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EC number: 304-780-6
CAS number: 94279-36-4
All available acute oral toxicity studies within this category resulted in acute oral LD50 > 2000 mg/kg bw. All available acute inhalation toxicity studies within the category resulted in acute inhalation LC50 > 2.6 mg/L.All available acute dermal toxicity studies within the category resulted in acute inhalation LD50 > 2000 mg/kg bw.
Justification for grouping of substances and read-across
The Polyfunctional acid ester (PFAE) aromatic category covers
fatty alcohol esters of Benzene-1,2,4-tricarboxylic acid. The category
contains both mono constituent and UVCB substances with fatty alcohol
carbon chain lengths from C8-C13 (linear and iso-alcohols) building
tri-esters with Benzene-1,2,4-tricarboxylic acid in variable
proportions. A further surrogate substance of similar structure is
included, namely a triester of Benzene-1,2,4-tricarboxylic acid with a
C8 alcohol, but the alcohol moiety is branched (2-ethylhexyl).
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, 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 Sections
7.1 and 13) and within Chapter 5.1 of the CSR.
Endpoint specific data matrix:
Table: Acute toxicity
Acute toxicity: Oral
Acute toxicity: Inhalation
Acute toxicity: Dermal
Experimental result:LD50 > 2000 mg/kg bw
Experimental result:LD50 > 2.6 mg/L
90218-76-1 (b) (former CAS: 67989-23-5)
Experimental result:LD50 > 3000 mg/kg bw
Experimental result:LD50 > 4800 mg/kg bw
RA: CAS 3319-31-1
RA: CAS 90218-76-1
RA: CAS 36631-30-8
(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. Lack of data for a given endpoint is
indicated by “--“.
(c) Surrogate substances are either chemicals forming part of a
related category of structurally similar fatty acid esters or
precursors/breakdown products of category members (i.e. alcohol and
fatty acid moieties). Available data on these substances are used for
assessment of toxicological properties by read-across on the same basis
of structural similarity and/or mechanistic reasoning as described below
for the present category.
Acute oral toxicity
One study performed according to OECD 401 under GLP conditions is
available to evaluate the acute oral toxicity of
1,2,4-Benzenetricarboxylic acid, tri-C9-11-alkyl esters (CAS
94279-36-4). The acute oral toxicity of 1,2,4-Benzenetricarboxylic acid,
tri-C9-11-alkyl esters (no data on purity) was investigated in 5
Sprague-Dawley rats per sex, which received the undiluted test substance
at a limit dose of 2000 mg/kg bw via oral gavage (Dreher, 1991). No
mortality occurred during the 14-day observation period and no clinical
signs were observed. Based on the results, the oral LD50 value was
considered to be greater than 2000 mg/kg bw.
The acute toxicity via the oral route of
1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters has
been investigated in rats in two studies (CAS 90218-76-1).
In an acute oral study performed according to OECD 401(no GLP), 5
Wistar rats per sex were treated via oral gavage with undiluted
1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters (99%
pure) at a limit dose of 3000 mg/kg bw (Mürmann, 1989). No mortality or
clinical effects were seen within the observation period of 14 days.
Thus, the oral LD50 value for rats was considered to be greater than
3000 mg/kg bw.
In a further study performed according to a protocol similar to
OECD 401 (no GLP), Wistar rats were orally administered different doses
of 1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters (no
data on purity) per gavage and observed for 14 days (Billmeyer, 1978).
Applied doses included 10.0, 13.3, 17.8, 23.7, and 31.6 mL/kg body
weight, corresponding to 9730, 12940, 17320, 23060, and 30750 mg/kg bw,
respectively (based on a density of 0.973 g/mL). The dose groups
consisted of 5 rats in the low dose group and 10 rats in the remaining
groups. Mortality occurred in the three higher dose groups; 3/10 both at
17320 and 23060 mg/kg bw and 8/10 at 30750 mg/kg bw. No animal died at a
dose of 9730 or 12940 mg/kg bw. Based on this result, the LD50 was
calculated to be 24230 mg/kg bw. Animals of all dose groups showed
reduced spontaneous activity, narrow palpebral fissures, soft faeces,
and reduced quantity of faeces.
In summary, the oral LD50 of 1,2,4-Benzenetricarboxylic acid,
mixed decyl and octyl triesters was greater than 3000 mg/kg bw.
The acute toxicity via the oral route of Tris(2-ethylhexyl)
benzene-1,2,4-tricarboxylate has been investigated in rats in two
studies (CAS 3319-31-1).
