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Administrative data

Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics, other
Remarks:
Expert Statement
Type of information:
other: Expert Statement
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Type:
absorption
Results:
Oral: yes, Dermal: very limited, Inhalative: neglible based on vapour pressure
Type:
distribution
Results:
restricted within the organism, accumulate in lipophilic tissues
Type:
excretion
Results:
most likely via kidney

Description of key information

Experimental toxicokinetic studies are not available. The log Pow of >5.7 is suggestive of accumulation of unchanged test substance in fatty tissues subsequent to absorption from gastro-intestinal tract or from lungs. However, on the basis of the molecular structure excretion into urine is assumed to be a preferred route of elimination. This is supported by data from subacute toxicity studies performed for a surrogate of the same chemical class. Elimination is assumed to be rapid. Therefore, no potential for bioaccumulation is to be expected.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
100

Additional information

Assessment of oral toxicokinetics based on the physicochemical properties of ECHA Substance:

Molecular weight 364

Water solubility <0.9 mg/L

Partition coefficient log Kow > 5.7

The following remarks on the toxicokinetics of the test item are based on the available studies. Experimental toxicokinetic studies were not available.

ABSORPTION

In an acute toxicity study in rats (limit test) no signs of systemic toxicity were observed after oral administration of the target molecule (1 -Ethoxy-2,3 -difluoro-4 -[trans-4 -(trans-4 -propylcyclohexyl)-cyclohexyl]-benzene) (1).

Toxicity after repeated oral administration of the source compound ((trans(trans))-4'-Vinyl-4 -(4 -methylphenyl)bicyclohexyl) was investigated in two experimental studies: a subacute toxicity study with oral treatment of rats with doses of 1000, 200, and 40 mg/kg bw for 28 days and a 14 -day treatment-free recovery period according to OECD 407 (2); and a combined repeat dose reproduction screening study with oral treatment of rats with doses of 135, 45 and 15 mg/kg bw for 42 days (males) and up to 49 days (females) (3).

Based on the findings of these toxicity studies it can be concluded that the compound of this same chemical class is absorbed after oral administration. Given a logP of the target molecule of > 5.7 (4), exposure via the skin cannot be excluded although it might be very low. Exposure via inhalation is considered negligible as the vapour pressure of the target molecule is low (0.0019 Pa at 20°C) (5).

DISTRIBUTION

The water solubility of the target molecule in water is very low (<0.0009 g/L) (6) and, therefore, distribution of the substance will be restricted within the organism. Considering a logP of 5.7 (4) the substance may potentially accumulate in lipophilic tissues.

EXCTRETION

Information on the excretion of the target substance is not available. As the effects observed in the subacute toxicity studies of the source compound were fully reversible within the 14-day treatment free recovery period, rapid excretion of the substance can be assumed. Based on the molecular weight of the target substance and based on findings for the source compound, excretion via the kidneys is considered to be the main route of elimination. As the target substance has a low water solubility it can be assumed that the substance is metabolized (Phase I and II) prior excretion. Based on the low vapour pressure of both compounds, excretion via exhalation is not assumed.

REFERENCES

1.       Heusener A, Jacobs M. Acute toxicity study in rats after oral administration. Institute of Toxicology, Merck KGaA, Darmstadt, Germany; 1997 May. Report No.: T14265.

2.       Broich K, Braun WH, Flade D, Alumà J. 28-Day Oral Toxicity (Gavage) Study in the Wistar Rat. RCC, Roßdorf, Germany; 2014 Oct. Report No.: A72617.

3.       Emde B, Jacobs M, Knippel A. Combined repeat dose oral toxicity study with the reproduction/developmental toxicity test in rats. Institute of Toxicology, Merck KGaA, Darmstadt, Germany; 2013 Oct. Report No.: T16235.

4.       Fichtner N. Bestimmung des Verteilungskoeffizienten (HPLC-Methode). Zentrale Dienste Analytik, Merck KGaA, Darmstadt, Germany; 2007 Apr. Report No.: 02/07.

5.       Möller M. Boiling point, vapour pressure. Prozess-Sicherheit, Siemens AG, Frankfurt am Main, Germany; 2007 May. Report No.: 20070255.01.

6.       Schönig HJ. Bestimmung der Wasserlöslichkeit (Säulen-Elutions-Methode). Zentrale Dienste Analytik, Merck KGaA, Darmstadt, Germany; 2007 Nov. Report No.: 13/07.