Ototoxicity of trichloroethylene in concentrations relevant for the working environment

2008 ◽  
Vol 27 (3) ◽  
pp. 195-200 ◽  
Author(s):  
A Vyskocil ◽  
T Leroux ◽  
G Truchon ◽  
F Lemay ◽  
F Gagnon ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Convincing Evidence ◽  
Working Environment ◽  
Exposure Limits ◽  
Additive Interaction ◽  
Animal Data ◽  
Short Term Exposure ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Permissible Exposure Limits

Organic solvents can cause hearing loss themselves or promote noise-induced hearing loss. The objective of this study was to review the literature on the effects of low-level exposure to trichloroethylene on the auditory system and consider its relevance for the occupational settings. Both human and animal investigations were evaluated only for realistic exposure concentrations based on the Quebec permissible exposure limits: 50 ppm 8-h time-weighed average exposure value (TWAEV) and 200 ppm short-term exposure value (STEV). In humans, the upper limit for considering ototoxicity data relevant to the occupational exposure situation was set at the STEV. Animal data were evaluated only for exposure concentrations up to 100 times the TWAEV. There is no convincing evidence of trichloroethylene-induced hearing losses in workers. In rats, trichloroethylene affects the auditory function mainly in the cochlear mid- to high-frequency range with a lowest observed adverse effect level (LOAEL) of 2000 ppm. No studies on ototoxic interaction after combined exposure to noise and trichloroethylene were identified in humans. In rats, supra-additive interaction was reported. Further studies with sufficient data on the trichloroethylene exposure of workers are necessary to make a definitive conclusion. In the interim, we recommend considering trichloroethylene as an ototoxic agent.

Ethyl benzene should be considered ototoxic at occupationally relevant exposure concentrations

2008 ◽  
Vol 24 (4) ◽  
pp. 241-246 ◽  
Author(s):  
A Vyskocil ◽  
T Leroux ◽  
G Truchon ◽  
F Lemay ◽  
M Gendron ◽  
...  
Keyword(s):  
Animal Studies ◽  
Current Evidence ◽  
Ethyl Benzene ◽  
Combined Exposure ◽  
Exposure Limits ◽  
Short Term ◽  
Animal Data ◽  
Short Term Exposure ◽  
Permissible Exposure Limits ◽  
Occupational Settings

Organic solvents can produce ototoxic effects in both man and experimental animals. The objective of this study was to review the literature on the effects of low-level exposure to ethyl benzene on the auditory system and consider its relevance for the occupational settings. Both human and animal investigations were evaluated only for realistic exposure concentrations based on the permissible exposure limits. In Quebec, the Time-Weighed Average Exposure Value for 8 h (TWAEV) is 100 ppm (434 mg/m3) and the Short-Term Exposure Value for 15 min (STEV) is 125 ppm (543 mg/m3). In humans, the upper limit for considering ototoxicity data relevant to the occupational exposure situation was set at STEV. Animal data were evaluated only for exposure concentrations up to 100 times the TWAEV. In workers, there is no evidence of either ethyl benzene-induced hearing losses or ototoxic interaction after combined exposure to ethyl benzene and noise. In rats, ethyl benzene affects the auditory function mainly in the cochlear mid-frequency range and ototoxic interaction was observed after combined exposure to noise and ethyl benzene. Further studies with sufficient data on the ethyl benzene exposure of workers are necessary to make a definitive conclusion. Given the current evidence from animal studies, we recommend considering ethyl benzene as an ototoxic agent.

Occupational ototoxicity of n-hexane

2008 ◽  
Vol 27 (6) ◽  
pp. 471-476 ◽  
Author(s):  
A Vyskocil ◽  
T Leroux ◽  
G Truchon ◽  
M Gendron ◽  
N El Majidi ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inhalation Exposure ◽  
Weighted Average ◽  
Convincing Evidence ◽  
Auditory Function ◽  
Exposure Limits ◽  
Upper Limit ◽  
Animal Data ◽  
Time Weighted Average ◽  
Occupational Settings

The ability of chemicals to produce hearing loss themselves or to promote noise-induced hearing loss has been reported for some organic solvents. The objective of this study was to review the literature on the effects of low-level exposure to n-hexane on the auditory system and consider its relevance for occupational settings. Both human and animal investigations were evaluated only for realistic exposure concentrations based on the permissible inhalation exposure limits. In Quebec, the time-weighted average exposure value (TWAEV) for 8 h is 50 ppm. In humans, the upper limit for considering ototoxicity data relevant to the occupational exposure situation was set at five times the TWAEV. Animal data were evaluated only for exposure concentrations up to 100 times the TWAEV. There is no convincing evidence of n-hexane-induced hearing loss in workers. In rats, n-hexane seems to affect auditory function; however, the site of these alterations cannot be determined from the present data. Further studies with sufficient data on the exposure of workers to n-hexane are necessary to make a definitive conclusion. In the interim, we recommend considering n-hexane as a possibly ototoxic agent.

