1,1,1,3,3,3-Hexamethyldisilazane (2018)

2019 ◽  
Vol 35 (3) ◽  
pp. 189-195
Keyword(s):  
Inhalation Exposure ◽  
Male Rats ◽  
Feed Consumption ◽  
High Dose ◽  
Exposure Level ◽  
Short Term ◽  
Adhesion Promoter ◽  
Inhalation Study ◽  
Short Term Exposure ◽  
Dose Inhalation

1,1,1,3,3,3-Hexamethyldisilazane (HMDZ) is used industrially to treat the surface of silica, as an intermediate adhesion promoter or silylating agent in the semiconductor industry, as a chemical modifier of inorganic fillers, and as a water scavenger silicone sealant. In animal studies, HMDZ is considered to be slightly to at most moderately toxic following acute administration via oral, dermal, and inhalation routes of exposure. HMDZ is neither an eye irritant nor was it dermally irritating under semiocclusive conditions; however, it caused dermal necrosis in two studies under occlusive conditions. HDMZ is not genotoxic or mutagenic in in vitro assays and was not reproductively or developmentally toxic in an inhalation screening study in rats. Short-term and subacute, high-dose inhalation exposure to HMDZ produced respiratory tract irritation, reduced feed consumption, changes in clinical chemistry parameters, and reversible central nervous system depression in rats. In a 90-day inhalation exposure study in rats, HMDZ exposure-related effects were observed in the kidneys of male rats but were determined to be alpha-2µ-nephropathy, thus, not relevant to humans. Based on the results of the 90-day (subchronic) inhalation study, 75 ppm was determined to be the no-observed adverse effect level (NOAEL) and was selected as the point of departure for the derivation of the 8-h time-weighted average (TWA), health-based workplace environmental exposure level (WEEL) value. This subchronic inhalation NOAEL was adjusted to account for duration of exposure, interindividual variability, and intraindividual variability. The resulting 8-h TWA WEEL value of 10 ppm is fully expected to provide a significant margin of safety against any potential adverse health effects in workers following long-term inhalation exposure to HMDZ vapor. A 15-min short-term exposure limit of 50 ppm was also established to protect workers from reversible effects produced by acute, high-dose inhalation of HMDZ vapor. A skin notation (Skin) is warranted because of the potential for the dermal route to significantly contribute to the overall exposure to HMDZ.

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.

Short-Term Rat Inhalation Study With Aerosols of Acrylic Ester-Based Polymer Dispersions Containing a Fraction of Nanoparticles

2012 ◽  
Vol 31 (1) ◽  
pp. 46-57 ◽  
Author(s):  
Lan Ma-Hock ◽  
Robert Landsiedel ◽  
Karin Wiench ◽  
Dominik Geiger ◽  
Volker Strauss ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Raw Materials ◽  
Inhalation Exposure ◽  
Male Rats ◽  
Short Term ◽  
Limit Values ◽  
Inhalation Study ◽  
Acrylic Ester ◽  
Materials Used ◽  
Polymer Dispersions

Aqueous polymer dispersions are important raw materials used in a variety of industrial processes. They may contain particles with diameters ranging from 10 to 1500 nm. Polymer exposure alone may cause pulmonary lesions after inhalation exposure. Polymer dispersions with increased proportions of nano-sized particles are being developed for improved material characteristics, and this may pose even increased pulmonary hazards upon potential inhalation exposure. In a 5-day screening study, male rats were nose-only exposed to aerosols generated from 2 dispersions of acrylic ester polymers with identical chemical composition but different nano-sized particle proportions at particle concentrations of 3 and 10 mg/m3. Immediately and 19 days after the end of inhalation, necropsies were conducted with major emphasis on respiratory tract histopathology. Three and 23 days after the end of inhalation, bronchoalveolar lavage was performed to screen for early pulmonary injury and inflammation. In contrast to the adverse effects known for other materials in short-term inhalation studies, none of the tested preparations of acrylic ester polymers elicited any adverse effect at the end of the inhalation or postinhalation periods. No shift in toxicity could be observed by the increased proportion of nano-sized polymer particles. Under the conditions of this study, the no observable adverse effect levels for both preparations were >10 mg/m3, that is 2- to 3-fold beyond current nuisance dust threshold limit values.

