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EC number: 701-023-5
CAS number: 85408-61-3
waiver for the requirement to perform an extended one-generation
reproduction toxicity study (standard configuration or with additional
modules) was included, as the study is not scientifically necessary and,
considering concerns regarding the use of vertebrate animals for
experimental purposes, unjustified.
Two prenatal developmental toxicity (dermal) studies are available. One study result in NOAEL of 2000 mg/kg bw and the second one in a NOAEL < 800 mg/kg bw.One prenatal developmental toxicity (oral) is available, which results in NOAEL of 1000 mg/kg bw.
Justification for grouping of substances and read-across
The polyol esters category comprises of 51 aliphatic esters of
polyfunctional alcohols containing two to six reactive hydroxyl groups
and one to six fatty acid chains. The category contains mono
constituent, multi-constituent and UVCB substances with fatty acid
carbon chain lengths ranging from C5 - C28, which are mainly saturated
but also mono unsaturated C16 and C18, polyunsaturated C18, branched C5
and C9,branched C14 – C22 building mono-, di-, tri-, and tetra esters
with an alcohol (i.e.polyol).
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 of 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 Section 7.1 and 13) and
within Chapter 5.1 of the CSR.
Data matrix for developmental toxicity
RA: CAS 11138-60-6
former CAS 85186-86-3
RA: CAS 67762-53-2
NOAEL = 2000 mg/kg bw
RA: CAS 189200-42-8
RA: CAS 189200-42-8RA: CAS 11138-60-6
NOAEL < 800 mg/kg bw
RA: CAS 189200-42-8RA: CAS 67762-53-2
NOAEL = 1000 mg/kg bw
(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.
For all category members registered under REACh a full data set
for each endpoint is provided. For substances not subject to the current
REACh Phase-in registration, lack of data for a given endpoint is
indicated by "--".
(c) CAS 68434-31-7 – Lead registrant
(d) Separate registration of CAS 68434-31-7
(e) Separate registration of CAS 68434-31-7 (2-ethylhexanoic acid)
There are three studies available within the polyol esters category to
assess the potential to induce developmental effects.
Fatty acids, 8-10 (even numbered), di- and triesters with
propylidynetrimethanol (CAS 11138-60-6) was tested in a prenatal
developmental toxicity study comparable to OECD Guideline 414 (Azuka and
Daston, 2004). The test substance was percutaneously applied to
Sprague-Dawley rats for 6 h/day under occlusive conditions. 25 animals
per sex per dose were treated with 200, 600 or 2000 mg/kg bw/day in corn
oil on Days 6-15 of gestation. Control animals (25 per sex per dose)
received the vehicle. The middle and the high dose levels caused some
local irritation at the site of application, but no decreases in
maternal weight gain or food consumption. There were no differences from
control in any of the developmental parameters measured, including
embryo/fetal viability, fetal weight, malformations, or variations.
Therefore, a NOAEL of 2000 mg/kg bw/day was derived for prenatal
development and for systemic maternal toxicity. Due to the irritation
effects on skin, the local maternal NOAEL was found to be 200 mg/kg
The developmental toxicity of Fatty acids, C5-9, tetraesters with
pentaerythritol (CAS 67762-53-2) was investigated comparable to OECD
Guideline 414 (prenatal developmental toxicity study) (Feusten, 1988).