scholarly journals Trifluoroiodomethane (CF3I) (2019)

2020 ◽  
Vol 36 (5) ◽  
pp. 310-321
Keyword(s):  
Adverse Effect ◽  
Thyroid Hormone ◽  
Weighted Average ◽  
High Dose ◽  
Exposure Level ◽  
Inhalation Toxicity ◽  
Inhalation Study ◽  
Short Term Exposure ◽  
Adverse Effect Level ◽  
Effect Level

Trifluoroiodomethane (CF3I) is a colorless and odorless gas used primarily as a fire suppressant. CF3I has low acute inhalation toxicity. The no-observed adverse effect level (NOAEL) of CF3I for cardiac sensitization in dogs was 2000 ppm. The potential effects of 4-week inhalation exposure in both rats and mice have been examined. In rats, the NOAEL was 10,000 ppm, and in mice, the NOAEL was 10,000 ppm. In a subchronic inhalation study in rats, the lowest observed adverse effect level (LOAEL) was 20,000 ppm for thyroid-related effects; the study NOAEL (for non-thyroid-related effects) was 20,000 ppm. In a reproductive/developmental inhalation toxicity study in rats, 20,000 ppm CF3I produced minimal general toxicity and no indication of reproductive or developmental toxicity. The LOAEL for parental toxicity (based on thyroid hormone effects) was 2000 ppm; excluding thyroid effects, the parental NOAEL was 7000 ppm CF3I. The observed effects on the thyroid in rats were considered of less relevance to human risk assessment than the other observed systemic effects because of known species-specific differences in sensitivity to thyroid hormone perturbations. There are no chronic toxicity or carcinogenicity studies available. CF3I had mixed results in various in vitro and in vivo genotoxicity assays. The NOAEL of 7000 ppm from the reproductive/developmental inhalation study was used as the point of departure (POD) for workplace environmental exposure level (WEEL) value development. This POD was adjusted to account for interindividual variability, duration of exposure, and database limitations. The resulting 8-h time-weighted average WEEL value of 500 ppm is expected to provide a significant margin of safety against any potential adverse health effects in workers exposed to CF3I. A 15-min short-term exposure limit of 1500 ppm was also established to protect workers from potential cardiac effects produced by acute, high-dose inhalation of CF3I.

Defining a tolerable concentration of methanol in alcoholic drinks

2001 ◽  
Vol 20 (11) ◽  
pp. 563-568 ◽  
Author(s):  
A J Paine ◽  
A D Dayan
Keyword(s):  
Alcoholic Beverages ◽  
Appreciable Effect ◽  
Personal Factors ◽  
Exposure Limits ◽  
Public Health Perspective ◽  
Toxic Dose ◽  
Adverse Effect Level ◽  
Margin Of Safety ◽  
General Limit ◽  
Effect Level

Methanol, a potent toxicant in humans, occurs naturally at a low level in most alcoholic beverages without causing harm. However, illicit drinks made from “industrial methylated spirits” [5% (v/v) methanol:95% (v/v) ethanol] can cause severe and even fatal illness. Since documentation of a no-adverse-effect level for methanol is nonexistent in the literature a key question, from the public health perspective, is what is the maximum concentration of methanol in an alcoholic drink that an adult human could consume without risking toxicity due to its methanol content? Published information about methanol-intoxicated patients is reviewed and combined with findings in studies in volunteers given small doses of methanol, as well as occupational exposure limits (OELs), to indicate a tolerable (“safe”) daily dose of methanol in an adult as 2 g and a toxic dose as 8 g. The simultaneous ingestion of ethanol has no appreciable effect on the proposed “safe” and “toxic” doses when considering exposure over several hours. Thus, assuming that an adult consumes 425-ml standard measures of a drink containing 40% alcohol by volume over a period of 2 h, the maximum tolerable concentration (MTC) of methanol in such a drink would be 2% (v/v) by volume. However, this value only allows a safety factor of 4 to cover variation in the volume consumed and for the effects of malnutrition (i.e., folate deficiency), ill health and other personal factors (i.e., ethnicity). In contrast, the current EU general limit for naturally occurring methanol of 10 g methanol/l ethanol [which equates to 0.4% (v/v) methanol at 40% alcohol] provides a greater margin of safety.

scholarly journals Palmitoylethanolamide: Prenatal Developmental Toxicity Study in Rats