Trans-1,1,1,4,4,4-hexafluoro-2-butene (HFO-1336mzz-E) (2018)

2019 ◽  
Vol 35 (3) ◽  
pp. 204-210
Keyword(s):  
Body Weight ◽  
Female Rats ◽  
Male Rats ◽  
Repeated Dose ◽  
Exposure Level ◽  
Inhalation Study ◽  
Male And Female ◽  
Range Finding ◽  
Male And Female Rats ◽  
Dose Inhalation

Trans-1,1,1,4,4,4-hexafluoro-2-butene (HFO-133mzz-E) is an odorless gas that finds uses as a foam transfer agent, heat transfer fluid, and specialty gas. The acute 4-h LC50 (in rats) for HFO-133mzz-E is > 17,000 ppm; it was not an eye or dermal irritant in 3- and 13-week repeated-dose inhalation studies in rats at concentrations up to 1.5% (15,000 ppm). HFO-133mzz-E was not a cardiac sensitizer at 70,000 ppm in a standard epinephrine challenge study in Beagle dogs. In a 3-week, repeated-dose (non-GLP) inhalation range-finding study in male and female rats, HFO-133mzz-E concentrations of 7500 and 15,000 ppm were determined to be well-tolerated. In the follow-up, GLP-compliant, 28-day repeated-dose inhalation study (as per OECD 412), male and female rats were exposed to 0, 1000, 10,000, or 15,000/20,000 ppm (20,000 ppm concentration was decreased to 15,000 ppm after week 1 because of deaths and body weight loss). The study no-observed-adverse-effect level (NOAEL) was established at 10,000 ppm based on reduced body weight gain and mortality observed at 15,000 ppm. In a 90-day GLP-compliant repeated-dose study (as per OECD 413), male and female rats were exposed to 0, 1000, 5000, 7500, or 15,000 ppm HFO-133mzz-E. Three male rats exposed to 15,000 ppm HFO-133mzz-E died during exposure; clinical signs such as restlessness, blepharospasm, and myoclonic jerks were also observed, during the first month of the study, at 15,000 ppm. There were no significant gross or histopathological organ/tissue lesions attributable to HFO-133mzz-E exposure. The study NOAEL was established at 7500 ppm. In a GLP prenatal developmental study (OECD 414), groups of time-mated nulliparous female rats were exposed via inhalation to 0, 1000, 5000, 7500, or 15,000 ppm HFO-1336mzz-E beginning on gestation day (GD) 6 up to and including GD 19. Under the conditions of this study, the NOAEL for maternal and fetal effects was established at 7500 ppm. HFO-1336mzz-E was not genotoxic in either in vitro or in vivo assays. Based on the results of the 90-day inhalation study, 7500 ppm was determined to be the NOAEL and was selected as the point of departure for the derivation of the 8-h time-weighted average (TWA), health-based workplace environmental exposure level (WEEL) value. This subchronic inhalation NOAEL was adjusted to account for duration of exposure, interindividual variability, and intraindividual variability. The resulting 8-h TWA WEEL value of 400 ppm is fully expected to provide a significant margin of safety against the production of any potential adverse health effects in workers following long-term inhalation exposure to HFO-1336mzz-E.

Nitroethane Documentation of proposed values of occupational exposure limits (OELs)

2017 ◽  
Vol 33 (1(91)) ◽  
pp. 97-113
Author(s):  
Andrzej Sapota ◽  
Małgorzata Skrzypińska-Gawrysiak ◽  
ANNA KILANOWICZ
Keyword(s):  
Occupational Exposure ◽  
The Body ◽  
Exposure Level ◽  
Occupational Exposure Limits ◽  
Exposure Limits ◽  
Short Term ◽  
Cellulose Esters ◽  
Limit Values ◽  
Exposure Limit ◽  
Short Term Exposure

