI for caries detection is likely to be cost-effective, mainly as fewer lesions remain undetected. Notably, this cost-effectiveness requires dentists to manage detected early lesions nonrestoratively.

The effect of lockdown on intentional and nonintentional injury during the COVID-19 pandemic in Cape Town, South Africa: A preliminary report.

BACKGROUND: In response to the coronavirus pandemic, lockdown restrictions and a ban on alcohol sales were introduced in South Africa. Objectives. To investigate the impact of lockdown measures on the number of patients who visited a tertiary urban trauma centre. Methods. The period of investigation was from 1 February to 30 June 2020 and was segmented into three intervals: pre-lockdown (February and March 2020), hard lockdown (April and May 2020) and immediately post lockdown (June 2020). The electronic HECTIS health record registry was interrogated for the total number of patients that were seen per month. These were further categorised according to mechanism of injury (stab, gunshot, blunt assault and road traffic injuries). Penetrating (stab and gunshot) and blunt assault victims were collectively grouped as violent trauma. Results. The mean total number of patients seen decreased by 53% during the hard lockdown period. There was a moderate reduction (15%) in patients with gunshot injuries seen during the hard lockdown phase, but there was an 80% increase in the post-lockdown period. The proportion of patients injured in road traffic collisions pre lockdown, hard lockdown and immediate post lockdown was 16.4%, 8.9% and 11.1%, respectively. Patients injured in road traffic collisions decreased by 74% during the hard lockdown period and maintained a reduction of 32% during the immediate post-lockdown period. The mean total number of patients who visited the trauma unit returned to pre-lockdown levels in June. Conclusions. There was an overall trend of reduced number of patients who visited the trauma unit during the hard lockdown period; however, these numbers returned to pre-lockdown levels during the immediate post-lockdown period. The number of road traffic injury admissions remained reduced during all three phases of lockdown, while the number of gunshot victims increased substantially during the post-lockdown period.

Mapping Cell Membrane Organization and Dynamics Using Soft Nanoimprint Lithography.

Membrane shape is a key feature of many cellular processes, including cell differentiation, division, migration, and trafficking. The development of nanostructured surfaces allowing for the in situ manipulation of membranes in living cells is crucial to understand these processes, but this requires complicated and limited-access technologies. Here, we investigate the self-organization of cellular membranes by using a customizable and benchtop method allowing one to engineer 1D SiO2 nanopillar arrays of defined sizes and shapes on high-performance glass compatible with advanced microscopies. As a result of this original combination, we provide a mapping of the morphology-induced modulation of the cell membrane mechanics, dynamics and steady-state organization of key protein complexes implicated in cellular trafficking and signal transduction.

The effect of lockdown on intentional and nonintentional injury during the COVID-19 pandemic in Cape Town, South Africa: A preliminary report.

BACKGROUND: In response to the coronavirus pandemic, lockdown restrictions and a ban on alcohol sales were introduced in South Africa. Objectives. To investigate the impact of lockdown measures on the number of patients who visited a tertiary urban trauma centre. Methods. The period of investigation was from 1 February to 30 June 2020 and was segmented into three intervals: pre-lockdown (February and March 2020), hard lockdown (April and May 2020) and immediately post lockdown (June 2020). The electronic HECTIS health record registry was interrogated for the total number of patients that were seen per month. These were further categorised according to mechanism of injury (stab, gunshot, blunt assault and road traffic injuries). Penetrating (stab and gunshot) and blunt assault victims were collectively grouped as violent trauma. Results. The mean total number of patients seen decreased by 53% during the hard lockdown period. There was a moderate reduction (15%) in patients with gunshot injuries seen during the hard lockdown phase, but there was an 80% increase in the post-lockdown period. The proportion of patients injured in road traffic collisions pre lockdown, hard lockdown and immediate post lockdown was 16.4%, 8.9% and 11.1%, respectively. Patients injured in road traffic collisions decreased by 74% during the hard lockdown period and maintained a reduction of 32% during the immediate post-lockdown period. The mean total number of patients who visited the trauma unit returned to pre-lockdown levels in June. Conclusions. There was an overall trend of reduced number of patients who visited the trauma unit during the hard lockdown period; however, these numbers returned to pre-lockdown levels during the immediate post-lockdown period. The number of road traffic injury admissions remained reduced during all three phases of lockdown, while the number of gunshot victims increased substantially during the post-lockdown period.

