Recommended Occupational Exposure Limits for GMA Using Benchmark Dose and Bayesian Model Averaging.

This chapter covers (1) esters of carbonic and orthocarbonic acid, (2) esters of organic phosphorous compounds, (3) esters of monocarboxylic halogenated acids, alkanols, or haloalcohols, and (4) organic silicon esters. Other classes of esters are summarized in Chapters 79 and 80. Refer to the Introduction in Chapter 79 for a more detailed overview of general properties of esters.Unfortunately, as shown in the two prior chapters, mainly fragmented toxicological evaluations are available for esters. Most of these esters are characterized by low toxicity. Indeed, as expressed in Chapter 79, lethal dose (e.g., LD50) values are frequently difficult or impractical to measure. Localized dermal irritation is one common effect characteristic of exposures to most organic solvents. Few esters are readily absorbed, but there are exceptions, such as tri‐o‐cresyl phosphate (TOCP). Several of the halogenated derivatives, such as ethylchloro‐ and ethylbromo‐, are potent lacrimators. Ethyl fluoroacetate and fluoroacetic acid exhibit about the same mode of action, which may indicate that the acetate is rapidly hydrolyzed and metabolized in the mammalian system. The unsaturated carbonates are also associated with high lacrimatory activity.TOCP is an example of an ester that can cause neuropathy in a variety of animal species. The initial weakness and paralysis are normally reversible in early stages, but repeated or massive assaults result in demyelination of the nerve fibers. The mechanism of action is not yet certain, but it appears to involve phosphorylation of proteins. Only selected phosphates exhibit neuropathic effects, including diisopropyl fluorophosphorate andN,N′‐diisopropyl phosphorodiamidic fluoride.As was expressed in Chapter 79, industrial hygiene evaluation of esters involves collecting and analyzing air samples to determine their airborne concentrations. Published industrial hygiene air sampling and analytical methods, however, are unavailable for most esters. In relation, there are few occupational exposure and biological limits. A list of ester compounds covered in this chapter that have industrial hygiene sampling and analytical methods are presented here along with their respective occupational exposure limits, established by the American Conference of Governmental Industrial Hygienists (ACGIH), the Occupational Safety and Health Administration (OSHA), and the National Institute for Occupational Safety and Health (NIOSH). As stated in Chapter 79, since sampling and analytical methods and occupational exposure limits are subject to periodic revision, the reader is encouraged to refer to current publications of ACGIH, OSHA, and NIOSH.

Coke oven emissions (COEs) can cause oxidative stress of the body, which in turn induces the occupational lung disease and also increases the risk of other diseases. COEs are the major occupational hazard factors for coke oven workers. The aim of the study is to explore the influences of COEs exposure on oxidative damage and estimate the benchmark dose (BMD) of COEs. A group of 542 workers exposed to COEs and 237 healthy controls from the same city were recruited in this study. The corresponding measuring kits were used to determine the plasma biomarkers of oxidative damage level. Generalized linear models and trend tests were used to analyze the relationship between COEs exposure and biomarkers. EPA Benchmark Dose Software was performed to calculate BMD and the lower confidence limit of the benchmark dose (BMDL) of COEs exposure. The results showed the significant dose-response relationship was observed between COEs exposure and oxidative damage with T-AOC as a biomarker. The BMD of COEs exposure were 2.83 mg/m3 and 1.39 mg/m3 in males and females, respectively, and the corresponding BMDL were 1.47 mg/m3 and 0.75 mg/m3 in males and females, respectively. Our results suggested the exposure level of COEs below the current national occupational exposure limits (OELs) would induce oxidative damage, and the OEL of COEs based on the T-AOC damage was suggested at 0.03 mg/m3 in this study.Keywords: Coke oven emissions, polycyclic aromatic hydrocarbons, oxidative damage, plasma total antioxidant capacity, benchmark dose, occupational exposure limits

