1,1,2-Trichlorethan. MAK-Begründung, Nachtrag (original) (raw)
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1,1,2,2-Tetrachlorethan. MAK-Begründung, Nachtrag
2020
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re-evaluated the maximum concentration at the workplace (MAK value) and the carcinogenicity classification of 1,1,2,2tetrachloroethane [79-34-5]. Available publications and unpublished study reports are described in detail. The critical effect is liver toxicity in humans, rats and mice. Valid inhalation studies are not available. After oral application, 1,1,2,2-tetrachloroethane is a liver tumour promoter and induces neoplastic nodules and carcinomas in rats and mice. The NOAEL for carcinogenic effects in rats is 43 mg/kg body weight. 1,1,2,2-Tetrachloroethane is not genotoxic. The mechanism responsible for tumour development in the liver is most likely the formation of reactive metabolites, e.g. dichloroacetic acid and free radicals. As the primary mode of action is non-genotoxic, 1,1,2,2-tetrachloroethane is classified in Carcinogen Category 4. After 14-week oral application, the NOAELs for liver effects are 20 and 80 mg/kg body weight for rats and male mice, respectively. Based on the NOAEL of 20 mg/kg body weight, a MAK value of 2 ml/m 3 is derived. Irritation is not expected to occur at this concentration because 10-minute exposure of volunteers to 13 ml/m 3 did not induce local effects. As the critical effect of 1,1,2,2-tetrachloroethane is systemic and its half-life is not known, the assignment to Peak Limitation Category II and the excursion factor of 2 are retained. 1,1,2,2-Tetrachloroethane remains classified in Pregnancy Risk Group D because sufficient data for developmental toxicity are not available. 1,1,2,2-Tetrachloroethane can be absorbed via the skin in toxicologically relevant amounts and remains designated with "H". A sensitizing potential is not expected from the data available.
1,1-Dichlorethan. MAK-Begründung, Nachtrag
2020
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re-evaluated 1,1-dichloroethane [75-34-3] considering all toxicological end points. The critical effect is kidney toxicity. Inhalation of 1000 ml/m 3 led to histopathologic injury to the kidneys, increased serum urea and creatinine after three-month exposure of cats. A NOAEL of 500 mg/kg body weight and day for changes in the urinary excretion of acid phosphatase and N-acetylglucosaminidase was found in rats after 13-week oral exposure. Based on the NOAEC of 500 ml/m 3 , the maximum concentration at the workplace (MAK value) has now been lowered to 50 ml/m 3 taking into account the increased respiratory volume at the workplace because the blood:air partition coefficient of 1,1-dichloroethane is > 5 (see List of MAK and BAT Values, Section I b and I c). The same MAK value is obtained based on the oral NOAEL of 500 mg/kg body weight and day. As a systemic effect is critical, Peak Limitation Category II and the default excursion factor of 2 are retained. MAK-Begründungen-1,1-Dichlorethan MAK-Wert (2019) 50 ml/m 3 (ppm) ≙ 210 mg/m 3 Spitzenbegrenzung (2001) Kategorie II,
Pentachlorethan. MAK-Begründung
2020
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated pentachloroethane [76-01-7] considering all toxicological end points. MAK-Begründungen-Pentachlorethan MAK-Wert (2019) 2 ml/m 3 (ppm) ≙ 17 mg/m 3 Spitzenbegrenzung (2001) Kategorie II, Überschreitungsfaktor 2 Hautresorption (2019)
2020
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated data for cyanuric chloride [108-77-0] considering all toxicological end points. Unpublished study reports and publications are described in detail. Cyanuric chloride is irritating to the nose, eyes and throat of workers (according to earlier studies at about 0.3 mg/m 3) and corrosive to the skin and eyes of rabbits and rats. The model best suited to estimate a long-term exposure threshold for workers with respect to lung function loss is based on a calculated cumulative exposure of 0.3 mg/m 3-years. An irritant effect was not reported. As wearing a protective mask was obligatory for workers exposed to higher cyanuric chloride concentrations, the extent to which the workers in this study were exposed is unclear. No NOAEC for repeated exposure of humans is known. A 90-day inhalation study with rats observed a small increase of inflammatory cells in the nose without other changes in the mucosa at 0.032 ml/m 3 (0.25 mg/m 3); the NOAEC is 0.0065 ml/m 3 (0.05 mg/m 3). A maximum concentration at the workplace (MAK value) of 0.001 ml/m 3 has been established based on the rat NOAEC after considering extrapolation to humans, a possible increase of effects with long-term exposure and the preferred value approach. Cyanuric chloride is classified in Peak Limitation Category I because of its local effects. As the human odour threshold is about 0.0025 ml/m 3 , an excursion factor of 2 is set, although a NOAEC has not been established for sensory irritation in humans. A developmental toxicity study in rats determined a NOAEC of 50 mg cyanuric chloride/kg body weight and day, which corresponds to a concentration of about 11.5 ml/m 3 after toxicokinetic scaling; the margin to the MAK value is sufficiently large. Therefore, damage to the embryo or foetus is unlikely when the MAK value is not exceeded and cyanuric chloride is assigned to Pregnancy Risk Group C. Cyanuric chloride is not mutagenic in vitro or clastogenic in vivo and no studies in germ cells are available. No carcinogenicity study was performed. Cyanuric chloride shows a skin sensitizing potential in animals and is therefore designated with "Sh" (for substances which cause sensitization of the skin). Data relating to a potential sensitization of the airways are not conclusive. The dermal absorption is expected to be low at non-irritating concentrations and does not contribute significantly to systemic toxicity. MAK-Begründungen-Cyanurchlorid MAK-Wert (2019) 0,001 ml/m 3 (ppm) ≙ 0,0076 mg/m 3 Spitzenbegrenzung (2019) Kategorie I, Überschreitungsfaktor 2
Methylamin. MAK-Begründung, Nachtrag
The MAK Collection for Occupational Health and Safety, 2020
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re-evaluated methylamine [74-89-5]. The critical effect is irritation of the nasal airways as observed in a 2-week study in rats with a NOAEC of 75 ml/m 3. The RD 50 data for methylamine show that its irritation potency is lower than that of other aliphatic amines with a MAK value of 2 ml/m 3. Overall, a MAK value of 5 ml/m 3 has been derived from these data. As the critical effect is local irritation, Peak Limitation Category I has been retained. An excursion factor of 2 has been set by analogy with trimethylamine and cyclohexylamine. For both amines, a momentary value (ceiling limit) was set at two times the MAK value. Therefore, the momentary value of 10 ml/m 3 for methylamine has been retained. The NOAELs for developmental toxicity obtained in an oral screening study in rats (230 mg/kg body weight and day) and a teratogenicity study with i.p. application in mice (155 mg/kg body weight and day) are sufficiently high. Therefore, damage to the embryo or foetus is unlikely when the MAK value is not exceeded and methylamine is classified in Pregnancy Risk Group C. Methylamine is not genotoxic. Carcinogenicity studies are not available. According to calculations, methylamine is not taken up via the skin in amounts that can induce systemic effects. There are no data that show that methylamine is a skin or airway sensitizer.
