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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

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Administrative data

Link to relevant study record(s)

Description of key information

There are no experimental studies available in which the toxicokinetic behaviour of 4,4'-(9H-fluoren-9-ylidene)bis(2-chloroaniline) has been assessed. Based on the physico-chemical data possible absorption via the oral route may occur due to micellar solubilisation. Dermal absorption is supposed to be rather low (approximately 1%). Inhalation of the test substance as such is supposed to be possible. Aerosol formation may enhance possible absorption via inhalation. If the substance enters the body it may be accumulated in lipid tissues. Excretion is assumed to take place via bile and faeces.

Key value for chemical safety assessment

Additional information

Basic toxicokinetics

There are no experimental studies available in which the toxicokinetic behaviour of 4,4'-(9H-fluoren-9-ylidene)bis(2-chloroaniline) (CAS 107934-68-9) has been assessed.

In accordance with Annex VIII, Column 1, Item 8.8.1, of Regulation (EC) 1907/2006 and with Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2012), assessment of the toxicokinetic behaviour of the substance is conducted to the extent that can be derived from the relevant available information. This comprises a qualitative assessment of the available substance specific data on physicochemical and toxicological properties according to the relevant Guidance (ECHA, 2012).

The substance of 4,4'-(9H-fluoren-9-ylidene)bis(2-chloroaniline) is a monoconstituent substance with a molecular weight of 417.3 g/mol. It is a solid white powder with a water solubility of < 0.052 mg/L at 20 °C and a vapour pressure < 0.0001 Pa. Analysis of particle size revealed that 91.7% of the particles are <100 µm, 4.08% are <10 µm, and 0.312% are < 5.5 µm. The log Pow was determined to be > 4.49 at 21°C (pH 5.28-5.88) and was calculated to be 6.49.


Absorption is a function of the potential for a substance to diffuse across biological membranes. The most useful parameters to provide information on this potential are the molecular weight, octanol/water coefficient (log Pow) value and water solubility (ECHA, 2012). The log Pow value provides information on the relative solubility of the substance in water and lipids (ECHA, 2012). 


The molecular weight of 4,4'-(9H-fluoren-9-ylidene)bis(2-chloroaniline) is lower than 500 g/mol, indicating that the substance is available for absorption (ECHA, 2012). The high log Pow in combination with the low water solubility suggests that any absorption will happen via micellar solubilisation (ECHA, 2012).

The available acute oral toxicity data revealed a LD50 > 5000 mg/kg bw and no systemic effects were observed (Glaza, 1988a). In a 28-day repeated dose toxicity study no toxicologically relevant effects were noted up to and including the highest dose level of 1000 mg/kg bw/day (Edwards, 1991). This indicates that 4,4'-(9H-fluoren-9-ylidene)bis(2-chloroaniline) has a low potential for oral toxicity, although no assumptions can be made regarding the absorption potential based on the experimental data.


The dermal uptake of liquids and substances in solution is higher than that of dry particulates, since dry particulates need to dissolve into the surface moisture of the skin before uptake can begin. Molecular weights below 100 favour dermal uptake, while for those above 500 the molecule may be too large. Dermal uptake is anticipated to be low, if the water solubility is < 1 mg/L; low to moderate if it is between 1-100 mg/L; and moderate to high if it is between 100-10000 mg/L. Dermal uptake of substances with a water solubility > 10000 mg/L (and log Pow < 0) will be low, as the substance may be too hydrophilic to cross the stratum corneum. Log Pow values in the range of 1 to 4 (values between 2 and 3 are optimal) are favourable for dermal absorption, in particular if water solubility is high. For substances with a log Pow above 4, the rate of penetration may be limited by the rate of transfer between the stratum corneum and the epidermis, but uptake into the stratum corneum will be high. Log Pow values above 6 reduce the uptake into the stratum corneum and decrease the rate of transfer from the stratum corneum to the epidermis, thus limiting dermal absorption (ECHA, 2008).

The substance 4,4'-(9H-fluoren-9-ylidene)bis(2-chloroaniline) is poorly soluble in water, indicating a low dermal absorption potential (ECHA, 2012). The molecular weight (417.3 g/mol) indicates that dermal absorption is possible. The log Pow is > 4.49 (>6.49, QSAR), which means that the uptake into the stratum corneum is likely to be slow and the rate of transfer between the stratum corneum and the epidermis will be slow (ECHA, 2012).

