scholarly journals Experimental substantiation for 2-hydroxypropanoic (lactic) acid temporary occupational exposure standard

2021 ◽  
Vol 90 (1) ◽  
pp. 70-74
Author(s):  
VA Turkina ◽  
HV Pryzyhlei ◽  
OI Grushka
Keyword(s):  
Lactic Acid ◽  
Single Dose ◽  
Skin Irritation ◽  
Reproductive Toxicity ◽  
Inhalation Exposure ◽  
Exposure Level ◽  
Inhalation Toxicity ◽  
Toxicology Study ◽  
Workplace Air ◽  
Sensitizing Effect

Lactic (2-hydroxypropanoic) acid is an important metabolic component of living organisms. It is also widely used in various industries. Such a wide application of the acid in manufacturing necessitates the regulation of its content in the workplace air. Toxic effects of lactic acid are described in the literature. It was found that 2-hydroxypropanoic acid belongs to hazard level IV by the criterion of acute oral and inhalation toxicity, it causes skin irritation, severe eye damage, has no skin-resorptive or sensitizing effect, does not cause reproductive toxicity and teratogenicity. Aim of the Research. Substantiation for 2-hydroxypropanoic (lactic) acid indicative safe exposure level (ISEL) in the workplace air. Methods and Materials. Analytical, toxicological, statistical. Results. In the process of conducting toxicology study, it was found that in the conditions of inhalation experiment (intranasal modelling) 2-hydroxypropanoic acid causes changes in the state of the nervous system and affects the cellular composition of bronchoalveolar lavage of experimental animals. Therefore, after a single-dose intranasal instillation Limir = Limac, it can be classified as a substance with non-specific irritant effect. It was found that the threshold of a single-dose inhalation exposure is 20 mg/m3. Conclusions. According to the data obtained in the process of the experiment and data on toxicity parameters and health-based exposure standards of the chemical analogues, the value of ISEL for 2-hydroxypropanoic (lactic) acid in the workplace air was calculated, it is 1.0 mg/m3, aerosol. Key Words: 2-hydroxypropanoic acid, lactic acid, ISEL, workplace air.

scholarly journals Toxicological substantiation for didecyldimethylammonium chloride occupational exposure standard

2020 ◽  
Vol 88 (1) ◽  
pp. 54-60
Author(s):  
P.G. Zhminko ◽  
V.M. Voronina ◽  
S.S. Svitlyi ◽  
L.O. Rudaya
Keyword(s):  
Gastrointestinal Tract ◽  
Occupational Exposure ◽  
Active Ingredient ◽  
Lethal Dose ◽  
Inhalation Exposure ◽  
Raw Material ◽  
Laboratory Animals ◽  
Exposure Level ◽  
Workplace Air ◽  
Scientific Substantiation

Dydetsyldymetylammonium chloride (DDAC) is used as a raw material in the chemical industry for the production of some insecticidal, fungicidal and aldehydic preparations and disinfectants in which it is an active ingredient. Aim of the Research. To establish a scientific substantiation for DDAC indicative safe exposure level (ISEL) in the workplace air by analyzing and summarizing the bibliographic data about the degree of DDAC danger. Methods. To establish a scientific substantiation for DDAC occupational exposure standard the following properties were analyzed: its physical and chemical characteristics; LD50 (lethal dose) for oral and dermal exposure; LC50 (lethal concentration) for inhalation exposure; irritant and sensitizing properties; NOAELs (no-observed adverse effect level) for DDAC were determined in sub-acute and subchronic experiments under different conditions of exposure as well as its long-term effects. The calculation of DDAC ISEL in the workplace air was performed using equations which make allowance for the toxicity properties of the preparation when it is administered to laboratory animals through different routes. Results. DDAC is an imported product used as an active ingredient in the production of certain pesticides and disinfectants. DDAC falls into the category of non-volatile substances: its vapor pressure is <1x10-2 Pa at 20° C, at 50оC – 2,3x10-4 Pa (US ISC) When introduced into the gastrointestinal tract, the substance is classified as moderately dangerous – Category 3 (in accordance with Globally Harmonized System of Classification and Labeling of Chemicals / GHS / United Nations, New York and Geneva, 2017) and has a mild skin-resorptive effect (Category 4, GHS). Its adverse local impact on the skin has been identified. The substance LC50 after inhalation exposure is 70 mg/m3 (Category 2, GHS). DDAC produces marked irritant action on the skin and conjunctiva of rabbits (Category1B, GHS). Erythema, crust and swelling were recorded on skin. Burns, corrosion, acute keratoconjunctivitis were observed when the substance got onto conjunctiva. No sensitizing effect of the preparation was found (not classified, GHS). The cumulative properties of the substance are incomplete. NOAELs were determined in sub-acute and sub-chronic experiments after oral, dermal and inhalation exposure. The most affected organs and systems are skin, eyes, gastrointestinal tract, liver. Mutagenic, carcinogenic, embryotoxic, teratogenic and toxic effects on the reproductive function are not limiting harmful criteria. Calculation of the value of DDAC ISEL in the workplace air was conducted by the equations of regressive dependence, which take into consideration the parameters of acute toxicity. Making allowance for the degree of its hazard and the risk of developing the pathology of general genesis under the effect of the substance, the recommended ISEL value in the workplace air is 0.2 mg/m3, aggregate state “a” with the mark “protection of eyes and skin is necessary”. Key Words: dydetsyldymetylammonium chloride, DDAC, ISEL in the workplace air, insecticides, disinfectants.