The acute oral toxicity of Tris(2-ethylhexyl)
benzene-1,2,4-tricarboxylate (> 99% pure) was investigated in a study
performed according to OECD guideline 401 under GLP conditions (Ohba,
1996). 5 Crj: CD(SD) rats per sex were treated with Tris(2-ethylhexyl)
benzene-1,2,4-tricarboxylate (40% in corn oil) via oral gavage at a
limit dose of 2000 mg/kg bw followed by a 14-day observation period. No
mortality occurred and no clinical signs were observed except loose
stool until 5 hours after administration. Based on this results the LD50
was greater than 2000 mg/kg bw.
In the second study that was performed equivalent to OECD 401 (no
data on GLP), 5 Alderley Park SPF albino rats per sex were treated with
Tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate (no data on purity) in
corn oil at a limit dose of 5200 mg/kg bw via oral gavage (Southwood,
1987). No mortality occurred and no significant clinical signs were
observed during the observation period of 14 days. Thus, the LD50 was
greater than 5200 mg/kg bw based on the result of this study.
In summary, the oral LD50 with Tris(2-ethylhexyl)
benzene-1,2,4-tricarboxylate was greater than 2000 mg/kg bw.
The acute toxicity via the oral route of Triisodecyl
benzene-1,2,4-tricarboxylate has been investigated in rats in one study
The acute oral toxicity of Triisodecyl
benzene-1,2,4-tricarboxylate (no data on purity) was investigated in a
study performed according to a protocol equivalent to OECD 401 (no data
on GLP). 5 Wistar rats per sex were treated with undiluted Triisodecyl
benzene-1,2,4-tricarboxylate via oral gavage (Bouffechoux, 1996) at a
limit dose of 5 mL/kg bw (corresponding to 4800 mg/kg bw based on a
density of 0.96 g/mL). No mortality occurred and no clinical signs of
toxicity were observed. Based on this result the LD50 was greater than
4800 mg/kg bw.
Acute inhalation toxicity
The acute inhalation toxicity of Tris(2-ethylhexyl)
benzene-1,2,4-tricarboxylate was investigated in an inhalation standard
acute test performed equivalent to OECD 403 under GLP conditions
(Hagensen and Cholakis, 1982) in male rats (Birch, 1972). 5
Sprague-Dawley rats per sex were whole body exposed to aerosols of
Tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate (98.95% pure) at a limit
concentration of 2588.6 mg/m³ (approx. 2.6 mg/L) for 4 hours following
an observation period of 14 days. The concentration was determined
gravimetrically but no data on particle size was given. No mortality
occurred and no clinical signs were noted except matted and drenched
coats for the first 2 days. At necropsy, reddening patches on the lungs
were detected in all males and in 3/5 females. Based on this result, the
LC50 (4 h) was greater than 2.6 mg/L.
Acute dermal toxicity
In an acute dermal toxicity study performed according to OECD 402
under GLP conditions undiluted 1,2,4-Benzenetricarboxylic acid, mixed
decyl and octyl triesters (> 97.5% pure) was dermally applied to 5
Sprague-Dawley rats per sex at a limit dose of 2000 mg/kg bw under
semiocclusive conditions (Salvador, 2009). The site of application was
the dorsal surface of the trunk with coverage of at least 10%. After
treatment duration of 24 hours, test substance residues were gently
washed off. No mortality occurred during the observation period of 14
days and no clinical signs of toxicity were observed. At necropsy, red
areas (multiple, pinpoint) in the right lobe of the thymus were noted in
a single female animal. However, this effect was not considered
treatment-related. Based on the result of this study, the dermal LD50
was greater than 2000 mg/kg bw.
Conclusion for acute toxicity
In summary, 6 studies are available studying the acute oral
toxicity of PFAE aromatic category members resulting in oral LD50 values
greater than 2000 mg/kg bw. For acute inhalation toxicity,one study is
available within the PFAE aromatic category. From this study a LC50
value of >2.6 mg/L air were determined for male and female rats at the
highest achievable doses. An acute dermal toxicity study from one
category member showed no effects at the limit dose of 2000 mg/kg bw.
Thus, the available data indicate a very low level of acute
toxicity for the category members and thus no hazard for acute oral,
inhalation and dermal toxicity was identified.
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 PFAE aromatic Category, data will be generated from
representative reference substance(s) within the category to avoid
unnecessary animal testing. Additionally, once the group concept is
applied, substances will be classified and labelled on this basis.
Based on the group concept, all available data on acute toxicity
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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