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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 205-471-8 | CAS number: 141-23-1
- 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
Key value for chemical safety assessment
- Toxic effect type:
- dose-dependent
Effects on fertility
Description of key information
Not a reproductive toxicant
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- The analogue approach is used for the hazard assessment of toxicological, eco-toxicological and environmental fate endpoints for the registration of 12-hydroxstearate methyl ester (CAS 141-23- 1). The hypothesis is that data can be read-across between this ester and its structural analogues, based on structural similarity and which cause the same type of effect(s) in physical and biological systems (Scenario 2 of the Read-Across Assessment Framework (RAAF, ECHA, 2015). The primary fatty acids in this read-across are lauric acid (C12) and myristic acid (C14), as these are well studied with high-quality experimental data. Supplemental analogues are used which contribute understanding of the effects of other structural features not contained in the two primary analogues.
There are no GHS classifications for 12-hydroxstearate methyl ester for endpoints which are reliant on read-across. There is a high degree of confidence that hazards for these endpoints are not underestimated, based on a strong weight of evidence from multiple data sources.
Read-across data, all evaluated as reliable according to Klimisch scores of 1 or 2, to estimate the toxicity of the registered substance is used for fulfilling the data requirements of the REACH registration and classifying potential hazards. This read-across approach is adequate for the purposes of risk assessment and classification and labeling. - Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- GLP compliance:
- yes
- Limit test:
- no
- Justification for study design:
- The screening study is appropriate according to Annexes of Regulation EC No. 1907/2006.
- Specific details on test material used for the study:
- Dodecanoic acid methyl ester (abbreviation: MD, CAS No.:111-82-0, lot number: GD01, manufactured by Tokyo Chemical Industry Co., Ltd.) is a colorless transparent liquid and has a melting point of 5 ° C, a boiling point of 141 ° C. (15 mmHg) , Molecular formula C13 H26 O2, molecular weight 214.35, purity 99.2% (impurity unknown).
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- Crj: CD (SD), SPF
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Details on test animals and environmental conditions
TEST ANIMALS
- (Crj: CD (SD), SPF) male and female, 9-10 week old (initiation of dosing)
- Source: Charles River Japan Co., Ltd.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9-10 wks
- Weight at study initiation: 354 to 386 g for males and from 216 to 241 g for females
- Fasting period before study: 16 hours prior to sacrifice
- Housing: solid floor polypropylene cages with stainless steel mesh lids
. Males housed in groups; individually.
Cages were changed weekly.
- Diet (e.g. ad libitum): NMF solid feed (radiation sterilized feed) manufactured by Oriental Yeast Co., Ltd.
- Water (e.g. ad libitum): municipal supply, ad libitum.
- Acclimation period: 7 days
DETAILS OF FOOD AND WATER QUALITY:
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 +/- 2
- Humidity (%): 55 +/- 10%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12, 150-300 lux - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- The test substance was dissolved in corn oil (manufactured by Nacalai Tesque, Inc.) to prepare a dosing solution for each group to have concentrations of 5, 10 and 20 (w / v)%. After preparation, it was hermetically stored under cool and dark conditions until use, and it was used within 7 days after preparation. The test substance, 5% (w / v), in the preparation solution was confirmed to be stable for at least 8 days under cool and dark conditions in the case of a solution.
- Details on mating procedure:
- 1:1 male:female ratio
Mating confirmed by sperm presence, vaginal plug - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- For concentration analysis of the administration solution, samples were randomly extracted from batches of each group prepared at the start of preparation. As a result, it was prepared in the range of 98.6 to 104%, and it was confirmed that almost a predetermined amount of ____ was contained.
- Duration of treatment / exposure:
- 45 days (males); 41-55 days (females)
- Frequency of treatment:
- once daily, 7 days per week
- Details on study schedule:
- Body weight and food consumption were measured weekly.
Mating occured at a sex ratio of 1:1, documented by sperm confirmation in vagina and vaginal plugs. That day was taken as the 0th day of gestation.
The mating rate [(number of copulatory animals / number of living animals) × 100] and conception rate [(number of conception animals / number of copulates) × 100] were determined for each group. The sexual cycle was observed until the date of mating, and the length of the estrus cycle was calculated.
