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EC number: 201-289-8 | CAS number: 80-54-6
- 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
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Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- April 16th - August 22nd, 1985
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study: Restrictions acceptable (only 5 day/week treatment, no neurobehavioural examinations reported, only 14 animals per sex/dose)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 986
- Report date:
- 1986
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- (see below)
- Principles of method if other than guideline:
- DEVIATIONS FROM GUIDELINE
-Treatment for only 5d/week (guideline recommendation: 7d/week), no neurobehavioural examinations, not clear if fasting was performed before hematology and clinicochemical examinations. - GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 2-(4-tert-butylbenzyl)propionaldehyde
- EC Number:
- 201-289-8
- EC Name:
- 2-(4-tert-butylbenzyl)propionaldehyde
- Cas Number:
- 80-54-6
- Molecular formula:
- C14H20O
- IUPAC Name:
- 3-(4-tert-butylphenyl)-2-methylpropanal
- Details on test material:
- - Name of test material (as cited in study report): alpha-methyl-beta-(p-tert-butylphenyl)propionaldehyde
- Analytical purity: 97.8%
- Physical state and appearance: liquid, colourless to pale yellow
- Stabilty: 1 yr (as pure compound)
- Storage: under inert gas, closed container, room temperature (approx. 15° C)
- Batch: 109535
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Fuellinsdorf albino (also known as ibm:RORO (SPF))
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Institute of Biological and Medical Research, Fuellinsdorf, Switzerland
- Age at study initiation: 6-7 weeks
- Weight at study initiation: male, 134-171g; female, 104-105g
- Diet: ad libitum (NAFAG standard rat maintenance diet (ground) No.850; defined and certified for acceptable contaminant levels)
- Water: ad libitum except during urine collection period (tap water)
- Acclimation period: 12 days. Upon receipt all rats were examined for external signs of ill-health. Unhealthy animals were discarded.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 45-65
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: rapeseed oil (1ml/kg bw)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
Each day, fresh suspensions of the test article in rape oil were prepared by the use of a magnetic stirrer. The dose volume was kept constant at 1 ml/kg body weight. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The test article from each of the dose groups was extracted from the rape oil suspension and the extracts sent to Givaudan A.G., Duebendorf, for analysis (no further details given).
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- once daily, 5 days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0; 2; 5; 25; 50 mg/kg (Reanalysis of the test article showed a deviation from the theoretical values in the range from +9.59 % to -16.44 %)
Basis:
other: nominal
- No. of animals per sex per dose:
- 14
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Animal assignment: random
- Rationale for animal choice: Guideline prescribed. Furthermore, historical data of untreated animals of the strain as well as adequate references in literature was available to assist in assessment of results.
- Satellite group: Yes, 4/sex of control and additional 14/sex of 50 mg/kg bw/d dose group
- Rationale for selecting satellite groups: Test for reversibility of effects
- Length of post-exposure recovery (satellite groups): 4 weeks
The 1st treatment day was defined as day 0, week 0. The 2nd treatment day was defined as day 1, week 1. The 1st treatment week started on day 1 and terminated on day 7.
Examinations
- Observations and examinations performed and frequency:
- DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
MORTALITY: Yes
- Check conducted continuously
BODY WEIGHT: Yes
- Time schedule for examinations: on 1st day of treatment, then every other week
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: prior to start of treatment (control, 50 mg/kg bw/d, satellite group), week 13 (control, 50 mg/kg bw/d, satellite group)
- Dose groups that were examined: control and 50 mg/kg bw/d plus satellite group
- Comments: About 15-30 minutes prior to the examination, a mydriatic drug was instilled in each eye of the animals
FOOD CONSUMPTION : Yes
Time schedule for examinations: weekly
HAEMATOLOGY: Yes
- Time schedule for collection of blood: prior to treatment (10/sex/dose group), week 7 (all animals of satellite group), week 14 (all groups), and week 18 for the satellite group
- Anaesthetic used for blood collection: Yes, ketamine in combination with diazepam
- Animals fasted: no data
- Parameters examined: Red blood cell count, hemoglobin, mean corpuscular volume, packed cell volume, mean corpuscular hemoglobin, white blood cells, thrombocytes, reticulocytes, differential cell count.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: prior to treatment (10/sex/dose group), week 7 (all animals of satellite group), week 14 (all groups), and week 18 for the satellite group
- Animals fasted: no data
- Parameters examined: aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholineesterase, alkaline phosphatase (AP), glutamate dehydrogenase (GLDH), total plasma bilirubin, plasma glucose, plasma urea, plasma creatinine, plasma cholesterol, serum sodium, serum potassium, plasma calcium, plasma phosphate, total serum protein, electrophoresis of serum proteins.
