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EC number: 451-160-7
CAS number: 17913-76-7
28 d NOAEL
= 150 mg/kg bw/d (rat, OECD TG 407, RL1: 0, 15, 150 or 1000 mg/kg bw/d)
91 d NOAEL
= 500 mg/kg bw/d (rat, combined repeated dose/1 generation reproduction
study, no guideline; RL2: 0, 500, 1000, 2000 mg/kg bw/d) (read-across
from 2,4,7,9-Tetramethyl-5-decyne-4,7-diol )
91 d NOAEL
= 250 mg/kg bw/d (beagle dog, no guideline, RL2: 0, 200, 250 and 300
mg/kg/day) (read-across from 2,4,7,9-Tetramethyl-5-decyne-4,7-diol)
assessment of toxicity after repeated administration of 2,4,7,9-tetramethyldecane-4,7-diol
d study is available. In addition, a subacute (28 d) toxicity study in
rat and a subchronic (90 d) toxicity study in beagle dogs and in rats
are available for the source substance
2,4,7,9-Tetramethyl-5-decyne-4,7-diol. A detailed justification for
read-across is attached to iuclid section 13.
of this study was to determine the toxicity of the test article, 2,4,7,9-tetramethyldecane-4,7-diol,
following oral (gavage) administration to the rat for at least 28 days.
female HsdBrlHan:WIST rats were assigned to four groups (five
animals/sex/group). Each group received dose preparations at dose levels
of 0, 15, 150 or 1000 mg/kg of body weight at a dose volume of 5 mL/kg.
study run before the start of the study confirmed that in three male and
three female rats dosed at 1000 mg/kg for five days no severe toxicity
of toxicity was based on mortality, clinical observations, clinical and
anatomic pathology evaluations, clinical pathology and functional
observational battery and locomotor activity.
no decedents during the study.
cholesterol was seen to increase in a dose-related manner in both males
and females. Animals dosed at 1000 mg/kg/day recorded increases in total
cholesterol compared to control of 71% for males (p<0.001) and 63% for
dosed at 150 mg/kg/day also showed increases in both sexes (males 29%
and females 25%).
dose-related increase in globulin was seen in males dosed at 150
mg/kg/day (8%) and 1000 mg/kg/day (25%, p<0.01). Group mean globulin was
also increased in a dose-related manner in females. This was reflected
in an increase in total protein values in these animals.
liver weights adjusted to overall mean body weight increased in males
and females dosed at 150 mg/kg/day and at a greater magnitude in animals
dosed at 1000 mg/kg/day.
there was large or mottled liver, and pale or mottled kidney in some
in high dose animals, there was hepatocyte hypertrophy in the liver;
increased follicular cell hypertrophy in the thyroid; increased hyaline
droplets (males only) and focal nephropathy in the kidney; and minor
squamous cell hyperplasia in the forestomach, due to effects of the test
article. Liver hepatocyte hypertrophy and increased hyaline droplets in
the male kidney were also seen in intermediate dose animals.
findings in the liver, thyroid, male kidney and stomach of low dose
animals were similar to controls and therefore this dose was considered
to be the overall no observable effect level (NOEL).
conclusion, the test item was orally administered at dose levels of 0,
15, 150 and 1000 mg/kg/day for at least 28 days and was well tolerated.
There were no significant clinical observations, and only minor
increases in bodyweight and food consumption at 1000 mg/kg/day.
Increases in total cholesterol, globulin and total protein were of
unknown toxicological significance. Microscopic changes in the liver,
thyroid, male kidney and stomach were due to effects of the test
article, but only those in the liver and thyroid were of toxicological
significance. Microscopic findings in the liver, thyroid, male kidney
and stomach of animals dosed at 15 mg/kg/day were similar to controls.
increases in total cholesterol in animals dosed at 150 and 1000
mg/kg/day could be associated with changes in the liver which is the
site of cholesterol synthesis. High liver weights in animals dosed at
150 and 1000 mg/kg/day correlated with the large or mottled liver seen
macroscopically and those changes seen microscopically. The most notable
microscopic changes were the increase in hepatocyte hypertrophy, and the
associated thyroid follicular cell hypertrophy. In the rat, follicular
cell hypertrophy is generally considered to be an adaptive change due to
increased thyroid hormone
in the liver and is commonly associated with liver cell hypertrophy. The
hyaline droplets and associated tubular degeneration are common
background findings in the male rat, and whilst the incidence appeared
to be treatment-related they are considered to be of no toxicological
weight changes and the severity of the microscopic changes in the liver,
thyroid and kidney can be associated with the increased metabolism of
the test item, and therefore, 150 mg/kg/day was considered to be the
No-Adverse-Effect Level (NOAEL).
administered to Long-Evans rats (6/sex/dose level) at dose levels of
625, 1250, 2500 and 5000 ppm in the diet for a period of 28 days.