2021 ◽  
pp. 109158182098607
Author(s):  
Narendra S. Deshmukh ◽  
Shailesh Gumaste ◽  
Silma Subah ◽  
Nathasha Omal Bogoda
Keyword(s):  
Body Weight ◽  
Developmental Toxicity ◽  
Reproductive Toxicity ◽  
Toxicity Study ◽  
High Dose ◽  
Pregnant Rats ◽  
Human Dose ◽  
Adverse Effect Level ◽  
Female Wistar Rats ◽  
Effect Level

Palmitoylethanolamide (PEA) is an endogenous ethanolamine playing a protective and homeodynamic role in animals and plants. Prenatal developmental toxicity of PEA was tested following oral administration to pregnant female Wistar rats, from days 0 to 19 of gestation, at dosage of 250, 500, or 1,000 mg/kg body weight, according to Organisation for Economic Co-operation and Development Test Guideline No. 414. On gestation day 20, cesarean sections were performed on the dams, followed by examination of their ovaries and uterine contents. The fetuses were further examined for external, visceral, and skeletal abnormalities. Palmitoylethanolamide did not cause any alterations at any of the given dosages in the measured maternal parameters of systemic toxicity (body weight, food consumption, survival, thyroid functions, organ weight, histopathology), reproductive toxicity (preimplantation and postimplantation losses, uterus weight, number of live/dead implants and early/late resorptions, litter size and weights, number of fetuses, their sex ratio), and fetal external, visceral, or skeletal observations. Any alterations that were recorded were “normal variations” or “minor anomalies,” which were unrelated to treatment with PEA. Under the condition of this prenatal study, the no-observed-adverse-effect level of PEA for maternal toxicity, embryotoxicity, fetotoxicity, and teratogenicity in rats was found to be >1,000 mg/kg body weight/d. It indicates that PEA is well tolerated by and is safe to pregnant rats even at a high dose of 1,000 mg/kg body weight/d, equivalent to a human dose of greater than 9.7 g/d. This prenatal developmental toxicity study contributes greatly in building a robust safety profile for PEA.

scholarly journals Assessment of Occupational Exposure to BTEX in a Petrochemical Plant via Urinary Biomarkers

2021 ◽  
Vol 13 (13) ◽  
pp. 7178
Author(s):  
Višnja Mihajlović ◽  
Nenad Grba ◽  
Jan Suđi ◽  
Diane Eichert ◽  
Smilja Krajinović ◽  
...  
Keyword(s):  
Occupational Exposure ◽  
Urinary Biomarkers ◽  
Working Environment ◽  
Passive Samplers ◽  
Control Group ◽  
Petrochemical Plant ◽  
Exposure Limits ◽  
Multivariate Statistical ◽  
Mean Values ◽  
Relative Standard

This work presents the results of the first Serbian monitoring campaign performed to assess the occupational exposure of petrochemical industry workers to benzene (B), toluene (T), ethylbenzene (E), and xylene (X), known collectively as BTEX. The following urinary biomarkers were investigated: phenol, hippuric acid, o-Cresol, p-Cresol, and creatinine. BTEX compounds were collected in 2014 using Casella passive samplers. Multivariate statistical analysis was performed to put in evidence the correlation between the BTEX measured in air and the concentration of urinary biomarkers. While the results indicate an elevated presence of benzene in the air in the working environment studied that surpasses the national and European Occupational Exposure Limits (OEL), the levels of the remaining (TEX) parameters measured were below the OEL. The high relative standard deviations (RSD) for the concentrations of each BTEX compound (68–161 mg m−3) point toward an intensive occupational exposure to BTEX. This was confirmed by relevant urine biomarkers, particularly by the mean values of phenol, which were ten and fourteen times higher than the ones found in the control group (14–12 mg g−1 of creatinine). On average, workers are at a higher risk of developing cancer (6.1 × 10−3), with risk levels exceeding the US EPA limits. Benzene levels should therefore be maintained under tight controls and monitored via proper urinary biomarkers.

Safety of a novel galacto-oligosaccharide: Genotoxicity and repeated oral dose studies

2009 ◽  
Vol 28 (10) ◽  
pp. 619-630 ◽  
Author(s):  
T. Kobayashi ◽  
N. Yasutake ◽  
K. Uchida ◽  
W. Ohyama ◽  
K. Kaneko ◽  
...  
Keyword(s):  
Oral Dose ◽  
Kluyveromyces Lactis ◽  
Clinical Signs ◽  
Chinese Hamster ◽  
Metabolic Activation ◽  
Blood Chemistry ◽  
Control Group ◽  
Sprague Dawley ◽  
Adverse Effect Level ◽  
Effect Level

