Ethyl silicate Documentation of proposed values of occupational exposure limits (OELs)

2017 ◽  
Vol 33 (2(92)) ◽  
pp. 21-49
Author(s):  
ANNA KILANOWICZ-SAPOTA ◽  
MAŁGORZATA SKRZYPIŃSKA-GAWRYSIAK

Ethyl silicate is a colorless liquid with a slightly perceptible odor. This compound finds numerous applications in many industrial branches, e.g., paint and lacquer, chemical (in chemical coatings which has a contact with food), pharmaceutical, semiconductor and in nanotechnology. It is also used as an agent to harden natural stone, terra-cotta, artificial marble, frescoes and clay and in pro-duction of waterproof and acidproof mortar and cements. According to the State Sanitary Inspection data, in Poland in 2007, 2010 and 2013, there were no workers Ortokrzemian tetraetylu. Dokumentacja proponowanych dopuszczalnych wielkości narażenia zawodowego 23 exposed to ethyl silicate at levels exceeding maxi-mum allowable concentration (MAC) of 80 mg/m3. Ethyl silicate is well absorbed via respiratory and alimentary tracts, but its absorption through the skin is rather poor. In workers exposed to ethyl sil-icate, irritating properties to eye and nasal mucosa have been observed. Data on chronic ethyl silicate effects in humans are not available in the literature. In laboratory animals, ethyl silicate acute toxicity expressed in median lethal doses is relatively low. Ethyl silicate shows a mild irritating effect on rab-bit’s eyes, it does not cause dermal irritation or al-lergic effects. There are no data on ethyl silicate chronic toxicity. Short-term and subchronic studies performed on mice and rats exposed to ethyl sili-cate through inhalation and after its administration in other ways showed except for necrotic lesions in the olfactory epithelium of nasal cavity (in mice), changes in the liver (in rats) and kidneys. The latter comprised interstitial inflammation and necrotic lesions in renal tubules. Short-term exposure of rats to high ethyl silicate concentrations induced its toxic effect also on lungs. Ethyl silicate mutagenic effect has not been re-vealed in Ames tests. On the basis of few data, it has been proved that this compound did not cause reproductive and developmental toxicity. This compound has not been categorized by the Inter-national Agency for Research on Cancer (IARC) with respect to its potential carcinogenic risk. The presented evidence shows that the major toxic effect of ethyl silicate at high concentrations (over 2000 mg/m3) is eye and nasal mucosa irritation in humans, whereas the nephrotoxic effect and dam-age to the olfactory epithelium of nasal cavity are observed in laboratory animals. On the basis of the nephrotoxic effect of ethyl sili-cate, its maximum allowable concentration (MAC) was calculated. The results of two independent in-halation experiments in mice were used to deter-mine NOAEL value. Inhalation exposure of mice to ethyl silicate at concentration of 430 mg/m3 (50 ppm) for 90 days or 2 and 4 weeks did not cause nephrotoxic effects. This compound at higher con-centrations caused nephrotoxicity. Exposure to concentration of 760 mg/m3 (88 ppm) caused sig-nificant decrease in kidney weight, and after expo-sure to concentration of 865 mg/m3 (100 ppm) in 20% of animals interstitial inflammation of kidney tubules have been observed. The authors of the documentation proposed to adopt a concentration of 430 mg/m3 as NOAEC value of ethyl silicate for the nephrotoxic effects observed in mice. After adopting relevant uncertainty coefficients (total value, 8) the calculated MAC value for ethyl silicate is 54 mg/m3. Taking into consideration the fact that in 2008 SCOEL proposed a concentration of 44 mg/m3 as 8-h TWA for ethyl silicate, which was based on the same effects (nephrotoxicity) and NOAEC value adopted from the same experiments, it was pro-posed to assume a concentration of 44 mg/m3 as MAC value of ethyl silicate. This substance is in-cluded in the directive establishing the IV list of in-dicative occupational exposure limit values with-out establishing a short-term STEL value. The proposed MAC value for ethyl silicate should protect workers against systemic effect and poten-tial irritating effect. There are no reasons for adopt-ing STEL and BEI values for this compound.

2021 ◽  
Vol XXXVII (1) ◽  
pp. 17-47
Author(s):  
Elżbieta Bruchajzer ◽  
Jadwiga Szymańska ◽  
Barbara Frydrych