URINALYSIS: Yes
- Time schedule for collection of urine: week 6
- Dose groups that were examined: controls and 50 mg/kg bw/d and if protein > 30 mg/dl
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes, during collection period, no feed or water was provided to the animals.
- Parameters examined: colour, specific gravity, pH, protein content, glucose content, occult blood, bilirubin, urobilinogen, ketone bodies, sediment compositions - Sacrifice and pathology:
- SACRIFICE
- Number of animals: all survivors
- Method: exsanguination after CO2 narcosis
GROSS PATHOLOGY: Yes
- Organ weight (wet weight): brain, heart (without auricles), liver, kidneys, testes, ovaries, adrenals
HISTOPATHOLOGY: Yes
- Organs examined: All gross lesions and tumours, brain (cerebral cortex, medulla/pons, cerebellum), pituitary, thyroid and parathyroid, thymus, lung and trachea, heart, femur with bone marrow, salivary glands, liver, spleen, kidney, adrenals, pancreas, testes, uterus, oesophagus, stomach, duodenum, jejunum, ileum, caecum, colon, rectum, urinary bladder, intestinal lymph nodes, sciatic nerve, eyes and aorta.
- Groups examined: 10/sex/dose of control, 50 mg/kg bw/d. Livers were examined from all animals of both sexes, adrenals from all female rats and testes from all male rats of the study. - Statistics:
- Dunnett's-test: Multiple comparisons, control versus all treated groups. Error rate = 0.1..
Results and discussion
Results of examinations
- Details on results:
- CLINICAL SIGNS
- Male animals: Clinical signs; alopecia (1/14, 2 mg/kg bw/d; 2/14, 5 mg/kg bw/d; 1/14, 25 mg/kg bw/d; 1/14, 50 mg/kg bw/d) and incrusted eyes (1/14, 5mg/kg bw/d) and malposed tooth (2/14; control) and area with incrustation (2/14, 25 mg/kg bw/d, 1/14; 50 mg/kg bw/d) were described as not treatment related and judged to be background findings.
- Female animals: Clinical signs mostly in 50 mg/kg bw/d dose group and satellites included alopecia (2/14, 25 mg/kg bw/d; 15/28, 50 mg/kg bw/d and satellites vs 0/14 in control, considered treatment related), area with incrustation (1/14, 5 mg/kg bw/d; 5/28, 50 mg/kg bw/d and satellites vs 0/14 in control) and inflammation of skin (3/14).
MORTALITY
- 50 mg/kg bw/day: 1/14 females died in narcosis set for blood sampling (week 7). Not treatment related.
BODY WEIGHT AND WEIGHT GAIN
- no adverse effect was noted on body weight gain (see table 1 below)
FOOD CONSUMPTION AND COMPOUND INTAKE
- The feed intake was not influenced (see table 1 below)
- The results of analysis of the intake of the test article via diet showed a deviation from the theoretical values in the range from +9.59 % to -16.44 % .
HEMATOLOGY
- No treatment-related effect was apparent. All individual values of hematology parameters at weeks 0, 7, 14 and 18 were within the physiological range seen in the laboratory. At week 18, the statistical significances arose because of the small number of animals N = 4 of the control group.
CLINICAL CHEMISTRY
- Cholinesterase (male): decrease at termination by 30% and 35-60% (statistically significant) compared to control in the mid and high dose group. Effect reversible after 4 weeks recovery period reaching 78% of corresponding controls.
- Cholinesterase (female): statistically significant decrease at termination by 68% and 68-71% compared to control in the mid and high dose group, respectively. Reversible trend after 4 weeks recovery period reaching 63% of corresponding control.
- Cholestrol concentration (male): statistically significant decrease at termination: 35-39% and 60-66% of control in the high and mid dose group, respectively. Totally reversible after 4 weeks recovery period reaching 102% of corresponding control.
- Cholestrol concentration (female): statistically significant decrease at termination; 47-53% and 60-66% of control in the high and mid dose group, respectively. Totally reversible after 4 weeks recovery period reaching 114% of corresponding control.
- Aspartate aminotransferase (male): statistically significant increase (135% compared to mean of corresponding control at termination) in the high dose group. According to authors: not biologically meaningful or indicative of a treatment effect.
The lower cholesterol concentrations were categorized as treatment related but not necessarily adverse by the authors. With the exception of above mentioned parameters, all other statistically significant parameters were judged by the authors as not treatment related.
- Total proteins and electrophoresis: males dosed with 50 mg/kg bw; a trend towards increased albumin levels (absolute and relative) could be observed at week 14, which was accompanied by a slight increase of the albumin/globulin ratio. Finding was thought to reflect some adoptive changes due to treatment.
- Total proteins and electrophoresis: females dosed with 50 mg/kg; no effect was detected.
