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EC number: 306-232-1
CAS number: 96690-38-9
Justification for grouping of substances and read-across
The long-chain aliphatic ester (LCAE) category covers mono-esters
of a fatty acid and a fatty alcohol. The category contains both
mono-constituent and UVCB substances. The fatty acid carbon chain
lengths range is C8 - C22 (even and uneven numbered, including
saturated, unsaturated, branched and linear chains) esterified with
fatty alcohols with chain lengths from C8 - C22 (even and uneven
numbered, including saturated, unsaturated, branched and linear) in
varying proportions to mono-esters.
The available data allows for an accurate hazard and risk
assessment of the category and the category concept is applied for the
assessment of environmental fate and environmental and human health
hazards. Thus, where applicable, environmental and human health effects
are predicted from adequate and reliable data for source substance(s)
within the group, by interpolation to the target substances in the group
(read-across approach), applying the group concept in accordance with
Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. In particular, for
each specific endpoint the source substance(s) structurally closest to
the target substance is/are chosen for read-across, with due regard to
the requirements for adequacy and reliability of the available data.
Structural similarities and similarities in properties and/or activities
of the source and target substance are the basis of read-across.
A detailed justification for the grouping of chemicals and
read-across is provided in the technical dossier (see IUCLID Sections
7.1 and 13) and within Chapter 5.1 of the CSR.
Overview of skin sensitisation
RA: CAS 3687-46-5, 17673-56-2, 93803-87-3
Former CAS 97404-33-6
(a) Category members subject to the REACh Phase-in registration
deadline of 31 May 2013 are indicated in bold font.
(b) Substances that are either already registered under REACh or
not subject to the REACh Phase-in registration deadline of 31 May 2013
are indicated in normal font.
The skin sensitising potential of decyl oleate (CAS 3687-46-5) was
evaluated in a local lymph node assay (LLNA) performed according to OECD
429 (Beerens-Heijnen, 2010). 25 µl of a 25, 50 and 100% suspension of
test substance in acetone/olive oil (4:1 v/v) was applied to the dorsal
surface of both ears of 5 CBA mice/dose for 3 consecutive days. On Day
6, each animal was injected via the tail vein with 0.25 mL sterile
phosphate buffered saline containing 20 µCi of 3H-methyl thymidine.
After approximately 5 hours, the mice were sacrificed and the draining
lymph nodes of the ears were excised. The nodes were pooled for each
animal in PBS and the DNA precipitated with 5% TCA at 4 °C overnight.
Slight edema (score 1 of 4) was noted on the ears of 5/5 mice treated
with the undiluted substance. This is not considered to have had a
significant effect on the activity of the lymph nodes. All the nodes of
the animals in the control and treatment groups were normal in size, and
no macroscopic abnormalities were noted in the surrounding area. The
positive control group (hexyl cinnamic aldehyde) was valid. The mean
DPM/animal values for the control, 25, 50 and 100% groups were 488, 571,
951 and 1013, respectively. The SI values calculated for the 25, 50 and
100% groups were 1.2, 2.0 and 2.1, respectively. The SI was lower than 3
up to and including 100%, therefore the test substance is considered to
be not skin sensitising.
A Guinea pig maximisation test was performed with decyl oleate
according to the method described by Magnusson & Kligman (Gloxhuber,
1979). 19 female guinea pigs in the test group and 10 females in the
control group were induced by epicutaneous exposure to a 1% solution in
ethanol, without a dressing. The challenge was performed by open
epicutaneous exposure to a 1% formulation in Vaseline. The animals in
the treatment group and the control groups did not show any signs of a
sensitising effect at the reading time points (24 and 48 h after
challenge reaction). This study was considered insufficient for
assessment due to the limited data on methods and individual results.
The results of a skin sensitisation study performed in rabbits
according to a French national guideline (1971) were presented in a
publication (Guillot, 1977). During the induction phase, an epicutaneous
application of the undiluted test substance or a 15% solution (in 3%
polyoxyethylene sorbitan stearate, 80% water, 2% unknown preservative)
was repeated daily for 60 days. The epicutaneous challenge was performed
with the same concentration on Day 67. No sensitisation was reported.
The study was considered insufficient for assessment, as it does not
meet important criteria of today’s standard methods.
A skin sensitisation study withtetradecanoic
acid, tetradecyl ester (CAS 59231-34-4) wassummarised in a
review published by the Cosmetic Ingredient Review, (CIR Expert Panel,
1982). The Landsteiner and Jacobs guinea pig sensitisation procedure was
followed. No sensitisation was observed. Due to the limited information
reported, the results of the studies are considered to be inconclusive.
One non-guideline skin sensitisation study was performed with
Fatty acids, C8-10, C12-18 alkyl esters (CAS 95912-86-0) (Potokar,
1972). The induction and challenge phases were performed with a 25%
solution by intradermal injection; no skin sensitisation was reported.
As there was no positive control and very few details from the study
protocol were given, the study result was considered to be insufficient
In a human skin sensitisation study, 20 volunteers were exposed to
the test substance via dermal application (Herzberg, 1968). The
inductions were performed daily for 14 consecutive days and the
challenge was performed following a 14-day recovery period. No skin
sensitisation was reported. The results were considered insufficient for
assessment due to the very limited amount of data.
