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Key value for chemical safety assessment

Additional information

Acute toxicity: oral

In a key study to evaluate the acute oral toxicity of dimethyl 1,4-cyclohexanedicarboxylate (DMCD), mortality was 40% at a dose of 5000 mg/kg for male rats. For female rats, mortality was 20% at 2500 mg/kg and 100% at 4000 and 5000 mg/kg. No mortality was noted after Day 2 of the study. Abnormal clinical signs evident during the study included slight to severe weakness, prostration, diarrhea, and a reduced amount or lack of feces. Weakness was noted only on the day of dosing or the day following dosing. Severe weakness and prostration were only seen prior to death. By Day 2 of the study, all surviving animals appeared clinically normal. All animals which survived to termination of the 14-day observation period gained weight. The cause of death for rats which died after exposure to the test material was not determined. However, necrosis and hemorrhage in the glandular gastric mucosa may have contributed to the deaths. Based on these findings at necropsy, the test material was considered to be a gastric irritant. The acute oral LD50 for this test material was greater than 5000 mg/kg for male rats and was calculated to be 2812 mg/kg for female rats.

Earlier supporting studies for DMCD which predated GLP guidelines also were done in rats and mice. Administration of undiluted material to rats by oral gavage at a dose of 6400 mg/kg was lethal, and the LD50 was determined to be between 3200 mg/kg and 6400 mg/kg. Administration of undiluted material by oral gavage to mice at a doses ranging from 400 mg/kg to 6400 mg/kg indicated that the acute oral LD50 was between 1600 mg/kg and 3200 mg/kg.

Acute toxicity: inhalation

 

In an acute inhalation experiment, 3 rats were exposed to a chamber concentration of 0.97 mg/L (117 ppm) of DMCD for 6 hours, and a separate group of 3 rats were exposed to a chamber concentration of 2.91 mg/L (355 ppm) for 6 hours. At the end of the exposure period, there were no symptoms or adverse effects observed.

Justification for classification or non-classification

Dimethyl 1,4 -cyclohexanedicarboxylate (DMCD) is not classified for acute lethality by the oral or inhalation routes according to Annex I of Directive 67/548/EEC. Based on an acute oral LD50 value of >2000 mg/kg bw for rats in the key study, DMCD is not classified for acute lethality by the oral route of exposure under EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. The UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) defines a fifth category for acute toxicity for chemicals with oral LD50 values between 2000 and 5000 mg/kg bw. Insufficient data were available from the key studies to provide a definitive classification under UN GHS. However, although the acute oral LD50 for female rats was within this range, the acute oral LD50 for male rats was determined to be greater than 5000 mg/kg. Consequently, DMCD may meet the criteria for classification as Category 5 under GHS. Based on a 6-hr acute inhalation LC 50 of 2.91 mg/L air, DMCD is not classified for acute lethality by the inhalation route according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 or the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS).