2-hydroxy-2-methylpropiophenone

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Chemistry

The test material (164 Da) is a yellowish liquid, well soluble in water (13.3 g/l). The material has a density of 1.08 g/cm3 and the boiling point is at 252 °C. A vapour pressure of 0.0057 hPa indicates a very low volatility. The log Pow is 1.62 (at pH 5.75).

The substance is sensitive to UV-light induced photocleavage as it was designed to serve the technical function of a photoinitiator.

Absorption

In acute oral and dermal toxicity studies, rats were administered to the test substance. Mortality was observed in all treatment groups after oral administration (with exception of the lowest dose level) in a dose dependent manner. A few minutes after oral application animals showed sedation, dyspnoe, decreased activity and proned position. In animals which died fatty liver infiltration and dilation of the bladder (starting at 1800 mg/kg) as well as mucous content of the intestine (starting at 2000 mg/kg) was observed. Single dermal application resulted in mortality from 5000 mg/kg bw onward. Gross pathology of deceased animals revealed fatty infiltration of the liver and dilation of the urinary bladder with hemorrhaging of the mucosa (starting at 6400 mg/kg). Furthermore, staggered gait and decreased activity were observed. The NOAEL in male and female rats in a subacute oral repeated dose study is 300 mg/kg bw due to changes in liver and kidney weight as well as centrilobular hypertrophy and hepatocellular proliferation. Administration of the substance over a subchronic period resulted in gait ataxia in high dose males. Furthermore, basophillic tubules and granular cast in the kidneys were observed. Calcium oxalate and crystals were found in the urine of the top dose animals. The NOAEL after subchronic oral administration is therefore considered to be 50 mg/kg bw. In regard to the results of the acute and longterm studies and considering the low molecular weight uptake of the substance from the gastro-intestinal system is most likely. The test substance cannot undergo pH-dependent hydrolysis in the stomach, thus, the unchanged (parent) substance is taken up into the system. According to the model of Fitzpatrick [1], the test item is moderately skin permeable.

Metabolism

The results obtained from the subchronic toxicity study indicate the test item forms a complex with Ca2+ (2:1). A subsequent decrease of systemic calcium may cause mobilisation of calcium from the bones which results in turn in increased Ca-levels (as observed in the 90d study). Additionally, the Ca-complexes are presumably precipitated in kidney and urine.

Concerning xenobiotic metabolism, reduction of the aliphatic ketone followed by glucuronidation of the hydroxyl-groups seems plausible. Subsequently, the test substance will be excreted effectively. The primary elimination pathway of the test substance will be the urinary excretion of parent compound and the glucuronidation product.

Excretion 

The low molecular weight of the test item and its solubility in water enhance renal excretion. However, precipitation of the Ca-bound complex and crystal formation in kidney and urine was observed at the highest dose level when applied over a subchronic period. It is acceptable to assume that the precipitated material will be excreted over the time after discontinuation of administration. Accumulation in the body is therefore not expected.

[1] Modelling skin permeability in risk assessment––the future, D. Fitzpatrick et al, Chemosphere 55 (2004) 1309–1314