3-Nitro-1,2,4-triazol-5-one (2014)

2017 ◽  
Vol 34 (1) ◽  
pp. 8-14 ◽  
Keyword(s):  
Reproductive Toxicity ◽  
Liver Microsomes ◽  
Weighted Average ◽  
Exposure Level ◽  
Inhalation Toxicity ◽  
Developmental Studies ◽  
Developmental Defects ◽  
Toxicity Studies ◽  
Time Weighted Average ◽  
Rats And Mice

3-Nitro-1,2,4-triazol-5-one (NTO) is a potential replacement for energetics in military munitions. It is a component of IMX-101, a munition designed to prevent unintentional detonation. This report summarizes the dermal, oral, and inhalation animal toxicity data, including the results of genotoxicity and limited reproductive and developmental studies. NTO has an acute LD50 in rats and mice of >5000 mg/kg, is a potential eye and skin irritant, but does not induce skin sensitization. Acute inhalation toxicity studies in rats were negative, but testicular hypoplasia was observed in a 14-day oral study in rats administered NTO at >500 mg/kg/day. Similar findings were noted in an oral 90-day study at dosages >315 mg/kg/day and in reproductive toxicity studies at >125 mg/kg/day. NTO did not cause any developmental defects. All genotoxicity studies were negative. ADME and pharmacokinetics data showed rapid uptake and elimination of NTO from both inhalation and oral intakes. Biotransformation by liver microsomes demonstrated two separate pathways, one aerobic and the other anaerobic. NTO is not considered an endocrine disruptor. There is very little human data regarding NTO or the IMX-101 mixtures. Using testicular changes in rats as the point of departure for deriving a Workplace Environmental Exposure Level (WEEL) for NTO, the resulting BMDL10 was 40 mg/kg/day, and the 8-hour time-weighted average was 2 mg/m2.

1,1,1,2,3,4,4,5,5,5-Decafluoropentane (HFC-4310mee)

2021 ◽  
pp. 074823372110198
Keyword(s):  
Reproductive Toxicity ◽  
Inhalation Exposure ◽  
Clinical Signs ◽  
Inhalation Toxicity ◽  
Acute Response ◽  
Abnormal Gait ◽  
Volatile Liquid ◽  
Skin Sensitizer

