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Bromoethane
Sławomir Gralewicz, Dorota Wiaderna
Bromoethane is a colorless, volatile, flammable liquid. Bromoethane is an alkylating agent used in organic syn-thesis, in the manufacture of pharmaceuticals. It has been used as a refrigerant and solvent. In the last century bromoethane was used as an anesthetic.
Bromoethane is the eyes, skin and mucous membranes tract irritant. The vapor can cause hepatic, cardiovascular and nervous system damage. The substance is mutagenic to Salmonella typhimurium TA100, TA1535 strain and Escherichia coli both with and without metabolic activation.
The results of 2-year studies showed that inhalation exposure to bromoetane at the concentration of 445 ÷ 1780 mg/m³ (100 ÷ 400 ppm) significantly increases the number of adrenal glands, lungs and uterus tumors. Bromoethane is classified by ACGIH to A3 group and by NTP to A2 group.
The TLV value for bromoethane was estimated on the basis of 2-year studies (rats and mice). The concentration of 890 mg/m³, 5 days/week, and 6h/day is a NOAEL value. The following uncertainty factors were used: 2 for differences between individuals, 2 for differences between species and modifying factor-3. Based on these data, the TLV value for bromoethane is proposed as 50 mgm/m³, STEL value as 100 mg/m³. Due to dermal absorption bromoethane should be mark as Sk.
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Chlorodifluorometan
Konrad Rydzyński, Jolanta Gromadzińska
Chlorodifluorometan (CF22) is a colorless, nonflammable gas with very low toxicity. FC22 is used as an aerosol Extremely high vapors concentrations (177 g/m³) may cause headache, nausea and shortness of breath. Some epidemiological reports have shown excess irregular heartbreakin exposed population.
Based on the NOAEL value obtained in an experimental study (35400 mg/m³) and appropriate uncertainty fac-tors, a TLV has been calculated and proposed at 3000 mg/m³.
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N-Ethylmorpholine
Sławomir Czerczak, Maciej Stępnik
Under normal conditions of pressure and temperature N-ethylmorpholine (N-EM) constitutes a colorless liquid with ammonia-like odor.
In industry it is used as urethane foam catalyst, intermediate for dyestuffs, pharmaceuticals, rubber accelerators, emulsifying agents, as well as a pH regulator and a solvent for dyes, resins, oils.
N-EM can be absorbed through unbroken skin, digestive and respiratory tract.
It is relatively poorly toxic after oral and inhalation exposure. Corneal, nasal and tracheal irritation have been reported. A direct mutagenic effect was found with N-EM in mutagenicity tests with Salmonella typhimurium strains TA1535 and TA100, with and without metabolic activation. There are no scientific data indicating car-cinogenic, teratogenic or developmental toxicity of N-EM. According to existing data irritation to the eyes (cor-neal oedema), nose, and throat are the most important adverse effects.
Corneal edema was observed in workers exposed at 188 mg/m³ (40 ppm) and more N-EM for several hours. The lesions appeared near the end of the work shift and cleared within 3 to 4 hr after cessation of exposure.
Based on the study and taking into account the following uncertainty factors: 2 for calculation of NOAEL from LOAEL, 2 for differences in susceptibility of individuals, and 2 for incompleteness of data, the TLV value for N-ethylmorpholine is proposed as 23 mg/m³ and the STEL value as 46 mg/m³.
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Carbendazim
Krystyna Sitarek
Carbendazim is the most widely used representative of the benzimidazole family of fungicides. It is also the main metabolite of benomyl in mammals the degradation product of benomyl in the environment. This chemical is well absorbed after oral exposure. The absorption by male rats administered a single oral dose of 12 mg/kg 14C-carbendazim was determined to be 85%. The main metabolite of this compounds in urine is methyl 5-hydroxy-2-imidazolecarbamate. It is not a carcinogenic agent.
The Expert Group for Chemical Agents has established an 8-hour TWA value of 10 mg/m³ and suggested addi-tional notation: Ft (fetotoxic substance).
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2,4-Dichlorophenoxyacetic acid
Krystyna Sitarek
2,4-Dichlorophenoxyacetic acid (2,4-D) and its amine salts or esters are used as herbicides. 2,4-D has moderately acute toxicity for mammals. Acute oral LD50 values for rats are between 375 to 666 mg/kg b.w.
The available information has been inadequate for an assessment of the mutagenic activity and carcinogenic potential of 2,4-D. The Expert Group for Chemical Agents has established an 8-hour TWA value of 7 mg/m³. No STEL and BEI have been recommended.
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4-Methylpentan-2-one
Andrzej Sapota, Małgorzata Skrzypińska-Gawrysiak
4-Methylpentan-2-one (methyl isobutyl ketone, hexone, MIBK) is a clear liquid having nice odour. It is mainly used as a solvent, extracting agent and in chemical synthesis. MIBK is also a synthetic odorant for use in food industry.
In accordance with the classification accepted in the European Union, MIBK belongs to harmful compounds (Xn). It has irritating action on respiratory tract, weakly irritating on eyes and practically does not affect skin. MIBK demonstrates neither mutagenic nor genotoxic, embriotoxic or teratogenic action. On the basis of the results of investigations on animals, weak neurobehavioral effects were demonstrated, while the toxic effects on organs were limited only to one species and one sex (female rats – renal tubules granular degeneration).
