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Meta-analysis of animal studies applied to short-term inhalation exposure levels of hazardous chemicals.

ABSTRACT: For short-term chemical inhalation exposures to hazardous chemicals, the incidence of a health effect in biological testing usually conforms to a general linear model with a probit link function dependent on inhalant concentration C and the duration of exposure t. The National Academy's Acute Exposure Guideline Levels (AEGLs) Committee relies on these models when establishing AEGLs. Threshold concentrations at AEGL durations are established by the toxic load equation Cⁿ x t = constant, which toxic load exponent n (TLE or n-value) directly follows from the bivariate probit model. When multiple probit datasets are available, the AEGL Committee routinely pools studies' incidence data. Such meta-analytical models are valid only when the pooled data are homogeneous, with similar sensitivities and equivalent responses to exposure concentrations and durations. In the present study, the homogeneity of datasets meta-analyzed by the AEGL Committee was examined, finding that 70% of datasets pooled by the AEGL Committee are heterogeneous. In these instances, data pooling leads to a statistically invalid model and TLE estimate, potentially resulting in under- or over-estimated inhalation guidance levels. When data pooling is inappropriate, other meta-analysis options include categorical regression, fixed-effect and random-effects models, or even designation of a key study based on scientific judgement. In the present work, options of TLE meta-analysis are summarized in a decision tree contingent on statistical testing.

SUBMITTER: Prussia AJ

PROVIDER: S-EPMC8092449 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: A standard short-term inhalation study (STIS) was applied for hazard assessment of 13 metal oxide nanomaterials and micron-scale zinc oxide. METHODS: Rats were exposed to test material aerosols (ranging from 0.5 to 50 mg/m3) for five consecutive days with 14- or 21-day post-exposure observation. Bronchoalveolar lavage fluid (BALF) and histopathological sections of the entire respiratory tract were examined. Pulmonary deposition and clearance and test material translocation into extra-pulmonary organs were assessed. RESULTS: Inhaled nanomaterials were found in the lung, in alveolar macrophages, and in the draining lymph nodes. Polyacrylate-coated silica was also found in the spleen, and both zinc oxides elicited olfactory epithelium necrosis. None of the other nanomaterials was recorded in extra-pulmonary organs. Eight nanomaterials did not elicit pulmonary effects, and their no observed adverse effect concentrations (NOAECs) were at least 10 mg/m3. Five materials (coated nano-TiO2, both ZnO, both CeO2) evoked concentration-dependent transient pulmonary inflammation. Most effects were at least partially reversible during the post-exposure period.Based on the NOAECs that were derived from quantitative parameters, with BALF polymorphonuclear (PMN) neutrophil counts and total protein concentration being most sensitive, or from the severity of histopathological findings, the materials were ranked by increasing toxic potency into 3 grades: lower toxic potency: BaSO4; SiO2.acrylate (by local NOAEC); SiO2.PEG; SiO2.phosphate; SiO2.amino; nano-ZrO2; ZrO2.TODA; ZrO2.acrylate; medium toxic potency: SiO2.naked; higher toxic potency: coated nano-TiO2; nano-CeO2; Al-doped nano-CeO2; micron-scale ZnO; coated nano-ZnO (and SiO2.acrylate by systemic no observed effect concentration (NOEC)). CONCLUSION: The STIS revealed the type of effects of 13 nanomaterials, and micron-scale ZnO, information on their toxic potency, and the location and reversibility of effects. Assessment of lung burden and material translocation provided preliminary biokinetic information. Based upon the study results, the STIS protocol was re-assessed and preliminary suggestions regarding the grouping of nanomaterials for safety assessment were spelled out.

Project description:IntroductionExposure to hazardous chemicals released during hairdressing activities from hair care products puts hairdressers at risk of adverse health effects. Safety assessments of hair products are mainly focused on consumers, but exposure for professional hairdressers might be substantially higher.ObjectiveTo identify and assess available research data on inhalation exposures of professional hairdressers.MethodsA systematic search of studies between 1 January 2000 and 30 April 2021 was performed in Medline, Embase, Web of Science and in Cochrane registry, toxicological dossiers of the Scientific Committee on Consumer Safety (SCCS) of the European Commission as well as the German MAK Commission. Studies reporting quantitative data on airborne concentrations of chemicals in the hairdresser's workplace were considered. The outcome was an airborne concentration of chemicals in the working environment, which was compared, when possible, with current occupational exposure limits (OEL) or guidance levels.ResultsIn total, 23 studies performed in 14 countries were included. The average number of hairdressing salons per study was 22 (range 1-62). Chemicals most frequently measured were formaldehyde (n = 8), ammonia (n = 5), total volatile organic compounds (TVOC) (n = 5), and toluene (n = 4). More than fifty other chemicals were measured in one to three studies, including various aromatic and aliphatic organic solvents, hydrogen peroxide, persulfate, and particulate matter. Most studies reported environmental air concentrations, while personal exposure was measured only in seven studies. The measured air concentrations of formaldehyde, ammonia, and TVOC exceeded OEL or guidance values in some studies. There was large variability in measuring conditions and reported air concentrations differed strongly within and between studies.ConclusionHairdressers are exposed to a wide spectrum of hazardous chemicals, often simultaneously. Airborne concentrations of pollutants depend on salon characteristics such as ventilation and the number of customers but also on used products that are often country- or client-specific. For exposure to formaldehyde, ammonia, and TVOC exceeding OELs or guidance values for indoor air was observed. Therefore, occupational exposure should be taken into account by safety regulations for hair care products.

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Meta-analysis of animal studies applied to short-term inhalation exposure levels of hazardous chemicals.

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