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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 306-246-8 | CAS number: 96690-51-6
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Description of key information
Fertility: waiver - the study does not need to be conducted because a pre-natal developmental toxicity study is available
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- the study does not need to be conducted because a pre-natal developmental toxicity study is available
Reference
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
Additional information
Repeated dose toxicity (OECD TG 407)
The repeated dose toxicity of "Soybean oil, epoxidized, methyl ester, reaction products with propylene glycol" was assessed using the read across source substance: "Fatty acids, C16-C18 and C18-unsatd., ME esters, epoxidized”, which was examined in a OECD TG 407 study under GLP conditions. The test substance was administered orally by gavage to groups of 5 male and 5 female Wistar rats at dose levels of 0 mg/kg bw/day, 100 mg/kg bw/day, 300 mg/kg bw/day and 1000 mg/kg bw/day over a period of 4 weeks. Some reproduction toxicity parameters were also included such as: estrous cycle, sperm parameters (motility, morphology, head count testis, head count epididimis), and reproductive organs. Neither changes in estrous cycle/sperm parameters, nor treatment-related organ weight changes, gross lesions or histopathological findings were observed in the treated male and female animals including the reproductive organs.
Effects on developmental toxicity
Description of key information
Developmental toxicity/teratogenicity (OECD TG 414): NOAEL 1000 mg/kg bw/day (read across from Fatty acids, C16-C18 and C18-unsatd., ME esters, epoxidized)
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 09 Jul 2015 - 24 Feb 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.3700 (Prenatal Developmental Toxicity Study)
- Version / remarks:
- 2008
- GLP compliance:
- yes (incl. QA statement)
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH
- Age at study initiation: 10-12 weeks
- Housing: single caging
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: six days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: 1st cohort From: 2015-07-09 To: 2015-07-29, 2nd cohort: from 2015-07-10 to 2015-07-30
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The oily test substance preparations were prepared at the beginning of the administration period and thereafter at intervals, which took into account the period of established stability. The preparations were kept at room temperature. For the test substance preparations, the specific amount of test substance was weighed, topped up with corn oil in a graduated flask and intensely mixed with a magnetic stirrer until it is dissolved. During administration, the preparations were kept homogeneous with a magnetic stirrer.
VEHICLE
- Justification for use and choice of vehicle (if other than water): test item is insoluble in water.
- Concentration in vehicle: adjusted to amount of vehicle
- Amount of vehicle (if gavage): 4ml/kg bw - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The stability of the test substance in corn oil at room temperature over a period of 7 days had been verified prior to the start of the study. Given that test substance is completely miscible with corn oil Ph. Eur./DAB, solutions are considered to be homogenous without further analysis.
- Details on mating procedure:
- - Impregnation procedure: purchased timed pregnant
- Proof of pregnancy: referred to as day 0 of pregnancy - Duration of treatment / exposure:
- 14 days
- Frequency of treatment:
- daily
- Duration of test:
- GD 6-19 / 14 days
- No. of animals per sex per dose:
- 25
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: outcome of 28d studies (no adverse findings, NOAEL 1000 mg/kg bw)
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Mortality/Morbidity, pertinent behavioral changes and/or signs of overt toxicity were checked twice daily from Mondays to Fridays and once daily on Saturdays, Sundays and public holidays (GO 0 to 20).
DETAILED CLINICAL OBSERVATIONS: A cage-side examination was conducted at least once daily for any signs of morbidity, pertinent behavioral changes and signs of overt toxicity. If such signs occurred, the animals were examined several times daily (GD 0-20).
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
Food Consumption: The consumption of food was recorded for the intervals GD 0-1, 1-3, 3-6, 6-8, 8-10, 10-13, 13-15, 15-17, 17-19 and 19-20.
BODY WEIGHT: Yes
- Time schedule for examinations: GO 0, 1, 3, 6, 8, 10, 13, 15, 17, 19 and 20. Furthermore, the corrected body weight gain was calculated after terminal sacrifice (terminal body weight on GD 20 minus weight of the unopened uterus minus body weight on GD 6).
