N,N''-(methylenedi-4,1-phenylene)bis[N'-cyclohexylurea];N-(4-[[4-[[(phenylamino)carbonyl]amino]phenylmethyl]phenyl]-N'-cyclohexylurea;reaction mass of: N,N''-(methylenedi-4,1-phenylene)bis[N'-phenylurea]

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: expert statement

Adequacy of study:

key study

Study period:

October - November, 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Theoretical assessment taking all currrently available relevant information into account. Since this is a theoretical assessment, the Klimisch value cannot be 1.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Objective of study:

other: Assessment of toxicokinetic behaviour

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

423-070-8

EC Name:

-

Cas Number:

58890-25-8

Molecular formula:

not applicable (reaction mass)

IUPAC Name:

3-cyclohexyl-1-[4-({4-[(cyclohexylcarbamoyl)amino]phenyl}methyl)phenyl]urea; 3-cyclohexyl-1-[4-({4-[(phenylcarbamoyl)amino]phenyl}methyl)phenyl]urea; 3-phenyl-1-[4-({4-[(phenylcarbamoyl)amino]phenyl}methyl)phenyl]urea

Results and discussion

Any other information on results incl. tables

The acute oral and dermal toxicity of the substance is low (LD50 > 2000 mg/kg in both cases). Therefore, an extensive toxicokinetic assessment is considered of limited value. Below, an assessment of the anticipated toxicokinetic behaviour of the substance is given.

Dissolution of a compound is required for absorbtion from the gastro-intestinal tract into the blood. Based on the physico-chemical properties of the substance, the initial dissolution is expected to be low. In the presence of gastric acid and/or bile salts, the solubility of the substance may be somewhat increased in the gastro-intestinal fluids. However, it is unlikely that the compound will be absorbed to a high extent from the gastro-intestinal tract.
Although the substance shows a very low solubility in water, some dissolution may occur at low pH because of protonation
of the oxygen atom. The O-protonated amide will be greatly stabilised by resonance.
In the gastro-intestinal tract, especially the colon, dissolved substance may already be partly metabolised by amidases.
After absorption, the substance will be extensively distributed throughout the body, especially fatty tisues. In case the substance is absorbed, it will be extensively metabolised by amidases, but also hydroxylation of the phenyl rings may occur. The formed hydroxy-metabolites will then probably be conjugated and excreted via urine or bile.
Although theoretically aniline could be one of the metabolites, based on the toxicity studies, there are no indications that this compound is formed after ingestion or dermal application of the substance.
Since it is generally accepted that substances with log Pow ranging from 0.1 to 6 penetrate the skin easily, it is to be expected that the substance will be readily absorbed through the skin. This assumption is supported by the findings during the acute dermal toxicity study.
Based on the expected kinetic behaviour in the body, as described above, the substance will not accumulate in the body after prolonged exposure.
The anticipated kinetic behaviour is supported by the acute oral and dermal toxicity data.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Based on the expected kinetic behaviour in the body, as described above, the substance will not accumulate in the body after prolonged exposure. The anticipated kinetic behaviour is supported by the acute oral and dermal toxicity data.