Tricresyl phosphate, isomers, “free of o-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 Commission<sup>2

1</sup> 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, isomers [1330-78-5], “free of o-isomers” considering all toxicological end points. The para and meta isomers do not cause severe effects on the CNS. In a 90-day inhalation study with rats, 300 mg/m³ did not induce neurotoxic effects. The critical effects of tricresyl phosphate, isomers, “free of o-isomers” in oral 2-year studies were higher grades of cytoplasmic vacuolation in the adrenal glands and hyperplasia of the interstitial cells of ovaries at 15 mg/kg body weight and day in female rats. The NOAELs were 13 mg/kg body weight and day for male rats (highest dose tested) and 7 mg/kg body weight and day for females. In male mice, the NOAEL was 7 mg/kg body weight and day based on ceroid pigmentation, foci and changes in the fat cells of the liver at 13 mg/kg body weight and day. In female mice, ceroid pigmentation in the adrenals occurred as from the lowest dose of 8 mg/kg body weight and day. Ceroid pigmentation in adrenals is common in older mice and therefore of questionable relevance for humans. A maximum concentration at the workplace (MAK value) of 5 mg/m³ was derived for the inhalable fraction based on the NOAEL of 7 mg/kg body weight and day determined in female rats and male mice. As a systemic effect is critical, Peak Limitation Category II and the default excursion factor of 2 are assigned. A NOAEL of 100 mg/kg body weight and day was found in a developmental toxicity study in rats and a NOAEL of 62.5 mg/kg body weight and day in a 1-generation study in mice. Workplace concentrations of 175 and 88 mg/m³ are calculated from these values. Therefore, damage to the embryo or foetus is unlikely when the MAK value is not exceeded and tricresyl phosphate, isomers, “free of o-isomers” are assigned to Pregnancy Risk Group C. Tricresyl phosphate, isomers, “free of o-isomers” were not mutagenic or clastogenic in vitro and did not increase tumour incidences in a 2-year study in rats or mice. Model calculations do not predict dermal uptake in toxicologically relevant amounts. There are no data that show that tricresyl phosphate, isomers, “free of o-isomers” are skin or airway sensitizers.

---

---