The dermal permeability coefficient (Kp) can be calculated from log Pow and molecular weight (MW) applying the following equation described in US EPA (2004):

log(Kp) = -2.80 + 0.66 log Pow – 0.0056 MW

The Kp is thus 0.00673 cm/h. Considering the water solubility (0.052 mg/cm³) the dermal flux is estimated to be < 1 ng/cm²/h and thus the dermal absorption potential is estimated to be very low (1% dermal absorption; Kroes at al., 2007).

In addition the substance is not a skin irritant or corrosive, thus penetration is not supposed to be enhanced by damage to the skin surface (ECHA, 2012).

Data from an available acute dermal toxicity data revealed a LD50 > 2000 mg/kg bw and no systemic effects or other signs of toxicity were observed (Baldrick, 1991). This is in accordance with the estimated dermal absorption potential, but no direct conclusion can be drawn from this study regarding toxicokinetic behaviour, as absence of effects could also be due to chemical properties and not only toxicokinetic properties.


As the vapour pressure of 4,4'-(9H-fluoren-9-ylidene)bis(2-chloroaniline) is very low (< 0.0001 Pa at 20 °C and < 0.01 Pa at 110 °C), the volatility is also very low. Therefore, the potential for exposure and subsequent absorption via inhalation of vapour during normal use and handling is considered to be negligible. If the substance is available as an aerosol or as dust, the potential for absorption via the inhalation route is increased. While droplets and particles with an aerodynamic diameter < 100 μm can be inhaled, in principle, only droplets and particles with an aerodynamic diameter < 50 μm can reach the bronchi and droplets and particles < 15 μm may enter the alveolar region of the respiratory tract (ECHA, 2012). The substance includes particles <10 µm (4.08%) indicating that exposure of the alveolar region cannot be excluded, but will take place to a smaller amount, as the bigger part of the substance consists of bigger particle sizes. As for oral absorption, the molecular weight, log Pow and water solubility are suggestive of absorption across the respiratory tract epithelium by micellar solubilisation. In the available acute inhalation toxicity study a LC50 > 3 mg/L air (maximum attainable concentration) was derived in rats for 4,4'-(9H-fluoren-9-ylidene)bis(2-chloroaniline) (WIL Research Europe B.V., 2015). Body weight loss was seen for all females during the first week post-exposure. However, despite one female, the remaining animals regained weight until the end of the observation period thus exceeding the initial body weight. Overall body weight gain in males appeared normal. No clinical signs were noted. This indicates that the test substance has a low potential for inhalation toxicity, although no assumptions can be made regarding the absorption potential based on the experimental data. Absorption via inhalation is in general assumed to be possible, but will not exceed the oral absorption potential.

Distribution and Accumulation

Distribution of a compound within the body depends on the physicochemical properties of the substance; especially the molecular weight, the lipophilic character and the water solubility. In general, the smaller the molecule, the wider is the distribution. If the molecule is lipophilic, it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration, particularly in fatty tissues (ECHA, 2012).

If 4,4'-(9H-fluoren-9-ylidene)bis(2-chloroaniline) is absorbed systemically it may be distributed into cells particularly in fatty tissues. Substances with high log Pow (>4) may accumulate in fatty tissues or as poorly soluble particulates in the alveolar region.


No experimental data are available for the characterisation of metabolites of 4,4'-(9H-fluoren-9-ylidene)bis(2-chloroaniline). General metabolism would include hydroxylation of the amino moiety and/or the aromatic rings at various positions, as suggested by the OECD toolbox (v3.0). The metabolites proposed from the rat liver S9 metabolism simulator (OECD toolbox, 3.0) showed some alerts for DNA binding by OASIS v.1.1/DNA binding by OECD. As all genotoxicity tests performed with the test substance were negative and showed no difference between treatments with or without metabolic activation, it can be concluded that either no relevant metabolism takes place in vivo or the substance is scarcely bioavailable and thus not available for metabolism at all.


Based on the molecular weight of the substance and the possible metabolites as well as the low water solubility, excretion via bile is assumed. In case of conjugation of the parent substance or the oxidised metabolites with glucuronic acid, excretion via the faeces could also occur, as the molecular weight of the conjugates is > 300 g/mol.