HFC-43-10mee is a volatile liquid at room temperature and used as a cleaning agent, aerosol, etc. HFC-43-10mee has low acute inhalation toxicity; 4-hour LC50 in rats of approximately 11,000 ppm. The compound was not a skin or eye irritant and was not a skin sensitizer. A cardiac sensitization response was not observed at 5000 ppm. Inhalation exposure resulted in neurotoxicity consisting of tremors, convulsions, jerking, ataxia, abnormal gait, etc. at exposure concentrations of 2000 ppm and above. Within approximately 30 min of exposure the clinical signs appeared and resolved within 1–2 h during exposure; the rats appeared to adapt such that these clinical signs were no longer observed. The neurotoxicity observed was considered an acute response to HFC-43-10mee. In a 90-day study, rats exposed to 2000 ppm resulted in sporadic clinical signs of neurotoxicity. At 3500 ppm, the clinical signs were evident on most exposure days although as the study progressed the apparent incidence declined likely reflecting adaptation. The NOAEL was 500 ppm. Based on the occurrence of the clinical signs in this and other studies, an acute threshold for neurotoxicity was evident at approximately 2000 ppm and above. No developmental or reproductive toxicity were evident at 2000 ppm, although clinical signs of neurotoxicity occurred in maternal or parental rats at 2000 ppm. No effects on offspring were observed. HFC-43-10mee was not genotoxic in vitro or in vivo. Based on the data, the 8-h TWA WEEL value is 225 ppm (2320 mg/m3). The 15-min STEL is 700 ppm (7217 mg/m3).

Oral (Drinking Water) Two-Generation Reproductive Toxicity Study of Bromodichloromethane (BDCM) in Rats

2002 ◽  
Vol 21 (2) ◽  
pp. 115-146 ◽  
Author(s):  
M. S. Christian ◽  
R. G. York ◽  
A. M. Hoberman ◽  
L. C. Fisher ◽  
W. Ray Brown
Keyword(s):  
Drinking Water ◽  
Reproductive Toxicity ◽  
Clinical Signs ◽  
Sperm Parameters ◽  
Feed Consumption ◽  
Exposure Level ◽  
Organ Weights ◽  
Reduced Body ◽  
Body Weights ◽  
Adult Exposure

Bromodichloromethane (BDCM) was tested for reproductive toxicity in a two-generation study in CRL SD rats. Thirty rats/sex/group/generation were continuously provided BDCM in drinking water at 0 (control carrier, reverse osmosis membrane-processed water), 50, 150, and 450 ppm (0,4.1 to 12.6, 11.6 to 40.2, and 29.5 to 109.0 mg/kg/day, respectively). Adult human intake approximates 0.8 μg/kg/day (0.0008 mg/kg/day). P and F1 rats were observed for general toxicity (viability, clinical signs, water and feed consumption, body weights, organ weights [also three weanling F1 and F2 pups/sex/litter], histopathology [10/sex, 0-and 450-ppm exposure groups]) and reproduction (mating, fertility, abortions, premature deliveries, durations of gestation, litter sizes, sex ratios, viabilities, maternal behaviors, reproductive organ weights [also three weanling F1 and F2 pups/sex/litter], sperm parameters, and implantations. F1 rats were evaluated for age at vaginal patency or preputial separation. Ten P and F1 rats/sex from the 0-and 450-ppm exposure groups and rats at 50 and 150 ppm with reduced fertility were evaluated for histopathology (gross lesions, testes, intact epididymis, all F1 dams for number of primordial follicles). Developmental parameters in offspring included implantation and pup numbers, sexes, viabilities, body weights, gross external alterations, and reproductive parameters (F1 adults). Toxicologically important, statistically significant effects at 150 and/or 450 ppm included mortality and clinical signs associated with reduced absolute and relative water consumption, reduced body weights and weight gains, and reduced absolute and relative feed consumption (P and F1 rats). Significantly reduced body weights at 150 and 450 ppm were associated with reduced organ weights and increased organ weight ratios (% body and/or brain weight). Histopathology did not identify abnormalities. Small delays in sexual maturation (preputial separation, vaginal patency) and more F1 rats with prolonged diestrus were also attributable to severely reduced pup body weights. Mating, fertility, sperm parameters, and primordial ovarian follicular counts were unaffected. The no-observable-adverse-effect level (NOAEL) and the reproductive and developmental NOAELs for BDCM were at least 50 ppm (4.1 to 12.6 mg/kg/day), 5125 to 15,750 times the human adult exposure level, if delayed sexual maturational associated with severely reduced body weights is considered reproductive toxicity. If considered general toxicity, reproductive and developmental NOAELs for BDCM are greater than 450 ppm (29.5 to 109.0 mg/kg/day), or 36,875 to 136,250 times the human adult exposure level. Regardless, these data indicate that BDCM should not be identified as a risk to human reproductive performance or development of human conceptuses.

