Acetone oxime

Endpoint summary

Additional information

TOXICOKINETIC BEHAVIOUR

 

Physico-chemical properties:

Acetone oxime is a white solid at room temperature and pressure and the molecular weight is 73.09 g/mol. The mean measured Log P (octanol-water) of acetone oxime is1.19 at 22.7 ± 1.0 °C and the mean water solubilityhas been determined to be in the range 30.3 to 32.7 % w/w of solution at 20.0 ± 0.5 °C, making this substance very soluble in water.The vapour pressure value is 242 Pa at 25 degC which is indicative that the substance is not volatile at room temperature and pressure, therefore inhalation exposures are not a concern.

 

Absorption:

Acetone oxime readily absorbs into systemic circulation via all routes

 

Oral: When orally dosed, given the low molecular weight of acetone oxime and its high degree of water solubility, it absorbs readily across the gut and into the systemic circulation. Effects seen in the acute oral study and repeat-dose 90-day study (histopathological changes to liver and spleen) are indicative of widespread systemic exposure via the oral route.

 

Inhalation: no data, as the substance is not volatile and not expected to be inhaled.

 

Dermal: acetone oxime dosed to rabbit skin in water at 1000 mg/kg can induce mortality and can cause changes to blood parameters. Hence, acetone oxime in water can absorb readily across the skin and into the systemic circulation. Acetone oxime is a mild skin irritant and therefore the skin barrier properties could be affected thereby enhancing skin absorption.

 

Intraperitoneal: Although not relevant to human exposure scenarios, acetone oxime was seen to absorb readily into the systemic circulation via the intraperitoneal route of dosing in rats (Kohl et al 1992), with parent acetone oxime and metabolite identified in urine.

 

Distribution

There are no specific data on differential distribution to organs. There is evidence that the substance and its metabolites are present in the liver, spleen and blood, given the effects seen in these organs. Given the low molecular weight and high degree of water solubility, it is expected that this substance will distribute readily to all tissues and organs in the body.

 

Metabolism

There is evidence from published in vitro studies (Kohl et al., 1992; Volkel et al, 1999) using rodent and human liver microsomes that acetone oxime can be converted to propane 2-nitronate as a major metabolite and 2-nitro-1-propanol as a minor metabolite.

 

In an in vivo study (Kohl et al., 1992) in Sprague Dawley rats dosed intraperitoneally with 3.36 mmol/kg of acetone oxime in saline, parent acetone oxime and primary metabolite propane-2-nitronate were detected in urine.

 

Acetone oxime is likely to undergo some degree of hydrolysis, particularly under acidic conditions to form acetone and hydroxylamine.

 

It is unknown as to whether effects seen in toxicology studies dosed via the oral route (liver, spleen and effects in blood) are due to acetone oxime or a metabolite. Similarly, it is unknown whether first pass metabolism is effected by the liver following dermal dosing, or whether metabolism occurs extra-hepatically.

 

There is no evidence from in vitro genotoxicity studies to suggest that metabolism plays a role in the genotoxic properties of this substance. Acetone oxime is non genotoxic in the absence and presence of metabolic activation.

 

Excretion

The test substance and its primary metabolite propane-2-nitronate have been identified as present in urine. There are no specific ADME data to quantify the rates or extent of excretion. It is expected that the substance absorbs significantly into the body by all routes, and that urinary excretion is the main clearance pathway.

 

No quantitative data are available to determine the rates or extent of absorption, distribution, metabolism and excretion.