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2-Chlorobuta-1,3-dien. Documentation
Andrzej Starek, Wiesław Szymczak
2-Chlorobuta-1,3-dien (chloroprene) is volatile and inflammable liquid with a characteristic, pun-gent odour. It is mainly used as a monomer in the production of neoprene elastomers.
Chloroprene is a harmful compound. High vapour exposure may cause irritation of the eyes and respiratory tract, as well as depression of the central nervous system. Chloroprene exerts embryo-toxic, teratogenic, mutagenic, and multiorgan toxic effects (hepatotoxicity, nephrotoxicity, pneu-motoxicity). Chloroprene is carcinogenic in mice and rats. Limited data on the carcinogenicity of chloroprene in humans are available. An increased risk of liver, lung or digestive tract cancers has been reported in some studies. The International Agency for Research on Cancer has classified chloroprene as a possible human carcinogen (group 2B) on the basis of positive studies in experi-mental animals.
The MAC (TWA) value for chloroprene was calculated on the basis of Melnick et al.'s (1999) chronic study conducted on mice and rats. As a critical effects taken into account tumor induction in lung (cancer) and liver (hemangiosarcoma and hepatocellular carcinoma). The dependence of the risk of lung cancer (female mice) and hemangiosarcoma (male mice), as well as hepatocellular carcinoma (female mice) on the concentration of chloroprene in workplace air was esta blished on the basis of a two-stage dose–response model. The risk of subjects exposed to chloroprene in the concentration of 2 mg/m³ developing lung cancer within 40 years was calculated as ≈ 7• 10-3.
The MAC (TWA) value of 2 mg/m³ and STEL value of 6 mg/m³ are recommended. Moreover, “I” (irritant) and a possible human carcinogen (Cat. 2) notation are also recommended.
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2-Diethylaminoethanol. Documentation
Małgorzata Kupczewska–Dobecka
2-Diethylaminoethanol is a colorless, light yellowish organic flammable liquid with an amine-like odor. The hygroscopic substance is micsible with water in all proportions. The vapor pressure is about 1.8 hPa at 20 °C.
2-Diethylaminoethanol is rapidly absorbed via the oral route. It is presumably absorbed by dermal and inhalation routes of administration. The LD50 for the rat after oral administration was 1320 mg/kg bw. The main clinical signs described were apathy and dyspnea. After inhalation of vapors of 2-diethy-laminoethanol an LC50 of 4600 mg/m³/4 h was estimated in rats. Severe signs of irritation were observed, e.g. mucous membrane irritation and dyspnea. A dermal LD50 in guinea pigs was reported to be 885 mg/kg bw.
2-Diethylaminoethanol was corrosive to the skin of rabbits; since the pH was measured to be 11.5 (100 g/l) at 20 °C. The potential for severe damage to the eyes can be expected. 2 Diethyla-minoethanol was not sensitizing to the skin in studies with guinea pigs.
Repeated exposure of rats to 2-diethylaminoethanol vapors (up to 365 mg/m³) for 14 weeks caused local toxicity (irritation) at the site of contact, namely, the upper respiratory tract and the eyes; however, systemic toxicity was not observed (NOAEC, systemic toxicity, 365 mg/m³ or 76 ppm). After inhalation exposure, the main symptom described was respiratory irritation which led to noises called rales and irritation of the eyes. The LOAEC for local toxicity (irritation) to the res-piratory tract was 120 mg/m3 (25 ppm) and the NOAEC for local toxicity was 53 mg/m³ (10 ppm) based on histopathological effects in the nasal cavity. 2-Diethylaminoethanol gave no evidence of in vitro mutagenic activity nor in vivo clastogenic potential. Repeated exposure of rats to 2-diethylaminoethanol vapors (365 mg/m³) for 14 weeks did not cause any adverse effects to the reproductive organs when administered by inhalation. In pregnant rats even the highest concentration tested of 486 mg/m³, which already produced maternally toxic effects, did not lead to adverse developmental effects. In a limited study, 2-diethylaminoethanol was not carcinogenic in rats when given by feed (tested up to approximately 11-400 mg/kg/day).
