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EC number: 500-239-5
CAS number: 68937-90-6
Justification for read-across from fatty acids, tall-oil (CAS
In accordance with the specifications listed in Regulation (EC)
No. 1907/2006 Annex XI, 1.5 Grouping of substances and read across, the
similarity of category members has been shown to be justified based on
the scope of variability and overlapping of composition, representative
molecular structure, physico-chemical properties, tox-, ecotoxicological
profiles and supporting Information by various validated QSAR methods.
This information is given in further detail within the category
justification for the grouping of chemicals and read-across (see IUCLID
Section 13) for the dimerised fatty acids and its derivatives, and once
more within the endpoint summary and discussion for Toxicokinetics.
For assessment of human health hazards of the category members,
trends and similarities in toxicokinetic behaviour are most relevant. In
particular, the molecular weight-dependent decrease in oral and dermal
absorption and common metabolic and pathways, which are explained by
trends in molecular structure and common functional groups (monomers,
dimers and trimers of similar long-chain fatty acids). This justifies
the assumption that the toxicological profile of all category members is
similar and effects or the lack of effects observed in toxicological
studies of one ore more substances can also be expected and explained
for the other substances in the category.
For the endpoint toxicity to reproduction,
within the chemical categoryDimerised Fatty Acids and its
Derivatives, a reproduction /
developmental toxicity screening test (OECD Guideline 416) is available
for fatty acids, C18-unsaturated, dimers (CAS No. 61788-89-4).
Reproduction Toxicity Study (similar to OECD Guideline 416)with
fatty acids, tall-oil(CAS No.
On the basis of Annex XI, Item 1.5, of Regulation (EC) No
1907/2006, whereby human health effects may be predicted from data for a
reference substance, provided that the physicochemical, toxicological
and ecotoxicological properties of the reference and target substances
are likely to be similar as a result of structural similarity,read-across
from the surrogate substance fatty acids, tall-oil (CAS No. 61790-12-3)
is conducted and the aforementioned study is selected as a key study for
assessment of potential reproduction toxicity effects of the members of
the category Dimerised Fatty Acids and its Derivates.
The similarities between fatty acids,
tall-oil and the category members are based on the following
The Dimerised Fatty Acids and its Derivates
category includes the following members:
61788-89-4 Fatty acids, C18-unsaturated,
68937-90-6 Fatty acids, C18-unsaturated,
68783-41-5 Fatty acids, C18-unsaturated,
dimers, hydrogenated, “Hydrogenated dimer”
71808-39-4 Fatty acids, C16-18 and C18
unsaturated, dimerized, “Crude dimer”
68955-98-6 Fatty acids, C16-18 and
C18-unsaturated, branched and linear, “Monomer acid”
68201-37-6 Octadecanoic acid, branched and
linear, “Hydrogenated monomer acid”
30399-84-9 Isooctadecanoic acid
All the members of this category of
substances are derived from unsaturated fatty acids, for example from
fatty acids, tall-oil, which contains predominantly C18 unsaturated and
saturated fatty acids.
Natural fatty acids, tall-oil has the
Chemical name: Fatty acids, tall-oil
Chemical formula: not available - UVCB
EC No.: 263-107-3
CAS Name: Fatty acids, tall-oil
CAS number: 61790-12-3
logKow: determined range 4.9 – 7.6 (Lightbody
et al., 2002)
Solubility in water (mg/L, at 20 °C): 12.6
(The quoted value represents the sum solubility of all the components of
the test material) (Dinwoodie,
Biodegradation at 28 days: 56-84% (Madsen,
1993; Aniol, 1999; Sewell, 1994)
The HPV report final submission for fatty
acids, tall-oil and related substances; CAS No. 61790-12-3 CAS No.