POST-MORTEM EXAMINATIONS
- Sacrifice on gestation day: GD 20.On GD 20, the dams were sacrificed under isoflurane anesthesia by decapitation, in randomizedorder.After the dams had been sacrificed, they were necropsied and assessed for gross pathology, in randomized order. The uteri and the ovaries were removed and the following data were recorded:
- Weight of the unopened uterus
The uteri and the ovaries were removed and the following data were recorded:
- Weight of the unopened uterus
- Number of corpora lutea
- Number and distribution of implantation sites classified as: Live fetuses
Dead implantations:
a) Early resorptions (only decidual or placental tissues visible or according to SALEWSKI from uteri from apparently non-pregnant animals and the empty uterus horn in the case of single horn pregnancy)
b) Late resorptions (embryonic or fetal tissue in addition to placental tissue visible)
c) Dead fetuses (hypoxemic fetuses which did not breathe spontaneously after the uterus had been opened) - 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
- Other: Site of implantations in the uterus - Fetal examinations:
- - External examinations: Yes: [all per litter ]
- Soft tissue examinations: Yes: [ half per litter ]
- Skeletal examinations: Yes: [ half per litter ] - Statistics:
- DUNNETT's test: Food consumption, body weight, body weight change, DUNNETT's test corrected body weight gain, carcass weight, weight ofthe unopened uterus, weight of the placentas andfetuses, corpora lutea, implantations, pre- andpostimplantation losses, resorptions and live fetuses
FISHER's exact test: Number of pregnant animals at the end of the study, FISHER's exact test mortality rate (of the dams) and number of litters with fetal findings
WILCOXON test: Proportion of fetuses with findings per litter - Indices:
- The conception rate (in %): (number of pregnant animals / number of fertilized animals) x 100
The preimplantation loss (in %): ((number of corpora lutea – number of implantations) / number of corpora lutea) x 100
The postimplantation loss (in %): ((number of implantations – number of live fetuses) number of implantations) x 100 - Historical control data:
- yes, period over 5 years
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- Most of the females (18 out of 25) of the high-dose group (1000 mg/kg bw/d) and one female of the mid-dose group (300 mg/kg bw/d) showed transient salivation during the treatment period. Salivation occurred in the respective animals only within the 2-hour examination interval (i.e. <2h after treatment). It is considered to be treatment-related, likely as a result of the bad taste of the test substance/vehicle preparation or due to local irritation of the upper digestive tract. It is not considered to be a sign of systemic toxicity.
- Mortality:
- no mortality observed
- Description (incidence):
- There were no substance-related or spontaneous mortalities in any females of all test groups (0, 100, 300 or 1000 mg/kg bw/d).
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- The mean body weights (BW) and the average body weight gains (BWC) of the low-, mid and high-dose dams (100, 300, 1000 mg/kg bw/d) were in general comparable to the controls throughout the entire study period. The corrected body weight gain of test groups 1-3 (100, 300 and 1000 mg/kg bw/d) revealed no difference of any biological relevance to the concurrent control group.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- The mean food consumption of the dams in test groups 1, 2 and 3 (100, 300 and 1000 mg/kg bw/d) was generally comparable to the concurrent control throughout the entire study period.
- Food efficiency:
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- no changes of general behavior were detected in any female of all test groups.
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- The mean gravid uterus weights of the animals of test groups 1-3 (100, 300 and 1000 mg/kg bw/d) were not influenced by the test substance.
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No necropsy findings which could be attributed to the test substance were seen in any dam. There occurred one spontaneous finding in test groups 0 and 1 (0 and 100 mg/kg bw/d), i.e. dilated renal pelvis. This finding was detected in one control and two low-dose animals and was therefore assessed as incidental.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
- 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:
- no effects observed
- Changes in pregnancy duration:
- no effects observed
- Changes in number of pregnant:
- no effects observed
- Description (incidence and severity):
- The conception rate reached 96% in the mid-dose group (300 mg/kg bw/d) and 100% in the control, low- and high-dose groups (0, 100 and 1000 mg/kg bw/d). All observed differences are considered to reflect the normal range of fluctuations for animals of this strain and age
- Other effects:
- no effects observed
- Details on maternal toxic effects:
- There were no test substance-related and/or biologically relevant differences between the test groups 0-3 (0, 100, 300 and 1000 mg/kg bw/day) in conception rate, in the mean number of corpora lutea and implantation sites or in the values calculated for the pre- and the postimplantation losses, the number of resorptions and viable fetuses. All observed differences are considered to reflect the normal range of fluctuations for animals of this strain and age
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: Highest dose tested
- Key result
- Abnormalities:
- no effects observed
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- The mean fetal weights of test groups 1, 2 and 3 (100, 300 and 1000 mg/kg bw/day) were not influenced by the test substance and did not show any biologically relevant differences in comparison to the concurrent control group.
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The sex distribution of the fetuses in test groups 1-3 (100, 300 and 1000 mg/kg bw/day) was comparable to the concurrent control fetuses.