scholarly journals Generation and Characterization of Indoor Fungal Aerosols for Inhalation Studies

2016 ◽  
Vol 82 (8) ◽  
pp. 2479-2493 ◽  
Author(s):  
Anne Mette Madsen ◽  
Søren T. Larsen ◽  
Ismo K. Koponen ◽  
Kirsten I. Kling ◽  
Afnan Barooni ◽  
...  
Keyword(s):  
Species Composition ◽  
Indoor Environment ◽  
Building Materials ◽  
Inhalation Exposure ◽  
Single Species ◽  
Fungal Species ◽  
Exposure Level ◽  
Exposure System ◽  
Content Type ◽  
Water Damage

ABSTRACTIn the indoor environment, people are exposed to several fungal species. Evident dampness is associated with increased respiratory symptoms. To examine the immune responses associated with fungal exposure, mice are often exposed to a single species grown on an agar medium. The aim of this study was to develop an inhalation exposure system to be able to examine responses in mice exposed to mixed fungal species aerosolized from fungus-infested building materials. Indoor airborne fungi were sampled and cultivated on gypsum boards. Aerosols were characterized and compared with aerosols in homes. Aerosols containing 107CFU of fungi/m3air were generated repeatedly from fungus-infested gypsum boards in a mouse exposure chamber. Aerosols containedAspergillus nidulans,Aspergillus niger,Aspergillus ustus,Aspergillus versicolor,Chaetomium globosum,Cladosporiumherbarum,Penicillium brevicompactum,Penicillium camemberti,Penicillium chrysogenum,Penicillium commune,Penicillium glabrum,Penicillium olsonii,Penicillium rugulosum,Stachybotrys chartarum, andWallemia sebi. They were all among the most abundant airborne species identified in 28 homes. Nine species from gypsum boards and 11 species in the homes are associated with water damage. Most fungi were present as single spores, but chains and clusters of different species and fragments were also present. The variation in exposure level during the 60 min of aerosol generation was similar to the variation measured in homes. Through aerosolization of fungi from the indoor environment, cultured on gypsum boards, it was possible to generate realistic aerosols in terms of species composition, concentration, and particle sizes. The inhalation-exposure system can be used to study responses to indoor fungi associated with water damage and the importance of fungal species composition.

Comparative Acute Toxicity of Shale and Petroleum Derived Distillates

1985 ◽  
Vol 5 (6) ◽  
pp. 1005-1016 ◽  
Author(s):  
Charles R. Clark ◽  
Paul W. Ferguson ◽  
Mark A. Katchen ◽  
Michael W. Dennis ◽  
Douglas K. Craig
Keyword(s):  
Acute Toxicity ◽  
Skin Irritation ◽  
Inhalation Exposure ◽  
Petroleum Products ◽  
Health Impacts ◽  
Shale Oil ◽  
Potential Health ◽  
Low Toxicity ◽  
Distillate Fractions ◽  
Comparative Acute Toxicity

In anticipation of the commercialization of its shale oil retorting and upgrading process, Unocal Corp. conducted a testing program aimed at better defining potential health impacts of a shale industry. Acute toxicity studies using rats and rabbits compared the effects of naphtha, Jet-A, JP-4, diesel and “residual” distillate fractions of both petroleum derived crude oils and hydrotreated shale oil. No differences in the acute oral (> 5 g/kg LD50) and dermal (> 2 g/kg LD50) toxicities were noted between the shale and petroleum derived distillates and none of the samples were more than mildly irritating to the eyes. Shale and petroleum products caused similar degrees of mild to moderate skin irritation. None of the materials produced sensitization reactions. The LC50 after acute inhalation exposure to Jet-A, shale naphtha, (> 5 mg/L) and JP-4 distillate fractions of petroleum and shale oils was greater than 5 mg/L. The LC50 of petroleum naphtha (> 4.8 mg/L) and raw shale oil (> 3.95 mg/L) also indicated low toxicity. Results demonstrate that shale oil products are of low acute toxicity, mild to moderately irritating and similar to their petroleum counterparts. The results further demonstrate that hydrotreatment reduces the irritancy of raw shale oil.

