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EC number: 939-638-8
CAS number: 90268-37-4
A combined repeated dose and reproductive/developmental screening study was performed with read across substance CAS No. 90268-36-3 (Butanedioic acid, sulfo-, 1-C12-18-alkyl esters, disodium salts) according to OECD guideline 422, showed NOAEL-levels of 60 mg/kg bw for paternal/maternal toxicity, 120 mg/kg bw for reproductive toxicity and 120 mg/kg bw for developmental toxicity. A 90-day study was also available for the read across substance CAS No. 37294 -49 -8 (Disodium C-isodecyl sulphonatosuccinate) in the mono-ester subgroup, given to rats at 0.25, 1 and 4% in the diet. This study showed a NOAEL of 1% in the diet, corresponding with 750 mg/kg bw. For risk assessment, the lowest NOAEL of 60 mg/kg bw in the OECD 422 study was selected as this approach was considered most conservative.
data were available for the registered substance, but read across data
were available from subgroup member CAS No. 90268-36-3 (Butanedioic
acid, sulfo-, 1-C12-18-alkyl esters, disodium salts):
A key study for subacute toxicity was performed by means of an oral
combined repeated dose and reproduction/development screening study
according to OECD guideline 422 (Hansen, 2013a). The test item was a
solid formulation (containing >93% active ingredient) which was
administered as a watery solution orally by gavage to rats at dose
levels of 60, 120 and 300 mg act. ingr./kg bw/day for at
least 28 days in male rats up to 54 days in female rats. One of 10 male
and one of 10 female animals at 300 mg/kg bw/day died prematurely on
test day 33 or on gestation day 9. Slight to moderate salivation was
noted in a few male and female animals at 120 mg/kg bw/day; at 300 mg/kg
bw/day, piloerection and a slight to extreme salivation was noted for
several to all male and female animals on several days. Reduced body
weight was noted for the male animals at 120 mg/kg bw/day and for both
sexes at 300 mg/kg bw/day. Increases in ALAT, aP and ASAT and decreases
in globulin, cholesterol, chloride and potassium concentrations were
noted for the male and/or female animals of the intermediate and/or the
high dose group (120 and/or 300 mg/kg bw/day). Several organ weights
were seen in males and females dosed at 120 and 300 mg/kg bw/day, most
remarkably for the thymus and liver weights of the animals of the high
dose group. Macroscopic inspection revealed changes in the stomach of
male animals dosed at 300 mg/kg bw/day and female animals dosed at 120
and 300 mg/kg bw/day. Histopathological examination revealed changes in
the liver (hepatocellular hypertrophy and macrovesicular vacuolation)
and the non-glandular stomach (squamous cell hyperplasia) of male and
female animals dosed at 300 mg/kg bw/day. These latter changes are
considered to be related to a local activity of the test item. As humans
lack a forestomach, the relevance of these changes for humans is
were as follows: 60 mg/kg bw for paternal/maternal toxicity and 120
mg/kg bw for reproductive and developmental toxicity (see Section 7.8.1
and 7.8.2). The reproductive and developmental changes were seen at
paternal/maternal toxic doses, and were considered to be secondary to
A supporting 14-day dose-range-finding study (Hansen, 2013b) was
conducted with test item containing >95 % active ingredient to select
the dose levels for a combined repeated dose toxicity study with the
reproduction/developmental toxicity screening test of the test item in
rats. The animals were treated once daily with100, 300 and 1000 mg act.
ingr./kg bw/day by oral administration. Four of 5 males and all (5)
females treated orally with 1000 mg/kg bw/day died prematurely. Oral
treatment with 1000 mg/kg bw/day caused signs of systemic toxicity in
form of pilo-erection, reduced motility, pultaeous faeces/diarrhoea,
salivation, increased drinking water consumption, ataxia or decreased
body temperature in the male and/or female rats. A decrease in body
weight, body weight at autopsy and food consumption was noted for the
male and female rats treated with the intermediate and the high dose. At
necropsy, whitish deposits on the stomach mucosa were observed in the
male rats treated orally with 300 mg/kg bw/day. The high dose of 1000
mg/kg bw/day led to further changes in the gastro-intestinal tract in
both sexes such as inflation or discolourations. The examination of
organ weights revealed a dose-related increase of liver weights. The
dose of 300 mg/kg bw was considered as NOAEL, and dose levels selected
for the repeated dose and reproduction/developmental toxicity screening
test were 60, 120 and 360 mg/kg bw/day.
conclusion, NOAEL-levels of 60 mg/kg bw for paternal/maternal toxicity,
60 mg/kg bw for reproductive toxicity and 120 mg/kg bw for developmental
toxicity were obtained in a combined repeated dose and
reproductive/developmental screening study which was performed with
registered substance according to OECD guideline 422. Therefore, no
classification is needed.
