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EC number: 282-104-8 | CAS number: 84100-23-2
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2022-07-11 to 2022-08-12
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 023
- Report date:
- 2023
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.3700 (Prenatal Developmental Toxicity Study)
- Version / remarks:
- August 1998
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.31 (Prenatal Developmental Toxicity Study)
- Version / remarks:
- May 2008
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Version / remarks:
- June 2018
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- 4-(1,1-dimethylethyl)cyclohexyl acrylate
- EC Number:
- 282-104-8
- EC Name:
- 4-(1,1-dimethylethyl)cyclohexyl acrylate
- Cas Number:
- 84100-23-2
- Molecular formula:
- C13H22O2
- IUPAC Name:
- 4-tert-butylcyclohexyl prop-2-enoate
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Remarks:
- Crl: WI(Han)
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld
- Age at study initiation: 11-15 weeks old
- Weight at study initiation: 184 – 274 g
- Fasting period before study: no
- Housing: individually housed in Polycarbonate cages (Makrolon type MIII)
- Diet: ad libitum, pellets, SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany
- Water: ad libitum, Municipal tap water
- Acclimation period: 5-6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 51-73
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 06 Jul 2022 To: 29 Jul 2022
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Test material dosing formulations were kept at room temperature until dosing.
VEHICLE
- Justification for use and choice of vehicle: solubility
- Concentration in vehicle: 0, 15, 45 and 135 mg/mL
- Amount of vehicle: 4 mL/kg - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The concentrations analyzed in the formulations of Groups 2, 3 and 4 were in agreement with target concentrations. No test material was detected in the Group 1 formulation. The formulations of Groups 2 and 4 were homogeneous (i.e., coefficient of variation ≤ 10%).
- Details on mating procedure:
- - Impregnation procedure: purchased timed pregnant
- Duration of treatment / exposure:
- Day 6 to Day 20 post-coitum
- Frequency of treatment:
- once daily
- Duration of test:
- 14 days
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Remarks:
- Group 1
- Dose / conc.:
- 60 mg/kg bw/day (actual dose received)
- Remarks:
- Group 2
- Dose / conc.:
- 180 mg/kg bw/day (actual dose received)
- Remarks:
- Group 3
- Dose / conc.:
- 540 mg/kg bw/day (actual dose received)
- Remarks:
- Group 4
- No. of animals per sex per dose:
- 22
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: The doses have been selected based on a dose range finding study (see supporting study).
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: At least once daily 1 to 2 hours post-dose, starting on Day 6 post coitum up to and including the day prior to necropsy.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: On Days 2, 6, 15 and 21 post-coitum
BODY WEIGHT: Yes
- Time schedule for examinations: On Days 2, 6, 9, 12, 15, 18 and 21 post-coitum.
FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
- Over Days 2-6, 6-9, 9-12, 12-15, 15-18 and 18-21 post-coitum
WATER CONSUMPTION AND COMPOUND INTAKE:
Water consumption was monitored by visual inspection of the water bottles.
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 21
- Organs examined: ovaries and uterus, thyroid - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Blood sampling:
- - Serum: Yes
- Volume collected: 1 mL
- T3, T4 and TSH analysis in serum - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter
- Head examinations: Yes: half per litter
- Anogenital distance of all live rodent pups: Yes - Statistics:
- Parametric/Non-Parametric:
Levene’s test was used to assess the homogeneity of group variances. The groups were compared using an overall one-way ANOVA F-test if Levene’s test was not significant or the Kruskal-Wallis test if it was significant. If the overall F-test or Kruskal-Wallis test was found to be significant, then pairwise comparisons was conducted using Dunnett’s or Dunn’s test, respectively.
Non-Parametric:
The groups will be compared using an overall Kruskal-Wallis test. If the overall Kruskal-Wallis test was found to be significant, then the above pairwise comparisons was conducted using Dunn’s test. - Indices:
- See "Any other information on materials and methods incl. tables"
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- No test material-related clinical signs were noted at 60 mg/kg/day.
At 540 mg/kg/day, tremors (slight) were observed in 5/22 females on one or multiple days between Days 14-16 post-coitum and generalized twitches (slight to moderate) were noted in 13/22 females between Days 16-20 post-coitum. Moreover, erected fur was observed in 10/22 females on various days mainly during the second week of treatment. Hunched posture was observed for a single female on Day 10 post-coitum.
Slight salivation was seen on one or multiple days after treatment among animals of the 180 and 540 mg/kg/day dose groups. Taking into account the nature and in general minor severity of the effect and its time of occurrence (i.e., after treatment), this sign was considered to be a physiological response rather than a sign of systemic toxicity.
Any other clinical signs noted during the treatment period occurred within the range of background findings to be expected for rats of this age and strain which are housed and treated under the conditions in this study and did not show any apparent dose-related trend. At the incidence observed, these were considered to be unrelated to treatment with the test material. - Mortality:
- no mortality observed
- Description (incidence):
- No mortality occurred during the study period.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Mean body weights, body weight gain and gravid uterus adjusted body weight gain of test material treated animals remained in the same range as control over the treatment period at 180 mg/kg/day.
At 540 mg/kg/day, mean body weight loss was observed over Days 6-9 post-coitum (-6.4 vs. +12.3 grams in control), followed by normal body weight gain over Days 9-18 post-coitum and a lower body weight gain over Days 18-21 post-coitum (35.0 vs 39.6 grams in control). The combination of body weight loss early during gestation and lower body weight gain towards the end of gestation resulted in a lower overall body weight gain over Days 6-21 post coitum (89.3 vs. 114.4 gram in control) and lower mean body weights between Days 9 21 post-coitum (up to 7% lower than control). Also, body weight gain corrected for gravid uterus weight was lower (12.99 vs. 35.61 gram in control). - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- No test material-related changes in food consumption were recorded at 180 mg/kg/day.
