Tricresyl phosphate, sum of all ortho isomers
MAK Value Documentation – Translation of the German version from 2020
Andrea Hartwig1 (Chair of the Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Deutsche Forschungsgemeinschaft)MAK Commission2
1 Institute of Applied Biosciences, Department of Food Chemistry and Toxicology, Karlsruhe Institute of Technology (KIT), Adenauerring 20a, Building 50.41, 76131 Karlsruhe, Germany
2 Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Deutsche Forschungsgemeinschaft, Kennedyallee 40, 53175 Bonn, Germany
Abstract
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated tricresyl phosphate, sum of all ortho isomers [78-30-8], considering all toxicological end points. The ortho isomers of tricresyl phosphate can cause organophosphate-induced delayed neuropathy (OPIDN), while the para and meta isomers do not severely affect the central nervous system. In the past, thousands of people have suffered from delayed neuropathy in the legs caused by the consumption of food or beverages contaminated with ortho-tricresyl phosphate. In spite of the numerous reports of human poisoning, these data are insufficient to derive a dose-response relationship and to determine a maximum concentration at the workplace (MAK value). The neurotoxic effects of ortho-tricresyl phosphates were demonstrated also in hens and cats, while rodents showed only slight effects with a different mechanism of action. Dermal subchronic treatment with triortho-cresyl phosphate produced hindlimb weakness in cats with a no observed adverse effect level (NOAEL) of 0.5 mg/kg body weight and day, resulting in a MAK value of 0.01 ml/m3. Investigations in hens show that the relative potency of monoortho-tricresyl phosphate, di-ortho-tricresyl phosphate and tri-ortho-tricresyl phosphate to induce OPIDN is 10 : 5 : 1. Therefore, a MAK value of 0.001 ml/m3 has been established for the sum of all ortho-tricresyl phosphate isomers, as all three ortho isomers are assumed to be present in technical tricresyl phosphate. Tricresyl phosphate, sum of all ortho isomers, is classified in Pregnancy Risk Group D because sufficient data for developmental toxicity are not available. Carcinogenicity studies are not available. In rats, DNA adducts were detected in the liver, kidneys, lung and heart after oral application of tri-ortho-cresyl phosphate. Therefore, ortho-tricresyl phosphates are classified in Carcinogen Category 3 B for suspected carcinogens. The ortho-tricresyl phosphates are not regarded as mutagenic in germ cells. Skin contact is suspected to contribute to systemic toxicity and ortho-tricresyl phosphates are designated with “H”. Studies of the sensitization potential are not available.