Pregnant females delivered naturally between days 20-25, and the length of pregnancy calculated. The day of delivery (nursing, lactation) was designated PND0. If labor/delivery occurred after 10 am, the following day was designated PND0. The birth rate (pregnant/delivery x 100) was calculated. - Dose / conc.:
- 250 mg/kg bw/day (nominal)
- Dose / conc.:
- 500 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 12
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Details on study design:
- Dose selection rationale:
A dose-range finding study was performed at 100, 250, 500 and 1000 mg/kg/d for 14 days. There were no observed unscheduled deaths or adverse effects on body weight, food intake, autopsy findings, organ weight, hematology values or blood biochemical values. Doses selected for the main study were 250, 500 and 1000 mg/kg bw/d.
- Rationale for animal assignment: Animals were stratified based on the body weight at the start of dosing, and 12 animals per group were sorted by a random sampling method.
Pairing of males and females (1:1) within each treatment group on day 15, and females were allowed to deliver and rear offspring to day 4 of lactation.
Reproductive parameters were assessed in males and females. Observations included clinical signs, behavioural assessments, estrous cycle assessments, body weight development and food and water consumption. Haematology and blood chemistry evaluations were made prior to mating and at the end of treatment. - Positive control:
- none
- Parental animals: Observations and examinations:
- Observations and examinations performed and frequency
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations checked were included. see discussions
BODY WEIGHT: Yes
- Time schedule for examinations:
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily food consumption was calculated as g food/kg body weight/day: Yes, weekly, and for females, during gestation and during lactation
WATER CONSUMPTION AND COMPOUND INTAKE: no data
- Time schedule for examinations: no data
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: males: at end of treatment in all animals from each dose group; in females: prior to mating and at end of treatment in all dose groups
- Anaesthetic used for blood collection: yes, ether
- Animals fasted: Yes
- How many animals: all control and high dose groups.
- Parameters checked were examined. see discussions
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at termination of the experiment
- Animals fasted: Yes
- How many animals: all control and high dose groups
- Parameters checked were examined. see discussions
URINALYSIS: no
NEUROBEHAVIOURAL EXAMINATION: no
IMMUNOLOGY: No
OTHER:CAGE SIDE OBSERVATIONS: no - Oestrous cyclicity (parental animals):
- length of estrus cycle
- Sperm parameters (parental animals):
- none
- Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: yes
- If yes, births/pregnancies, pups/litter, pups/sex/litter.
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring: number and sex of pups, stillbirths, live births, body weight PND 0 and 4, postnatal mortality (PND4), presence of gross anomalies, weight gain, physical abnormalities
GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities
ASSESSMENT OF DEVELOPMENTAL NEUROTOXICITY: no
ASSESSMENT OF DEVELOPMENTAL IMMUNOTOXICITY: no - Postmortem examinations (parental animals):
- All males in each group underwent a necropsy. Animals were fasted for about 16 hours from the evening of the final administration day (administration period: 45 days) to the next morning, then opened under ether anesthesia, and blood was collected from the abdominal aorta.
Hematology examinations:
In the tests, the number of white blood cells (WBC: dark field plate method), number of red blood cells (RBC: dark field plate method), hematocrit value (HCT: dark field plate method) was calculated by using THMS H · 1 E (Calculated from RBC, MCV), hemoglobin amount (HGB: cyanomethemoglobin method), mean red blood cell volume (MCV: dark field plate method), mean red blood cell hemoglobin amount (calculated from MCH: HGB, RBC), average red blood cell hemoglobin concentration (MCHC : Calculated from HGB, HCT), platelet count (PLT: dark field plate method) and white blood cell percentage (flow cytochemistry method) were measured. The percentage of white blood cells was measured with the instrument described above, but a blood sample specimen was prepared separately and stored by May / Grunwald-Giemsa stain. Regarding the calculation of the reticulocyte (RC) ratio, a blood smear specimen was prepared after EDTA-3K added blood was stained with New Methylene Blue. Since no anemia tendency was observed in each group, no specimen was observed.
Blood clinical biochemical examination:
For the test, blood was collected in a clean seal (Yatron Co., Ltd.), and the serum obtained by standing for 30 minutes and then centrifuging at 3000 rpm for 7 minutes was analyzed using a multi-item biochemical automatic analyzer Centrifi Chem ENCORE II (Baker) and EKTACHEM 700N Total protein (Buret method), albumin (BCG method), A / G (calculated value), blood sugar (glucose oxidase method), total cholesterol (cholesterol oxidase method), urea nitrogen (urease ammonium indicator ), Creatinine (Jaff method), total bilirubin (diazo method), glutamic acid oxaloacetate transaminase (IFCC method), glutamic pyruvic acid transaminase (IFCC method), γ-glutamyl transpeptidase (Orl wski method), potassium (electrode method) , Chlorine (electrode method), calcium (arsenazo III method) and inorganic phosphorus (molybdic acid blue method) were measured.