A series of safety tests were undertaken on a novel galacto-oligosaccharide (GOS) produced from lactose by a two-step enzymatic process involving Sporobolomyces singularis and Kluyveromyces lactis. Bacterial reverse mutation and chromosomal aberration tests, with or without metabolic activation, were performed. These tests showed no mutagenesis in the Ames assay or in Escherichia coli WP2uvrA, and no chromosomal aberrations in cultured fibroblast cells from Chinese hamster lungs (CHL/IU). Micronuclei were not induced in the reticulocytes of mouse peripheral blood following oral administration of GOS. In a 90-day repeated oral dose toxicity study in rats, GOS was administered at 0, 500, 1000 and 2000 mg/kg to male and female Sprague-Dawley rats. There were no GOS-related changes in clinical signs, body weight, water intake, feed intake, urinalysis, ophthalmology, haematology, blood chemistry, organ weights, gross pathology or histopathology in any of the treatment groups compared to the control group. The no observed adverse effect level (NOAEL) of GOS was at least 2000 mg/kg/day in both males and females.

Mobile Decontamination Units—Room for Improvement?

2012 ◽  
Vol 27 (5) ◽  
pp. 425-431 ◽  
Author(s):  
Pascale Ribordy ◽  
David Rocksén ◽  
Uno Dellgar ◽  
Sven-Åke Persson ◽  
Kristina Arnoldsson ◽  
...  
Keyword(s):  
Toxic Substances ◽  
Industrial Chemicals ◽  
Exposure Limits ◽  
Publication Type ◽  
Toxic Industrial Chemicals ◽  
Environment Effects ◽  
Short Term Exposure ◽  
Technical Solutions ◽  
And Training ◽  
Accident Site

AbstractIntroductionMobile decontamination units are intended to be used at the accident site to decontaminate persons contaminated by toxic substances. A test program was carried out to evaluate the efficacy of mobile decontamination units.ObjectiveThe tests included functionality, methodology, inside environment, effects of wind direction, and decontamination efficacy.MethodsThree different types of units were tested during summer and winter conditions. Up to 15 test-persons per trial were contaminated with the imitation substances Purasolve ethyl lactate (PEL) and methyl salicylate (MES). Decontamination was carried out according to standardized procedures. During the decontamination trials, the concentrations of the substances inside the units were measured. After decontamination, substances evaporating from test-persons and blankets as well as remaining amounts in the units were measured.ResultsThe air concentrations of PEL and MES inside the units during decontamination in some cases exceeded short-term exposure limits for most toxic industrial chemicals. This was a problem, especially during harmful wind conditions, i.e., wind blowing in the same direction as persons moving through the decontamination units. Although decontamination removed a greater part of the substances from the skin, the concentrations evaporating from some test-persons occasionally were high and potentially harmful if the substances had been toxic. The study also showed that blankets placed in the units absorbed chemicals and that the units still were contaminated five hours after the end of operations.ConclusionsAfter decontamination, the imitation substances still were present and evaporating from the contaminated persons, blankets, and units. These results indicate a need for improvements in technical solutions, procedures, and training.RibordyP, RocksénD, DellgarU, PerssonS, ArnoldssonK, EkåsenH, HäggbomS, NerfO, LjungqvistA, GrythD, ClaessonO. Mobile decontamination units—room for improvement?. Prehosp Disaster Med.2012;27(4):1–7.

scholarly journals Beagle dog 90-day oral toxicity study of a novel coccidiostat – ethanamizuril

2020 ◽  
Author(s):  
Keyu Zhang ◽  
Xiaoyang Wang ◽  
Shuya Wei ◽  
Chunmei Wang ◽  
Mi Wang ◽  
...  
Keyword(s):  
Clinical Pathology ◽  
Dosage Level ◽  
Oral Toxicity ◽  
Safety Database ◽  
Clinical Observations ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Anticoccidial Activity ◽  
Anticoccidial Agent ◽  
Histologic Changes

Abstract Background: Triazine coccidiostats are widely used in chickens and turkeys for coccidiosis control. Ethanamizuril is a novel triazine compound that exhibits anticoccidial activity in poultry. To support the safety assessment of the new potent anticoccidial agent, the subchronic toxicity of ethanamizuril was studied in beagle dogs administered ethanamizuril by diet at doses of 12, 60 or 300 mg/kg/day for 90 days.Results: Ethanamizuril was well tolerated at low and middle dosages and there were no ethanamizuril related effects on survival, clinical observations, clinical pathology parameters, organs weight, macroscopic or microscopic evaluations. The ethanamizuril related changes were limited to effects on food consumption and histologic changes of kidneys in the 300 mg/kg/day group in both sexes. However, the characteristic toxicities of ethanamizuril in kidneys are recoverable in convalescence dogs of 300 mg/kg/day group. Conclusions: Therefore, the no-observed-adverse-effect level (NOAEL) was considered to be 60 mg/kg/day, the middle dosage level tested. These results add to the safety database for ethanamizuril with potential for use as a novel coccidiostat.

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