[[4-[[2-(4-cyclohexylphenoxy)ethyl]ethylamino]-2-methylphenyl]methylene]malononitrile

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

Assessment

Type of information:

other: Expert assessment

Adequacy of study:

supporting study

Study period:

2018

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

[[4-[[2-(4-cyclohexylphenoxy)ethyl]ethylamino]-2-methylphenyl]methylene]malononitrile

EC Number:

258-964-5

EC Name:

[[4-[[2-(4-cyclohexylphenoxy)ethyl]ethylamino]-2-methylphenyl]methylene]malononitrile

Cas Number:

54079-53-7

Molecular formula:

C27H31N3O

IUPAC Name:

2-[(4-{[2-(4-cyclohexylphenoxy)ethyl](ethyl)amino}-2-methylphenyl)methylidene]propanedinitrile

Applicant's summary and conclusion

Executive summary:

There are no experimental toxicokinetic data available for the substance and this statement is based on available data as physico-chemical data and toxicological data. This assumption was conducted based on the REACH ECHA “Guidance on information requirements and chemical safety assessment chapter R.7c” of the ECHA guidance document (Version 3.0, June 2017).

Available physico-chemical information taken into account:

Physical state:

The substance is a solid orange powder (CURRENTA Report No 2016/0113/01).

Identification: Macrolex Gelb 6G

CAS Name: Propanedinitrile, 2-[[4-[[2-(4-cyclohexylphenoxy) ethyl] ethylamino]-2-methylphenyl]methylene]-

CAS Number: 54079-53-7

EC Name: [[4-[[2-(4-cyclohexylphenoxy)ethyl] ethylamino]-2-

methylphenyl]methylene] malononitrile

EC Number: 258-964-5

Structural Formula:

Molecular weight:

413.6 g/mol

Water solubility:

Lower than 0.0007 mg/L measured at 20 °C (pH-value approx. 6).(CURRENTA Report No 2008/0021/02)

Log Pow:

Log Pow = 6.8 at 25 °C (pH 7).(CURRENTA Report No 2016/0113/04)

Vapor pressure:

Low: 9.3 x 10-09 Pa at 25 °C (QSAR determination of the vapor pressure using the model MPBPWIN included in the Estimation Program Interface (EPI) Suite v4.11)

General considerations:

In general, log Kow values between 1 and 4 and molecular weight below 500 are favorable for absorption regarding oral/GI absorption, respiratory absorption and dermal absorption. Low water solubility of <0.0007 mg/L might limit absorption. No information of metabolic transformation of Macrolex Gelb 6G is available.

Estimation of oral absorption:

In an acute oral toxicity study with 10 female rats dosed with 5000 mg/kg bw no mortality, no clinical signs and no impact on body weight were observed in any animal; discriminating dose (rat, female) > 5000 mg/kg bw

Overall: the molecular weight is in the range of compounds absorbed after oral dosing. Based on the low water solubility and the high LogPow an absorption following ingestion is not likely. This is supported by toxicological data after acute oral dosing.

Estimation of dermal absorption:

There are no dermal studies available; the substance is not irritating to the skin or eyes. Based on the low water solubility, a low absorption after dermal contact is assumed.

Estimation of absorption via inhalation:

There are no inhalation studies available; the substance is not irritating to the skin or eyes. Based on the very low vapor pressure and low water solubility, a low absorption after inhalation is assumed.

Estimation of distribution:

Based on the low water solubility it is not assumed that the substance distributes into cells.

Estimation of accumulation:

In general substances with high log Pow values have long biological half-lives. Substances with log Pow values of 3 and less would be unlikely to accumulate with the repeated intermittent exposure patterns normally encountered in the workplace but may be accumulate if exposures are continuous.

Based on the log Pow of 6.8 but low water solubility, significant accumulation is not assumed.

Estimation of metabolism:

In vitro genotoxicity data do not indicate any genotoxic metabolites. The substance is negative in the absence and in the presence of S9 extracts (Ames test (Bacterial Reverse Mutation Assay), the MNT (in vitro mammalian cell Micronucleus Test) and the HPRT test (In Vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene)).

Estimation of excretion:

Characteristics favorable for urinary excretion are low molecular weight (below 300 in the rat), good water solubility and ionization of the molecule at the pH of urine.

Based on the physicochemical data an excretion via feces is assumed.