Pathology examination:
Necropsy and organ weights
(1) male animals:
From the evening on the day of administration for 45 days, after fasting for about 16 hours, animals were exsanguinated under ether anesthesia and euthanized. At necropsy, macroscopic observation of the main organs was performed and the weights of the thymus, lung, liver, kidney, testis and epididymis were measured to calculate organ weight / body weight ratio (relative weight). Also, skin was fixed with 10% neutral buffered formalin solution as organs / tissues in which change was observed as brain, heart, spleen, adrenal gland, seminal vesicle, prostate, pituitary gland and macroscopic findings in addition to weight measurement organ of all animals did. The testis and epididymis were fixed with Bouin's solution.
(2) females spontaneously delivered:
On PND4, animals were exsanguinated and euthanized by ether anesthesia. At necropsy, macroscopic observation of the main organs was performed, and then the thymus, lung, liver, kidney and ovary weight were measured to calculate organ weight / body weight ratio (relative weight). The large intestine was also fixed with 10% neutral buffered formalin solution as organs / tissues in which changes were observed as brain, heart, spleen, adrenal gland, pituitary gland and macroscopic findings in addition to weight measuring instruments of all animals. At the time of necropsy, the number of corpus luteum and the number of implantation traces were examined, and the implantation rate [(number of implantation / number of pregnant corpus luteum) × 100] was obtained.
(3) females not undergoing natural births:
On GD 25, animals were exsanguinated and euthanized by ether anesthesia. At necropsy, after macroscopic observation of the main organs, macroscopic observation of the main organs was carried out, and the skin, mammary gland, lymph node, salivary gland, sternum, femur (including bone marrow), thymus, trachea, lung and bronchus, heart, thyroid and parathyroid, The esophagus, stomach, duodenum, small intestine, large intestine, liver, pancreas, spleen, kidney, adrenal gland, bladder, ovary, uterus, vagina, eyeball, Harder's gland, brain, pituitary and spinal cord were fixed with 10% neutral buffered formalin . Animals that did not show implantation marks were judged to be infertile.
(4) Females who delivered all stillborns:
On the day when all the surviving offspring were confirmed dead or were sacrificed, animals were euthanized after exsanguination under ether anesthesia. At necropsy, after macroscopic observation of the main organs, macroscopic observation of the main organs was carried out, and the skin, mammary gland, lymph node, salivary gland, sternum, femur (including bone marrow), thymus, trachea, lung and bronchus, heart, thyroid and parathyroid, The esophagus, stomach, duodenum, small intestine, large intestine, liver, pancreas, spleen, kidney, adrenal gland, bladder, ovary, uterus, vagina, eyeball, Harder's gland, brain, pituitary and spinal cord were fixed with 10% neutral buffered formalin . At necropsy, the number of corpus luteum and the number of implantation traces were examined, and the implantation rate [(number of implantation / number of pregnant corpus luteum) × 100] was determined.
Histopathology examination
(1) Males who successfully mated: brain, thymus, heart, lung, liver, kidney, spleen, adrenal gland and testis of all control and high dose groups.
(2) females spontaneously delivered :Brain, thymus, heart, lung, liver, kidney, spleen, adrenal gland and ovary of the control group and all the high dose groups.
(3) males who did not successfully mate and females who failed to become pregnant: on all animals, brain, thymus, heart, lung, liver, kidney, spleen, adrenal gland, vagina, uterus, ovary, testis, epididymis, seminal vesicle, prostate and pituitary.
(4) Females who delivered all stillborns: mammary gland, lymph node, salivary gland, sternum, femur (including bone marrow), thymus, trachea, lung and bronchus, heart, thyroid and parathyroid, tongue, esophagus, stomach, duodenum, small intestine, large intestine, Liver, pancreas, spleen, kidney, adrenal gland, bladder, ovary, uterus, vagina, eyeball, Harderian gland, brain, pituitary and spinal cord. - Statistics:
- Data was assessed by multiple comparison methods using Bartlett’s test, one way ANOVA, Dunnett’s or Scheffe’s pair wise comparison test, Kruskal-Wallis or Dunnett or Scheffe’s rank sum test, and Chi square test. For birth rate, mating rate and conception rate, Chi square tests were used. Fisher's probability test method was used for the abnormality frequency. For the results on newborns during the post-natal period, the average per mother (litter) was taken as one sample. The levels of significance for p < 0.05 and p < 0.01.