65997-03-7 CAS No. 68955-98-6 CAS No. 68201-37-6 CAS No. 61790-44-1 CAS
No. 61790-45-2 Submitted to the US EPA August 2004 was screened by the
US EPA and a screening level hazard characterisation report was
published in 2007 (U. S. Environmental Protection Agency, 2007). This
report prepared by the High Production Volume Chemicals Branch indicated
that fatty acids, tall-oil are non-toxic following acute oral exposure
(LD50 (rat) > 10000 mg/kg bw) and following a 90-day test in rats the No
Observed Effect Level (NOEL) was 5% (approximately 2500 mg/kg bw/day).
Fatty acids, tall-oil were negative in an Ames test with 5 S.
typhimurium strains and in an in vitro chromosomal aberration assay with
Chinese Hamster Ovary cells. In a Two-Generation Reproduction Toxicity
study in rats, the NOEL for reproduction and systemic toxicity was 10%
in diet (ca. 5000 mg/kg bw/day). Furthermore, fatty acids, tall-oil were
not acute toxic in fish (96 h NOELr 1000 mg/L), daphnia (48 h NOELr 1000
mg/L) and algae (72 h NOELr 845 mg/L).
Given their chemical nature, fatty acids,
tall-oil are expected to be absorbed, metabolised and excreted following
the same well-known pathways of dietary fatty acids.
In conclusion, the physicochemical,
toxicological and ecotoxicological properties of fatty acids, tall-oil
and the members of the category Dimerised Fatty Acids and its Derivates
are considered to be similar, and similarity is based on common
functional groups (long-chain fatty acids, saturated and unsaturated)
and the likelihood of common breakdown products via the metabolism of
fatty acids. It is therefore considered appropriate that the data of
fatty acids, tall-oil on toxicity to reproduction is used for
read-across purposes to this category.
The selected study fulfils the requirements laid down in Annex XI,
Item 1.5, of Regulation (EC) No 1907/2006 for read-across, i.e. the
results are adequate for the purpose of classification and labelling
and/or risk assessment; have adequate and reliable coverage of the key
parameters addressed in the corresponding test method referred to in
Article 13(3); cover an exposure duration comparable to or longer than
the corresponding test method referred to in Article 13(3); and adequate
and reliable documentation of the applied method is provided.
Effects on fertility
The toxicity to reproduction of fatty acids,
C18-unsaturated, dimers was assessed in a reproduction / developmental
toxicity screening test according to OECD Guideline 421 and compliant
with GLP (Clubb and Sutherland, 2004).
Sprague-Dawley rats (10/sex/dose) were
administered the test material via the diet at 0, 200, 2000 and 20000
ppm (14.5, 147 and 1450 mg/kg bw/day and 16.5, 166, 1692 mg/kg bw/day
for males and females, respectively). Males were treated for at least 4
weeks, starting from 2 weeks prior to mating; females were treated for 2
weeks prior to mating, during mating and gestation until at least day 4
of lactation. The animals were monitored for clinical signs, body
weight, food consumption, mating and litter performance. All animals
were submitted to necropsy, which included weighing of testes and
epididymides. Histopathology was conducted on male and female
reproductive organs of the control and high dose group. The observed
effects were limited to the 20000 ppm males and included slightly
decreased body weight gain during the first week of treatment and an
increased incidence of piloerection. However, weight gain for males at
20000 ppm was essentially similar to control animals for the rest of the
study on weeks 2-4 and the incidence of piloerection lacked any
dose-relationship. There were no effects on testes, epididymides and
ovaries and on reproductive performance between control and test
animals. The fertility index was 100% for males and females in all dose
groups. A NOAEL (reproductive toxicity/fertility) of ≥ 1450 mg/kg bw/day
and ≥ 1692 mg/kg bw/day for males and females, respectively, was
determined based on no toxicologically significant effects at the
highest dose tested.