Nitroethane is a colorless oily liquid with a mild fruity odor. It is used mainly as a pro-pellant (e.g., fuel for rockets), and as a solvent or dissolvent agent for cellulose esters, resins (vinyl and alkyd) and waxes, and also in chemical synthesis.Occupational exposure to nitroethane may occur during the process of its production and processing. There are no data on air concentra-tions of nitroethane in occupational exposure. In 2010–2015, workers in Poland were not exposed to nitroethane concentrations exceed-ing the maximum allowable value – 75 mg/m3 (the limit value valid since 2010).Nitroethane can be absorbed into the body via inhalation of its vapors or by ingestion.The discussed cases of nitroethane acute poi-soning caused by an accidental ingestion of artificial fingernail remover containing pure nitroethane concerned children under three years. Few hours after ingestion, cyanosis and sporadic vomiting were observed in children. The methemoglobin level reached 40÷50%.Neither data on chronic nitroethane poisoning in humans nor data obtained from epidemio-logical studies are available.On the basis of the results of acute toxicity studies nitroethane has been categorized in the group of hazardous compounds. However, eye and dermal irritation or allergic effects have not been evidenced. The studies of sub-chronic (4 and 90 days) and chronic (2 years) exposure to nitroethane per-formed on rats and mice (concentration range 310 ÷ 12 400 mg/m3) revealed the methemo-globinogenic effect of this compound and a minor damage to liver, spleen, salivary gland and nasal turbinates.Niroethane has shown neither mutagenic nor carcinogenic effects. Its influence on fertility has not been evidenced either. After chronic exposure (2 years) of rats to ni-troethane at concentration of 525 mg/m3 (the lowest observed adverse effect level – LOAEL), a slight change in a body mass of exposed fe-male animals and subtle changes in biochemi-cal parameters were observed, but there were no anomalies in hematological and histopatho-logical examinations.The value of 62 mg/m3 has been suggested to be adopted as the MAC value for nitroethane after applying the LOAEL value of 525 mg/m3 and relevant coefficients of uncertainty. The STEL value for nitroethane was proposed ac-cording to the methodology for determining short term exposure level value for irritating substances as three times MAC value (186 mg/m3) to prevent the effects of sensory irri-tations in humans. Because of its methemoglo-binogenic effect, 2% Met-Hb has been suggest-ed to be adopted as the value of biological ex-posure index (BEI), like the value already adopted for all methemoglobinogenic sub-stances.The Scientific Committee on Occupational Exposure Limits (SCOEL) proposed the time-weighted average (TWA) for nitroethane (8 h) as 62 mg/m3 (20 ppm), short-term exposure limit (STEL, 15 min) as 312 mg/m3 (100 ppm) and “skin” notation.Proposed OEL and STEL values for nitroethane were subjected to public consultation, con-ducted in 2011 by contact points, during which Poland did not raise any objections to the pro-posals. The proposed values for nitroethane by SCOEL has been adopted by the Advisory Committee on Safety and Health at Work UE (ACSH) and included in the draft directive establishing the IV list of indicative occupa-tional exposure limit values.

The repeated cytogenetic analysis of subjects occupationally exposed to nanoparticles: a pilot study

Mutagenesis ◽  
2019 ◽  
Vol 34 (3) ◽  
pp. 253-263 ◽  
Author(s):  
Andrea Rossnerova ◽  
Daniela Pelclova ◽  
Vladimir Zdimal ◽  
Pavel Rossner ◽  
Fatima Elzeinova ◽  
...  
Keyword(s):  
Pilot Study ◽  
Human Study ◽  
Inhalation Exposure ◽  
Micronucleus Assay ◽  
Short Term ◽  
Short Term Exposure ◽  
Occupationally Exposed ◽  
Chromosomal Breaks ◽  
Clastogenic Effect

