Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1977
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Well performed and reported study with design equivalent to OECD 408/415.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 977
- Report date:
- 1977
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- test animals were exposed to substance in utero before study start, ophthalmology and FOB not performed
- Principles of method if other than guideline:
- 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 that had been fed the test diets for 31 days before mating and during gestation and lactation.
- GLP compliance:
- no
- Remarks:
- study was performed before GLP implementation
- Limit test:
- no
Test material
- Reference substance name:
- Bis-(3,3-di-(4-oxy-3-tert. Butyl-phenyl)butane acid)-gylcolester
- IUPAC Name:
- Bis-(3,3-di-(4-oxy-3-tert. Butyl-phenyl)butane acid)-gylcolester
- Reference substance name:
- DTB-glycolester
- IUPAC Name:
- DTB-glycolester
- Test material form:
- solid: crystalline
- Details on test material:
- white crystalline material, pure substance
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: : the rats were selected from the first litter of parents which had been fed diets containing the test item at levels of 0, 0.1, 0.4 and 1.6% for 31 days before mating and during gestation and lactation; these parent rats were obtained from the Central Institute for the Breeding of Laboratory Animals TNO, Zeist, The Netherlands
- Age at study initiation: weanling age (parent animals were also treated with the test substance while reproduction phase)
- Weight at study initiation: 37.1 - 46.5 g (males), 37.7 - 46.2 g (females)
- Housing: in suspended, screen-bottomed, stainless steel cages (5 per cage)
- Diet (e.g. ad libitum): CIVO stock diet by means of a mechanical blender (Lödige type) at levels of 0, 0.1, 0.4 or 1.6 % test substance, ad libitum
- Water (e.g. ad libitum): water, ad libitum
- Acclimation period:
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24-26°C
- Humidity (%): 50%
- Photoperiod (hrs dark / hrs light): 12
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- other: CIVO stock diet
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION
- Rate of preparation of diet (frequency): The test material was thoroughly mixed into CIVO stock diet by means of a mechanical blender (Lödige type) at levels of 0 (control), 0.1, 0.4 or 1.6%. Batches of 40 kg of each diet were freshly prepared every three to four weeks and stored in an unheated room at ambient temperature.
VEHICLE: CIVO stock diet - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 16 weeks via diet (test animals were pretreated in utero via parent animals and lactation)
- Frequency of treatment:
- continuously
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0.1 %
Basis:
nominal in diet
- Remarks:
- Doses / Concentrations:
0.4 %
Basis:
nominal in diet
- Remarks:
- Doses / Concentrations:
1.6 %
Basis:
nominal in diet
- No. of animals per sex per dose:
- 50
- Control animals:
- yes, plain diet
- Details on study design:
- The toxicity of DTB-glyoclester 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 test 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, haematology, 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.
- Positive control:
- no
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
The animals were observed at intervals for signs of illness and or abnormal behavior.
BODY WEIGHT: Yes
Individual body weights were recorded at the end of weeks 0, 1, 2, 4, 6, 8, 10, 12 and 16.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
The food intake of 20 males and 20 females of each group was measured during the first four weeks and in weeks 12 and 13.
FOOD EFFICIENCY:
Food efficiencies were calculated from the gain in body weight and the total food consumption over the first four weeks.
HAEMATOLOGY: Yes
Blood samples from the tip of the tail of ten rats/sex/group were taken at week 15 for measurements of the following parameters: Haemoglobin, Packed cells volume as microhaematocrit, red cell count, white cell count, differential white cell count (Lymphocytes, Neutrophils, Monocytes and Eosinophils)
CLINICAL CHEMISTRY: Yes
At necropsy, blood was collected from 15 rats/sex/group by punction of the aorta abdominalis. In sera, which were obtained by centrifugation the following determinations were carried out: Serum alkaline phosphatase (SAP), Serum glutamic-oxalacetic transaminase (SGOT), Serum glutamic-pyruvic transaminase (SGPT), total Serum protein (TSP), Albumin
URINALYSIS: Yes
Individual urine samples were collected at week 15 from 10 rats/sex/group and at week 16 from 10 rats/group in females only. Collections were made during the last 16 hours of a 14-hour period of deprivation of food and water. The following measurements were made of individual urine samples: volume, urine glutamic-oxalacetic transaminase, specific gravity. The following qualitative tests were made in pooled samples from 10 rats/sex/group: pH, protein, sugar, occult blood, ketones and microscopy of spun deposit (Erythrocytes, Leucocytes, epithelial cells, amorph deposits, crystalline deposit, casts, bacteria, worm eggs and sperm cells. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
At week 17, 15 animals/sex/group were ether-anaesthetized, bled to death by puncture of the aorta abdominalis and examined grossly for pathological changes.