There are no further data available on the
reproductive/developmental toxicity of fatty acids, C18-unsaturated,
dimers or another member of the chemical category the substance belongs
A two-generation study with the surrogate substance fatty acids,
tall-oil, (CAS No. 61790-12-3)is
available andread-across from this
surrogate was conducted for assessment of potential toxic effects to
The reproductive toxicity of fatty acids,
tall-oil (CAS No. 61790-12-3) was evaluated by oral administration in a
Two-Generation Reproduction Toxicity Study similar to OECD Guideline 416
performed at a time before implementation of GLP (Tegeris, 1977). 30
male and 15 female Sprague-Dawley rats per dose group were administered
the test material at concentrations of 0, 5 or 10% (w/w) in the diet
(corresponding to 0, 2000 and 4000 mg/kg bw/day for males and 0, 2500
and 5000 mg/kg bw/day for females, respectively). Additionally, groups
of rats were concurrently treated with oleic acid at 5 and 10% (w/w) in
diet as controls.
The parental animals were fed the test substance starting at 20
days pre-mating.Treatment continued
through weaning of the first generation (F1). After weaning, 20 F1 males
and 20 F1 females per group were maintained on the parental diet and
mated at 100 days of age (with the members of each sex coming from a
different dam). The delivered F2 generation survived through weaning.Parameters
evaluated included F1 reproductive parameters, F1 fertility, viability,
lactation, and gestation indices. Haematology, serum chemistry,
urinalysis, and organ weights for F1 animals, gross pathology of F1 and
F2 animals and microscopic pathology of various organs of the F2 pups
There were no treatment effects on reproductive performance, the
number of liveborn or stillborn F1 litters and pups, or weaning weight
of the F1 pups.No treatment-related
changes in fertility, viability, lactation, or gestation indices were
measured. Clinical chemistry, haematology and urinalysis parameters were
similarly unchanged, organ weights were unchanged, and gross and
microscopic pathology revealed no treatment-related effects.
Fatty acid, tall-oil had no effect on the
reproductive physiology of rats at doses as high as 10% (w/w) in diet.
The no-observed-adverse-effect-level (NOAEL) for reproduction toxicity
was therefore considered to be ≥ 4000 and ≥ 5000 mg/kg bw/day for males
and females, respectively.
As previously discussed (see Toxicokinetics),
physicochemical data and the weight of evidence on toxicokinetic
behaviour of fatty acids, C18-unsaturated, dimers and/or structurally
related substances indicate a low level of systemic absorption and
bioavailability both via the oral and the dermal routes. Furthermore,
the whole body of available data on the toxicity of fatty acids,
C18-unsaturated, dimers and/or structurally related substances indicates
as well a low level of toxicological activity. Thus, fatty acids,
C18-unsaturated, dimers are considered non-toxic after acute oral
exposure, not irritating to skin and eyes, not skin sensitising and not
genotoxic (in vitro). In a 90-day feeding study with fatty acids,
C18-unsaturated, dimers no changes were found after histopathological
examination of male and female reproductive organs up to the highest
dose tested (ca. 3590 and 4085 mg/kg bw/day for males and females,
respectively) (see Repeated dose toxicity).
Taken together, the available data on
physicochemical properties, toxicokinetics and toxicological activity of fatty
acids, C18-unsaturated, trimers and/or supporting
substances do not suggest or indicate any potential for adverse effects
Read-across based on grouping of substances (category approach):NOAEL (developmental toxicity) ≥ 1692 mg/kg bw/day (OECD 421)No developmental toxicity was observed in a study similar to OECD 416 performed with the surrogate substance fatty acids, tall-oil.
are no data available on potential developmental/teratogenic effects of fatty
acids, C18-unsaturated, trimers.
There are data on developmental toxicity / teratogenicity after oral
exposure of the category member fatty acids, C18-unsaturated, dimers,
which was analysed in a reproduction/developmental toxicity screening
test performed according to OECD Guideline 421 (Clubb and Sutherland,
2004). Thus, read-across based on a category approach was conducted.
Sprague-Dawley rats (10/sex/dose) were
administered fatty acids, C18-unsaturatred, dimers via the diet at 0,
200, 2000 and 20000 ppm (14.5, 147 and 1450 mg/kg bw/day and 16.5, 166,
1692 mg/kg bw/day for males and
females, respectively). Males were treated for at least 4 weeks,
starting from 2 weeks prior to mating; females were treated for 2 weeks
prior to mating, during mating and gestation until at least day 4 of
lactation. The females were allowed to litter normally. No effects on
litter size and litter survival and on litter and pup weights were
noted. No externally visible abnormalities were noted among all pups.
