The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the developmental toxicity of acetone. Available unpublished study reports and publications are described in detail. The maximum concentration at the work place (MAK value) of acetone is 500 ml/m 3 , based on the irritant effect and the state of health of volunteers. In a development toxicity study after inhalation exposure no teratogenic effects were found in the mouse up to 6600 ml/m 3 . The diversity of malformations was increased at 11 000 ml/m 3 in the rat, and there was a linear trend for variations of asymmetric sternebrae and delayed ossifications of the sternum. Reduced foetal weights were found in both rats and mice. The NOAEC for developmental toxicity in rats and mice is 2200 ml/m 3 ; the NAEC (no adverse effect concentration) could be even higher than 2200 ml/m 3 . As a greater diversity of malformations was observed in rat pups at concentrations that caused only slight maternal toxicity, and only a four‐fold margin lies between the NOAEC for developmental toxicity and the MAK value of 500 ml/m 3 , damage to the embryo or foetus cannot be excluded after exposure to concentrations at the level of 500 ml/m 3 and acetone is assigned to Pregnancy Risk Group B. In view of the NOAEC for developmental toxicity of 2200 ml/m 3 , prenatal toxicity is not to be expected at acetone concentrations of about 200 ml/m 3 or below, corresponding to the definition of Pregnancy Risk Group C.
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has derived a maximum concentration at the work place (MAK value) for calcium hydroxide, considering all toxicity endpoints. Available publications are described in detail. The critical effect of calcium hydroxide is irritation of eyes and upper airways. From studies in volunteers with calcium oxide, which is hydrolysed in aqueous media to calcium hydroxide, a MAK value of 1 mg/m 3 for the inhalable fraction is derived. Since local effects are critical, calcium hydroxide is assigned to Peak Limitation Category I and as there were no irritation effects after 20 minutes exposure to 2 mg/m 3 , an excursion factor of 2 is set. Studies with the read‐across calcium oxide show that damage to the embryo or foetus is unlikely when the MAK value for calcium hydroxide is observed, and the substance is assigned to Pregnancy Risk Group C. Calcium hydroxide is neither genotoxic nor carcinogenic. Skin contact is not expected to contribute significantly to systemic toxicity or to lead to sensitization.
MAK Value Documentation for Methyl acetate The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the work place (MAK value) of methyl acetate of 100 ml/m 3 considering the critical endpoint respiratory tract irritation. A 28‐day study with rats shows a NOAEC for degeneration and necrosis of the olfactory epithelium of 350 ml/m 3 . A chronic NAEC of 125 to 167 ml/m 3 can be extrapolated. Since 2014, the Commission uses an empirical approach to set MAK values for substances with critical effects on the upper respiratory tract or the eyes. According to this approach, the NAEC would correspond to a concentration of 63 to 84 ml/m 3 for work place air. However, acetic acid resulting from the local enzymatic cleavage of methyl acetate by carboxylesterases is responsible for the effects to the olfactory epithelium, and not the substance itself. Thus, the activity of rat and human carboxylesterases is decisive in the respiratory tract irritation of methyl acetate. Based on a comparative analysis on vinyl acetate, in which rat olfactory enzyme activity was shown to be almost equivalent to that in humans, the same is assumed for methyl acetate and the interspecies extrapolation step is deemed unnecessary. The MAK value is retained at 100 ml/m 3 . As local effects are critical, the assignment to Peak Limitation Category I and the excursion factor of 4 are also retained.
MAK Value Documentation for Ethyl acrylate 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) of ethyl acrylate of 5 ml/m 3 , considering all toxicity endpoints. Available unpublished study reports and publications are described in detail. The critical effect of ethyl acrylate is irritation of eye and nose in humans and the olfactory mucosa in rats and mice. The chronic NOAEC in rats is 5 ml/m 3 . Since 2014 the Commission uses an empirical approach to set MAK values for substances with critical effects on the upper respiratory tract or the eyes. Accordingly, the MAK value has to be lowered to 2 ml/m 3 , which is confirmed in a recent volunteer study with a NOAEC of 2.5 and a LOAEC of 5 ml ethyl acrylate/m 3 . As local effects are critical, the assignment to Peak Limitation Category I and the excursion factor of 2 are confirmed. Developmental toxicity studies with ethyl acrylate show that damage to the embryo or foetus is unlikely if the MAK value is observed, and the assignment to Pregnancy Risk Group C is retained. Ethyl acrylate is not genotoxic in vivo and not carcinogenic. Skin contact may contribute significantly to systemic toxicity and ethyl acrylate is designated with an “H” notation. The available data confirm that the substance is a skin sensitizer and the designation with “Sh” is retained. There are no data concerning the potential for respiratory sensitization.
MAK Value Documentation for Trimethylamine The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the work place (MAK value) of trimethylamine of 2 ml/m 3 , considering the endpoints local and systemic toxicity as well as developmental toxicity. Available publications are described in detail. Daily exposure of rats to trimethylamine for 14 days resulted in inflammation of the respiratory epithelium at 74 ml/m 3 , the lowest concentration tested. Since 2014, the Commission uses an empirical approach to set MAK values for substances with critical effects on the upper respiratory tract or the eyes. According to this approach, the MAK value would have to be lowered to 1 ml/m 3 . However, several data show, that the previous MAK value can be retained. Workers reported no irritation at 5 ml trimethylamine/m 3 . In addition cyclohexylamine and dimethylamine with a MAK value of 2 ml/m 3 are used as a read‐across due to similar alkalinity and RD 50 values, and in a recent volunteer study a NOAEC of 2 ml cyclohexylamine/m 3 is found. The MAK value will also protect from possible blue hazy vision which is caused by other tertiary amines since trimethylamine is assumed to be less effective than N,N‐dimethylethylamine with a MAK value of 2 ml/m 3 . The assignment is to Peak Limitation Category I, because local effects are critical, and the excursion factor of 2 is confirmed. Developmental toxicity studies with trimethylamine show that damage to the embryo or foetus is unlikely if the MAK value is observed, and the assignment to Pregnancy Risk Group C is retained.
MAK Value Documentation for Dipropylene glycol The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the work place (MAK value) for dipropylene glycol has been set at 100 mg/m 3 for the inhalable fraction, considering the endpoints respiratory tract irritation and systemic toxicity as well as absorption through the skin. A 2‐year drinking water study with rats shows a NOAEL for focal inflammation of the liver in males of 115 mg/kg body weight and day and a NOAEL for olfactory epithelium degeneration in males and females of 470 and 530 mg/kg body weight and day, respectively. This raises the question, whether the olfactory epithelium could also be a local target tissue after inhalation. Inhalation studies with dipropylene glycol are not available. The substance shows very slight irritation of skin and eyes, if any. Thus, there are no indications of a potential local irritative effect to the upper airways. Therefore, the MAK value of 100 mg/m 3 derived from systemic effects is validated. As systemic effects are critical, the assignment to Peak Limitation Category II and the excursion factor of 2 are retained. A recent in‐vitro study with human skin shows that skin contact does not contribute significantly to systemic toxicity and the former designation with an “H” notation is withdrawn.
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