Groups of 15 presumed pregnant female Sprague-Dawley rats received daily
dermal doses of the test substance at concentrations of 800 and 2000
mg/kg bw/day during gestational days 0 to 19. Control animals remained
untreated. On day 20 of gestation the animals were euthanized and
examined for maternal and fetal parameters. There were no adverse
effects found for all parameters examined in maternal animals. Based on
the number of implantations, number of total litter losses by
resorption, mortality, clinical signs, body weight, gross pathology and
organ weights of maternal animals the NOAEL for maternal toxicity was
found to be 2000 mg/kg bw/day. Examination of fetus litter size and
weights, offspring viability (number alive and number dead), sex ratio,
grossly visible abnormalities, external, head, soft tissue and skeletal
abnormalities revealed no differences to controls and thus no indication
for teratogenic effects. The only effect found was a dose-dependently
increased number of fetuses with levocardia, although no hearth
malformations have been detected. Furthermore levocardia was observed in
vehicle control foetuses (Smith et al. 1988) and in the control foetuses
conducted in the test laboratory. Since levocardia was observed in both
treated groups, the NOAEL for embryo-/fetotoxicity and teratogenicity in
rats Fatty acids, C5-9, tetraesters with pentaerythritol was found to be
< 800 mg/kg bw/day and the LOAEL = 800 mg/kg bw/day.
The developmental toxicity of Fatty acids C8-10, mixed esters with
dipentaerythritol, isooctanoic acid, pentaerythritol and
tripentaerythritol (CAS 189200-42-8) was investigated according to OECD
Guideline 414 (prenatal developmental toxicity study) and under GLP
conditions (Trimmer, 1995). 50 male Sprague-Dawley rats were mated with
females to achieve groups of 25 pregnant Sprague-Dawley rats which then
received daily oral gavage doses of the test substance at concentrations
of 100, 500 and 1000 mg/kg bw/day during gestational days 6 to 15.
Control animals received the vehicle polyethylene glycol (PEG 400). On
day 21 of gestation the animals were euthanized and examined for
maternal and fetal parameters. There were no adverse effects found for
all parameters examined in maternal animals. Based on the number of
implantations, number of total litter losses by resorption, mortality,
clinical signs, body weight, gross pathology and organ weights of
maternal animals the NOAEL for maternal toxicity was found to be 1000
mg/kg bw/day. Examination of fetus litter size and weights, offspring
viability (number alive and number dead), sex ratio, grossly visible
abnormalities, external, head, soft tissue and skeletal abnormalities
showed only incidental malformations in two high dose females. The NOAEL
for embryo-/fetotoxicity and teratogenicity in rats for Fatty acids
C8-10, mixed esteres with dipentaerythritol, isooctanoic acid,
pentaerythritol and tridipentaerythritol was found to be 1000 mg/kg
Conclusion for developmental toxicity
There are three studies available from the Polyol PE and TMP esters
which were used to assess the developmental toxicity/teratogenic
potential of the polyol esters category members.
The prenatal developmental toxicity study with Fatty acids, C5-9,
tetraesters with pentaerythritol (CAS 67762-53-2) using Sprague-Dawley
rats resulted in a NOAEL lower than 800 mg/kg bw/day since levocardia
was found in the pups of both treated groups, although not internal
heart malformation was detected. However, prenatal developmental
toxicity studies conducted with Fatty acids, 8-10 (even numbered), di-
and triesters with propylidynetrimethanol (CAS11138-60-6) and PE ester
Fatty acids C8-10, mixed esters with dipentaerythritol, isooctanoic
acid, pentaerythritol and tripentaerythritol (CAS 189200-42-8) did not
show any developmental toxic effects. The NOAELs are 2000 mg/kg bw/day
and 1000 mg/kg bw/day, respectively. Therefore, the members of the
polyol esters category were not considered to have a potential for
waiver for the requirement to perform a prenatal developmental toxicity
study in a 2nd species was included, as this requirement is considered
not to add new information for hazard assessment and therefore is
scientifically and, considering concerns regarding the use of vertebrate
animals for experimental purposes, unjustified.
A detailed reference list is provided in the technical dossier (see
IUCLID, section 13) and within 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 category concept is applied to the polyol esters, data gaps
will be filled by interpolation, as part of a read across approach from
a representative category member(s) to avoid unnecessary animal testing.
Additionally, once the category concept is applied, substances will be
classified and labelled on this basis.
Therefore, based on the group concept, all available data on toxicity to
reproduction 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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