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EC number: 204-260-8 | CAS number: 118-56-9
- 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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Toxicity to reproduction: other studies
Administrative data
- Endpoint:
- toxicity to reproduction: other studies
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- From October 30, 2001 to March 25, 2002.
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: OECD guideline test with GLP compliance.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 002
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: OECD 440
- GLP compliance:
- yes
- Type of method:
- in vivo
Test material
- Reference substance name:
- Homosalate
- EC Number:
- 204-260-8
- EC Name:
- Homosalate
- Cas Number:
- 118-56-9
- Molecular formula:
- C16H22O3
- IUPAC Name:
- 3,3,5-trimethylcyclohexyl salicylate
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- The test animals were juvenile female rats- animals recommended in OECD protocol for these validation studies. At the start of the study, the animals were 19 days old and had starting weights of 29-36 g.
SPF-bred Wistar rats of the strain HsdCpb: WU from the Harlan Winkelmann GmbH Experimental Animal Breeders in Borchen, District of Paderborn were used.
The animals were transported together with foster dams from the supplier to Bayer AG. After the arrival, the animals intented for this study were acclimatized to conditions in the animal room for 3 days, until the commencement of the study. Their healthy situation was monitored during this period.
Only healthy animals showing no clinical signs were taken for the study. The rats were not vaccinated or dealt with anti-infectives either before receipt or during the acclimatization or treatment periods.
During the adaptation phase, the rats were conventionally kept in polycarbonate cages type III (one foster dam with six or seven inmature animals per cage). The cages were not changed during the acclimatization.
During the test period, the animals were conventionally kept in polycarbonate cages type III (three animals per cage). Low-dust wood shaving type BK 8/15 (supplier: Ssniff, Spezialdiäten GMBH, Soest/ Westphalia) were used as litter. The wood shavings were spot-checked for contaiminants levels and records are filed at Bayer AG. The analytical results afforded no evidence for an effect on the study objective.
Cages and bedding material were not changed during the test. The cages containing the experimental rats were palced on racks, separated by groups, in ascending animal number order. All animals taking part in the study were kept in the same animal room.
Administration / exposure
- Route of administration:
- subcutaneous
- Vehicle:
- corn oil
- Details on exposure:
- The dose levels were chosen on basis of the previous study (T9071164). In the study female rat was treated sub-cutaneously with 1000 mg/kg. No effects on the treatment area were observed.
Groups of 6 juvenile female rats of the strain HsdCpb:WU were administered the test substance once per day at levels of 0 (untreated), 0 (vehicle control), 200 and 1000 mg/kg body weight sub-cutaneously for a period of three days. Two additional groups of 6 juvenile female rats were set. The two groups were respectively treated with 0.3 and 1.0 μg/kg 17 α-Ethinylestradiol (positive control) once a day for 3 consecutive days.
In this study the dose schedule and the distribution of control animals and animals treated with the test substance by group are shown in table 1 in the section of "Any other information on materials and methods incl. tables"
Before administration, the animals were weighted, sorted according to weight, and randomly allocated to the individual groups. The randomization lists were generated by a computer program. - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 3 days
- Frequency of treatment:
- once per day
- Duration of test:
- 4 days
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
1000 mg/kg bw
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
200 mg/kg bw
Basis:
nominal conc.
- No. of animals per sex per dose:
- Each group contains 6 female immature rats. 6 groups were set in total, thus 36 rats were used totally.
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Environmetal conditions:
The environmental conditions in the animal room were standardized as follows:
Room temperature: 22±2 ℃
Relative humidity: approx. 55±5%
Light/dark cycle: 12-hour artificial lighting
air exchange rate: approx. 10 times per hour
Occasional deviations from these conditions occured, e.g. due to cleaning the animal room. They had no perceptible effect on the study routine.
Diet
The animals were given "NAFAG No.9441 long life W 10'' (manufacturer: Eberle Nafag AG, Gossau - CH), and tap water (drinking bottles). Food and water were available for ad-libitum consumption.
The tap water was of drinking water quality (in accordance with the German Drinking Water Standards "Trinkwasserverordnung" of December 5, 1990, Bundesgesetzblatt No. 66, part 1, issued on December 12, 1990, pages 2612-2629) and was supplied from polycarbonate bottles. The results of the water analyses were archived at BAYER AG. The available data did not indicate that the objective of the study had been influenced.
Inspection of experimental animals
The animals were inspected at least once a day. Any clinical signs and abnormalities were recorded. Body surfaces and orifices, posture, general behavior, breathing and excretory products were assessed. Findings and abnormalities were recorded both using a coding system and uncoded.
If animals get sick, they are set apart, observed more frequently and sacrificed prematurely, if death seems imminent.