Abstract The application of nanomaterials has been rapidly increasing during recent years. Inhalation exposure to nanoparticles (NP) may result in negative toxic effects but there is a critical lack of human studies, especially those related to possible DNA alterations. We analyzed pre-shift and post-shift a group of nanocomposite researchers with a long-term working background (17.8 ± 10.0 years) and matched controls. The study group consisted of 73.2% males and 26.8% females. Aerosol exposure monitoring during a working shift (involving welding, smelting, machining) to assess the differences in exposure to particulate matter (PM) including nanosized fractions <25–100 nm, and their chemical analysis, was carried out. A micronucleus assay using Human Pan Centromeric probes, was applied to distinguish between the frequency of centromere positive (CEN+) and centromere negative (CEN−) micronuclei (MN) in the binucleated cells. This approach allowed recognition of the types of chromosomal damage: losses and breaks. The monitoring data revealed differences in the exposure to NP related to individual working processes, and in the chemical composition of nanofraction. The cytogenetic results of this pilot study demonstrated a lack of effect of long-term (years) exposure to NP (total frequency of MN, P = 0.743), although this exposure may be responsible for DNA damage pattern changes (12% increase of chromosomal breaks—clastogenic effect). Moreover, short-term (daily shift) exposure could be a reason for the increase of chromosomal breaks in a subgroup of researchers involved in welding and smelting processes (clastogenic effect, P = 0.037). The gender and/or gender ratio of the study participants was also an important factor for the interpretation of the results. As this type of human study is unique, further research is needed to understand the effects of long-term and short-term exposure to NP.

Neuroimmunological Effects of Exposure to Methylmercury Forms in the Sprague-Dawley Rats. Activation of the Hypothalamic-Pituitary-Adrenal Axis and Lymphocyte Responsiveness

1997 ◽  
Vol 13 (1) ◽  
pp. 57-66 ◽  
Author(s):  
Hector G. Ortega ◽  
Manuel Lopez ◽  
Atsushi Takaki ◽  
Qin-Heng Huang ◽  
Akira Arimura ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Low Dose ◽  
Fold Increase ◽  
Exposed Group ◽  
Blood Levels ◽  
High Dose ◽  
Sprague Dawley ◽  
Short Term ◽  
Hypothalamic Pituitary Adrenal ◽  
Short Term Exposure

The effects of different methylmercury (MeHg) forms on the immune system and the hypothalamic pituitary adrenal (HPA) axis were assessed. The lymphocyte response to Concanavalin A (Con A) stimulation, blood levels of interleukin-6 (IL-6), adrenocorticotrophin hormone (ACTH), and corticosterone in the presence of different MeHg compounds was measured. Rats were exposed to methylmercury sulfide [(MeHg)2S] and methylmercury chloride (MeHgCl) at concentrations of 5 and 500 μg per liter in the drinking water for 8 or 16 weeks. Short-term exposure (8 weeks) at both, low- and high-doses of (MeHg)2S significantly enhanced lymphocyte responsiveness. MeHgCl only induced increased lymphocyte responsiveness at the low-dose exposure. Circulating levels of IL-6 after short-term exposure were increased in the MeHgCl-exposed group. The HPA axis activation was demonstrated by increased levels of ACTH and corticosterone levels. This response was predominant in low-dose exposed animals. Long-term (16 weeks) exposure resulted in a reduction in lymphocyte proliferation after both low- and high-dose MeHgCl exposures. The (MeHg)2S exposure resulted in a 3-fold increase in the proliferative response. Levels of ACTH were elevated 3-fold in the (MeHg)2S-exposed group, and no increase of corticosterone was observed in the high-dose exposed group at 8 weeks, no effect of(MeHg)2S was observed at 16 weeks. The MeHgCl exposed group showed an increase in ACTH and corticosterone levels at 8 weeks; this response was not observed at 16 weeks. These data indicate that exposure to MeHg compounds enhances T-cell proliferation in most of the cases, in a dose- and time-dependent fashion. Release of IL-6 also depends on the length of exposure. Early increases in circulating ACTH at 8 weeks also suggest activation of the HPA axis. This may contribute to the production of IL-6 and surveillance of regulatory homeostatic responses against environmental agents that mimic stress-like responses.

A high dose of short term exogenous d-galactose administration in young male rats produces symptoms simulating the natural aging process

Life Sciences ◽  
2015 ◽  
Vol 124 ◽  
pp. 110-119 ◽  
Author(s):  
Saida Haider ◽  
Laraib Liaquat ◽  
Sidrah Shahzad ◽  
Sadia Sadir ◽  
Syeda Madiha ◽  
...  
Keyword(s):  
Aging Process ◽  
Natural Aging ◽  
Young Male ◽  
Male Rats ◽  
High Dose ◽  
Short Term
Sign in / Sign up

Export Citation Format

Share Document