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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: - | CAS number: -
- 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
Description of key information
Weight-of-Evidence for repeated dose oral toxicity was obtained from subacute and chronic toxicity studies with read-across substances Epoxidized tall-oil 2 -EH (ETP: subacute oral combined repeated dose toxicity and reproductive screening study in rats) and Epoxidized soybean oil (ESBO: chronic oral toxicity in rats and dogs). Read-across data from ESBO indicate that increased liver and kidney effects in rats (1 and 5% in the diet) and fatty infiltration in the liver of dogs (5% in the diet at 12 months) were identified after 12 and 24 months, respectively. A LOAEL of 250 mg/kg/d was identified in rats after 24 months dosing, whereas in dogs a NOAEL of 250 mg/kg/d was identified after 12 months dosing. For ETP, subacute dosing in rats did not result in any parental or reproductive changes up to 1000 mg/kg/d, therefore this dose was considered as subacute NOAEL. For PSLG-5, a chronic LOAEL of 250 mg/kg/d in rats was retained as most relevant descriptor.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- chronic toxicity: oral
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Study period:
- 1960
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The study was conducted according to valid methods and considered reliable, adequate and relevant. Limited details were available.
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- other: young albino
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Not provided
- Age at study initiation: young
- Housing: . The rats were individually caged.
- Diet (e.g. ad libitum): Finely ground Purina Dog Chow Kibbled Meal served as the basic diet - Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Remarks:
- Finely ground Purina Dog Chow Kibbled Meal as basic diet
- Details on oral exposure:
- - Mixing appropriate amounts with (Type of food): Finely ground Purina Dog Chow Kibbled Meal served as the basic diet, and into this was incorporated amounts of Paraplex G-60 calculated to achieve the dietary concentrations of 0, 0.1, 0.5, 1.0, 2.5, and 5.0%.
- Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- Estimate of the effective concentration by analysis of regression of the data with 95 % confidence limits
- Duration of treatment / exposure:
- 1 year continuous for the subgroups with 5 M/F per group.
2 years ciontinuous for the subgroups with 10 M/F per group. - Frequency of treatment:
- daily in food
- Remarks:
- Doses / Concentrations:
0, 0.1, 0.5, 1.0, 2.5, and 5.0%
Basis:
nominal in diet - No. of animals per sex per dose:
- 15: Each group of 15 was subdivided into subgroups of 10 and 5 animals. At the end of one year, the survivors in the subgroups of 5 were sacrificed for histopathologic studies; organ to body weight measurements were made for liver, kidney, and testes. The subgroups of 10 were continued on diet for a second year.
- Control animals:
- yes, plain diet
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
- Time schedule for examinations: The rats were weighed once weekly.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): no
HAEMATOLOGY: Yes
- Time schedule for collection of blood:
Paraplex G-60: Blood studies (hemoglobin, red blood cell, and differential white cell counts) were made during the eleventh and twenty-fourth months.
Paraplex G-62: Hematologic studies were made at 6 as well as at 12 and 24 months
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: subgroups of 10
- Parameters examined: hemoglobin, red blood cell, and differential white cell counts
CLINICAL CHEMISTRY: No
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY:
No data
HISTOPATHOLOGY: Yes.
-Paraplex G-60: At the end of one year, the survivors in the subgroups of 5 were sacrificed for histopathologic studies; organ to body weight measurements were made for liver, kidney, and testes. Histopathologic studies were made on two-year survivors from the 0, 2.5, and 5.0% diets.
-Paraplex G-62: : At the end of 6 months, the survivors in the subgroups of 5 were sacrificed for histopathologic studies; organ to body weight measurements were made for liver, kidney, and testes. Histopathologic studies were made on two-year survivors from the 0, 2.5, and 5.0% diets. - Statistics:
- Estimate of the effective concentration, liver ratio and kidney ratio by analysis of regression of the data with 95 % confidence limits.
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No definite effect on survival is apparent.
- Mortality:
- no mortality observed
- Description (incidence):
- No definite effect on survival is apparent.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- see details on results
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- see details on results
- Gross pathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- no lesions attributable to treatment
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No definite effect on survival is apparent.
BODY WEIGHT AND WEIGHT GAIN
-Paraplex G-60: In both sexes there was early depression of growth at the 5% dietary level (P = < 0.05 at 2 and 4 weeks); this was followed by accelerated growth.
-Paraplex G-62: Among female rats, growth was significantly depressed during the early period on the diet. Analysis of regression of the data (linear at 2 and 8 weeks; curvilinear being required by the data at 4 weeks) with 95% confidence limits indicated the effective concentration to be about 3.75% at 2 weeks and 1.0% at 4 weeks, followed by no significant depression by 8 weeks. Among male rats, growth was also depressed during the early period. Analysis of linear regression of the data with 95 % confidence limits indicated the effective concentration to be about 2.1% at 2 weeks, 1.6% at 4 weeks, and 3.7% at 8 weeks, after which the effect gradually disappeared.