- Reproductive indices:
- Corpora lutea, implantation sites, number of births, number of stillbirths, estrus cycle length, length of gestation, matings/pregnancies
- Offspring viability indices:
- sex ratio, average sex, delivery rate, birth rate, outlier abnormality incidence rate, survival on PND4
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- In males, the average daily food intake was high in the 250 and 500 mg / kg group on the 43 to 45 days of administration compared with the control group. In females, there was no difference between the control group and each test substance-administered group over the administration period.
- Water consumption and compound intake (if drinking water study):
- not specified
- 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
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
- Reproductive function: oestrous cycle:
- no effects observed
- Description (incidence and severity):
- No effects were seen on estrus cycle parameters or fertility.
- Reproductive function: sperm measures:
- no effects observed
- Description (incidence and severity):
- No effects were seen on sperm viability or motility parameters or fertility.
- Reproductive performance:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Key result
- Critical effects observed:
- no
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
- Other effects:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Key result
- Critical effects observed:
- no
- Key result
- Reproductive effects observed:
- no
- Conclusions:
- In the reproductive toxicity portion of an OECD 422 Combined repeated dose toxicity with reproductive toxicity screening test in CD rats at doses of 250, 500 and 1000 mg/kg bw/d, the test substance did not show evidence of maternal toxicity or toxicity to offspring. The NOAEL(maternal toxicity) was > 1000 mg/kg bw/d, and the NOAEL(F1) was > 1000 mg/kg bw/d. There is no evidence for classification for reproductive hazard according to Regulation EC No. 1272/2008.
Reference
Table: Summary of reproductive/developmental toxicity/offspring
Dose (mg/kg bw/day) |
0 |
250 |
500 |
1000 |
Number of pregnant females |
12 |
10 |
12 |
12 |
Number of pregnant females with live pups |
12 |
10 |
12 |
12 |
Gestation index (%) |
100.0 |
100.0 |
100.0 |
100.0 |
Gestation length in days |
22.9 ± 0.5 |
22.6 ± 0.5 |
22.6 ± 0.5 |
22.4 ± 0.5 |
Number of corpora lutea |
18.4 ± 4.2 |
16.8 ± 1.5 |
17.0 ± 2.7 |
17.4 ± 2.2 |
Number of implantation sites |
15.7 ± 4.2 |
16.1 ± 1.4 |
14.4 ± 3.2 |
15.0 ± 2.6 |
Implantation index |
84.0 ± 19.3 |
95.9 ± 4.9 |
85.2 ± 19.2 |
86.7 ± 15.5 |
Day 0 of lactation |
||||
Number of pups born |
14.3 ± 4.2 |
14.7 ± 2.2 |
13.1 ± 3.7 |
13.6 ± 3.1 |
Delivery index(%) |
89.8 ± 12.6 |
91.2 ± 9.4 |
88.9 ± 12.7 |
90.6 ± 13.0 |
Number of live pups |
14.2 ± 4.1 |
14.6 ± 2.0 |
13.0 ± 3.6 |
13.6 ± 3.1 |
Male |
8.3 ± 3.0 |
8.1 ± 2.8 |
6.1 ± 2.2 |
5.5 ± 2.1 |
Female |
5.8 ± 2.3 |
6.5 ± 1.8 |
6.9 ± 2.9 |
8.1 ± 3.0 |
Sex ratio (male/female) |
1.58 ± 0.79 |
1.41 ± 0.71 |
0.96 ± 0.60 (11) |
0.79 ± 0.46* |
Live birth index (%) |
99.5 ± 1.6 |
99.4±1.8 |
99.8 ± 1.8 |
100 ± 0 |
Number of dead pups born |
||||
stillbirth |
0.0±0.0 |
0.1±0.3 |
0.1±0.3 |
0.0±0.0 |
cannibalism |
0.1±0.3 |
0.0±0.0 |
0.0±0.0 |
0.0±0.0 |
Pups weight (g) |
||||
Male |
6.1 ± 0.6 |
6.2 ± 0.5 |
6.7 ± 0.7 |
6.5 ± 0.6 |
Female |
5.8 ± 0.6 |
5.8 ± 0.6 |
6.2 ± 0.5 |
6.1 ± 0.6 |
Day 4 of lactation |
||||
Number of live pups |
||||
Male |
7.0±4.0 |
7.2 ± 2.7 |
5.9 ± 2.1 |
5.3 ± 2.3 |
Female |
4.8 ± 2.7 |
6.1 ± 1.7 |
7.4 ± 2.0 |
8.1 ± 3.0* |
Viability index (%) |
||||
Male |
76.7 ± 39.9 |
91.3 ± 20.0 |
97.8 ± 5.2 |
95.1 ± 11.5 |
Female |
78.2 ± 37.8 |
94.5 ± 9.6 |
97.5 ± 5.8 |
100 ± 0.0 |
Pups weight (g) |
||||
Male |
8.8 ± 1.4 |
7.9 ± 1.4 |
9.4 ± 1.4 |
9.2 ± 1.3 |
Female |
8.5 ± 1.3 |
7.6 ± 1.3 |
8.8 ± 1.2 |
8.8 ± 1.3 |
Sex ratio (male/female) on day 4 (%)
Parenthesis indicates the number of litters evaluated.