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- no effects observed
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- One fetus with two external malformations was recorded in test group 3 (1000 mg/kg bw/day, anal atresia, thread-like tail). The total incidence of external malformations in treated animals did not differ significantly from the concurrent control group and was covered by the historical control data.
- Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- A number of skeletal malformations were detected in fetuses of test groups 0, 1 and 2 (0, 100 and 300 mg/kg bw/day) affecting the skull and humerus. An association of these malformations to the treatment is not assumed.
For all test groups, skeletal variations of different bone structures were observed, with or without effects on corresponding cartilages. The observed skeletal variations were related to several parts of fetal skeleton and appeared without a relation to dosing. The overall incidences of skeletal variations were covered by the historical control data. - Visceral malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Three soft tissue variations were detected, i.e. misaligned palatal rugae, dilated renal pelvis and dilated ureter. These variations were neither significantly different from the concurrent control nor dose-dependently altered. Therefore, they were not considered to be biologically relevant
- Other effects:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- Fetal examinations revealed that there is no effect of the compound on the respective morphological structures up to the highest dose tested (1000 mg/kg bw/d).
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Highest dose tested
- Key result
- Abnormalities:
- no effects observed
- Key result
- Developmental effects observed:
- no
- Conclusions:
- The administration of "Fatty acids, C16-C18 and C18-unsatd., ME esters, epoxidized" by gavage to male and female Wistar rats for 4 weeks did not cause test substance-related adverse signs of maternal or developmental or reproductive toxicity. Therefore, under the conditions of the present study the no observed adverse effect level (NOAEL) was 1000 mg/kg bw/day in Wistar rats and the substance does not need to be classified for developmental toxicity in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).
- Executive summary:
The developmental toxicity of “Fatty acids, C16-C18 and C18-unsatd., ME esters, epoxidized” was examined in a OECD TG 414 study under GLP conditions. The test substance was administered to pregnant Wistar rats daily by gavage from implantation to one day prior to the expected day of parturition (GD 6-19) to evaluate its potential maternal and prenatal developmental toxicity. Generally, clinical observations including water consumption, food consumption and body weight gain revealed no toxicologically relevant difference between the animals receiving the test substance at 100, 300 or 1000 mg/kg bw/day and controls.
Most of the females (18 out of 25) of the high-dose group (1000 mg/kg bw/day) and one female of the mid-dose group (300 mg/kg bw/day) showed transient salivation during the treatment period. Salivation occurred in the respective animals only within the 2-hour examination interval. It is considered to be treatment-related, likely as a result of the bad taste of the test substance/vehicle preparation or due to local irritation of the upper digestive tract. It is not considered to be a sign of systemic toxicity.
No differences of toxicological relevance between the control and the treated groups (100, 300 or 1000 mg/kg bw/day) were determined for any reproductive parameters, such as conception rate, mean number of corpora lutea, mean number of implantations, as well as pre- and postimplantation loss. Similarly, no influence of the test substance on fetal weight and sex distribution of the fetuses was noted at any dose. Finally, fetal examinations revealed that there is no developmental effect of the compound on the examined morphological structures up to the highest dose tested (NOAEL = 1000 mg/kg bw/day), the substance therefore does not need to be classified for developmental toxicity in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- The full read across justification report is attached under "Attached justification".
30 April 2018 READ-ACROSS STUDY / SOYBEAN OIL, EPOXIDIZED, ME ESTER, REACTION PRODUCTS WITH PROPYLENE GLYCOL/ REPRODUCTIVE TOXICITY I&BBE2863R001F1.0
Executive Summary
According to Annex VIII, 8.7 of the REACh Regulation (EC) No 1907/2006, Reproductive toxicity is standard information required for the registration of substances manufactured or imported in quantities of ten tonne per year or more. However, according to Annex XI, 1.5 of the REACH Regulation, Read-across and grouping approaches can be used to adapt the standard testing regime. This read-across study report follows notably the recommendations made by the European Chemicals Agency in its “Guidance on information requirements and chemical safety assessment Chapter R.6 – QSARs and grouping of chemicals” (ECHA, 2008) and in its document “Read-Across Assessment Framework (RAAF)” (ECHA, 2017).
A read-across approach appears appropriate to predict the endpoint “Reproductive toxicity” for the substance Soybean oil, epoxidized, methyl ester, reaction products with propylene glycol because:
Both the source and target substances are part of a chemical group consisting of Epoxidized Oils and Derivatives (EOD). The composition of the source chemical: Fatty acids, C16-C18 and C18-unst, Me esters, epoxidized, closely resembles the target substance.
