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EC number: 947-899-4
CAS number: -
Oral: NOAEL (male/female, rat, 90 d) ≥ 1000 mg/kg bw/day
Read-across from structural analogue source substance pentanoic
acid, mixed esters with PE, isopentanoic acid and isononanoic acid (CAS
There are no data on the repeated dose toxicity of fatty acids
C18-C22 (even numbered), tetraesters with pentaerythritol. The
assessment was therefore based on studies conducted with analogue
substances as part of a read-across approach, which is in accordance
with Regulation (EC) No. 1907/2006, Annex XI, 1.5. 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 analogue read-across approach is provided
in the technical dossier (see IUCLID Section 13).
A 28 day study with fatty acids, C5-10, esters with
pentraerythritol (CAS 68424-31-7) was conducted similar to OECD 407 and
under GLP conditions (Zeneca, 1993). The test substance was administered
in concentrations of 1000 ppm, 5000 ppm and 12500 ppm (corresponding to
112, 562 and 1450 mg/kg bw/day for male and 119, 586 and 1613 mg/kg
bw/day for female rats) to 5 Alpk:APfSD rats per sex and dose for 28
consecutive days. Control animals (5 per sex and dose) received the
plain diet. There were no toxicologically significant effects on body
weight, food consumption and clinical condition and mortality up to and
including the highest dose level. Changes in clinical chemistry and red
cell-related parameters were observed in male rats at 12500 ppm, but
these were minor and considered not to be of toxicological significance.
A minimal hepatocyte hypertrophy present in males of the 12500 ppm group
was observed and considered to be evidence of an adaptive response.
Microscopic examination of the kidneys from male animals from all dose
groups revealed an increase in hyaline droplet formation (the main
constituent of which is alpha-2µ-globulin) and tubular basophilia. This
phenomenon is widely accepted to be specific to the male rat and as such
is considered to have no relevance to man. A NOAEL of 1450 and 1613
mg/kg/d could be identified for male and female rats, respectively.
A 28 day study with fatty acids, C8-10 mixed esters with
dipentaerythritol, isooctanoic acid, pentaerythritol and
tripentaerythritol (CAS 189200-42-8) was conducted similar to OECD 407
and under GLP conditions (ExxonMobil, 1995). The test substance was
administered by gavage in concentrations of 100, 500 and 1000 mg/kg
bw/day to 5 Crl:CD BR rats per sex and dose for 28 consecutive days.
Control animals (5 per sex and dose) received the concurrent vehicle
polyethylene glycol (PEG 400). There were no toxicologically significant
effects on body weight, food consumption and clinical condition and
mortality up to and including the highest dose level. One male animal of
the 500 mg/kg bw group died after the first application due to a gavage
error. This animal was replaced on Day 1 with another animal that
received one less dose than the other animals. All animals survived the
study period to the scheduled termination. The neurobehavioural
observations made on Day 8 and Day 27 were unremarkable for the animals
treated with the test substance. Due to the absence of a dose-response
pattern, these effects were judged to be incidental and not related to
treatment. Changes in clinical chemistry and haematology were not
considered to be clinically significant due to the absence of a clear
dose-response pattern. In the mid dose group, there was a statistically
significant increase in the mean relative testes weight. Due to the
absence of a dose-response pattern, this effect was judged to be
incidental. The necropsy revealed no treatment-related findings.
Moreover, no treatment-related histopathologic changes were observed in
any of the organs or tissues examined. Since no adverse and
treatment-related effects were observed up to and including the highest
tested dose level were observed, the NOAEL was found to be ≥ 1000 mg/kg
A 90-day oral feeding toxicity study with pentaerythritol ester of
pentanoic acids and isononanoic acid (CAS 146289-36-3) was performed
according to OECD 408 and under GLP conditions (ToxLabs, 1998). Groups
of 10 male and 10 female Wistar rats were exposed to the substance at
100, 300 and 1000 mg/kg bw/day by gavage daily, 7 days/week for 90 days.
Satellite control and high dose groups containing 10 male and female
animals each were observed for additional 28 days. Control animals (10
per sex and dose) received the concurrent vehicle, distilled water
containing 1% Tween 80. Observations and examinations of the animals
included clinical signs, body weight, food consumption, haematology,
clinical chemistry, organ weights, neurobehaviour, gross necropsy and
histopathology. The daily oral administration of the test substance was
tolerated without any adverse effects up to 1000 mg/kg bw/day. No
mortality was observed except for two animals that died shortly after
administration due to incorrect gavage. Absolute and relative kidney
weights were increased in all male animals in the high dose group which
was still present after the recovery period. However, histopathology
revealed no adverse effects in the kidney. Absolute and relative liver
weights were increased in both sexes but this was no longer apparent
after the recovery period in females. Other significant differences seem
to be incidental. The activity of alkaline phosphatase of the serum
significantly increased in the high dose group, males and females. This
indicates damage to liver cells and/or an increased function rate. This
finding was no longer apparent at the end of the treatment-free period.
Except for the increased kidney weights and liver weight in the males,
all changes (e.g. clinical chemical changes) were no longer apparent at
the end of the treatment-free period. The increase in kidney weights in
all male animals could be correlated to the formation of hyaline
droplets a phenomenon widely accepted to be specific to the male rat and
as such considered to have no relevance to man, a 90-day oral NOAEL of
1000 mg/kg bw/day was found for Pentaerythritol ester of pentanoic acids
and isononanoic acid in male and female rats.
Overall conclusion for repeated dose toxicity
The data for the analogue source substances considered for
read-across showed that no effects were observed up to and including the
recommended limit values. Therefore and based on read-across, as the
available data from analogue substances did not identify any hazard for
repeated dose toxicity, the target substance fatty acids C18-C22 (even
numbered), tetraesters with pentaerythritol is not expected to be
hazardous following repeated exposure.
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 analogue concept is applied to
fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol,
data will be generated from data for reference source substance(s) to
avoid unnecessary animal testing. Additionally, once the analogue
read-across concept is applied, substances will be classified and
labelled on this basis.
Therefore, based on the analogue read-across approach, the
available data on repeated dose toxicity do not meet the classification
criteria according to Regulation (EC) 1272/2008 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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