2-methyl-1-(4-methylthiophenyl)-2-morpholinopropan-1-one

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: assessment

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Because of limited data (which are provided by ECHA) it is difficult to make a full toxicokinetic assessment.

Data source

Reference

Reference Type:

other: Body responsible for the test

Title:

No information

Year:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance, R.7.12 Guidance on Toxicokinetics

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-methyl-1-(4-methylthiophenyl)-2-morpholinopropan-1-one

EC Number:

400-600-6

EC Name:

2-methyl-1-(4-methylthiophenyl)-2-morpholinopropan-1-one

Cas Number:

71868-10-5

Molecular formula:

C15H21NO2S

IUPAC Name:

2-methyl-1-(4-methylthiophenyl)-2-morpholinopropan-1-one

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Oral/GI absorption
With a moderate log P value (3.09), substance has relative low water solubility (17.9 mg/L).
Substance is considered to have oral/GI absorption because of not only its log P value but also signs of systemic toxicity (acute toxicity oral: LD50 = 1984 mg/kg bw).
However, the oral toxicity data showing the LD50 being 1984 mg/kg bw will gives no indication of the amount of substance that has been absorbed. It is to be expected that the oral bioavailability and the systemic exposure of the substance will be relatively low.

Respiratory absorption – Inhalation
Substance has the potential to be inhaled. Because of the relatively large particle size uptake via the lungs is not expected.

Dermal absorption
With low water solubility, dermal absorption of the substance is anticipated to be low. Since Log P value favours dermal absorption, it is to be expected that substance may penetrate the skin to some extent.

Details on distribution in tissues:

System effects were observed in the 90-day oral toxicity study with paresis of the hind limbs, loss of hair, dim, opaque eyes, also small effects on liver-derived enzymes were observed in the higher dose group. It is therefore possible to conclude that the substance is transported. Despite the low water solubility , substance is considered to have a relatively low adsorption coefficient. Accumulation in fat or in other tissues is unlikely. The plasma protein binding is expected to be high.

Details on excretion:

Due to its low molecular weight (below 300), in the case absorption of substance occurs, substance will be excreted via bile and/or urine.

Metabolite characterisation studies

Metabolites identified:

not measured

Details on metabolites:

In the case absorption of substance occurs, both the saturated and the unsaturated ring may undergo extensive hydroxylation, followed by rapid sulfation or glucuronidation. Furthermore, S-demethylation is anticipated. Substance will be extensively metabolised in the liver and rapidly excreted via bile and/or urine. Therefore, accumulation in the body during prolonged exposure will be very low.

Applicant's summary and conclusion

Conclusions:

Based on the expected kinetic behaviour in the body, there is sufficient evidence that some oral/GI absorption takes place and there is likely to be adaptive changes to the animals following transportation and possible metabolism. Because of the relatively large particle size uptake via the lungs is not expected. Dermal absorption is anticipated to be low thanks to low water solubility. If absorption occurs, substance will be extensively metabolised in the liver. Because of its lower molecular weight (< 300) and slight solubility in water (17.9 mg/L), substance is favourable for urinary excretion. Substance was predicted to has no bioaccumulation potential.