Vinylacetat. MAK-Begründung, Nachtrag
2020
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re-evaluated vinyl acetate [108-05-4]. The critical effects are nasal irritation and the induction of nasal tumours observed in a 2-year study in rats. From mechanistic studies it was concluded that acidification by acetic acid formed metabolically from vinyl acetate is responsible for the cell proliferation in the nasal epithelia and probably also for clastogenicity and DNA-strand breaks. Acetaldehyde formed from vinyl acetate induces DNA-protein cross-links and clastogenicity. The DNA damage can lead to tumours after cell proliferation which is induced at cytotoxic concentrations of vinyl acetate. Non-linear dose-response curves were obtained in several carcinogenicity studies as well as in genotoxicity studies in vitro. This implies that the genotoxicity of vinyl acetate is not primarily responsible for the induction of nasal tumours. As they occurred only at concentrations that damaged the nasal epithelia of rats and NOAECs for this effect as well as for acidification in the nasal epithelia and for sensory irritation in humans could be derived, vinyl acetate has been classified in Carcinogen Category 4. According to a PBPK model, the NOAEC for acidification in the nasal epithelia of humans at the workplace is 19 ml/m 3. In volunteer studies with limited validity, slight sensory irritation was observed at 20 ml/m 3. Therefore, a maximum concentration at the workplace (MAK value) of 10 ml/m 3 has been derived for vinyl acetate. As the critical effect is local irritation, the substance has been assigned to Peak Limitation Category I. To avoid local irritation by short-term peaks, an excursion factor of 2 and a momentary value of 20 ml/m 3 have been set. The NOAEC for developmental toxicity in rats of 200 ml/m 3 and the NOAEL of 477 mg/kg body weight obtained from a 2-generation study are sufficiently high. Therefore, damage to the embryo or foetus is unlikely when the MAK value is not exceeded and vinyl acetate is classified in Pregnancy Risk Group C. Vinyl acetate is clastogenic in vitro. It is a clastogen in vivo when given intraperitoneally at high doses but not after inhalation or when administered with the drinking water. It did not induce micronuclei in spermatids of rats. According to the results of an in vitro study, vinyl acetate is labelled with "H" for substances which can be taken up via the skin in toxicologically relevant amounts. There are no data that show that vinyl acetate is a skin or airway sensitizer. MAK-Begründungen-Vinylacetat MAK-Wert (2019) 10 ml/m 3 (ppm) ≙ 36 mg/m 3 Spitzenbegrenzung (2019) Kategorie I, Überschreitungsfaktor 1 Momentanwert (2019) 20 ml/m 3 (ppm) ≙ 71 mg/m 3 Hautresorption (2019) H Sensibilisierende Wirkung-Krebserzeugende Wirkung (2019) Kategorie 4 Fruchtschädigende Wirkung (2019) Gruppe C Keimzellmutagene Wirkung-BAT-Wert-Molmasse 86,09 g/mol Löslichkeit bei 20 ℃ 20 g/l Wasser (ECHA 2019) log K OW bei 25 ℃ 0,73 (ECHA 2019) Dampfdruck bei 20 ℃ 113 hPa (ECHA 2019) 1 ml/m 3 (ppm) ≙ 3,572 mg/m 3 1 mg/m 3 ≙ 0,280 ml/m 3 (ppm)
Kresol (alle Isomere). MAK-Begründung, Nachtrag
2020
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re-evaluated the Carcinogen Category and evaluated the maximum concentration at the workplace (MAK value) and the Pregnancy Risk Group of all cresol isomers (o-cresol [95-48-7], m-cresol [108-39-4], p-cresol [106-44-5] and the mixture of isomers [1319-77-3]). Available publications are described in detail.
Dichloressigsäure und ihre Salze. MAK-Begründung, Nachtrag
2020
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated the developmental toxicity of dichloroacetic acid [79-43-6] and its salts. In 2019, a maximum concentration at the workplace (MAK value) of 0.2 ml/m 3 , corresponding to 1.1 mg/m 3 , was set for dichloroacetic acid. Accordingly, a MAK value of 1.1 mg/m 3 for the inhalable fraction, measured as the acid, has been set for the salts. The critical effects are irritation, carcinogenicity in the liver of rats and mice as well as neurotoxicity.