The epoxide value for the source substance is higher than for the target substance indicating that this substance is potentially more reactive and thus an acceptable (worst-case) candidate regarding the prediction of possible toxicological effects.
This report follows the RAAF method and so presents:
1) The hypothesis: analogue read-across approach, based on the similarity of the substances and the absence of reproductive toxicity for these types of structures;
2) The scientific justifications (“Assessment Elements”) and their evaluation (“Assessment Options”); which demonstrate the confidence that can be put in this prediction.
3) The conclusions, usable for classification assessment or risk assessment, which are summarised hereafter. - Reason / purpose for cross-reference:
- read-across source
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- Most of the females (18 out of 25) of the high-dose group (1000 mg/kg bw/d) and one female of the mid-dose group (300 mg/kg bw/d) showed transient salivation during the treatment period. Salivation occurred in the respective animals only within the 2-hour examination interval (i.e. <2h after treatment). It is considered to be treatment-related, likely as a result of the bad taste of the test substance/vehicle preparation or due to local irritation of the upper digestive tract. It is not considered to be a sign of systemic toxicity.
- Mortality:
- no mortality observed
- Description (incidence):
- There were no substance-related or spontaneous mortalities in any females of all test groups (0, 100, 300 or 1000 mg/kg bw/d).
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- The mean body weights (BW) and the average body weight gains (BWC) of the low-, mid and high-dose dams (100, 300, 1000 mg/kg bw/d) were in general comparable to the controls throughout the entire study period. The corrected body weight gain of test groups 1-3 (100, 300 and 1000 mg/kg bw/d) revealed no difference of any biological relevance to the concurrent control group.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- The mean food consumption of the dams in test groups 1, 2 and 3 (100, 300 and 1000 mg/kg bw/d) was generally comparable to the concurrent control throughout the entire study period.
- Food efficiency:
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- no changes of general behavior were detected in any female of all test groups.
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- The mean gravid uterus weights of the animals of test groups 1-3 (100, 300 and 1000 mg/kg bw/d) were not influenced by the test substance.
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No necropsy findings which could be attributed to the test substance were seen in any dam. There occurred one spontaneous finding in test groups 0 and 1 (0 and 100 mg/kg bw/d), i.e. dilated renal pelvis. This finding was detected in one control and two low-dose animals and was therefore assessed as incidental.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
- 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:
- no effects observed
- Changes in pregnancy duration:
- no effects observed
- Changes in number of pregnant:
- no effects observed
- Description (incidence and severity):
- The conception rate reached 96% in the mid-dose group (300 mg/kg bw/d) and 100% in the control, low- and high-dose groups (0, 100 and 1000 mg/kg bw/d). All observed differences are considered to reflect the normal range of fluctuations for animals of this strain and age
- Other effects:
- no effects observed
- Details on maternal toxic effects:
- There were no test substance-related and/or biologically relevant differences between the test groups 0-3 (0, 100, 300 and 1000 mg/kg bw/day) in conception rate, in the mean number of corpora lutea and implantation sites or in the values calculated for the pre- and the postimplantation losses, the number of resorptions and viable fetuses. All observed differences are considered to reflect the normal range of fluctuations for animals of this strain and age
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: Highest dose tested
- Key result
- Abnormalities:
- no effects observed
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- The mean fetal weights of test groups 1, 2 and 3 (100, 300 and 1000 mg/kg bw/day) were not influenced by the test substance and did not show any biologically relevant differences in comparison to the concurrent control group.
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The sex distribution of the fetuses in test groups 1-3 (100, 300 and 1000 mg/kg bw/day) was comparable to the concurrent control fetuses.
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- no effects observed
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- One fetus with two external malformations was recorded in test group 3 (1000 mg/kg bw/day, anal atresia, thread-like tail). The total incidence of external malformations in treated animals did not differ significantly from the concurrent control group and was covered by the historical control data.
- Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- A number of skeletal malformations were detected in fetuses of test groups 0, 1 and 2 (0, 100 and 300 mg/kg bw/day) affecting the skull and humerus. An association of these malformations to the treatment is not assumed.
For all test groups, skeletal variations of different bone structures were observed, with or without effects on corresponding cartilages. The observed skeletal variations were related to several parts of fetal skeleton and appeared without a relation to dosing. The overall incidences of skeletal variations were covered by the historical control data. - Visceral malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Three soft tissue variations were detected, i.e. misaligned palatal rugae, dilated renal pelvis and dilated ureter. These variations were neither significantly different from the concurrent control nor dose-dependently altered. Therefore, they were not considered to be biologically relevant
- Other effects:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- Fetal examinations revealed that there is no effect of the compound on the respective morphological structures up to the highest dose tested (1000 mg/kg bw/d).