HAEMATOLOGY
-Paraplex G-60: Hematologic values were within normal limits at all dietary level.
-Paraplex G-62: Hematologic values were within normal limits at each examination.
ORGAN WEIGHTS
-Paraplex G-60: Male rats receiving the 5% diet had significantly elevated liver to body weight ratios.
-Paraplex G-62: Analysis of regression of the liver ratio data ( curvilinear for females, linear for males) with 95 % confidence limits indicate that significantly elevated ratios result from the treatment and that the effective concentration should fall at 0.5% for females and 2.3% for males. Similar statistical treatment of the kidney ratio data indicates the occurrence of significantly elevated ratios from the treatment for females only and that the effective concentration should fall at 1.6%.
HISTOPATHOLOGY: NON-NEOPLASTIC
-Paraplex G-60: Histopathologic studies on heart, lung, liver. kidney, spleen, gastroenteric, thyroid, adrenal pancreas, gonad. muscle, and bone marrow tissues of the rats at one and two years on the diet showed no lesions attributable to treatment.
-Paraplex G-62: Histopathologic studies made on the same tissues as listed above for Paraplex G-60 showed no lesions attributable to treatment. - Dose descriptor:
- LOAEL
- Effect level:
- 1 other: % nominal in diet
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: liver & kidney
- Critical effects observed:
- not specified
- Conclusions:
- Two epoxidized soybean oils, Paraplex G-60 and Paraplex G-62, were added to the diets of rats for a two-year period in concentrations up to 5%. No effects were observed on survival or on the blood picture and histologic examination of tissues revealed no lesions attributable to treatment. Early depression in growth was observed in rats from both materials (Paraplex G-62 being the most potent), but this effect disappeared on continued feeding.
Elevated liver to body weight ratios resulted at the 5% concentration in male rats receiving Paraplex G-60 and at lower concentrations in both male and female rats receiving Paraplex G-62; kidney to body weight ratios were also elevated with the latter material in female rats. - Executive summary:
Two epoxidized soybean oils, Paraplex G-60 and Paraplex G-62, were added to the diets of rats for a two-year period in concentrations up to 5%. Groups of rats (15/sex) were given diets containing 0, 0.1, 0.5, 2.5 or 5% (up to approximately 1250 mg/kg bw) ESBO for up to 2 years. Five rats/sex/group were sacrificed at 6 months. Organ to body weight measurements were made for liver, kidney and testes. Blood studies (hemoglobin, red blood cell and differential white cell counts) were made during the eleventh and twenty-fourth months. Histopathology of heart, lung, kidney, spleen, gastroenteric, thyroid, adrenal, pancreas, gonad, muscle and bone marrow tissues was conducted on survivors from the 0, 2.5% and 5% diet groups. Growth appeared to be essentially normal at 2.5%, but appeared to be permanently low in the 5% group. A limited evaluation of the blood (red blood cell and white blood cell counts) revealed no effects. Liver weight was increased in both sexes at 1% and above. There was some evidence that kidney weight was increased in the females at 1% and above.
Microscopic examination of the major tissues revealed no cellular changes at 2.5% or 5% (only dose groups examined). In conclusion, Lowest Adverse Effect Level (LOAEL) was 1% in the diet (approximately 250 mg/kg bw).
Reference
-Paraplex G-60
Fifteen young male and 15 female albino rats were placed on each of the following dietary levels of the test material: 0, 0.1, 0.5, 1.0, 2.5, and 5.0%. Finely ground Purina Dog Chow Kibbled Meal served as the basic diet, and into this was incorporated amounts of Paraplex G-60 calculated to achieve the above dietary concentrations. The rats were individually caged and were weighed once weekly. Each group of 15 was subdivided into subgroups of 10 and 5 animals. At the end of one year, the survivors in the subgroups of 5 were sacrificed for histopathologic studies; organ to body weight measurements were made for liver, kidney, and testes. The subgroups of 10 were continued on diet for a second year. Blood studies (hemoglobin, red blood cell, and differential white cell counts) were made during the eleventh and twenty-fourth months.
Histopathologic studies were made on two-year survivors from the 0, 2.5, and 5.0% diets.
-Paraplex G-62
This study on rats was identical in all respects to that described above for Paraplex G-60 except that the rat subgroups of 5 were sacrificed at the end of 6 months and hematologic studies were made at 6 as well as at 12 and 24 months.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LOAEL
- 250 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- Reliable
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Weight-of-Evidence for repeated dose oral toxicity was obtained from subacute and chronic toxicity studies with read-across substances. A read-across justification based on molecular, physicochemical and toxicological properties was written as a separate document provided under Section 13 (Assessment reports). The following data were used:
-Epoxidized tall-oil 2 -EH (ETP) was administered once daily orally (by gavage) to male Wistar rats at least for 28 days (including 14 days prepairing) and to female Wistar rats throughout the 14 day prepairing period and throughout pairing and gestation up to lactation day 4 (RCC, 2005a). The dose levels were 0 (vehicle control), 100, 300 and 1000 mg/kg bw/d. A standard dose volume of 2 mL/kg body weight with a daily adjustment to the actual body weight was used. Control animals were dosed with vehicle alone (corn oil).