Determination of feed consumption:
The feed intake of the rats was determined per group at the end of the study on the day 3. These primary data were used to calculate the means for feeding period, the consumption per animal/day, per group/day and per kg body weight per day. The algorithm used for calculating intake of feed is described in the annex of the report.
Determination of body weight
The body weights of the individual experimental animals were determined before the beginning of the study and daily thereafter up to scheduled necropsy.
Necropsy
The animals were necropsied after exsanguination under deep ether anesthesia. Uterus and vagina of all animals were fixed in 10% neutral buffered Formalin.
The fixed material was retained (pathology no. 6136). Due to the request of the sponsor, histopathological investigations were not performed.
Organ Weights
The following exsanguinated organs of the animals sacrificed at necropsy were weighted in the unfixed state:
uterus (wet and blotted).
The uterine weights are specified in both absolute and relative terms. The relative weights were calculated by normalization to 100 g body weight (individual organ weight divided by body weight times 100). The body weight used as a basis for this calculation was determined immediately prior to necropsy of the pertinent animal. - Statistics:
- The results of the animal observations, organ, body and feed weights were collected and processed on-line and off-line.
The quatitative results for individual animals were used to calculate arithmetic group means and standard deviations. The results for the groups that received the test substance were compared with those for the vehicle control group. The vehicle control group was additionally compared with the untreated control group. Significant differences were indicated by "+" for p ≤ 0.05 and "++" for p ≤ 0.01.
The statistical evaluation of data related to body and organ weights as well as feed intake was performed by SAS® routines.
Statistical evaluation on body weight and organ weight data were processed by Dunnset test in connection with a variance analysis. Relative organ weights were submitted to a logarythmic transformation before the statistical analysis.
Results and discussion
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: Oestrogenic/uterine increasing
Observed effects
No systemic clinical signs were observed;
Mortality
No animal died throughout the treatment period.
Feed consumption
No toxicologically relevant differences in mean feed consumption per animal/day, or per kg body weight/day were detected. The detailed results please refer to the table 2 in the section of "Any other information on results incl. tables".
Body weights
Comparing with the untreated control and vehicle control, there was no significant effect of the treatment group on body weight observed.
Findings at Necropsy
No pathological change has been observed at 1000 mg/kg of the test substance and below. However, the uteri were enlarged at 0.3 and 1.0 μg/kg 17α-Ethinylestradiol.
Oragn Weights
At 1000 mg/kg of the test substance and below no effect was observed on uterine weight. The positive controls gave the results the significantly higher uterine weights than the controls. Details please refer to the table 3 in the section of "Any other information on results incl. tables".
Any other information on results incl. tables
Table 2 Feed consumption
Feed consumption | ||
Dose | 3days | |
g/day/animal | g/kg b.w./day | |
Females | ||
0(untreated) | 1.9 | 59 |
0(vehicle) | 1.9 | 58 |
0.3μg/kg 17α-Ethinylestradiol | 2.0 | 63 |
1.0μg/kg 17α-Ethinylestradiol | 2.3 | 71 |
200 mg/kg test substance | 2.1 | 67 |
1000 mg/kg test substance | 1.8 | 56 |
Table 3 Organ weight
Dose | Body weight | absolute uterus weight | Relative uterus weight | ||||||
g | mg | mg/100g b. w. | |||||||
wet | blotted | wet | blotted | ||||||
0(untreated) | 32 | 33 | 27 | 102 | 83 | ||||
0(vehicle) | 33 | 32 | 27 | 97 | 83 | ||||
0.3μg/kg 17α-Ethinylestradiol | 32 | 59 | ++ | 53 | ++ | 184 | ++ | 166 | ++ |
1.0μg/kg 17α-Ethinylestradiol | 33 | 120 | ++ | 89 | ++ | 366 | ++ | 270 | ++ |
200 mg/kg test substance | 31 | 30 | 25 | 96 | 82 | ||||
1000 mg/kg test substance | 32 | 29 | 26 | 92 | 82 |
Applicant's summary and conclusion
- Conclusions:
- No oestrogenic effects were detected at doses of 1000 mg/kg of the test substance and below.
- Executive summary:
Groups of immature female rats were administered the test substance once a day at levels of 0 (untreated), 0 (vehicle control), 200 and 1000 mg/kg body weight sub-cutaneously for a period of consecutive tree days. Besides two additional positive control groups containing 0.3 and 1.0 μg/kg 17α-Ethinylestradiol were set and treated same with testing groups. The vehicle used for all groups except untreated control was corn oil.
Regarding state of health and general behavior of the animals, there was no difference between the untreated and treated animals of all groups.
No treatment related mortality has been found.
No toxicologically significant effect on the feed intake was observed.
Body weights were not affected by treatment.
After necropsy, a dose-dependent enlargement of uteri and an increased uterine wet and blotted weight were observed in the positive controls. However, no effect on uteri was observed at either 200 or 1000 mg/kg test substance treated groups.
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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