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Highest dose tested
- Key result
- Abnormalities:
- no effects observed
- Key result
- Developmental effects observed:
- no
- Conclusions:
- Based on the read across of the results of the developmental toxicity study for the source substance "Fatty acids, C16-C18 and C18-unsatd., ME esters, epoxidized", to the target "Soybean oil, epoxidized, methyl ester, reaction products with propylene glycol", no observed adverse effect level (NOAEL) was 1000 mg/kg bw/day in Wistar rats and the substance does not need to be classified for developmental toxicity in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).
- Executive summary:
The repeated dose toxicity of "Soybean oil, epoxidized, methyl ester, reaction products with propylene glycol" was assessed using the read across source substance: "Fatty acids, C16-C18 and C18-unsatd., ME esters, epoxidized”, which was examined in a OECD TG 407 study under GLP conditions. The test substance was administered to pregnant Wistar rats daily by gavage from implantation to one day prior to the expected day of parturition (GD 6-19) to evaluate its potential maternal and prenatal developmental toxicity. Generally, clinical observations including water consumption, food consumption and body weight gain revealed no toxicologically relevant difference between the animals receiving the test substance at 100, 300 or 1000 mg/kg bw/day and controls.
Most of the females (18 out of 25) of the high-dose group (1000 mg/kg bw/day) and one female of the mid-dose group (300 mg/kg bw/day) showed transient salivation during the treatment period. Salivation occurred in the respective animals only within the 2-hour examination interval. It is considered to be treatment-related, likely as a result of the bad taste of the test substance/vehicle preparation or due to local irritation of the upper digestive tract. It is not considered to be a sign of systemic toxicity.
No differences of toxicological relevance between the control and the treated groups (100, 300 or 1000 mg/kg bw/day) were determined for any reproductive parameters, such as conception rate, mean number of corpora lutea, mean number of implantations, as well as pre- and postimplantation loss. Similarly, no influence of the test substance on fetal weight and sex distribution of the fetuses was noted at any dose. Finally, fetal examinations revealed that there is no developmental effect of the compound on the examined morphological structures up to the highest dose tested (NOAEL = 1000 mg/kg bw/day), the substance therefore does not need to be classified for developmental toxicity in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).
Referenceopen allclose all
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Quality of whole database:
- Guideline study
Additional information
Developmental toxicity/teratogenicity (OECD TG 414)
The repeated dose toxicity of "Soybean oil, epoxidized, methyl ester, reaction products with propylene glycol" was assessed using the read across source substance: "Fatty acids, C16-C18 and C18-unsatd., ME esters, epoxidized”, which was examined in a OECD TG 407 study under GLP conditions. The test substance was administered to pregnant Wistar rats daily by gavage from implantation to one day prior to the expected day of parturition (GD 6-19) to evaluate its potential maternal and prenatal developmental toxicity. Generally, clinical observations including water consumption, food consumption and body weight gain revealed no toxicologically relevant difference between the animals receiving the test substance at 100, 300 or 1000 mg/kg bw/day and controls.
Most of the females (18 out of 25) of the high-dose group (1000 mg/kg bw/day) and one female of the mid-dose group (300 mg/kg bw/day) showed transient salivation during the treatment period. Salivation occurred in the respective animals only within the 2-hour examination interval. It is considered to be treatment-related, likely as a result of the bad taste of the test substance/vehicle preparation or due to local irritation of the upper digestive tract. It is not considered to be a sign of systemic toxicity.
No differences of toxicological relevance between the control and the treated groups (100, 300 or 1000 mg/kg bw/day) were determined for any reproductive parameters, such as conception rate, mean number of corpora lutea, mean number of implantations, as well as pre- and postimplantation loss. Similarly, no influence of the test substance on fetal weight and sex distribution of the fetuses was noted at any dose.
Finally, fetal examinations revealed that there is no developmental effect of the compound on the examined morphological structures up to the highest dose tested (NOAEL = 1000 mg/kg bw/day), the substance therefore does not need to be classified for developmental toxicity in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).
Justification for classification or non-classification
Based on the available data "Soybean oil, epoxidized, methyl ester, reaction products with propylene glycol", no observed adverse effect level (NOAEL) was 1000 mg/kg bw/day in Wistar rats and the substance does not need to be classified for developmental toxicity in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).
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.