At 540 mg/kg/day, lower mean food consumption was observed over the whole treatment period (not reaching statistical significance over Days 18-21 post-coitum). Changes compared to control were highest during the first days of treatment (46% lower than control over Days 6-9 post-coitum), followed by partial recovery. Overall mean food consumption was 22% lower than control. - Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Endocrine findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Serum levels of TSH and T4 were considered to be unaffected by treatment with the test material.
T3 serum levels were considered to be unaffected by treatment with the test material at 60 mg/kg/day.
At 180 and 540 mg/kg/day, mean T3 serum levels were lower compared to control (0.87 and 0.73x of control, respectively). Mean values remained within the central 95% range of the historical control data.
Historical Control Data for pregnant Han Wistar Rats (2020-2022):
T3 (ng/mL); mean (central 95% range): 0.424 (0.270-0.683); n=347 - Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No test material-related changes in thyroid gland weight (absolute and relative to body weight) were observed up to 180 mg/kg/day.
At 540 mg/kg/day, mean absolute thyroid weight was 7% lower compared to control, without reaching statistical significance. This was ascribed to the lower terminal body weight at the high dose (6.7% below control), as mean thyroid weight relative to body weight was comparable to control. - Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Macroscopic observations at necropsy did not reveal any alterations that were considered to be related to treatment with the test material up to 180 mg/kg/day.
At 540 mg/kg/day, 2/22 females were observed with a small-sized thymus. As this was observed at the high dose only, a test material-relation could not be excluded.
Other findings that were noted, including those in the thyroid gland were considered to be unrelated to treatment with the test material, as they occurred in control animals only, or in the absence of a dose response. - Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no test material-related microscopic observations in the thyroid glands.
In one female at 60 mg/kg/day, hypertrophy of the follicular cell epithelium was observed at a minimal degree. This was the only recorded microscopic finding and regarded unrelated to treatment in the absence of a dose response and single occurrence at the 60 mg/kg/day. - Histopathological findings: neoplastic:
- not examined
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The numbers of pre- and postimplantation loss in the control and test material-treated groups were comparable and in the range of normal biological variation.
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- not examined
- Changes in number of pregnant:
- no effects observed
- Description (incidence and severity):
- The numbers of pregnant females in the control and test material-treated groups were comparable and in the range of normal biological variation. In total, 20/22, 20/22, 17/22 and 21/22 females of the control, 60, 180 and 540 mg/kg/day groups, respectively, were pregnant and therefore available for ovarian and uterine examination at scheduled necropsy.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- materal
- Effect level:
- 180 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- clinical signs
- food consumption and compound intake
Maternal abnormalities
- Key result
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Mean fetal weights (both sexes) were considered to be unaffected by treatment with the test material up to 180 mg/kg/day.
At 540 mg/kg/day, mean fetal weights (male, female and combined) were 2.22, 3.63 and 2.84% lower, respectively, when compared to the control group (only reaching statistical significance for females). - Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Description (incidence and severity):
- The male:female ratio was considered to be unaffected by treatment with the test material.
- Changes in litter size and weights:
- no effects observed
- Description (incidence and severity):
- There were no test material-related effects in litter size.
- Anogenital distance of all rodent fetuses:
- no effects observed
- Description (incidence and severity):
- Anogenital distance (absolute and corrected for body weight) in male and female fetuses was considered not to be affected by treatment with the test material.
- Changes in postnatal survival:
- not examined
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No test material-related external malformations and variations were recorded.
External malformations were observed in two fetuses originating from two litters at 180 mg/kg/day. Fetus No. 53-R10 had a malpositioned eye bulge, cleft lip, meningoencephalocele and absent palatal rugae. Fetus No. 64-L4 presented with a curled tail. As these malformations were each observed only once and in the mid-dose group only, they were considered to be unrelated to treatment with the test material.
External variations or incidental findings were not observed. - Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No test material-related skeletal malformations and variations were recorded.
Skeletal malformations were observed in a single fetus at 60, 180 and 540 mg/kg/day each. Due to the single occurrences of all recorded malformations, they were considered unrelated to treatment with the test material.
The skeletal malformations observed for Fetus No. 53-R10 corresponded to the external malformations noted for this fetus.
Skeletal variations were observed in the forelimb, pelvic girdle, (supernumerary) rib, scapula, skull, sternebra and vertebra. All were observed either infrequently, at instances comparable to the control group, in the absence of a dose response or were limited to a control fetus only. Therefore, they were considered not to be related to treatment with the test material. - Visceral malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No test material-related visceral malformations and variations were recorded.
Visceral malformations were observed in a single fetus at 60 mg/kg/day (Fetus No. 41-10). This fetus was observed with a malpositioned testis and epididymis. As this occurred in a single low-dose fetus, these occurrences were considered to be unrelated to the treatment with the test material.
Visceral variations in this study were infrequently observed. They were found in the carotid artery, thoracic wall, liver and ureter. As these variations were observed at low incidences, within the available historical control data and/or in the absence of a dose response, these were considered not related to treatment with the test material.
The incidental findings of discolored liver and spleen, not otherwise classified as malformation or variation, were observed in a single fetus at 540 mg/kg/day and deemed to be a chance discovery.
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- developmental
- Effect level:
- > 540 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: highest dose without effects
Fetal abnormalities
- Key result
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Key result
- Developmental effects observed:
- no
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.