Occupational exposure to MIBK occurs through inhalation and dermal contact during production and application of this compound.
In volunteers exposed 2 ÷ 7 h to MIBK of concentrations 80 ÷ 410 mg/m³ there were observed symptoms of eyes, nose and throat irritation, nausea, dizziness, headache and “odour discomfort” and their degree intensified during exposure to the compound of higher concentrations.
The results of investigations performed on 25 volunteers (including 12 women) by Dick et al. (1992) were accepted as basis for new MAC value determination. In about 20 ÷ 30% of the investigated subjects after 4 h exposure to MIBK vapours of 410 mg/m³ concentration, symptoms of eyes and throat irritation, headache and nausea were observed. No behavioral effects measured with 5 different tests were demonstrated in the examined subjects. This concentration (410 mg/m³) was accepted as LOAEL value.
To calculate MAC value the following uncertainty factors were accepted: A associated with individual sensitivity differences in humans of the value 2 and B resulting from the application of LOAEL value calculations instead of NOAEL value = 2. After substitution to the formula the MAC value 410/4 = 102,5 mg/m³ is obtained.
We suggest to accept the MAC MIBK value equal to 83 mg/m³ as mean value expressed by 8 h worktime, according to the value accepted in the European Union.
In respect of weak irritating action of the compound, we also suggest to accept STEL value, which after substi-tuting to the appropriate formula, should be contained within 193 ÷ 295 mg/m³. We propose to accept STEL 4-methylpentan-2-one value = 200 mg/m³. It is the MAC value so far in force in Poland.
Both values should enough protect workers against potential irritating action and other toxic symptoms of systemic action.
Due to significant discrepancies in the accepted BEI values at various MAC values in the USA and Germany it was decided not to determine BEI 4-methylpentan-2-one value.
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Tetrahydrofuran
Jolanta Skowroń
Tetrahydrofuran (THF) is a liquid smelling of acetone; it is obtained by catalytic hydrogenation of malonyl an-hydride or furane and catalytic dehydratation of 1,4-butandiole. THF is used as a solvent of oils, fats, natural and synthetic resins and polymers, especially vinyl polychloride. It is used to produce varnishes, inks, paints and glues, in synthesis of fuels, vitamins, hormones, pharmaceuticals, synthetic perfumes, insecticides and magnetic cassettes. It is an intermediary compound in chemical syntheses.
Data concerning THF toxicity are scarce. In inhalatory exposition THF in low concentrations causes headaches and irritation of oral and nasal mucosa. Eye irritation has been observed after exposure to THF in concentrations approximating 15 000 mg/m³. Concentration of approx. 75 000 mg/m³ causes general anesthesia, accompanied by lowering of blood pressure and tachypnea. Prolonged exposure to THF may result in dermatitis.
Acute poisonings in humans have not been observed. In experiments performed on animals it shows medium toxicity. DL50 value for animals after intragastrical administration varies between 1650 and 6210 mg/kg. The value of medial lethal concentration (CL50) for almost all species exposed for 3 hours or shorter is above 61 740 mg/m³ (21 000 ppm).
Single inhalatory exposure (up to 3 hours) of rats to THF at concentrations between 290 and 14 700 mg/m³ has usually resulted in slight, local irritation of the skin and mucose membranes. Increasing concentrations to 24 000 ÷ 191 000 mg/m³ caused somnolence, reduced respiratory rate, cyanosis, changes in the liver, kidneys, spleen and lungs.
After repeated exposure of rats to THF at concentrations between 294 and 590 mg/m³, insignificant irritating effect on mucous membranes of trachea and nose were detected. Concentration of 1000 ÷ 2000 mg/m³ caused loss in the rats’ bodyweight, slight histological changes and lowering of blood pressure. Exposure lasting for 12 ÷ 18 weeks at concentrations approximating 2900 mg/m³, apart from an irritating effect, resulted in changes in the liver, damage of trachea epithelium and increase in the activity of acethylcholinesterase in the muscles. Exposing rats to THF at concentrations between 5880 and 8800 mg/m³ caused, among others, loss in body-weight, impairment of the liver functions, slight histological changes and leucocytosis, lowered blood pressure, as well as changes in the lungs. The highest concentration of THF (14 700 mg/m³) to which rats were exposed for 12 ÷ 13 weeks, apart from the effects mentioned before, also caused ataxia, impairment of the liver and lungs.
THF did not display a mutagenic effect, and data concerning the possibility of chromosomal aberrations are not certain and not complete. THF might be embryotoxic in mice.
Toxicokinetic data are very scarce. It is known that THF is quickly absorbed in the respiratory tract. After inha-latory exposure of rats, THF was detected in the brain and fat tissue. Data concerning THF metabolism in vitro suggest the possibility of hydroxylation by means of microsomal enzymes and the possibility of splitting the THF ring. THF half-life in humans was 30 minutes. No data about the mechanism of THF toxicity were found in literature.
The authors of this study suggest reducing the MAC value accepted in Poland from 600 mg/m³ to 150 mg/m³, and the MAC (STEL) value from 750 mg/m³ to 300 mg/m³. The changes are suggested on the basis of inhalatory experiments on animals, where THF caused irritation of mucous membranes at concentrations of approx. 600 mg/m³.
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