Under OSHA and American Conference of Governmental Industrial Hygienists (ACGIH®) guidelines, the mixture formula (unity calculation) provides a method for evaluating exposures to mixtures of chemicals that cause similar toxicities. According to the formula, if exposures are reduced in proportion to the number of chemicals and their respective exposure limits, the overall exposure is acceptable. This approach assumes that responses are additive, which is not the case when pharmacokinetic interactions occur. To determine the validity of the additivity assumption, we performed unity calculations for a variety of exposures to toluene, ethylbenzene, and/or xylene using the concentration of each chemical in blood in the calculation instead of the inhaled concentration. The blood concentrations were predicted using a validated physiologically based pharmacokinetic (PBPK) model to allow exploration of a variety of exposure scenarios. In addition, the Occupational Safety and Health Administration and ACGIH® occupational exposure limits were largely based on studies of humans or animals that were resting during exposure. The PBPK model was also used to determine the increased concentration of chemicals in the blood when employees were exercising or performing manual work. At rest, a modest overexposure occurs due to pharmacokinetic interactions when exposure is equal to levels where a unity calculation is 1.0 based on threshold limit values (TLVs®). Under work load, however, internal exposure was 87% higher than provided by the TLVs. When exposures were controlled by a unity calculation based on permissible exposure limits (PELs), internal exposure was 2.9 and 4.6 times the exposures at the TLVs at rest and workload, respectively. If exposure was equal to PELs outright, internal exposure was 12.5 and 16 times the exposure at the TLVs at rest and workload, respectively. These analyses indicate the importance of (1) selecting appropriate exposure limits, (2) performing unity calculations, and (3) considering the effect of work load on internal doses, and they illustrate the utility of PBPK modeling in occupational health risk assessment.

Beyond the Clock: Revisiting Occupational Exposure Limits (OELs) for unusual work schedules in the South African Mining Industry

There are three commonly used occupational exposure limits for respirable (quartz) silica: the American Conference of Governmental Industrial Hygienists' (ACGIH's) threshold limit value (TLV®)of 0.1 mg/m3; the National Institute for Occupational Safety and Health (NIOSH) recommended exposure limit (REL) of 0.05 mg/m3; and the U.S. Department of Labor/Occupational Safety and Health Administration (USDOL/OSHA) permissible exposure level (PEL) for silica that uses a formula where 10 mg/m3 is divided by the sum of the percent SiO2 and 2. It is commonly stated that there is no significant difference between the TLV and the PEL, and it is assumed that the REL is more stringent than the PEL. In fact, the PEL is always a more conservative value than the TLV and, at silica percentages at or below 2%, the PEL is more stringent than the REL. Although at the higher silica concentrations the ratio of the TLV to the PEL is virtually 1.0, at lower silica concentrations the differences become geometrically larger, reaching greater than 1.2 at 10% SiO2 and 1.4 at 5% SiO2. Below 5% SiO2 the difference is most significant, and the PEL is three times more conservative than the TLV at 196 SiO2. For these reasons one should not assume that meeting the TLV or REL for silica assures compliance with the PEL for silica. Further, the change proposed in the 1989 Air Contaminants USDOL/OSHA rulemaking would increase the allowable silica exposure level in the workplace.

Biological monitoring and standard setting in the USA: a critical appraisal

Occupational exposure limits: A comparative study

Recognition of the carcinogenic properties of ethanol has resulted from comprehensive evidence regarding the effect of consumption of alcohol; indeed, ethanol in alcoholic beverages is now considered a Group 1 carcinogen by the International Agency for Research on Cancer. However, there is little information on the effects of ethanol following exposure via the occupationally relevant routes of inhalation and dermal exposure. This review therefore focuses on these exposure routes, to assess potential carcinogenic risk associated with occupational exposure to ethanol. Inhalatory exposure at the current occupational exposure limit (OEL) for the United Kingdom (1000 ppm ethanol over an 8-h shift) was estimated to be equivalent to ingestion of 10 g ethanol (approximately 1 glass of alcohol) per day. However, in the occupational setting the dose-rate delivery of this amount of ethanol is low, allowing for its rapid and effective elimination, for the majority of individuals. Similarly, while dermal absorption in an occupational setting could potentially add to overall body ethanol burden, additional carcinogenic risk of such exposure is considered negligible. Thus, on balance, there appears little cause to suppose occupational exposure at or below the current OEL associates with any appreciable increase in risk of cancer. However, available occupational exposure data to confirm this view are currently limited. It is also suggested that adoption of a more flexible classification regime, considering risk in the context of hazard and exposure (such as that adopted by the German MAK commission), would represent an improvement over traditional occupational risk assessment practices.