[The association between allergic rhinitis control and sleep quality]. / Assoziation zwischen Kontrolle der allergischen Rhinitis und Schlafqualität.

BACKGROUND: Allergic rhinitis (AR) is the most common form of atopic disease, comprising 50% of atopic diseases. Recently, this disease has increasingly been the focus of intensive research. Previous work has shown that AR has a significant impact on sleep quality. To date there are no published studies demonstrating a quantitative association between the extent of control of AR and the severity of compromised sleep quality. METHODS: Patients with AR were prospectively recruited into our cross-sectional study. Sleep quality was assessed using five of the sleep subdomain questions from the 22-item Sinonasal Outcome Test (SNOT-22). Control of AR was assessed using the Rhinitis Control Assessment Test (RCAT). Association was sought between the degree of allergic rhinitis control (RCAT) as independent variable and sleep quality as dependent variable using linear regression. RESULTS: A total of 104 patients (54.8% female and 45.2% male) with an average age of 41.4 years (SD: 15.9 years) were included in the study. There were statistically significant associations between the RCAT score and the score of each of the five SNOT-22 questions used to assess decreased sleep quality (p < 0.001). These associations remained significant (p < 0.001) even after controlling participants' clinical and demographic characteristics. CONCLUSION: This is the first study showing that level of control of AR correlates with the severity of subjectively perceived sleep quality detriment. These results indicate that an improvement in AR control could lead to improved subjective sleep quality but a prospective interventional study is needed to confirm these results.

Skin permeation and metabolism of di(2-ethylhexyl) phthalate (DEHP).

Phthalates are suspected to be endocrine disruptors. Di(2-ethylhexyl) phthalate (DEHP) is assumed to have low dermal absorption; however, previous in vitro skin permeation studies have shown large permeation differences. Our aims were to determine DEHP permeation parameters and assess extent of skin DEHP metabolism among workers highly exposed to these lipophilic, low volatile substances. Surgically removed skin from patients undergoing abdominoplasty was immediately dermatomed (800 µm) and mounted on flow-through diffusion cells (1.77 cm(2)) operating at 32°C with cell culture media (aqueous solution) as the reservoir liquid. The cells were dosed either with neat DEHP or emulsified in aqueous solution (166 µg/ml). Samples were analysed by HPLC-MS/MS. DEHP permeated human viable skin only as the metabolite MEHP (100%) after 8h of exposure. Human skin was able to further oxidize MEHP to 5-oxo-MEHP. Neat DEHP applied to the skin hardly permeated skin while the aqueous solution readily permeated skin measured in both cases as concentration of MEHP in the receptor liquid. DEHP pass through human skin, detected as MEHP only when emulsified in aqueous solution, and to a far lesser degree when applied neat to the skin. Using results from older in vitro skin permeation studies with non-viable skin may underestimate skin exposures. Our results are in overall agreement with newer phthalate skin permeation studies.

Biological monitoring of exposure to di(2-ethylhexyl) phthalate in six French factories: a field study.