Thus, a NOAEL (developmental toxicity) of ≥ 1692 mg/kg bw/day was
determined based on no toxicologically significant effects at the
highest dose tested.
are no further data available on potential developmental/teratogenic
effects of any other member of the chemical category they belong to.
Taking into account the toxicokinetic
behaviour of fatty acids in general and the available toxicity studies
on fatty acids, C18-unsaturated, dimers and/or structurally related
substances, the weight of evidence does not indicate any potential for
the induction of developmental/teratogenic effects by any route of
Based on the toxicokinetic information
available, absorption and systemic bioavailability of fatty acids is
strongly dependent on their molecular weight, which in turn is related
to chain length and degree of saturation. Thus, C16-18 fatty acids are
generally less well absorbed than fatty acids of shorter chain length
via the oral route. For dimerised and trimerised fatty acids, a much
lower level of absorption by the gastrointestinal tract is expected.
Furthermore, and also considering
their low water solubility and lipophilic nature, a low level of
absorption is expected for C16-C18 fatty acids via the dermal route,
while for dimerised and trimerised fatty acids dermal absorption is
virtually ruled out.
The fraction of systemically absorbed
C16-C18 fatty acids is expected to undergo rapid metabolisation and
excretion mainly in the expired CO2, as it occurs in the case of dietary
fatty acids. By contrast, ingested dimerised and trimerised fatty acids
are expected to be mainly excreted in the faeces without being
The whole body of available
toxicological information on fatty acids, C18-unsaturated, dimers
(and/or other members of the chemical category they belong to, as well
as further structurally related substances) does not suggest or indicate
potential toxic effects after exposure by any route, and in particular
does not give rise to concern with regard to potential
developmental/teratogenic effects. Thus, in a 90-day feeding study
conducted with fatty acids, C18-unsaturated, dimers no changes were
found after histopathological examination of male and female
reproductive organs up to the highest dose tested (ca. 3590 and 4085
mg/kg bw/day for males and females, respectively) (Spurgeon and Hepburn,
1993). In a Two-Generation Reproduction Toxicity Study performed with
fatty acids, tall-oil (CAS No. 61790-12-3), no treatment-related effects
were observed in pups of the F1 and F2 generations of rats orally given
up to 5000 mg fatty acids, tall-oil/kg bw/day via the diet. In the same
study, no treatment-related effects were observed a control group
treated with oleic acid, a mono-unsaturated omega-9 C18 fatty acid, at
the same dose levels (Tegeris, 1977).
Additionally, publicly available
information on the potential toxic effects of naturally occurring fatty
acids was taken into account. Placental transfer of some fatty acids has
been reported for several species including humans (CIR, 1987). In a
combined repeated dose and reproductive/developmental toxicity test
according to OECD 422 with docosanoic acid (CAS No. 112-85-6) no adverse
effects on viability, sex ratio or body weight of pups were noted and no
morphological abnormalities in external and visceral observations in
pups were observed in concentrations up to and including 1000 mg/kg
bw/day (OECD SIDS, 2001).
In conclusion, considering the
available information on the physicochemical properties, the
toxicokinetic behaviour and toxicity of fatty acids, C18-unsaturated,
dimers (and/or other members of the chemical category they belong to, as
well as further supporting substances) no developmental/teratogenic
effects are expected. Therefore, based on the weight of evidence a
developmental toxicity study by any route of exposure is considered
scientifically unjustified and not necessary in terms of animal welfare.
References (not in IUCLID)
OECD SIDS (2001) DOCOSANOIC ACID; CAS
N°: 112-85-6, SIDS Initial Assessment Report for 13th SIAM, November
Based on read-across within the
category approach and on read-across from a surrogate substance, the
available information on the reproductive potential of fatty
acids, C18-unsaturated, trimers is 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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