The occupational exposure limit of 2.0 microg/m3 for beryllium has been used in the workplace since the late 1940s. In particular, the adequacy of the American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value (TLV) for beryllium has recently come into question. The symposium "Beryllium: Effect on Worker Health" was convened in September 1999, to bring together leading scientists to present and discuss current research activities on beryllium exposure and chronic beryllium disease (CBD). One of the key questions to be resolved at the symposium was, "Is there a sufficient understanding of exposure and the cause of CBD that would allow us to develop a TLV that we believe would prevent disease?" Seven scientists presented information regarding the current understanding of the disease, possible causes, and ongoing research. The topics were (1) biomonitoring approaches and their relationship with clinical effects, (2) historical and current exposure assessments, (3) sampling methods and aerosol characterization, and (4) epidemiology. Six basic hypotheses regarding the relationship between exposure to beryllium and CBD were generated from the information presented at the symposium. The six hypotheses that are related to issues such as beryllium form, particle size, industrial hygiene practices, extrapulmonary routes of exposure, and genetic susceptibility also appear to be the focus of ongoing and likely future research initiatives. This article summarizes both the presentations made at the meeting and the hypotheses generated. It is expected that an understanding of these issues should explain the inconsistent dose-response relationship observed between exposure and CBD. The ongoing and planned research is anticipated to provide sufficient data within two to three years to develop one or more scientifically sound TLVs for the different chemical forms of beryllium.

Beryllium is an ubiquitous element in the environment, and it has many commercial applications. Because of its strength, electrical and thermal conductivity, corrosion resistance, and nuclear properties, beryllium products are used in the aerospace, automotive, energy, medical, and electronics industries. What eventually came to be known as chronic beryllium disease (CBD) was first identified in the 1940s, when a cluster of cases was observed in workers from the fluorescent light industry. The U.S. Atomic Energy Commission recommended the first 8-hour occupational exposure limit (OEL) for beryllium of 2.0 microg/m3 in 1949, which was later reviewed and accepted by the American Conference of Governmental Industrial Hygienists (ACGIH), the American Industrial Hygiene Association (AIHA), the American National Standards Institute (ANSI), the Occupational Safety and Health Administration (OSHA), and the vast majority of countries and standard-setting bodies worldwide. The 2.0 microg/m3 standard has been in use by the beryllium industry for more than 50 years and has been considered adequate to protect workers against clinical CBD. Recently, improved diagnostic techniques, including immunological testing and safer bronchoscopy, have enhanced our ability to identify subclinical CBD cases that would have formerly remained unidentified. Some recent epidemiological studies have suggested that some workers may develop CBD at exposures less than 2.0 microg/m3. ACGIH is currently reevaluating the adequacy of the current 2.0 microg/m3 guideline, and a plethora of research initiatives are under way to provide a better understanding of the cause of CBD. The research is focusing on the risk factors and exposure metrics that could be associated with CBD, as well as on efforts to better characterize the natural history of CBD. There is growing evidence that particle size and chemical form may be important factors that influence the risk of developing CBD. These research efforts are expected to provide data that will help identify a scientifically based OEL that will protect workers against CBD.

Phenolphthalein is a colorless and odorless crystalline solid; in a powdered form white or pale yellow. It is non-volatile, practically insoluble in water, but it dissolves in ethanol. Phenolphthalein is not known to occur as a natural product. The synthetic substance is used as a pH indicator in laboratories, during work on metal surfaces in galvanizing plants as well as for measuring the saturation of concrete with carbon dioxide. Until the end of the 20th century, it was widely used as a component of non-prescription laxatives – in 1999 FDA removed phenolphthalein from the list of substances considered safe. In 2016 in Poland 255 enterprises were reported to work with phenolphthalein (mainly laboratories) and there were 2500 occupationally exposed people. Phenolphthalein used in therapeutic doses was well tolerated. Only a few side effects were reported: abdominal discomfort, nausea, reduced blood pressure and weakness. Chronic use of phenolphthalein resulted in widening of the colon, reduced thickness of the lining of the mucosa, gastric disorders, dehydration and electrolyte imbalance. In a 13-week study in which phenolphthalein was administered to laboratory animals with diets, mice turned out to be a more sensitive species from rats. Changes in testes and epididymides were observed in males and hypoplasia and bone marrow necrosis in males and females. The results of genotoxicity studies indicated that phenolphthalein acts as a promutagen and exerts a clastogenic effect after metabolic activation. Studies on the effect of phenolphthalein on the reproduction of animals indicated its harmful effect on reproductive functions of males. In the EU, phenolphthalein is classified as a category-2 mutagen and category-2 reproductive toxicant (due to its effect on fertility). A small increase in the risk of colorectal cancer and ovarian cancer was observed in case-control studies in patients using phenolphthalein-based laxatives (especially with intensive use of these agents), but the relationship was not statistically significant. In a 2-year NTP carcinogenicity study a significant increase in the number of benign phaeochromocytomas and adenomas of renal tubular epithelium was observed in male rats. There was also a significant increase in histiocytic sarcomas in mice of both sexes and in malignant lymphomas (of all types) and thymic lymphomas and benign ovarian tumors in females. Based on these experiments phenolphthalein has been identified as a substance reasonably anticipated as human carcinogen (NTP R). The experiment on heterozygous p53 (+/-) mice of both sexes confirmed an increase in lymphoma cases. Phenolphthalein is classified by European Union experts as a category-1B of carcinogenic substances, i.e. known or presumed human carcinogens, however the classification is largely based on animal evidence. The European Chemicals Agency (ECHA) identified phenolphthalein as a substance of very high concern (SVHC). Based on the NTP test results, the additional risk of malignant lymphoma at 8.25 mg/m3 occupational exposure to phenolphthalein for 40 years is 10-4. A concentration of 8 mg/m3 was proposed as the MAC-TWA value for phenolphthalein. Since phenolphthalein is a poorly water-soluble solid, only dust exposure of the substance will occur in the work environment, hence the proposed MAC value should concern the inhalable fraction of the substance. It is proposed to label phenolphthalein as "Carc. 1B" indicating that phenolphthalein is a category-1B carcinogen and "Ft" due to reprotoxicity. There are no bases for establishing the short-term exposure limit value (STEL) and the limit value in biological material (BEI).