N-Methylformamide is a colorless liquid with an ammoniacal odor, used as a solvent and an intermediate for chemical reactions. There are no data on occupational exposure in Poland. N-Methylformamide is very well absorbed into the human body. The LD50 values for N-methylformamide administered to animals in various routes are similar (2600 ÷ 4000 mg/kg bw). After single or short-term administration of the compound in doses of 100 ÷ 1200 mg/kg bw. worsening symptoms of liver damage have been observed. No-observed adverse effect concentration (NOAEC) was established at 120 mg/m3 (two-week inhalation exposure in rats). Increase of hepatotoxic effect of N-methylformamide were observed at concentrations of 320 mg/m3 and 980 mg/m3. There are no data on sub-chronic, chronic and carcinogenic effects of the compound in laboratory animals. N-Methylformamide was not mutagenic and genotoxic. It caused embryotoxic and teratogenic effects. The NOAEC value (120 mg/m3) was used as the basis for determining the MAC (maximum acceptable concentration) value for N-methylformamide, and the MAC value for N-methylformamide was calculated at 3.3 mg/m3. There are no basis to determine the short-term value (STEL) and biological limit value (BLV). It has been proposed to label the compound as "Ft" (toxic for reproduction) and "skin" (skin absorption of the substance may be as important as inhalation exposure). This article discusses the problems of occupational safety and health, which are covered by health sciences and environmental engineering


1999 ◽  
Vol 18 (5) ◽  
pp. 285-296
Author(s):  
Gene E. Schulze ◽  
Jim E. Proctor ◽  
Mark A. Dominick ◽  
Amy E. Weiss ◽  
Oliver P. Flint ◽  
...  

One-month intranasal toxicity studies were conducted with BMS-181885 at doses of 1.5, 9, or 15 mg/animal/day in rats and 4, 24, or 40 mg/animal/day in monkeys. A 1-month intermittent intranasal toxicity study was also conducted in monkeys at doses of 3, 6, and 12 mg/animal 3 days per week. BMS-181885 was generally well tolerated in rats but resulted in dose-dependent nasal mucosal injury, primarily characterized by subacute inflammation of the nasal mucosa, and degeneration, single-cell necrosis, and/or erosion of the olfactory epithelium and, to a lesser extent, the respiratory epithelium. In monkeys, daily BMS-181885 administration was well tolerated and produced similar dose-dependent nasal injury primarily characterized by subacute inflammation of the nasal mucosa with degeneration and erosion of the olfactory epithelium. In a separate experiment, intermittent administration also resulted in dose-dependent nasal injury. In cultured rat nasal mucosal cells, BMS-181885 was toxic to olfactory epithelial cells with a range of mean IC50s between 44 and 291 μM. In contrast, BMS-181885 had no effect on respiratory epithelial cells up to its maximum solubility. Cytochrome P450 inhibition had no effect on the toxicity of BMS-181885 in olfactory epithelial cells but produced dose-dependent toxicity in respiratory epithelial cells, which was not present previously. The in vitro data suggest that parent drug, rather than a toxic metabolite, caused the drug-associated nasal mucosal injury.


2015 ◽  
Vol 49 (6) ◽  
pp. 559-566 ◽  
Author(s):  
M. F. Kovtun ◽  
Ya. V. Stepanyuk

Abstract The Development of Olfactory Organ of Lissotriton vulgaris (Amphibia, Caudata). Kovtun, M. F, Stepanyuk, Ya. V. - Using common histological methods, the morphogenesis of olfactory analyzer peripheral part of Lissotriton vulgaris (Amphibia, Caudata) was studied, during the developmental period starting with olfactory pit laying and finishing with definitive olfactory organ formation. Special attention is paid to vomeronasal organ and vomeronasal gland development. Reasoning from obtained data, we consider that vomeronasal organ emerged as the result of olfactory epithelium and nasal cavity differentiation.


1998 ◽  
Vol 84 (3) ◽  
pp. 1030-1039 ◽  
Author(s):  
Ole Hilberg ◽  
Benny Lyholm ◽  
Axel Michelsen ◽  
Ole F. Pedersen ◽  
Oluf Jacobsen

The accuracy of the acoustic reflections method for the evaluation of human nasal airway geometry is determined by the physical limitations of the technique and also by the in vivo deviations from the assumptions of the technique. The present study 1) examines the sound loss caused by nonrigidity of the nasal mucosa and viscous loss caused by complex geometry and its influence on the estimation of the acoustic area-distance function; 2) examines the optimal relation between sampling frequency and low-pass filtering, and 3) evaluates advantages of breathing He-O2 during the measurements on accuracy. Measurements made in eight plastic models, with cavities exactly identical to the “living” nasal cavities, revealed only minor effects of nonrigidity of the nasal mucosa. This was confirmed by an electrical analog model, based on laser vibrometry admittance measurements of the nasal mucosa, which indicated that the error in the acoustic measurements caused by wall motion is insignificant. The complex geometry of the nasal cavity per se (i.e., departure from circular) showed no significant effects on the measurements. Low-pass filtering of the signal is necessary to cut off cross modes arising in the nasal cavity. Computer simulations and measurements in models showed that the sampling frequency should be approximately four times the low-pass filtering frequency (i.e., twice the Nyquist frequency) to avoid influence on the result. No advantage was found for the the use of He-O2vs. air in the nasal cavity.