In setting exposure limits, the results of a subchronic inhalation exposure in rats were considered. Based on the NOAEC value for histopathological effects in the nasal cavity (53 mg/m3) and the relevant uncertainty factors, a MAC (TWA) value was calculated at 13 mg/m³. The MAC (TWA) and MAC (STEL) values of 13 mg/m³ and 26 mg/m³, respectively were suggested. Because 2-diethylaminoethanol has been shown to penetrate the skin in amounts sufficient to induce systemic toxicity and exerts reproductive toxicity, a skin (Sk) and corrosive (C) notations are considered appropriate.
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N,N-Dimethylformamide. Documentation
Agnieszka Jankowska, Sławomir Czerczak
N,N-Dimethylformamide (DMF) is a colorless, hygroscopic liquid with a faint ammonia-like odor. It is predominately used as a solvent for liquids and gases in synthesis of fine chemicals, polyacrylonitrile fibre and in petrochemical industry. N,N-Dimethylformamide is also employed as a solvent in adhesives, printing inks and polyurethane coatings to artificial leather production.
In Poland 20 workers were exposed to N,N-dimethylformamide in concentration above 10 mg/m³ (MAK) in 2007. Respiratory tract and skin are the major routes of occupational exposure to N,N-dimethylformamide. The uptake from the respiratory tract was 90%. Percutaneous absorption of N,N-dimethylformamide can occur. The absorption rate is 9 mg/cm²/h following dermal application of liquid substance. Systemic effects were observed after dermal exposure to N,N-di-methylformamide (liver failure). Subjective responses to N,N-dimethylformamide including eyes and upper respiratory tract irritation were observed in humans. Alcohol intolerance is a characteristic effect following exposure to this substance. Symptoms may include a sudden facial flush, tightness of the chest, dizziness and nausea. A slight to moderate skin and eye irritation and hepatotoxicity of N,N-dimethylformamide occured in animals studies. N,N-Dimethylformamide indicated no sensitization potential. Developmental toxicity and teratogenicity occurred in rats and rabbits in inhalation, oral or dermal administration studies and in mice following oral administration. N,N-Dimethylformamide did not show genotoxic potential in various test systems in vivo and in vitro. N,N-dimethylformamide is not classifiable as to its carcinogenicity to humans (Group 3) according to The International Agency for Research on Cancer (IARC). Hepatotoxicity was assumed as a critical effect. In setting the exposure limit, the result of 2 years inhalation study in rats were considered. Based on NOAEL value of 75 mg/m³ and an appropriate uncertainty factors, a MAC value has been calculated at 12,5 mg/m³. A MAC value for N,N-dimethylformamide was proposed to be established at the same level as OEL recommended by SCOEL, it means 15 mg/m³. STEL value was set at 30 mg/m³ considering irritation potential. Biological monitoring is highly recommended because of extensive dermal absorption. BEI was set at 15 mg N-methylformamide/l urine. Considering evidence on skin absorption additional determination with Sk letters was proposed. With regard to and fetotoxic effects of formamide in laboratory animals an Ft notation was considered. Considering irritation potential determination with I letter was proposed.
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2-Methoxyethanol. Documentation
Jadwiga A. Szymańska, Elżbieta Bruchajzer
2-Methoxyethanol (2-ME) is a colorless liquid with a mild odor. 2-Methoxyethanol is used as a solvent in many products (e.g. dyes, resins, lacquers, inks, nitrocellulose, acethylcellulose). It has been used as a perfume fixative and a jet fuel de-icing additive. Industries using 2-methoxyethanol has included the printing, painting, furniture finishing, coating, and leather industries. 2-ME is used in photolithographic and photographic processes.
