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EC number: 251-073-2 | CAS number: 32509-66-3
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
With reference to the effects observed in several repeated dose
studies (low body weight and body weight gain, increased bilirubin
level, histopathological changes in adrenals and liver) a 14 day short
term oral toxicity study with special focus on the reported effects was
performed in rats (non-pregnant and pregnant). This study followed in
principle the design as lined out in OECD 407. The test item, Hostanox O
3 P, was administered to Wistar rats orally (by gavage) at the doses of
100 (low dose), 300 (mid dose) and 600 mg/kg/day (to 3 cohorts of rats:
the repeated dose phase (14 days), the satellite group (3 and 10 days
treatment) and the Embryo Fetal Developmental phase (gestation day 5 to
19 treatment). The repeated dose phase and the satellite group consisted
of 6 rats/sex/group, while the Embryo Fetal Developmental phase
consisted of 6 presumed pregnant rats (gestation day 0).
In this study, assessments included clinical signs, body weights, food
consumption, clinical laboratory investigations of blood (for
hematology, acute phase proteins, clinical chemistry and hormone
analysis), gross pathology, and histopathological evaluation (repeat
dose phase and satellite group). The microscopic examination was
initially performed for the control and high dose groups of males and
females, and extended to the following organs of lower dose groups as
higher incidence of lesions was present in high dose groups
The following observations were reported:
1. Immunological
response
- increased number of neutrophils, leukocytes and monocytes from day 10
on at 300 and 600 mg/kg bw/d (highest dose tested)
- increase
in inflammatory markers at day 10-group in all animals at doses ≥
300 mg/kg bw/d, at day 14-group at 600 mg/kg bw/d dose group and for the
developmental phase rats (Gestation Day 20) at all dose groups.
-
histopathological changes of thymus and spleen at 600 mg/kg bw/d and
- lymphangiectasis in the gastro intestinal tract from day 3 onwards ≥
300 mg/kg bw/d
2. Adrenals
Histopathological
changes were reported from day 3 onwards. However, it has to be
emphasized that the hormonal status remains unchanged and comparable to
that of the control animals. Therefore, an endocrine activity is
excluded.
3. Liver:
- the bilirubin concentration in blood is increased at 300 and 600 mg/kg
bw/d.
- furthermore, the AST and ALT level as well as the triglyceride level
are slightly elevated at 600 mg/kg bw/d
- vacuolization of hepatocytes from day 3 on at 300 and 600 mg/kg bw/d.
4. Stomach
- hyperplasia and
ulcers in non-glandular and glandular stomach.
Based on the above mentioned effects the NOAEL was set at 100 mg/kg bw/d.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 100 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- reliable without restriction
- System:
- immune system
- Organ:
- adrenal glands
- duodenum
- ileum
- jejunum
- liver
- stomach
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: inhalation, other
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: inhalation, other
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: dermal, other
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: dermal, other
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
A
combined chronic toxicity and carcinogenicity study (130 weeks) was
performed with Bis-(3,3-di-(4-oxy-3-tert. butyl-phenyl)butane acid)
glycol ester fed to rats at dietary levels of 0, 0.16, 0.4 or 1.0%.
The study was conducted with weanling rats obtained from mothers which
had been fed the same diets during 30 days before mating and during
gestation and lactation. From the results of the reproduction phase of
the study it was concluded that the test substance failed to induce any
deleterious effect other than a slight growth depression in parent males
at 0.4 and 1.0% and in pups at 1.0% (please refer to chapter 7.8.1).
This study deals with the results obtained with F1 rats during a
life-time period (130 weeks).
The data of mortality was not affected. Body weight was relatively low
at the 1.0% dose level from week 12 onwards in both sexes. The
differences with the controls were generally smaller than 10%. There
were no outstanding differences in food intake and food efficiency
amongst the groups.
There were no changes in haematological characteristics that could be ascribed to the feeding of DTB-glycolester. The only effect considered to be treatment-related occurred in the blood biochemistry and consisted of an increase in total Bilirubin in the groups treated with 0.4 and 1.0% DTB-glycolester in both sexes. The direct Bilirubin level was not affected. Since histologically no abnormality was found in the liver, bile ducts or spleen and the complete absence of signs of haemolytic anemia, the elevated total Bilirubin level in the mid- and high-dose group is considered to be of minor toxicological relevance. Kidney function tests did not show any dose-related changes. Organ to body weight ratios of 8 different organs were not affected. Gross examination did not reveal any treatment-related effects. Histopathological examination did not reveal any change. No indications were found for carcinogenic properties of the test item.
Based on the absence of toxicological relevant effects the NOAEL is considered to be 1.0% in diet corresponding to 500 mg/kg bw/d (considering a dietary conversion factor (ppm to mg/kg bw/d) of 20 for older rats).
The
toxicity of DTB-glycolester was examined in a sub-chronic (16 week)
study in which the test substance was fed to groups of 50 male and 50
female weanling rats each at levels of 0 (control), 0.1, 0.4 or 1.6% in
stock diet. The rats were derived from parents which had been fed the
diets for 31 days before mating and during gestation and lactation.
Observations were made on general appearance and behavior, growth, food
intake and food efficiency, hematology, blood biochemistry and urine
composition. At week 17 all rats were killed and examined grossly for
pathological changes. The major organs were weighed and extensive
histopathological examinations were carried out on 15 males and 15
females of each group.
General condition and behavior were not adversely affected at any level
of the test substance.
Gain in body weight was relatively low in males of the high-dose group.
Food intake was decreased at 1.6% dose level in both sexes during the
first two weeks. Food efficiencies were not adversely affected.