2020 ◽  
Vol 77 (4) ◽  
pp. 214-222 ◽  
Author(s):  
Jean-Bernard Henrotin ◽  
Eva Feigerlova ◽  
Alain Robert ◽  
Mathieu Dziurla ◽  
Manuela Burgart ◽  
...  

ObjectiveThe objective of the study was to examine the effects of occupational exposure to diisononyl phthalate (DINP) on serum testosterone levels in male workers.MethodsFrom 2015 to 2018, 97 male workers were recruited from six French factories in the plastics industry. In a short longitudinal study, changes over 3 days in the level of total or free serum testosterone and DINP exposure were measured. DINP exposure was measured by urinary biomonitoring: mono-4-methyl-7-oxo-octyl phthalate (OXO-MINP), mono-4-methyl-7-hydroxy-octyl phthalate (OH-MINP) and mono-4-methyl-7-carboxyheptylphthalate (CX-MINP). We further analysed changes in follicle-stimulating hormone, luteinising hormone, total testosterone to oestradiol ratio and two bone turnover markers (procollagen-type-I-N propeptide, C terminal cross-linking telopeptide of type I collagen), and erectile dysfunction via standardised questionnaires (International Index of Erectile Function, Androgen Deficiency in Aging Males). Linear mixed models were used with the variables ‘age’ and ‘abdominal diameter’ included as confounder.ResultsIncreased urinary OXO-MINP was associated with a significant decrease in total serum testosterone concentrations, but only for workers who exhibited the smallest variations and lowest exposures (p=0.002). The same pattern was observed for CX-MINP but was not significant; no association with OH-MINP was detectable. More self-reported erectile problems were found in workers exposed directly to DINP at the workstation (p=0.01). No changes were observed for the other biological parameters.ConclusionsShort-term exposure to DINP is associated with a decrease in total serum testosterone levels in male workers. Our results suggest that DINP could present weak antiandrogenic properties in humans, but these need to be confirmed by other studies.


2018 ◽  
Vol 47 (2) ◽  
pp. 150-164 ◽  
Author(s):  
Marian A. Esvelt ◽  
Zachary T. Freeman ◽  
Alexander T. Pearson ◽  
Jack R. Harkema ◽  
Gregory T. Clines ◽  
...  

Zibotentan, an endothelin-A receptor antagonist, has been used in the treatment of various cardiovascular disorders and neoplasia. Castrated athymic nude mice receiving zibotentan for a preclinical xenograft efficacy study experienced weight loss, gastrointestinal bloat, and the presence of an audible respiratory click. Human side effects have been reported in the nasal cavity, so we hypothesized that the nasal cavity is a target for toxicity in mice receiving zibotentan. Lesions in the nasal cavity predominantly targeted olfactory epithelium in treated mice and were more pronounced in castrated animals. Minimal lesions were present in vehicle control animals, which suggested possible gavage-related reflux injury. The incidence, distribution, and morphology of lesions suggested direct exposure to the nasal mucosa and a possible systemic effect targeting the olfactory epithelium, driven by a type 2 immune response, with group 2 innate lymphoid cell involvement. Severe nasal lesions may have resulted in recurrent upper airway obstruction, leading to aerophagia and associated clinical morbidity. These data show the nasal cavity is a target of zibotentan when given by gavage in athymic nude mice, and such unanticipated and off-target effects could impact interpretation of research results and animal health in preclinical studies.


1987 ◽  
Vol 6 (5) ◽  
pp. 385-393 ◽  
Author(s):  
G.N. Stradling ◽  
J.W. Stather ◽  
S.A. Gray ◽  
J.C. Moody ◽  
M. Ellender ◽  
...  

Aerosols produced from two commercially available ore concentrates in which the uranium was present essentially in the one as ammonium diuranate (ADU) and in the other as uranium octoxide (U3O8) were administered to rats. The results show that: 1 uranium in the ADU bearing material was cleared rapidly from the lungs, mainly to the blood, such that the retention kinetics were similar to those for a class D (highly transportable) compound as defined by ICRP; 2 uranium in the U 3O8 bearing material was removed from the lungs principally by mechanical processes, the retention kinetics in this case being similar to those defined for a class Y (poorly transportable) compound; 3 for both materials the distribution of uranium amongst body tissues and the fraction of the systemic content excreted in urine were similar to those obtained after the injection of soluble hexavalent compounds; 4 for workers potentially exposed to both these materials, urine monitoring and lung radioactivity counting measurements should be used in addition to air sampling procedures for assessing the intake of uranium. 5 intakes of the ADU bearing material should be restricted to those permitted for short-term exposures on the basis of chemical toxicity, whereas those for the U3O 8 bearing material should be governed by radiation dose.


2003 ◽  
Vol 54 (4) ◽  
pp. 287-291 ◽  
Author(s):  
Ryoichi Ohtsuka ◽  
Yasufumi Shutoh ◽  
Hideaki Fujie ◽  
Satoru Yamaguchi ◽  
Makio Takeda ◽  
...  

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