OBJECTIVE: The aim of this study was to assess, by biological monitoring, workers' exposure to di(2-ethylhexyl) phthalate (DEHP) in the flexible-PVC industry in France to provide additional occupational exposure data, which are particularly scarce. METHOD: Over 5 days of pre-and post-shift sampling, three urinary metabolites of DEHP, mono (2-ethylhexyl) phthalate (MEHP), mono (5-carboxy-2-ethylpentyl) phthalate (5cx-MEPP) and 2-ethylhexanoic acid (2-EHA) were quantified in 62 workers and 29 controls from six factories. Analyses were performed by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) after on-line extraction. RESULTS: Median concentrations of the pre- and post-shift urinary samples in the exposed workers were 12.6 and 28.7 µg/l for MEHP, 38.6 and 84.4 µg/l for 5cx-MEPP and 20.4 and 70.6 µg/l for 2-EHA, respectively. In the controls, the corresponding values were 4.8 and 4.7 µg/l for MEHP, 15.1 and 12.4 µg/l for 5cx-MEPP and 21.8 and 20.5 µg/l for 2-EHA, respectively. There was a significant increase (Mann-Whitney U-test, P < 0.05) of post-shift excretion in the exposed workers versus the unexposed controls and in the post-shift versus pre-shift concentrations only in the exposed workers. Values of 250 and 500 µg/l (100 and 280 µ/g creatinine) for MEHP and 5cx-MEPP, respectively, are proposed as guidance values. CONCLUSION: There is clear evidence of occupational exposure of workers in these factories. The guideline values proposed should prevent high exposures in the soft PVC industry, particularly in factories where DEHP compounds or plastisols are employed. An epidemiological survey is needed to complete the DEHP risk assessment.

Biological monitoring of occupational exposure to di(2-ethylhexyl) phthalate: survey of workers exposed to plastisols.

OBJECTIVE: The aim of this study was to perform a biological monitoring survey of workers exposed to di(2-ethylhexyl)phthalate (DEHP) in a factory using polyvinyl chloride plastisols and to contribute additional occupational data of exposure particularly sparse in the industrial sectors where this plasticizer is used. METHOD: Three urinary metabolites of DEHP, mono(2-ethylhexyl)phthalate (MEHP), mono(5-carboxy-2-ethylpentyl)phthalate (MCEPP) and 2-ethylhexanoic acid (2-EHA) were quantified in five workers using a plastisol (containing 33% of DEHP) and in five unexposed workers (controls), during 5 days with pre- and post-shift sampling. Analyses were performed by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) with on-line extraction. RESULTS: Median concentrations of pre- and post-shift urinary samples in the exposed workers (n = 25) were 16.1 and 55.9 microg/l for MEHP, 37.6 and 103.7 microg/l for MCEPP and 46.3 and 72.1 microg/l for 2-EHA, respectively. In the controls (n = 19), the corresponding values were 12.0 and 10.4 microg/l for MEHP, 38.1 and 11.4 microg/l for MCEPP and 31.9 and 46.0 microg/l for 2-EHA, respectively. There is a significant increase (Mann-Whitney U-test, P < 0.05) of post-shift excretion in the exposed workers versus unexposed controls and in post-shift versus pre-shift concentrations only in the exposed workers. CONCLUSION: MEHP and MCEPP are shown to be suitable biomarkers to assess DEHP exposure while 2-EHA, less specific but classified in the category 3 of the European Union (EU) reproductive toxicants, is also an interesting biomarker. There is clear evidence of occupational exposure of workers in this factory.

N-nitrosodiethanolamine urinary excretion in workers exposed to aqueous metalworking fluids.