Haematological examinations did not reveal any treatment related
differences amongst various groups.
There were no toxicologically significant differences amongst the groups
with respect to enzyme activities and protein values of blood serum.
Kidney-function tests and urine composition did not exhibit any harmful
effects of the test substance.
There were slight increases in the relative weights of the kidneys,
liver and ovaries at the high-dose level. The weights of ovaries were
also increased in the medium-dose group.
Gross and microscopic pathology failed to reveal changes that could be
attributed to ingestion of the test substance.
It was concluded that the NOAEL of DTB-glycolester in the present study
was 1.6% (1600 mg/kg bw/d, considering a diet conversion factor (ppm to
mg/kg bw/d) of 10) in the diet of rats for 16 weeks.
Bis-(3,3
-Di-(4 -oxy-3 -tert. butyl-phenyl)-butanic acid)-glycol ester has been
tested in a 90 day feeding study with SPF Wistar K rats in a control
group and 3 dosage groups of 5%, 1% and 0.1% in food. All animals within
the testing groups 1% and 0.1% showed normal behaviour and no indication
of toxicity. All animals of the dosing group 5% died within day 10 and
39 after the start of the study. Food consumption of all animals in the
two lower dose groups was comparable to the control group. Animals of
the top dose group (5%), however, did not take up sufficient food. These
animals showed significant body weight loss until they died.
Histological findings of the animals in the lower dosed groups were not
different from control. Histology examination of the top dose animals
were diagnosed as significant tissue changes of lung, liver, spleen,
adrenals, pancreas and testes which might be related to the
malnutrition. The diagnosis was partially disturbed by autolyis.
Based on the results of this study, the no-observed-effect-level (NOEL)
for the test item, Hostanox O 3, was considered to be 1% in diet
(corresponding to 1000 mg/kg bw/d considering a diet conversion factor
(ppm to mg/kg bw/d) of 10 for young rats)).
After dosing dogs (6 animals/sex/dose level) with 100, 500 or 600-1100 ppm DTB-Glykolester (Hostanox O 3) in diet for 2 years no treatment-related clinical/neurological changes as well macroscopical/microscopical effects were observed. Food consumption and body weight gain were slightly reduced in males at 1100 ppm compared to the control animals.The NOAEL is set at 1100 ppm substance in diet corresponding to 84.6 mg/kg bw/d (males, highest dose tested) and 75.2 mg/kg bw/d (females, highest dose tested), respectively.
After dosing dogs (4 animals/sex/dose level) with 100, 500 or 750 ppm DTB-Glykolester (Hostanox O 3) in diet for 90 days no clinical/neurological changes as well macroscopical/microscopical effects were observed. The NOEL is set at 750 ppm substance in diet corresponding to 47.6 mg/kg bw/d (males, highest dose tested) and 39.6 mg/kg bw/d (females, highest dose tested), respectively.
With reference to the effects observed in several repeated dose
studies (low body weight and body weight gain, increased bilirubin
level, histopathological changes in adrenals and liver) a 14 day short
term oral toxicity study with special focus on the reported effects was
performed in rats (non-pregnant and pregnant). This study followed in
principle the design as lined out in OECD 407. The test item, Hostanox O
3 P, was administered to Wistar rats orally (by gavage) at the doses of
100 (low dose), 300 (mid dose) and 600 mg/kg/day (to 3 cohorts of rats:
the repeated dose phase (14 days), the satellite group (3 and 10 days
treatment) and the Embryo Fetal Developmental phase (gestation day 5 to
19 treatment). The repeated dose phase and the satellite group consisted
of 6 rats/sex/group, while the Embryo Fetal Developmental phase
consisted of 6 presumed pregnant rats (gestation day 0).
In this study, assessments included clinical signs, body weights, food
consumption, clinical laboratory investigations of blood (for
hematology, acute phase proteins, clinical chemistry and hormone
analysis), gross pathology, and histopathological evaluation (repeat
dose phase and satellite group). The microscopic examination was
initially performed for the control and high dose groups of males and
females, and extended to the following organs of lower dose groups as
higher incidence of lesions was present in high dose groups
The following observations were reported:
1. Immunological
response
- increased number of neutrophils, leukocytes and monocytes from day 10
on at 300 and 600 mg/kg bw/d (highest dose tested)
-increase
in inflammatory markers at day 10-group in all animals at doses≥
300 mg/kg bw/d, at day 14-group at 600 mg/kg bw/d dose group and for the
developmental phase rats (Gestation Day 20) at all dose groups.
-
histopathological changes of thymus and spleen at 600 mg/kg bw/d and
- lymphangiectasis in the gastro intestinal tract from day 3 onwards≥
300 mg/kg bw/d
2. Adrenals
Adrenals
were identified as target organ. Histopathological changes were reported
from day 3 onwards. However, it has to be emphasized that the hormonal
status remains unchanged and comparable to that of the control animals.
Therefore, an endocrine activity is excluded.
3. Liver:
- the bilirubin concentration in blood is increased at 300 and 600 mg/kg
bw/d.
- furthermore, the AST and ALT level as well as the triglyceride level
are slightly elevated at 600 mg/kg bw/d
- vacuolization of hepatocytes from day 3 on at 300 and 600 mg/kg bw/d.
4. Stomach
- hyperplasia and
ulcers in non-glandular and glandular stomach.
Based on the above mentioned effects the NOEAL was set at 100 mg/kg bw/d.
Justification for classification or non-classification
According to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC) and based on available data no classification is warranted for the registration substance.
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.
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