*: significant difference from control, p<0.05
Gestation index (%) = (Number of females with live pups/Number of pregnant females) x 100
Implantation index (%) = (Number of implantation sites/Number of corpora lutea) x 100
Deliver index (%) = (Number of pups born/Number of implantation sites) x 100
Live birth index (%) = (Number of live pups on day 0/Number of pups born) x 100
Viability index (%) = (Number of live pups on day 4/Number of live pups on day 0) x 100
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- adequate
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
- Quality of whole database:
- adequate
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
- Quality of whole database:
- adequate
Effects on developmental toxicity
Description of key information
Not fetotoxic or teratogenic
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- Guideline study under GLP
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- yes
- Remarks:
- Additionally under GV-SOLAS (Animal Welfare Legislation and Guidelines issues by the Society of Laboratory Animal Science)
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS: animals were supplied at day 0 (GD0) of gestation, confirmed by vaginal plug.
- Source: Charles River, Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: 8, weeks
- Weight at study initiation: 195.9-198.6 g
- Fasting period before study: no data
- Housing: semi-barrier sustained animal room, individually in Markrolon type M3 cages
- Diet (e.g. ad libitum): Altromin No. 1324, Altromin GmbH, Lage, Germany, ad libitum
- Water (e.g. ad libitum): community tap water, ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 40-56
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: To: - Route of administration:
- oral: gavage
- Vehicle:
- other: arachidis oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION
- Rate of preparation of diet (frequency): daily
- Mixing appropriate amounts with (Type of food):
- Storage temperature of food:
VEHICLE
- Justification for use and choice of vehicle (if other than water): optimal solubility
- Concentration in vehicle:
- Amount of vehicle (if gavage):
- Lot/batch no. (if required): arachidis oil, DAB 10
- Purity:PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION
- Rate of preparation of diet (frequency):
- Mixing appropriate amounts with (Type of food):
- Storage temperature of food:
VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Concentration in vehicle:
- Amount of vehicle (if gavage): 5 ml/kg body weight
- Lot/batch no. (if required):
- Purity: - Details on mating procedure:
- No mating in the experiment; animals were supplied at GD0 of gestation, confirmed by vaginal plug.
- Duration of treatment / exposure:
- GD 6-15
- Frequency of treatment:
- once daily
- Duration of test:
- 20 days
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 24
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Animals were randomly assigned to test groups using random tables. They were treated and euthanised (ether) on GD20 in accordance with Animal Welfare legislation and guidelines. Foetuses were removed by Caesarian section.
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: GD0, 6, 16 and 20
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 20 by ether overdose. Foetuses removed by caesarean section.
- Organs examined: Gross macroscopic examination of all maternal organs according to OECD 414 requirements, with emphasis on uterus, uterine contents,and record of the number of corpora lutea noted. The number and distribution of intrauterine implantations were recorded. The pre- and post-implantation loss and intrauterine resorption sites were evaluated. Intrauterine deaths were classified on the basis on absence (early resorption) and of the presence (late resorption) of foetal or decidual tissue in addition to placental tissue. Living and dead foetuses were sexed, weighed individually with placentaie and examined for gross extrernal abnormalities.
OTHER: - Ovaries and uterine content:
- Examination was made of each animal's uterus, uterine contents, position of the foetuses and presence of corpora lutea, and pre- and post-implantations. The pre-implantation and post-implantation loss and intrauterine resorption sites were evaluated. Intrauterine deaths were classified on the basis of the absence (early resorption) and of the presence (late resorption) of foetal or decidual tissue in addition to placental tissue.