In a review publication by the Cosmetic Ingredient Review, two
animal studies and a study in human volunteers withtetradecanoic
acid, tetradecyl ester (CAS 3234-85-3)were briefly
summarised (CIR Expert Panel, 1982). In the animal studies, the
Landsteiner and Jacobs guinea pig sensitisation procedure was followed
(Landsteiner and Jacobs, 1935). The first study was performed with 10
epicutaneous induction phases and an epicutaneous challenge phase, while
the second study was performed with 10 intradermal induction phases and
an intradermal challenge phase. Due to the limited information reported,
the results of the studies are considered to be inconclusive. An 8%
formulation of the test substance (cologne stick) was applied to the
skin on one arm of 196 volunteers and covered with an occlusive dressing
3 days a week for a total of 10 induction exposures. After a rest period
of 14 days, one challenge application was performed and the skin
assessed for sensitisation reactions. No sensitisation reactions were
The skin sensitising potential of (Z)-octadec-9-enyl
(Z)-docos-13-enoate (CAS 17673-56-2) was evaluated in a Buehler
test performed according to a protocol similar to OECD 406 (Pitterman,
1995). The induction treatments were performed on 20 Dunkin Hartley
guinea pigs on Day 0, 7 and 14. A 70% solution of the test substance in
peanut oil was applied to the shaved skin on the flank of the animals,
and covered with an occlusive dressing for 6 hours. On Day 28, all the
animals were challenged with a 60% solution of the test substance via
topical application on the flank for 6 hours, using an occlusive
dressing. 10 guinea pigs in the control group were treated according to
the same protocol with the vehicle as the control substance. During the
first reading, 1/20 treated animals and 1/10 negative control animals
had a positive reaction, respectively. In the second reading, 2/20
treated animals and 1/10 negative control animals had a positive
reaction, respectively. The slight, patchy erythema was limited to the
left flank, where both the induction and challenge doses were applied.
It is possible that the reaction was skin irritation, rather than a
sensitisation reaction. All skin irritation effects had cleared within
72 hours after the challenge exposure ended. The result of the
reliability check was inconclusive. During the first challenge
application with 25% alpha-hexyl cinnamic aldehyde, a sensitisation
reaction was induced in 25% (5/20) of the Dunkin Hartley guinea pigs,
while the second challenge application did not cause sensitisation
reactions. In the negative control group, the first challenge
application induced sensitisation in 20% (2/10) of the animals, and the
second challenge application did not cause sensitisation reactions.
Under the conditions of this study, the test substance is considered to
be not skin sensitising.
The skin sensitising potential of 2-octyldodecyl isooctadecanoate
(CAS 93803-87-3) was evaluated in a Guinea Pig Maximisation Test (GMPT)
performed according to a protocol similar to OECD 406 (Busschers, 1998).
The first induction (Day 1) was performed on 10 animals by intradermal
injection of the undiluted test substance. On Day 7, the animals were
treated with 10% sodium lauryl sulphate (SDS) in vaseline, to induce
skin irritation. During the second induction on Day 8, the undiluted
test substance was applied topically and held in place with a
semi-occlusive dressing for 48 hours. On Day 21, all the animals were
challenged with the undiluted test substance via topical application
under semi-occlusive conditions for 24 hours. 5 guinea pigs in the
control group were treated according to the same protocol with the
vehicle (corn oil). 48 hours after the intradermal induction, slight to
severe erythema was noted at most of the injection sites in the treated
and control animals. 4/5 control animals also exhibited necrosis at the
FCA/test substance injection site. These effects were caused primarily
by the injection and not by a reaction to the test substance. Following
the topical induction, severe erythema and scabs were observed at the
test site in 3/10 treated animals. No sensitisation was observed in the
treated animals during the reading time points 48 and 72 hours after the
challenge. The test substance did not cause skin sensitisation under the
conditions of the study.
Overall conclusion for skin sensitisation
Two Guinea Pig Maximisation Tests and a Local Lymph Node Assay
performed with the category members decyl oleate (CAS 3687-46-5),
(Z)-octadec-9-enyl (Z)-docos-13-enoate (CAS 17673-56-2) and
2-octyldodecyl isooctadecanoate (CAS 93803-87-3), show that no skin
sensitisation was induced and indicate that the remaining category
members are not expected to have a skin sensitising potential
(Beerens-Heijnen, 2010; Busschers, 1998; Pitterman, 1995).
A detailed reference list is provided in the technical dossier
(see IUCLID, section 13) and within the CSR.
According to Article 13 of Regulation (EC) No. 1907/2006 "General
Requirements for Generation of Information on Intrinsic Properties of
substances", information on intrinsic properties of substances may be
generated by means other than tests e.g. from information from
structurally related substances (grouping or read-across), provided that
conditions set out in Annex XI are met. Annex XI, "General rules for
adaptation of this standard testing regime set out in Annexes VII to X”
states that “substances whose physicochemical, toxicological and
ecotoxicological properties are likely to be similar or follow a regular
pattern as a result of structural similarity may be considered as a
group, or ‘category’ of substances. This avoids the need to test every
substance for every endpoint". Since the group concept is applied to the
members of the LCAE category, data will be generated from data for
reference source substance(s) to avoid unnecessary animal testing.
Additionally, once the group concept is applied, substances will be
classified and labelled on this basis.
Therefore, based on the group concept, the available data on skin
sensitisation do not meet the classification criteria according to
Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore
conclusive but not sufficient for classification.
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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