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EC number: 217-568-2
CAS number: 1889-67-4
oral administration, the likelihood of systemic absorption through the
walls of the intestinal tract depends on several physicochemical
substance properties. In order to obtain a conclusive judgement of a
substance’s potential to be able to reach the systemic circulation,
important physicochemical factors such as molecular weight, water
solubility and the log Pow value need to be considered. Generally, the
smaller the molecule the more easily it may be absorbed through the
walls of the gastrointestinal tract. As the molecular weight of
1,1’-(1,1,2,2-tetramethylethylene)dibenzene is 238.7 g/mol, an uptake of
the compound into the systemic circulation via the gastro-intestinal
(GI) tract is likely (ECHA, 2008). The compound is highly lipophilic
(log Pow = 6.68) and has a low water solubility. Therefore the
absorption is limited by the extent to which such substances dissolve
into the GI fluids and hence set in contact with the mucosal surface.
The absorption can however be enhanced via micellular solubilisation by
bile salts. An uptake of nanosized particles by pinocytosis can be
neglected because the measured particle size distribution indicates that
1,1’-(1,1,2,2-tetramethylethylene)dibenzene does not contain particles
in the nanosize region.
possible gastrointestinal absorption is further strengthened by the
results achieved in the oral toxicity studies with rats. Although no
effects were seen in the acute oral toxicity study the repeated dose
tests showed some toxic effects after oral administration of the
substance (the NOAEL in the 90-day repeated dose toxicity study was 10
mg/kg bw/day based on reduced body weight development at 30 mg/kg bw/d
which was not reversible in female animals). In the prenatal
developmental toxicity study (OECD 414) the NOAEL was also found to be
10 mg/kg bw/day based on effects found at 30 mg/kg bw/day such as
reduced food consumption and body weights in both dams and offspring.
the low vapour pressure of 1,1’-(1,1,2,2-tetramethylethylene)dibenzene
and the resulting low volatility, exposure of the substance as vapour is
very limited if handled at room temperature. Based on the particle size
distribution, it is unlikely that dust particles are inhaled or reach
the lower lung region in order to become systemically available. Even if
inhaled, the poor water solubility of the compound would prevent that
particles dissolve into the mucus lining of the respiratory tract.
Therefore, direct absorption will be negligible. Instead of being
absorbed, inhaled particles could be coughed or sneezed out of
respiratory tract and swallowed.
general, substances with a molecular weight below 100 are favoured for
dermal uptake. Above 500 the substances are considered to be too large
to be readily absorbed through the skin. As
1,1’-(1,1,2,2-tetramethylethylene)dibenzene has a molecular weight of
238 g/mol a dermal uptake can be expected. Due to a high lipophilicity
of the test item, it will not easily pass the skin layers and therefore
shows a rather limited skin penetration. As the chemical consists of a
particulate at room temperature, it has to dissolve into the surface
moisture of the skin before systemic uptake can begin. These
pre-requisites will drastically limit the bioavailable amount of the
chemical when placed in contact to the skin.
assumption that low or no dermal absorption occurs is strengthened by
the results achieved from the dermal toxicity testing. In an acute
dermal toxicity study, 1,1’-(1,1,2,2-tetramethylethylene)dibenzene did
not cause any toxic effects. The LD50 was determined to be greater than
the limit dose (2000 mg/kg bw).
application of 1,1’-(1,1,2,2-tetramethylethylene)dibenzene onto the skin
of rabbits also caused no sign of irritation as observed in a skin
irritation study. No evidence of tissue damage was observed which in
turn could have favoured direct absorption into the systemic circulation.
the positive immunological response obtained in the LLNA assay, at least
small amounts of 1,1’-(1,1,2,2-tetramethylethylene)dibenzene seem to
become systemically available.
on the physical-chemical properties and the results of the testing with
dermal application, 1,1’-(1,1,2,2-tetramethylethylene)dibenzene is
considered to be systemically available to a small degree by absorption
or penetration through skin.
on the physicochemical properties and the results achieved from the
comprehensive toxicity testing, small amounts of
1,1’-(1,1,2,2-tetramethylethylene)dibenzene can become systemically
available. Once adsorbed, the substance will most likely be transported
within the body via the blood stream and gain access to the body tissues
potentially bound to macromolecules due to its low water solubility. Due
to the highly lipophilic properties, the substance might be enriched in
body fats if no metabolism and formation of more polar metabolites takes
amounts of 1,1’-(1,1,2,2-tetramethylethylene)dibenzene may be
transformed within the body by Phase I enzymes while undergoing
functionalisation reactions aiming to further increase the
hydrophilicity. Furthermore, Phase II conjugation reactions may
covalently link an endogenous substrate to the absorbed chemicals or the
respective Phase I metabolites in order to ultimately facilitate
excretion. Potential reactions are e.g. hydroxylation of the phenyl
rings forming phenols and to a minor extent hydroxylation of the methyl
groups forming the respective alcohols can be expected.
to the published data a structural analogue (Diphenylmethane) is mainly
excreted unchanged via the urine and to a lesser extent via feces.
Present metabolites in the urine were 2- and 4-hydroxydiphenylmethane
showing Phase I functionalisation as indicated above. A similar
metabolism can also be assumed for
After oral intake, parts of the substance
will be excreted via the faeces in its unchanged form. After absorption,
the parent compound as well as its metabolites are likely to be excreted
via the urine as its molecular weights are well below 500 Da or via the
faeces, if intrinsic Phase II conjugation takes place. According to the
calculated BCF value, bioaccumulation cannot be totally excluded for
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