HISTOPATHOLOGY: Yes
Detailed microscopic examination was performed on all of the 15 male and 15 female rats of the highest dose group and of the control group. Haematoxylin-eosin stained paraffin sections of the organs weighed and also of the following organs were examined: lung, trachea, salivary glands, prostate, seminal vesicle, coagulating gland, epididymis, uterus, urinary bladder, skeletal muscle, thoracic aorta, oesophagus, gastro-intestinal tract, pancreas and axillary and mesenteric lymph nodes.
The remaining 35 animals/sex/group were killed by decapitation. A wide variety of organs was collected and preserved in a 4% neutralized Formaldehyde solution for possible, additional histological examination in the future. - Other examinations:
- Organ weight:
The following organs were weighed: heart, kidneys, liver, spleen, brain, testicles/ovaries, thymus, thyroid and adrenals. - Statistics:
- All data were analysed statistically by means of Student’s t-test.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- one male, cause of death could not be detected
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- one male, cause of death could not be detected
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- decreased body weight gain in males
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- Clinical signs:
No abnormalities of condition or behavior were observed.
Mortality:
One male rat of the control group died in week 16 of the study. No cause of death could be detected.
Body weights/food efficiency:
Already at the start of the study, body weights were statistically significant decreased at the highest dose level (1.6%) as compared to controls. The low initial body weight was caused by growth depression during lactation period. In males, the differences with the controls increased during the course of the study, but this did not happen in females. Body weights in the medium-dose (0.4%) were slightly higher than in controls, especially in males; in the low-dose group (0.1%) body weights were similar to those of the controls.
Food intake was distinctly decreased in the group fed 1.6% DTB-glycolester during the first two weeks of the study. Thereafter, the difference with the controls diminished and at weeks 12 and 13 the figures for males were similar and for females even higher than those of the controls. The food intake in the medium and low dose groups was generally comparable to that of the controls.
Food efficiency figures were not adversely affected by feeding DTB-glycolester.
Hematology:
There were no changes in the parameters examined which could be attributed to treatment. The only statistically significant difference with the controls consisted of a decrease in the percentage of lymphocytes in males at 0.1%. Since at the higher dose levels no such difference occurred, the low value at 0.1% is considered to be incidental.
Blood chemistry:
The activities of the serum enzymes Glutamic-oxalacetic transaminase, Glutamic-pyruvic transaminase and Alkaline phosphatase did not show any dose-related difference amongst the various groups.
Total serum protein values showed a slight though statistically significant decrease in males of the top-dose group. Since the serum Albumin content of this group was equal to that of the controls, the decrease in total serum protein is probably caused by a relatively low Globulin level. The other statistically significant decreases in total serum protein and serum Albumin occurred in the medium and low-dose groups and are, therefore, considered to be incidental findings.
Kidney function/Urinalysis:
There was a dose-related decrease in specific gravity, with a simultaneous increase in the volume of the urine in females fed 0.4 and 1.6% DTB-glycolester. These findings were, however, not confirmed by determinations, one week later, of the same parameters in the animals. Therefore, these changes are considered to be incidental. Glutamic-oxalacetic transaminase values of urine samples were comparable in the various groups.
There were no changes in the composition of the urine which could be ascribed to the feeding of DTB-glycolester. The occurrence of occult blood in females at week 15 was probably caused by a contamination of blood from the tail-tips, since the collection of blood and urine was done on the same day. Moreover, at week 16 no occult blood was found in the animals.
Relative Organ weights:
The relative organ weights of the liver were slightly increased in females of the high-dose group. In males of this group the liver weights also tended to be increased, but the difference with the controls was not statistically significant.
The relative weight of the kidneys only showed a statistically significant increase in the top-dose group males.
The increase in the relative weights of brain and testicles exhibited the well-known inverse relationship with body weight and are, therefore, not considered to be of toxicological significance.
The relative weights of ovaries showed a dose-related increase in the medium-dose and high-dose-groups.
The statistically significant changes in the weights of the spleen and thyroid in females were either not dose-related or only occurred in the intermediate-dose level. Therefore, they are not attributed to the feeding of the test substance.
Gross examination:
Gross examination at necropsy did not reveal pathological findings that could be ascribed to treatment.
Microscopy:
The degree and incidence of the changes observed were about equally distributed among the test groups and controls or they occurred only in a single animal. None of these abnormalities, which are common findings in the strain of rats used, could, therefore, be related to the feeding of the test compound. Although special attention was paid to the microscopic appearance of ovaries and testes, because of their increased relative weights, no abnormalities could be detected. The cause of death of the control animal, which died in week 16 of the experiment, could not be established.
Effect levels
- Dose descriptor:
- NOEL
- Effect level:
- 1.6 other: % in diet
- Sex:
- male/female
- Basis for effect level:
- other: no deleterious effects of toxicological relevance observed up to 1.6% in diet
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Since no treatment-related, deleterious effect occurred in the medium-dose group it was concluded that the NOAEL of the compound was 1.6% in the diet, which is equivalent to 1600 mg/kg bw/d considering a diet conversion factor (ppm to mg/kg bw/d) of 10.
- Executive summary:
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) in the diet of rats for 16 weeks.
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.