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EC number: 915-730-3
CAS number: -
Skin corrosion: Not corrosive based on absence of acid and based groups
indicating corrosion. In a HRIPT test up to 75% no corrosion and no
irritation was seen. Absence of skin corrosion is further supported in
the in vitro skin irritation test where the substance is borderline
- Skin (OECD TG 439): irritating (borderline irritant/non irritant)
- Eye (QSAR): not irritating
- Respiratory irritation: Based on absence of human data and absence of
other data indicating such an effect.
Not corrosive based on absence of acid and based groups indicating
corrosion. The functional ketone group is not very reactive in absence
of adjacent (beta position) electrophilic groups such as halogens,
oxygens and/or double bonds. Absence of skin corrosion is further
supported in the in vitro skin irritation test where the substance is
borderline irritant/non-irritant. Also in a HRIPT study no corrosion was
found up to 75%.
In vitro skin irritation according to OECD TG 439: The key
study was an in vitro skin irritation study that was performed in
accordance with OECD TG 431 (EPISKIN). The key study indicated that OTNE
is irritating to the skin, based on a mean tissue viability of <50%
(48%). The key study was performed as a repeat of a supporting in vitro
skin irritation study, in which a mean tissue viability of 55% was
measured, which would lead to non-classification. As the tissue
viability was a borderline result in the range 45 -55% a conservative
approach is applied and the substance is considered a skin irritant.
Skin irritation: Human patch test
Another supporting study is a human skin irritation patch test. In
this occlusive patch test, 0.3 ml OTNE in 3:1 diethyl phthalate:ethanol
or 3:1 ethanol:diethyl phthalate at concentrations of 20, 40, 60, and
75% was applied to the backs of male and female subjects for two 24-hour
periods over a 96-hour study period. Sites were assessed approximately
48 hours after each treatment period. Under these conditions, OTNE
elicited negligible dermal irritation potential in humans.
In vivo skin irritation in a 90 -day repeated dose dermal toxicity
studies: Skin irritation observed in subchronic (90 -day) dermal
toxicity studies performed in rats and mice are included in the present
section. Solutions of OTNE in ethanol were applied to the skin of rat
and mice for 5 days per week for 3 months, without occlusion. 10 rodents
were tested in each dose group. Doses were 6.25%, 12.5%, 25% and 50%
OTNE in ethanol and 100% OTNE, on approx. 10% of body surface area.
In rats these doses correspond approximately to 31.25 to 500
mg/kg bw in rats. In all male and female rats (except in 62.5 mg/kg
bw/day OTNE males) the incidences of minimal to mild hyperplasia and
hyperkeratosis at the site of application were
significantly greater than those in their respective control groups.
Therefore the NOEC in rats is 6.25%.
In mice these dosed correspond to 125 to 2.000 mg/kg bw. All
exposure groups developed skin hyperkeratosis, hyperplasia, chronic
active inflammation, fibrosis, epidermal suppurative inflammation, and
hair follicle hyperplasia. No corrosion was observed but a clear NOAEC
in mice is not found. The LOEC is 6.25%.
Both rats and mice were dermally exposed to OTNE in ethanol
without occlusion of the treated site. Therefore, the local effects
observed as a result of dermal exposure may have been confounded, as
grooming by the animals can have influenced the skin effects, actual
dermal dose and/or dermal exposure time. The effects seen may be an
under or over-estimation of repeated dose skin irritation. As a result
of these methodological limitations, the derivation of a dose descriptor
(NOAEC or LOAEC) for local effects via the dermal exposure route is
deemed inappropriate. Nevertheless, the skin irritant effects reported
in this study are considered to support the conclusion for the skin
The key information available for the eye irritating potential of
OTNE was adequate QSAR. The model of AP Worth and MTD Cronin as
published in Journal of Molecular Structure (TheoChem) 622 (2003) 97-111
("The use of discriminant analysis, logistic regression and
classification tree analysis in the development of classification models
for human health effects") was used to predict the irritating potential
of OTNE based on its molecular weight and structural analogues.
The substance has a MW of 234 g/mol, which is higher than the
model's threshold value (137 g/mol) for prediction of eye irritation.
Additionally, two structural analogues (2,6-dimethyl-4-heptanone,
6,10,14-trimethyl-2-pentadecanone) of OTNE are classified as not
irritating to the eyes.
Based on the predicted values in the model, the substance does not
need to be classified as irritant (molecular weight higher than
threshold value and non-irritating property of structural analogues).
Tabulated summary on the QSAR prediction, the (Q)SAR methodology
and the relevance for REACH:
Reliability of prediction
Scientific validity of
Relevance for REACH C&L
QSAR based on OECD TG 405 information and DSD criteria
REACH requires information similar to OECD TG 405
Prediction according to algorithm: OTNE has MW of 234, which is much > 137 and therefore not an eye irritant
Liquid organic substances with MW >137 are not eye irritants
(Q)SARs are allowed methodology when used according to Annex XI
OTNE is within the domain, considering i) being a liquid; ii) MW range used in the model and; iii) other cyclic ketons are present in the training set
See substances in training set, cyclic ketons are included
Eye irritation hazards for OTNE has to be assessed under REACH
Limited, because OTNE does not have additional groups which may lead to higher eye irritation e.g. higher electrophilicity
Limited uncertainty, see paper of Worth and Cronin, 2000
The uncertainty of the result is limited, because the QSAR is based on OECD TG 405. In addition OTNE is within the domain
Mode of action explanation
OTNE has insufficient reactive properties to cause eye irritation or corrosion
Not explained, but liquids with MW > 137 are expected to limitedly penetrate the eye barriers
The QSAR result of OTNE covers the mode of actions in OECD TG 405 because the training set is based on this type of tests
Not an eye irritant according to DSD and therefore also not CLP
Uses DSD criteria: CLP criteria are very similar to DSD
Result is based on DSD criteria which are very similar to CLP
Actual use into DSD and CLP
Not an eye irritant
Sufficiently adequate, no further information needed
For respiratory irritation mostly human data are used for the
assessment because no suitable in vitro or in vivo tests are available
that can identify respiratory irritation (REACH guidance R.7.2.12).
There are no human data such as indicated in R7.2.12 the ECHA guidance
that indicate respiratory reactions of the substance e.g. from consumer
experience or occupational exposure. Also in view of the borderline skin
irritation potential, the substance is not corrosive or severely
irritating which further minimizes the respiratory irritation hazard
(ECHA guidance: R.220.127.116.11, 2017).
Based on the available information OTNE needs to be classified as
a skin irritant (Skin Irrit. Cat 2) according to EU CLP (EC 1272/2008
and its updates): H315 and the phrase -Causes skin irritation-, needs to
Based on the available information the substance does not need
classified for eye and respiratory irritation, according to EU CLP (EC
1272/2008 and its updates).
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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