OBJECTIVE: This work was intended to clarify the extent of exposure of workers occupationally exposed to N-nitrosodiethanolamine (NDELA), a carcinogenic nitrosamine, while working with aqueous metalworking fluids (MWFs) formulated with ("nitrite-formulated") or without ("nitrite-free") nitrite and to study the relationships between the nitrite and NDELA content of the MWFs as well as between the concentration of NDELA in MWFs and in urine. METHOD: Pre-shift and post-shift urine samples from 100 workers directly exposed to MWFs in 15 factories were analysed for NDELA with chemiluminescent detection (TEA) according to a previously described analytical procedure. The method was also applied to eight indirectly exposed workers and to 48 unexposed subjects. The NDELA and concentrations in 84 fluids used by the workers were also determined. RESULTS: No detectable NDELA could be observed in the control group. The mean post-shift NDELA excretion in workers exposed to "nitrite-formulated" and "nitrite-free" MWFs were 44.6 and 0.4 microg/l, with maxima of 277 and 2.7 microg/l, respectively. According to the correlation between the nitrite and NDELA concentrations in "nitrite-free" MWFs, there is a low probability of fluids exceeding 5 mg/l NDELA when the nitrite content does not exceed 20 mg/l. The NDELA concentrations in the fluids and urine were found to be highly correlated, particularly after correction for creatinine (r=0.917 in post-shift samples). Cutaneous contact probably contributes, at least in part, to the overall body uptake of NDELA: CONCLUSION: Due to clear evidence of urinary NDELA excretion in workers exposed to contaminated MWFs, and despite a lack of knowledge of the human risk following NDELA exposure, levels of NDELA in MWFs should be kept as low as possible. NDELA fluid concentrations of less than 1 mg/l must be considered as the objective to be attained, even if the limit of 5 mg/l is temporarily satisfactory and consistent with a nitrite limit of 20 mg/l that is easy to verify with inexpensive colorimetric tests. "Nitrite-formulated" fluids, still sometimes used, should be prohibited. Meanwhile, the material safety data sheets (MSDS) of commercially available products should be clearly labelled to indicate their nitrite content.

Determination of N-nitrosodiethanolamine in urine by gas chromatography thermal energy analysis: application in workers exposed to aqueous metalworking fluids.

OBJECTIVE: The aim of this study was to describe a detailed and validated methodology designed for the analysis of carcinogenic N-nitrosodiethanolamine (NDELA) down to sub-microgram/l levels in urine and its application to a number of workers exposed to NDELA-contaminated aqueous metalworking fluids (MWF). METHODS: Following a work-up procedure based on solid-phase extraction of NDELA, the urinary extracts were analysed without derivatization by gas chromatography on a polar wide-bore column with chemiluminescent detection using a thermal energy analyser (TEA). N-Nitroso-(2-hydroxypropyl)amine was used as an internal standard. The method was applied to 12 workers using "nitrite-free" or "nitrite-formulated" MWF and to 15 unexposed subjects. The NDELA content of the MWF was also determined using a similar, but simpler method able to easily quantify NDELA down to at least 0.1 mg/l. RESULTS: Contamination by NDELA traces of some chemicals used for the sample preparation, particularly ethyl formate, must be carefully checked since it can give rise to false-positive results of up to 1 or 2 micrograms/l. The response was linear in the range of 0-500 micrograms/l. Between 0.5 and 10 micrograms/l, the recovery rate was close to 95%, while repeatability ranged from 12.5 to 6.4% (n = 5). The detection limit was 0.3 microgram/l (Signal/noise = 3). No detectable NDELA could be observed in the control workers. There was no significant increase in NDELA levels at the end of shift spot samples from an exposed worker over 1 week. Higher NDELA concentrations were found in two workers (4.3 and 10.7 micrograms/l) exposed to "nitrite-formulated" fluids (contaminated with 65 and 18 mg NDELA per 1, respectively) than in nine workers (range, 0.4-1.3 micrograms/l exposed to "nitrite-free" fluids with lower levels of NDELA (range, 0.5-6.6 mg/l). CONCLUSION: The detailed methodology described in this work and applied to a limited industrial situation was found to be suitable for monitoring NDELA in the urine of workers exposed to aqueous MWF. A much larger screening has been undertaken with the aim of obtaining better information on the real exposure of workers sometimes exposed to "nitrite-formulated" fluids that are still used.

Evaluation of the interaction of benzene and toluene on the urinary excretion of t,t-muconic acid in rats.