Evaluation of mortality, physical observations, body weight, and food
consumption data, as well as gross necropsy observations did not reveal
any adverse effects considered to be attributable to the administration
any of the dose levels. However, histopathology was not performed in
fed to the rat during a single generation reproduction study and for
ninety one days to the F1a weanlings. The test material was mixed into
the rats’ feed to provide dose levels of 0, 500, 1000, and 2000
mg/kg/day. Sexually mature Sprague-Dawley albino rats were divided into
four groups, each consisting of ten male and twenty female rats. All Fo
male rats, both test and control, were fed their respective diets until
their litters reached the age of 21 days for weaning, when the Fo dams
were sacrificed. The weanlings were randomized to their respective
groups and carried on the same dose levels to the termination of the
experiment. The only pertinent findings observed in the Fo parents were:
1. Slight decrease in the mean weaning weight of both male and female
pups of the high-dose group, 2. Slight decrease in lactation indices of
the high-dose group, 3. Decreased body weight and feed consumption of
the high-dose female group, 4. Normal histology of the reproductive
organs in the Fo parents. The following pertinent findings were observed
in the F1a rats: 1. Slight decrease in the mean rate of body weight gain
in the mid- and high-dose male and female rats; there was also
significant decrease in this parameter in the low-dose male group during
the first eight weeks, 2. Normal mean hematological findings, clinical
chemistry findings, and urinalysis findings after 91 days on test, 3.
Significant increase in the liver weight of the mid- and high-dose male
and female test groups with corresponding increase in the liver-to-body
weight ratios, 4. Corresponding histopathology of the liver of the mid-
and high-dose male and female rats, showing mild to moderate
centrilobular cloudy swelling of hepatocytes.
when fed to rats under the conditions of this experiment, showed no
effect at 500 mg/kg/day but did have a toxic effect in the F1a
generation at greater than or equal to 1,000 mg/kg/day while in the
reproduction phase of this experiment there was a toxic effect at the
2,000 mg/kg/day level, a borderline effect at the 1,000 mg/kg/day level
and no effect at 500 mg/kg/day.
administered orally to beagle dogs in gelatin capsules at dose levels of
0, 200, 250 and 300 mg/kg/day for 91 days. Because the dogs had to be
gradually acclimated from 50 mg/kg/day to higher dose levels of the test
item to avoid vomiting, the total test period was 130 days. The control
animals received capsules of granulated table sugar. Capsule
administration followed feeding by approximately one hour. All
dogs survived for the duration of this study with few clinical signs.
Occasional dogs in the mid- and high-dose groups exhibited sporadic,
compound-related, neurological disturbances (convulsions, tremors,
incoordination and/or paralysis) during the study. All other
observations, including feed consumption, body weight gains, organ
weights (except liver), clinical chemistries, hematology, urinalysis,
gross pathology, and histology were judged to reflect no
compound-related/ biologically significant changes. This
study did not establish a no-observed-effect-level (NOEL) of test item
in dogs, since mean liver weights and liver-to-body weight ratios in all
test item-treated groups were higher than in corresponding control
groups. However, since no histological abnormalities were observed in
these livers, the liver enlargement was judged to be due to hyperplasia
of the hepatic endoplasmic reticulum, where xenobiotic/drug metabolizing
enzymes are located. These common adaptive liver changes are generally
reversible, after test compound exposure is discontinued. The NOAEL was
established at 200 mg/kg bw/d based on neurological disturbances at 250
and 300 mg/kg bw/d.
target and the source substance induced liver weight changes and
microscopic changes in the liver which are in general associated with
increased xenobiotic metabolism and thus, are considered to be adaptive
rather than adverse effects.
the available data, the overall dose descriptor for repeated dose
toxicity of 2,4,7,9-tetramethyldecane-4,7-diol
the subchronic NOAEL of 500 mg/kg bw/d obtained in the 90 d study in
rats conducted with the source substance
2,4,7,9-Tetramethyl-5-decyne-4,7-diol, since this NOAEL lead to the most
conservative DNEL (see iuclid section 7 – Toxicological information).
no data gaps for the endpoint repeated dose toxicity. No human data are
available. However, there is no reason to believe that these results
from rat and rabbits would not be applicable to humans.
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Labelling of Chemicals (GHS) Part 3 no classification required.
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