The fertility rate was high resulting in at least 9 litters per group for evaluation of reproduction data. There were no treatment-related effects on precoital time, fertility indices, mean duration of gestation, number of implantations, post-implantation loss, pup survival or litter size from birth through to scheduled pup sacrifice on day four post-partum at any dose level. No test article related histopathological findings were noted in the reproductive organs of either sex. In particular, the assessment of the integrity of the spermatogenetic cycle did not reveal any evidence of impaired spermatogenesis. In the absence of any adverse effects on parental systemic and reproductive parameters, the parental and reproductive NOAEL and NOEL were considered to be 1000 mg/kg bw/d.
- Two epoxidized soybean oils (ESBO), Paraplex G-60 and Paraplex G-62, were added to the diets of rats for a two-year period in concentrations up to 5% (Larson et al., 1960a). Groups of rats (15/sex) were given diets containing 0, 0.1, 0.5, 2.5 or 5% (up to approximately 1250 mg/kg bw) ESBO for up to 2 years. Five rats/sex/group were sacrificed at 6 months. Organ to body weight measurements were made for liver, kidney and testes. Blood studies (hemoglobin, red blood cell and differential white cell counts) were made during the eleventh and twenty-fourth months. Histopathology of heart, lung, kidney, spleen, gastroenteric, thyroid, adrenal, pancreas, gonad, muscle and bone marrow tissues was conducted on survivors from the 0, 2.5% and 5% diet groups. Growth appeared to be essentially normal at 2.5%, but appeared to be permanently low in the 5% group. A limited evaluation of the blood (red blood cell and white blood cell counts) revealed no effects. Liver weight was increased in both sexes at 1% and above. There was some evidence that kidney weight was increased in the females at 1% and above. Microscopic examination of the major tissues revealed no cellular changes at 2.5% or 5% (only dose groups examined). In conclusion, Lowest Adverse Effect Level (LOAEL) was 1% in the diet (approximately 250 mg/kg bw).
- Two epoxidized soybean oils (ESBO), Paraplex G-60 and Paraplex G-62, were added to the diets of dogs for one year in concentrations up to 5% (Larson et al., 1960b). Groups of three dogs were fed at 0.1, 1 or 5% (approximately 1250 mg/kg bw/day) Paraplex G-60 or G-62 once per day for one year. The dogs were weighed weekly and food intake was monitored. Hematologic studies were made at study initiation, at 6 months and at 12 months. Major tissues were examined microscopically. The dogs were sacrificed at 12 months. Dogs fed 5% Paraplex G-60 or G-62 lost weight. Survival and blood parameters (hemoglobin, red and white blood cell counts) were normal in all treated groups. The major tissues were microscopically normal except for fatty liver changes (fatty infiltration) in one dog given 5% Paraplex G-62. Food intake and body weight were decreased at 5% of either grade. Lowest Adverse Effect Level (LOAEL) was 5% in the diet (1250 mg/kg bw/day). For both batches tested, the 1% concentration (approximately 250 mg/kg bw/day) can be considered to be a NOAEL.
Read-across data from ESBO indicate that increased liver and kidney effects in rats (1 and 5% in the diet) and fatty infiltration in the liver of dogs (5% in the diet at 12 months) were identified after 12 and 24 months, respectively. A LOAEL of 250 mg/kg/d was identified in rats after 24 months dosing, whereas in dogs a NOAEL of 250 mg/kg/d was identified after 12 months dosing. For ETP, subacute dosing in rats did not result in any parental or reproductive changes up to 1000 mg/kg/d, therefore this dose was considered as subacute NOAEL. For PSLG-5, a chronic LOAEL of 250 mg/kg/d in rats was retained as most relevant descriptor.
The oral route was considered most appropriate for the hazard characterization of PLSG-5. Inhalation of the substance is unlikely as the vapour pressure is very low. Skin contact may be likely, however skin absorption is considered to be very low (see Toxicokinetics).
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Weight-of-Evidence from read-across substances; this endpoint has two target organs and LOAEL was identified.
Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver; urogenital: kidneys
Justification for classification or non-classification
Based on the results and according to the EC criteria for classification and labelling according to CLP regulation (EC No. 1272/2008 of 16 December 2008), 'fatty acids, C16 -18 and C18-unsaturated isopentyl esters, epoxidized' does not have to be classified and has no obligatory labelling requirement for repeated dose toxicity.
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.