Benchmark dose assessment for coke oven emissions-induced telomere length effects in occupationally exposed workers in China

Recommendations of the working group of the Anatomische Gesellschaft on reduction of formaldehyde exposure in anatomical curricula and institutes

Background: The operation of petroleum refineries and petrochemical plants is associated with the emission of organic compounds into the atmosphere, causing local and regional pollution that is harmful to people's health. Objectives: The present study aimed at determining and evaluating personal exposure to hazardous compounds in ambient air of petrochemical complex in south of Iran. Methods: A total of 716 air samples were collected at 18 complexes of an Iranian petroleum complex. A charcoal desorption tube was used to obtain samples from VOCs, and a gas chromatography equipped to flame ionization detector (GC-FID) was used for analyzing the compounds. A gas chromatography-mass spectrophotometer (GC-MS) was used to determine the quantity of the compounds. Results: More than 40 VOCs were detected in all samples and high concentrations of benzene were observed in 12 complexes, but the concentrations of non-carcinogen compounds were below the occupational exposure limit. The greatest amount of exposure to the VOCs occurred in the groups of operators, site workers, analyzers, mechanics, samplers, and site men. Other possible carcinogenic compounds such as epichlorohydrin ethylbenzene were above the occupational permissible exposure limits in a few petrochemical complexes. The mean ratios of benzene to toluene (B/T), (benzene to xylenes) B/X, ethylbenzene to toluene (EB/T), and ethyl benzene to xylene (EB/X) were, respectively, 1.2, 1.9, 0.12, and 1.2 during the summer and were less than the same ratios in the winter. Conclusions: The results of this study revealed that benzene is a major pollutant in workplaces and is distributed throughout petrochemical complexes by wind. Thus, there is an urgent need to control the spread of benzene through air. Photochemical reaction is also an important factor in pollution in different seasons of the year.

Antimicrobial agents have become an essential tool in controlling the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and guidelines on their use have been issued by various public health agencies. Through its Emerging Viral Pathogen Guidance for Antimicrobial Pesticides, the US Environmental Protection Agency has approved numerous surface disinfectant products for use against SARS-CoV-2. Despite their widespread use and range of associated health hazards, the majority of active ingredients in antimicrobial products, such as surface disinfectants, lack established occupational exposure limits (OELs) to assist occupational health professionals in characterizing risks from exposures to these chemicals. Based on established approaches from various organizations, a framework for deriving OELs specific to antimicrobial agents was developed that relies on a weight-of-evidence evaluation of the available data. This framework involves (1) a screening-level toxicological assessment based on a review of the existing literature and recommendations, (2) identification of the critical adverse effect(s) and dose–response relationship(s), (3) identification of alternative health-based exposure limits (HBELs), (4) derivation of potential OELs based on identified points of departure and uncertainty factors and/or modification of existing alternative HBELs, and (5) selection of an appropriate OEL. To demonstrate the use of this framework, a case study is described for selection of an OEL for a disinfectant product containing quaternary ammonium compounds (quats). Three potential OELs were derived for this product based on irritation toxicity data, developmental and reproductive toxicity (DART) data, and modification of an existing HBEL. The final selected OEL for the quats-containing product was 0.1 mg/m3, derived from modification of an existing HBEL. This value represented the lowest resulting value of the three approaches, and thus, was considered protective of irritation and potential DART.