The influence of simultaneous exposure to benzene and toluene on the urine excretion of t,t-muconic acid (t,t-MA) was examined in rats. t,t-MA was measured from 24-h urine of rats subjected to a single 4-h exposure to 5 or 20 ppm benzene and/or 50, 100, 200 or 1000 ppm toluene. Coexposure lowered t,t-MA excretion in a concentration-dependent manner, especially in the 20 ppm benzene group where the decrease averaged 28, 44 and 85% after exposure to 100, 200 and 1000 ppm toluene, respectively, as compared to benzene-exposed groups alone. The data confirm the sensitivity of t,t-MA as an indicator of benzene exposure and point out that measurement of t,t-MA may underestimate the exposure to benzene in the presence of toluene.

trans,trans-Muconic acid, a reliable biological indicator for the detection of individual benzene exposure down to the ppm level.

trans,trans-Muconic acid (2,4-hexadienedioic acid) (t,t-MA) is a minor benzene metabolite which can be used as a biological indicator for benzene exposure. The purpose of the study was to evaluate the limits of use of t,t-MA for detection and quantification of occupational exposures to benzene, particularly on an individual scale, phenol being used as the metabolite of reference. A simple and sensitive method previously described by the authors was carried out to analyse t,t-MA in 105 end-of-shift urinary samples from 23 workers exposed to benzene used as an extraction solvent for "concretes" recovery in the perfume industry. Good correlations were found between atmospheric benzene and both metabolites (uncorrected or corrected for creatinine) or between the metabolites themselves, with correlation coefficients from 0.81 to 0.91 (P < 0.0001). Correlation- coefficients were not improved after correction for creatinine. The overall individual benzene exposure range, median, and arithmetic mean were respectively 0.1-75, 4.5, and 9.0 ppm with corresponding t,t-MA excretion of 0.1-47.9, 5.2 and 8.9 mg/l (uncorrected) and phenol excretion of 1.4-298, 30.9, and 42.2 mg/l (uncorrected). In the control group (145 determinations for t,t-MA and 76 for phenol from 79 individuals) the range, median, and arithmetic mean were respectively < 0.04-0.66, 0.08, and 0.13 mg/l (uncorrected t,t-MA) and 1.5-42.0, 9.85 and 11.3 mg/l (uncorrected phenol). t,t-MA was far more specific than phenol and could be easily and practically used to estimate with a given probability the upper or lower corresponding benzene concentrations down to around the ppm level.(ABSTRACT TRUNCATED AT 250 WORDS)

Improvement in HPLC analysis of urinary trans,trans-muconic acid, a promising substitute for phenol in the assessment of benzene exposure.

Urinary trans,trans-muconic acid (t,t-MA), a minor metabolite of benzene, is a potential candidate for biological monitoring of benzene. A clean-up procedure using SPE extraction cartridges was applied to urinary samples in order to improve the reliability of t,t-MA determinations by HPLC-UV greatly and to carry out convenient analyses on a routine scale, particularly at low levels of t,t-MA concentrations. The detection limit of the method is low enough to measure urinary t,t-MA at a concentration of 0.05-0.1 mg/l. The recovery rates and relative standard deviations from spiked urines (1 mg/l to 20 mg/l) were about 90% and 5%, respectively. t,t-MA was found to be rapidly excreted by rats and humans. In rats the background range never exceeded 0.5 mg/l with a mean concentration around 0.3 mg/l. In 49 human blank urines, t,t-MA average and median-value were respectively around 0.2 and less than 0.1 mg/l with a range of less than 0.1 to 0.5 mg/l. Experimental exposure of rats for 1 h to 10.2 ppm of benzene induced urinary excretion of 13 mg/l of t,t-MA during a 6-h post-exposure period while occupational exposures to 2.6 ppm (mean exposure level during 5 d-8 h) and 7 ppm (4 h) of benzene resulted in urinary excretion of 2.1 (mean excretion level) and 6.5 mg/l respectively at the end of the exposure. In humans, t,t-MA has a similar half-time as phenol. Analysis of urinary t,t-MA seems to be a better indicator than phenol for the assessment of exposure to low levels of benzene. Ingestion of 200 mg of sorbic acid, the only other known precursor of t,t-MA, interfered minimally with the background excretion of t,t-MA.

Occupational exposure to volatile nitrosamines in foundries using the "Ashland" core-making process.

