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EC number: 232-092-5
CAS number: 7786-17-6
2,2'-methylenebis(6-nonyl-p-cresol) is inferred to be poorly and slowly absorbed following oral exposure, highly absorbed following inhalation exposure (relative to the very low exposures anticipated by this route) and poorly absorbed following dermal exposure. In accordance with guidance, default values of 50% for oral absorption, 100% for inhalation, and 10% for dermal absorption, may be assumed. Absorbed 2,2'-methylenebis(6-nonyl-p-cresol) will be distributed within the body, and metabolised to some extent by the liver and possibly by the GI tract. It is not expected that 2,2'-methylenebis(6-nonyl-p-cresol) will bioaccumulate. The urine and bile are likely to be important routes of excretion.
In accordance with point 8.8.1 of column 1 (Standard Information
Required), Annex VIII of REACH (Regulation EC No. 1907/2006), assessment
of the toxicokinetic behaviour of the substance is performed to the
extent that can be derived from the relevant available information. The
following toxicokinetic assessment was performed based on the available
physical-chemical data and toxicological information available. Further
testing for the assessment of toxicokinetic behaviour is omitted on this
No toxicokinetic studies are available that directly address
absorption, distribution, metabolism, or excretion of
2,2'-methylenebis(6-nonyl-p-cresol) following oral administration;
however information is available from existing toxicology studies and
the physical chemical properties to infer potential toxicokinetic
The test material is in broad terms a dimer with purity
approximately 60%; containing approximately 25% dimeric isomers for
which toxicokinetics are probably similar to the test material, and
approximately 10% monomeric isomers which might be better absorbed.
Physical-chemical properties of
0.982 at 20°C
<0.0015 Pa at 20°C
Water Solubility (mg/L)
<0.16 mg/Lat 20 °C
Log KOW >6.5
Select toxicological end points for
Acute oral toxicity (rat)
LD50> 2000 mg/kg bw (symptoms profile available)
Acute dermal toxicity
LD50>16 mL/kg (no systemic effect)
In vivoSkin Irritation
In vivoEye Irritation
Skin Sensitization (Draize method)
Not a skin sensitizer
Repeat Dose (13 week, diet)
NOAEL 158 mg/kg bw/day (target organs identified)
Aquatic bioaccumulation factor
Significance of routes of exposure
Oral route: this is not considered a relevant route for
occupational exposure or for the general population. Slight exposure may
occur via accidental hand-to-mouth contact, but this is not expected to
contribute significantly to exposure.
Inhalation route: the substance has a low vapour pressure and a
high boiling point and therefore is unlikely to volatilize or be
released into the air. Under conditions of normal handling and use, the
substance will not be aerosolized. Water solubility is low and this can
enhance penetration to the inner respiratory tract.
Dermal route: this is considered to be the principal route for
occupational exposure, and also for exposure of the general population.
The main physical chemical properties that influence absorption are
molecular weight, and water and lipid solubility. The substance has a
molecular weight of 480.7, a water solubility <0.16 mg/L, and Log KOW
of >6.5. These properties suggest
2,2'-methylenebis(6-nonyl-p-cresol) would be poorly absorbed by the
gastro-intestinal tract following oral exposure. However, symptoms and
pathology seen in toxicity studies confirm a measure of absorption does
occur. There is a possibility of toxicity being associated with the
lower molecular weight impurities; also of some limited gastrointestinal
conversion (e.g. by lipase, or gut microflora) to enhance absorption.
The acute oral toxicity study showed low inherent systemic toxicity, but
with symptoms first seen by 4 hours post-dose and peaking at 1-2 days.
The profile is consistent with slow absorption, although the possibility
of symptoms being attributable to local GI discomfort (hyperaemia of the
GI tract was seen in decedents) cannot be dismissed. A default value for
oral absorption of 50% is assumed.
Based on the very low vapour pressure (<0.0015 Pa at 25°C)
2,2'-methylenebis(6-nonyl-p-cresol) is unlikely to volatilize or be
released into the air. It is likely that any (very low) inhalation
exposure will be absorbed if inhaled, based on available toxicity data
showing a degree of bioavailability after oral exposure. As a worst-case
assumption, inhalation absorption of 100% is appropriate for risk
Dermal absorption is likely to be extremely limited, because
2,2'-methylenebis(6-nonyl-p-cresol) is of high molecular weight and
extreme lipophilicity. No systemic toxicity was seen after dermal
exposure in an appropriate dermal toxicity study. In the absence of
specific data on dermal absorption, a dermal absorption value of no more
than 10% is appropriate.
Any 2,2'-methylenebis(6-nonyl-p-cresol) that is absorbed will be
distributed via the blood to the liver and other organs and tissues.
Liver and kidney are identified as target organs from toxicity studies.
The test material is highly lipophilic and might be expected to
distribute into fat.
Metabolism and potential for bioaccumulation
The test material is highly lipophilic and might be expected to
distribute into fat. However, the (aquatic) bioconcentration factor is
calculated to be moderate; some measure of mammalian metabolism may be
anticipated; and no specific toxicity to organs of high lipid content is
seen, so marked bioaccumulation is not expected.Based on its chemical
structure, 2,2'-methylenebis(6-nonyl-p-cresol) may be metabolized at
least via oxidative metabolism. High molecular weight implies biliary
elimination, and high lipophilicity would suggest hepatic conjugation to
be important. Metabolism may be incomplete.
No evidence of substance retention or bioaccumulation is seen in
toxicity studies, although absorption and therefore elimination will be
slow. Symptoms following acute oral administration persisted for several
days. However, since target organ toxicity was identified in subchronic
studies it cannot be determined if the prolonged symptoms were due to
pharmacokinetic persistence or to residual target organ damage;
pharmacokinetic persistence for the observed duration is improbable.
High molecular weight (above 400) suggests that biliary excretion will
be important; nephrotoxicity indicates urinary elimination is also
important. The urinary route would be more relevant for lower molecular
weight impurities and metabolites.
2,2'-methylenebis(6-nonyl-p-cresol) is inferred to be poorly and slowly
absorbed following oral exposure, highly absorbed following inhalation
exposure (relative to the very low exposures anticipated by this route)
and poorly absorbed following dermal exposure. In accordance with
guidance, default values of 50% for oral absorption, 100% for
inhalation, and 10% for dermal absorption, may be assumed. Absorbed
2,2'-methylenebis(6-nonyl-p-cresol) will be distributed within the body,
and metabolised to some extent by the liver and possibly by the GI
tract. It is not expected that 2,2'-methylenebis(6-nonyl-p-cresol) will
bioaccumulate. The urine and bile are likely to be important routes of
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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