Reproductive toxicity and toxicokinetics of lindane in the male offspring of rats exposed during lactation

1997 ◽  
Vol 16 (3) ◽  
pp. 146-153 ◽  
Author(s):  
PR Dalsenter ◽  
AS Faqi ◽  
J. Webb ◽  
H-J. Merker ◽  
I. Chahoud
Keyword(s):  
Single Dose ◽  
Testosterone Level ◽  
Reproductive Toxicity ◽  
Maternal Plasma ◽  
Male Offspring ◽  
Pronounced Effect ◽  
Toxicity Study ◽  
Testicular Weight

1 Reproductive toxicity and toxicokinetics of lindane during lactation were studied. For the reproductive toxicity study the dams were treated with a single dose of 6 mg/kg on day 9 or 14 of lactation, or with 1 mg/kg on days 9 to 14 of lactation. The male offspring were investigated at puberty and adulthood. For the toxicokinetic study, two groups of dams were treated with 6 mg/kg on day 9 or 14 of lactation. The concentration of lindane was measured in maternal plasma and milk, as well as in male offspring organs. 2 At adulthood, testicular weight and the number of sperm and spermatids were significantly reduced in all treated groups. 3 The testosterone level of the groups treated with 6 mg/ kg was significantly reduced to approximately 50% at puberty as well as in adulthood. In the group treated with 1 mg/kg, the testosterone level was in both age periods reduced, however, only at puberty was the reduction statistically significant. 4 The concentration oflindane in the testis was similar to that found in brain and was half the concentration found in the liver. 5 Histologically some areas of the testis exhibited distinct alterations ranging from small changes to a pronounced effect. 6 Exposure to lindane during lactation induces repro ductive hazards to male offspring rats which are detectable at adulthood.

1,1,2,2-Tetrafluoroethane (HFC-134) (2018)

2019 ◽  
Vol 35 (3) ◽  
pp. 196-203
Keyword(s):  
Adverse Effect ◽  
Adverse Effects ◽  
Toxicity Study ◽  
Whole Body ◽  
Exposure Level ◽  
Inhalation Toxicity ◽  
Hfc 134A ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Whole Body Inhalation

1,1,2,2-Tetrafluoroethane (HFC-134) is a colorless gas used as a foam expansion agent and heat transfer fluid. HFC-134 has a low acute inhalation toxicity with an LC50 of >244,000 ppm. The no-observed adverse effect level (NOAEL) and lowest-observed adverse effect level for cardiac sensitization (in epinephrine-challenged beagle dogs) were 75,000 and 100,000 ppm, respectively. A subacute 4-week GLP inhalation toxicity study exposed male and female Crl: CD®BR rats (10/sex) to 0, 2000, 10,000, or 50,000 ppm via whole-body inhalation. Transient and non-dose-response–related body weight changes were observed throughout the exposure period, but no statistically significant, test substance-related adverse effects were observed in any clinical observations, chemistry, hematology, or pathology. This study identified a NOAEL for HFC-134 of 50,000 ppm, the highest exposure level tested. HFC-134 is not genotoxic in in vitro studies; however, no in vivo studies are available. No developmental or maternal toxicity was found in female rats exposed to HFC-134 up to 50,000 ppm via whole-body inhalation in two different studies. Based on data for a similar material (HFC-134a), HFC-134 is not expected to be extensively metabolized or to cause genetic toxicity or carcinogenicity. The HFC-134 workplace environmental exposure level (WEEL) is based primarily on the subacute 4-week inhalation toxicity study in rats with the NOAEL of 50,000 ppm selected as the point of departure for the derivation of the 8-h TWA, health-based WEEL value. The developmental toxicity study also had a NOAEL of 50,000 ppm and was the highest exposure level tested. The subacute inhalation NOAEL was adjusted to account for interindividual variability, subacute to chronic duration, animal to human extrapolation, daily duration of exposure, and residual uncertainty. In addition, the lack of adverse effects noted in the toxicology studies for HFC-134a was considered. The resulting 8-h TWA WEEL value of 1000 ppm is 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 HFC-134.

Sign in / Sign up

Export Citation Format

Share Document