Eight foundries using the "Ashland" process for the production of cores were surveyed to assess the occupational exposure to carcinogenic volatile nitrosamines. Personal and area samples were collected by means of artifact-free cartridges during the core-making and the molding/casting/shake-out operations. Analyses were carried out with gas chromatography/Hall detector and gas chromatography/TEA (thermal energy analyzer) for validation. The core-making workshops had the highest concentration for at least two nitrosamines, N-nitrosodimethylamine (NDMA) and N-nitrosoethylmethylamine (NEMA), but the levels of NDMA never exceeded 0.35 microgram/m3 with an arithmetic mean between 0.23 and 0.02 microgram/m3. In a number of samplings, two other peaks, both on TEA and Hall detector, could not be identified. The foundries per se (molding/casting/shake-out) had lower nitrosamine levels (CNDMAmax = 0.15 microgram/m3, CNDMA less than 0.03 microgram/m3). For the first time NEMA was identified as an industrial contaminant in foundries but its concentration was always lower than that of NDMA. The nitrosamines found were presumably produced from dimethylethylamine (DMEA). Industries producing or using tertiary or secondary amines should be controlled for their possible nitrosamine contamination.

Guinea pig pulmonary response to sensitization by five preformed monoisocyanate-ovalbumin conjugates.

The ability of 5 dissimilar monoisocyanates conjugated to ovalbumin (OA) as a carrier protein to induce pulmonary hypersensitivity towards the hapten specific component was assessed by using a previously described method based on the determination of a respiratory index (RI) in the guinea pig. The test chemicals included the commercially available p-tolyl and hexyl monoisocyanates (TMI and HMI), with 4-isocyanoto-4'-diphenylmethane (IDM), 4-isocyanoato-4'-methyldiphenylmethane (IMDM) and 1-isocyanato-methyl-1,3,3-trimethylcyclohexane (IMTC) as synthetized monoisocyanates. Guinea pigs were exposed daily to an aerosol of the OA conjugate of each monoisocyanate up to day 15. Increases in respiratory rate and/or respiratory collapse occurred in the guinea pigs exposed to TMI-OA and HMI-OA conjugates by days 9 and 15, with RI values of 155 and 177, respectively, being recorded. The greatest mean RI values in guinea pigs exposed to IDM-OA, IMDM-OA and IMTC-OA conjugates up to day 15 were 20, 25 and 22, respectively, and were not indicative of any pulmonary reaction. Guinea pigs exposed in parallel to each test conjugate did not exhibit any pulmonary reaction when they were exposed to OA on the challenge days. All these findings evidence pulmonary hypersensitivity as the result of exposure to TMI-OA and HMI-OA conjugates and suggest a high degree of conjugation and strong linkage of all the monoisocyanates with OA.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of occupational exposure to 4,4'-methylene-bis-(2-chloroaniline) "MOCA" by a new sensitive method for biological monitoring.

A new specific and sensitive method for the urinary determination of 4,4'-methylene-bis-(2-chloroaniline) ("MOCA"), a known carcinogen in rats, mice and dogs, has been developed. After a brief study on rats to determine some peculiarities in "MOCA" urinary excretion, this method was used to assess occupational exposure in French industrial firms. Both the manufacture of "MOCA" and its use as a curing agent in the production of polyurethane elastomers were surveyed. "MOCA" excretion levels were distributed from non-detectable (less than 0.5 microgram/l) up to 1600 microgram/l. Concentrations of N-acetyl metabolites, when present, were largely lower than "MOCA" levels. The results seemed to reflect workers' overall exposure fairly. Preventive measures following analytical determinations often led to an obvious lowering of excretion levels.

N-nitrosodiethanolamine in antifreeze.

Carcinogenic N-nitrosodiethanolamine has been found at concentrations varying from 15 to 5700 mg/liter in several leading French brands of antifreeze. Moreover, mixtures of antifreezes which, separately, are innocuous, can form this nitrosamine which appears to arise from interaction of triethanolamine derivatives with sodium nitrite. It is recommended that sodium nitrite be abandoned as an anticorrosion additive.