- Fetal examinations:
- Living and dead foetuses were removed from the uterus. The living foetuses were sexed, weighed individually with placentae and examined for gross external abnormalities. Foetal soft tissue and skeletal development were investigated. The Wilson technique was applied to half of the foetuses to evaluate potential visceral changes (Wilson and Warkany, 1965). The remaining foetuses were cleared in a solution of potassium hydroxide and stained with Alizarin Red according to Dawson (1926). Alterations in foetuses were classified according into four categories (Klimisch et al., I992): variations, retardations, anomaly and malformations.
- Statistics:
- If the variables could be assumed to follow a normal distribution, the Dunnett test, based on a pooled variance, was applied for the comparison between the treated groups and the control group. The Steel test was applied when the data could not be assumed to follow a normal distribution. Fisher's exact test for 2 x 2 tables was applied if the variables could be dichotomized without loss of information (Bonferroni - Holm corrected).
- Indices:
- not specified but data provided in tables
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
- Details on results:
- 2-Ethylhexyl stearate did not cause adverse effect to the maternal rats at any time during pregnancy. No mortalities occurred in the dams during the study, either in the vehicle control or in the groups exposed to 2-ethyl hexyl stearate up to 1000 mg/kg body weight. The absolute and the corrected body weight (Table 2) and body weight gain was comparable between the groups. No deviation was observed during the treatment period. Gross macroscopic examination of the maternal organs including ovaries and uterus revealed no alterations. The no-adverse-effect dose of 1000 mg/ kg body weight corresponds to the NOAEL of the repeated dose toxicity data in rats.
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- effects observed, non-treatment-related
- Description (incidence and severity):
- One fetus was found dead in the 1000 mg/kg bw/d group; this was not different from the rate in concurrent controls or historical controls.
- Changes in pregnancy duration:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified - Changes in number of pregnant:
- no effects observed
- Other effects:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Key result
- Abnormalities:
- no effects observed
- Fetal body weight changes:
- no effects observed
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- One foetus in the control group had hydrops.
- Visceral malformations:
- no effects observed
- Description (incidence and severity):
- One foetus in the 100 mg/kg bw/d group had hydrocelphalus internus; not different from controls. The rate of hydronephrosis in treated fetuses was comparable to that of controls.
- Other effects:
- not examined
- Details on embryotoxic / teratogenic effects:
- The weights of live foetuses exhibited no significant differences on a litter and individual basis. In comparison with the control group in the 100 and 1000 mg/ kg body weight group, the post-implantation loss and total embryonic deaths were significantly decreased. Non-dose-related findings were considered to be incidental, compared to control values. Mean foetal placental and uterus weights were not affected by treatment. Foetal sex ratio was comparable in all groups. A hydrops was noted in one control group foetus.
Incidences were also compared to the historical controls of the OECD guideline No. 414 studies using the same strain (Sprague-Dawley CD). Findings both on the individual foetus and on the litter basis did not differ from the historical control. From the visceral examinations, one hydrocephalus internus was found which has to be considered as an individual non-dose-related finding which also occurs in the historical data at a comparable level (0.4 %). All other changes were slight and also occurred in the control population. Concerning the skeletal examinations on the basis of the foetal incidence, there are differentiated results in some findings such as 'non-ossification' of sternebrae (retardation). However, the total frequency of the findings ' incomplete ossification' including 'non-ossification' of all sternebrae show no substantial differences between the untreated and treated groups. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Key result
- Abnormalities:
- no effects observed
- Key result
- Developmental effects observed:
- no
- Conclusions:
- In a guideline OECD 414 developmental toxicity study of 2-ethylhexyl stearate in CD rats at 100, 300 and 1000 mg/kg bw/d in arachidis oil, no adverse maternal effects, fetotoxic effects or teratogenic effects or variations were observed. The NOAEL for maternal toxicity is > 1000 mg/kg bw/d, and the NOAEL for developmental toxicity is > 1000 mg/kg bw/d. The substance is not classified for developmental effects according to Regulation EC No. 1272/2008.
Reference
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Experimental exposure time per week (hours/week):
- 144
- Species:
- rat
- Quality of whole database:
- adequate
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
- Quality of whole database:
- adequate
Justification for classification or non-classification
There is no experimental evidence that analogues including fatty acid esters, which encompasses the registered substance, are reproductive toxicants or teratogens. The read-across is based on known biochemical lipid cycles and empiric evidence for target and source substances, and is valid for fulfilling the information requirements of this endpoint. The criteria for classification according to Regulation EC No. 1272/2008 is not met, and the substance is not classified for reproductive toxicity.
Additional information
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.