URINALYSIS
- No treatment related effect was apparent. Findings were similar and comparable to those in the respective control groups.
OPTHALMOSCOPY
- No treatment related finding as observed
ORGAN WEIGHTS
Dose dependent increase in absolute and relative weights of liver and adrenal seen at sacrifice. The effects were reversible after the 4 week recovery period (see below). The results are expressed as percentages of control values
- 25 mg/kg bw/d: male; absolute (24%) and relative (21%) increase of liver weight in comparison to controls.
- 25 mg/kg bw/d: female; absolute (57%) and relative (59%) increase of liver weight in comparison to controls. Absolute (16.4%) and relative (18%) weights of adrenals were also increased compared to controls.
- 50 mg/kg bw/d: male; absolute (45%) and relative (45%) increase of liver weight in comparison to controls.
- 50 mg/kg bw/d: female; absolute (69%) and relative (75%) increase of liver weight in comparison to controls. Absolute (30%) and relative (36%) weights of adrenals were also increased compared to controls.
- 50 mg/kg bw/d (satellite): male; after 4 weeks recovery period: absolute weight (6%) and relative (3.1 %) decrease of liver weight in comparison to controls. Absolute (5.6%) and relative (7.7%) weights of adrenals were increased compared to controls.
- 50 mg/kg bw/d (satellite): female; after 4 weeks recovery period: absolute weight (5.9%) and relative (7.7 %) increase of liver weight in comparison to controls. Absolute (6.5%) and relative (8.4 %) weights of adrenals were increased compared to controls.
GROSS PATHOLOGY
- 50 mg/kg bw/d: male; small testes (3/14 vs 1/10 control), spermatoceles (10/14 vs. 0/10 control)
- 50 mg/kg bw/d: male satellites; small testes (1/14 vs 1/4 control), spermatoceles (10/14 vs. 0/4 control)
All other findings were deemed not treatment related.
HISTOPATHOLOGY: NON-NEOPLASTIC
Testes:
The frequency of testicular atrophy was raised in males treated with 50 mg/kg. This finding persisted after the treatment-free follow -up period in control males and males treated formerly with 50 mg/kg
- 50 mg/kg bw/d: male; minimal to marked testicular atrophy (6/14 vs. 1/10 control), minimal to marked spermatoceles with inflammatory reactions (13/14 vs. 0/10 control)
- 50 mg/kg bw/d: satellites male; minimal to marked testicular atrophy (5/14 vs. 2/4 control)
Epididymides
Spermatoceles occured only in males of the 50 mg/kg bw/d dose groups. No recovery was detected after the 4 week treatment free period
- 50 mg/kg bw/d: male; minimal to marked spermatoceles with inflammatory reactions (13/14 vs. 0/10 control)
- 50 mg/kg bw/d: satellites male;minimal to marked spermatoceles with inflammatory reactions (13/14 vs. 0/4 control)
Liver:
The degree of the fat content of hepatic cells observed in all rats was higher in male and female rats treated with 50 mg/kg than in those treated with 0, 2, 5 and 25 mg/kg. After a treatment-free follow-up period of 4 weeks, there was no difference between the fat content of liver cells of control rats and that of rats treated formerly with 50 mg/kg
Adrenals:
A hypertrophy of the zona fasiculata was detected in two females treated with 50 mg/kg only. Because of the variable sections through the adrenal glands, a reliable diagnosis of this finding was not possible .
After completion of the study, a "second opinion" on the histological alterations observed in testes and epididymides of rats from this study and a tentative appraisal of possible mechanisms involved were sought from Dr Ettlin. R.A. The results of the second opinion are tabulated below (table 2)
Effect levels
open allclose all
- Dose descriptor:
- NOEL
- Effect level:
- 5 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: plasma cholinesterase
- Dose descriptor:
- NOAEL
- Effect level:
- 25 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: testes with additional systemic toxicity
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table 1: Summary of average body weight change and food consumption after 13 weeks
Dose group (mg/kg bw/d) |
Weight gain between begin and conclusion of study (g) |
Average daily food consumption (g/day) |
||
Male |
Female |
Male |
Female |
|
0 |
243.6 |
110.8 |
20.3 |
15.1 |
2 |
252.7 |
105.7 |
20.6 |
14.7 |
5 |
267.4 |
112.9 |
20.9 |
15.2 |
25 |
252 |
110.5 |
20.6 |
15.2 |
50 |
234.7 |
100.7 |
21.3 |
15.0 |
Satellite |
237.9 |
110.8 |
21.0 |
16.1 |
For histotological findings in Testes and Epididymides (Second opinion by Dr Ettlin), see Chapter 7.8.1
Applicant's summary and conclusion
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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