-day study was not available for the registered substance, however read
across data were available from a category member, CAS No. 37294-49-8
(Disodium C-isodecyl sulphonatosuccinate).
this read across substance, a 14 -day dose rang finding study was also
conducted as supporting study (Hansen, 2013c). Rats were treated once
daily with a test item (47% purity) at100, 300 and 1000mgact. ingr./kg
bw/day by oral gavage administration. None of the animals died
prematurely. The body weight of the male rats treated orally at 1000
mg/kg bw/day was slightly decreased on test days 8 and 15 compared to
the control group. Body weight gain and body weight at autopsy changed
accordingly. None of the male and female rats treated orally at 100, 300
or 1000 mg/kg bw/day revealed any test item-related changes in
behaviour, external appearance or faeces. No changes in the relative
food consumption were noted at any of the tested dose levels. At
macroscopic inspection at necropsy, test item-related changes in the
stomach (detachment of mucosa, haemorrhagic foci, mucosa
thickened/swollen, ulcer and cardia thickened) were noted for the
animals treated with 1000 mg /kg bw/day. Further, the absolute kidney
weights of the high dosed animals were decreased. In conclusion, 300
mg/kg body weight can be considered as NOAEL. This was comparable to the
registered substance, therefore read across was considered valid.
90-day toxicity study was performed in rats with this read across test
item containing ca. 50% active ingredient (Tegeris and Underwood, 1975a)
at 0.25%, 1.00% and 4.00% in the diet (corresponding to mean calculated
test article intake of 188, 750 and 3000 mg act.ingr./kg bw/day). At the
highest dose levels, it caused a significant difference in body weight
gain, most probably related to an effect by the compound during
absorption from the gastro-intestinal tract. There was one mortality in
the high dosed females. Haematology and serum analysis also indicated
toxicity at the high dose, whereas at the medium dose, only some
organ-to-body weight changes were observed (e.g. liver weight increases
in both sexes). Other organ-to-body weight changes were also observed at
the high dose group (e.g. slightly decreased gonad weights in males;
decreased gonad weight in females); increased relative kidney weights
were observed in all female dose groups. Chronic renal disease (mild)
was observed in 1/20 males and 6/20 females of the high dose groups. The
high dose was considered to be toxic, whereas the changes of the medium
dose may be considered adaptive. Therefore 1% (750 mg/kg bw/day) may be
considered as NOAEL.
A 90 -day toxicity study in dogs was performed with test item containing
ca. 50% active ingredient (Tegeris and Underwood, 1975b) at 0.12%, 0.50%
and 2.00% in the diet (corresponding to mean calculated test article
intake of 30, 125 and 500 mg act. ingr. /kg bw/day). There was a
decreased feed consumption, feed efficiency and corresponding weight
loss in the high dose (2.00%) group of dogs. Also testicular atrophy and
hepatic fatty infiltration were observed in the same group without
functional impairment of the liver. These observations were not
considered to be direct toxic manifestations of the test item, as
disturbed fat absorption is known as a physiological action of the
sulfosuccinate class of compounds. Effects at the highest dose were
considered to be secondary manifestations to disturbed fat absorption at
these high multiples of human intake. The dose of 500 mg/kg bw (2% in
the diet) was considered NOAEL.
The dog species was considered to be less appropriate due to the
disturbed fat absorption, by which systemic effects could not be
correctly interpreted. The NOAEL of 750 mg/kg bw/day in rats was
selected as main endpoint; this was also consistent with the selection
of the rat as main species and NOAELs from the Di-ester substances.
conclusion for the subchronic toxicity a NOAEL of 1% in the diet,
corresponding with 750 mg/kg bw, was obtained in a 90 -day study with
read across substance CAS No. 37294 -49 -8.
risk characterisation, the paternal/maternal NOAEL of 60 mg/kg bw in the
OECD 422 study with subgroup member CAS No. 90268-36-3 was selected as
most conservative value.
Further information supporting the safety of the test substance is
provided in the read across justification for the Mono-ester subgroup,
(justification with data matrix separately attached in Section 13).
As there were no relevant findings below classification
threshold of 100 mg/kg bw, classification for repeated dose toxicity is
not warranted according to the EC Directive (No.93/21/EEC) and CLP (No.
1272/2008 of 16 December 2008).
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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