No people have been expose in Poland to 2-methoxyethanol concentration in the air exceeding the TWA value which is 15 mg/m³ (data from 2000-2007).
Only limited information on the acute toxic effects of 2-methoxyethanol in human is available. These information come largely from case reports with accidental poisoning. In cases of uninten-tional ingestion of 2-ME (dose of 100 ml/man) muscular weakness, ataxia, nausea, vomiting and mental confusion and metabolic acidosis were apparent.
Haematologic abnormalities have been noted in human (26% of workers) after inhalation exposure on 2-ME at the concentration of 12 mg/m³. Epidemiologic studies have demonstrated that 2-methoxyethanol at the concentration of 17 ÷ 26 mg/m³ caused reproductive and fetotoxic effects.
The oral LD50 values for 2-methoxyethanol in rats were between 2370 and 3400 mg/kg of body weight. Short-term and repeated administration of 2-ME to animals resulted in haematologic ab-normalities and reproduction consequences.
There was no evidence for mutagenic, genotoxic and carcinogenic activity of 2-methoxyethanol.
No observed embriotoxicity and teratogenic effects after exposure pregnant female rats and mice on 2-methoxyethanol (during organogenesis) at the concentration 31 mg/m³. Fetotoxic effects on rodent embryos after inhalation on 2-ME at the concentration 155 ÷ 930 mg/m³ have been reported.
2-Methoxyethanol is readily absorber through the skin, lungs, and gastrointestinal tract. The metabolic transformation of 2-ME gives two primary metabolites: 2-methoxyacetic acid (MAA) and 2-methoxyacethyl glicine. A major portion of a dose is eliminated as a MAA in urine. The excretion of MAA is slow, with a half-life of about 77 h in man.
The MAC-TWA values was calculated on the basis of haematotoxic effect in human. The Expert Group for Chemical Agents suggest reducing the MAC-TWA (OEL) value accepted in Poland from 15 mg/m³ to 3 mg/m³. No MAC-STEL has been recommended. The value of BEI is proposed (8 mg of 2-methoxyacetic acid per gram of urinary creatinine). Notation “Sk” (substance absorbed through the skin) and “Ft” (fetotoxicity) are recommended.
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2-Methoxyethyl acetate. Documentation
Jadwiga A. Szymańska, Barbara Frydrych
2-Methoxyethyl acetate (2-MEA) is a colorless liquid with a pleasant odor. 2-MEA does not occur naturally, it is produced from 2-methoxyethanol by esterification. 2-Methoxyethyl acetate is used in photographic films, lacquers, and textile printing and as a solvent for waxes, oils, various gums and resins, cellulose acetate, and nitrocellulose.
The chemical structure and solubility properties of 2-MEA suggest that this substance is efficiently absorbed by all routes and rapidly distributed to the different tissues. Next it is rapidly and extensively hydrolysed to 2-methoxyethanol by carboxyl esterases in the nasal epithelium, liver, kidneys, lungs, and blood. The dominating metabolic pathway of 2-methoxyethanol is oxidation via methoxyacetaldehyde to methoxyacetic (MAA), which is eliminated in urine.
Repeated short-term exposures to 2-MEA via gavage, skin application, or inhalation have similar effects in several animal species including reduced thymus, spleen and testes weight, lower counts of white and red blood cells and platelets, lower hematocrit, haemoglobin levels and bone marrow cellularity, higher numbers of immature granulocytes.
2-MEA has been negative in all genotoxicity and carcinogenicity studies but it has shown reproductive toxicity in laboratory animals.
The proposed MAC-TWA (OEL) value was calculated at 5 mg/m³. No MAC-STEL has been recommended. The value of BEI is proposed (8 mg of 2-methoxyacetic acid per gram of urinary creatinine). Notation “Sk” (substance absorbed through the skin) and “Ft” (fetotoxicity) are recommended.
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