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EC number: 215-355-9 | CAS number: 1323-42-8
- 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
Repeated dose toxicity: oral
Some information in this page has been claimed confidential.
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 992
- Report date:
- 1992
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Test material form:
- liquid: viscous
- Details on test material:
- Castor oil (CAS 8001-79-4), lot #L-5G30-01, was obtained from Cas Chemical, Inc., Bayonne, NJ. (now owned by Vertellus LLC). Purity analysis indicated that it was consistent with the USP specifications and the reported composition for castor oil: Analysis was conducted by Midwest Research Institute (MRI), in Kansas City, MO, utilizing infrared, UV/Vis and NMR spectroscopy, Karl Fischer water analysis, TLC and HPLC, and a battery of USP standard analyses for castor oil.
Constituent 1
- Specific details on test material used for the study:
- 100% Castor Oil, from Cas Chemical Inc., Bayonne, NJ.
- Lot/batch no. (if required): Lot #L-5G30-01
- Purity: 100%
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Details on species / strain selection:
- F344/N
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Source: Simonsen Laboratories, Gilroy, CA
Age: 6 weeks
Quarantine: held 14-15 days
Rats housed 5/cage, mice housed individually
Cage type: Polycarbonate with heat-treated wood chips
Diet: NIH-07 diet, ad libitum. Water ad libitum
Temp--68-76°F; relative humidity--42-72%; fluorescent light 12 h/d; 10 room air changes/h.
Observations: Animals were observed twice daily, weighed initially and weekly thereafter.
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION
- Rate of preparation of diet (frequency): Prepared every 21 days. Feed within animal cages was changed every 3 days.
- Mixing appropriate amounts with (Type of food): NIH07, ad lib
- Storage temperature of food: at 5 degrees C, in the dark
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No. By cage, with 5 animals/cage.
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Purity analysis indicated that it was consistent with the USP specifications and the reported composition for castor oil: Analysis was conducted by Midwest Research Institute (MRI), in Kansas City, MO, utilizing infrared, UV/Vis and NMR spectroscopy, Karl Fischer water analysis, TLC and HPLC, and a battery of USP standard analyses for castor oil.
The stability of the test material during the toxicology studies was monitored by determination of peroxide content and by HPLC. The substance was stable during the course of the studies. - Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 400 mg/kg bw/day (nominal)
- Remarks:
- equivalent to 0.62% in the diet. Actual: male/female: 404/401 mg/kg bw/d
- Dose / conc.:
- 800 mg/kg bw/day (nominal)
- Remarks:
- equivalent to 1.25% in the diet. Actual: male/female: 809/797 mg/kg bw/d
- Dose / conc.:
- 1 500 mg/kg bw/day (nominal)
- Remarks:
- equivalent to 2.5% in the diet. Actual: male/female: 1583/1569 mg/kg bw/d
- Dose / conc.:
- 3 000 mg/kg bw/day (nominal)
- Remarks:
- equivalent to 5.0% in the diet. Actual: male/female: 3067/3045 mg/kg bw/d
- Dose / conc.:
- 6 000 mg/kg bw/day (nominal)
- Remarks:
- equivalent to 10% in the diet. Acutal: male/:females: 5835/5725 mg/kg bw/d
- No. of animals per sex per dose:
- 10 rats/sex/group in the core study, plus 10 rats/dose/sex were included for hematological and clinical chemistry parameters at days 5 and 21.
- Control animals:
- yes, plain diet
- Details on study design:
- The core study was conducted with groups of 10 rats and 10 mice per sex, each group receiving diets containing 0, 0.62%, 1.25%, 2.5%, 5.0% or 10% castor oil, continuously for 13 weeks. Ten additional rats/sex were included at each dose level for evaluation of hematological and clinical chemistry parameters. At days 5 and 21, these animals were anesthetized with CO2, and blood was collected from the orbital sinus. These animals were killed following the blood collection on day 21. Blood samples for hematology and clinical chemistry also were collected from core-study rats at study termination.
Clinical Examinations, Supplemental Studies and Pathology
At the study termination, all core-study animals were euthanized by CO2 anesthesia, and complete necropsies were performed. Complete histopathology examinations were conducted on all rats and mice from the control and 10% dose groups. Livers were examined from male rats in all other dose groups; histologic sections of gross lesions were examined from all rats. Organ weights were determined to the nearest milligram for the liver, right kidney, right testicle, heart, thymus, and lungs. All tissues were preserved in 10% neutral buffered formalin.
On days 5 and 21, and at sacrifice, blood samples were collected from the orbital sinus of non-fasted animals under CO2 anesthesia. Hematology parameters were determined on a Baker 9000 automated hematology analyzer (J.T. Baker, Phillipsburg, NJ) and included:
Red blood cell (RBC) count, red blood cell morphologic assessment, hematocrit (HCT), hemoglobin concentration (HGB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cell count (WBC), white blood cell differential count, reticulocyte count (absolute), and platelet counts (absolute). Clinical chemistry assays, performed with a Centrifichem 600 (J.T. Baker, Phillipsburg, NJ) using commercially available kits and standard methods developed for this instrument, included alkaline phosphatase activity (ALP), albumin (ALB), urea nitrogen (UN), creatinine (CREA), alanine aminotransferase activity (ALT), total bile acids (TBA), sorbitol dehydrogenase activity (SDH), total protein (TP), and creatinine kinase (CK).
Upon completion of the histologic evaluation by the laboratory pathologist, the slides, paraffin blocks, and residual wet tissues were sent to the NTP Archives for inventory, slide/block match, and wet tissue audit. The slides, individual animal data records, and pathology tables were sent to an independent pathology laboratory where quality assessment was performed; the results were reviewed and evaluated by the NTP.
Reproductive Toxicity Screen
To screen for potential reproductive toxicity, sperm motility and morphology were evaluated at necropsy, and vaginal cytology was evaluated on core-study animals during the week just preceding necropsy, following published procedures (Morrissey et al., 1988). For the 12 days prior to termination, females were subject to vaginal lavage with saline. The aspirated cells were air-dried onto slides, stained with Toluidine Blue O, and coverslipped. The relative preponderance of leukocytes, nucleated epithelial cells, and large squamous epithelial cells were used to identify the stages of the estrual cycle.
Sperm motility was evaluated at necropsy as follows: The left epididymis was removed and quickly weighed; the cauda epididymis was removed at the junction of the vas deferens and the corpus epididymis, then weighed. A small cut was made in the distal cauda epididymis. The sperm that were removed from the epididymis were dispersed and the number of moving and non-moving sperm were counted in 5 fields of 30 sperm or less on each slide. After sperm sampling for motility evaluation, the cauda was placed in phosphate buffered saline (PBS), and gently chopped with a razor blade. The solution was mixed gently and heat-fixed at 65°C. Sperm density was then determined using a hemocytometer.
The left testis was frozen and stored. After thawing, testicular spermatid head count was determined by removing the tunica albuginea and homogenizing the testis in PBS containing 10% DMSO. Homogenization spermatid nuclei were enumerated using a hemocytometer; the data were expressed as spermatid heads per total testis and per gram of testis. - Positive control:
- None
Examinations
- Observations and examinations performed and frequency:
- Animals were observed twice daily.
- Sacrifice and pathology:
- CO2 asphyxiation was followed by retroorbital blood sampling and complete necropsies for the control and high doses.
The following tissues were routinely processed for preparation of histologic sections and microscopic examination: adrenal glands, brain, cecum, colon, duodenum, epididymis/seminal vesicles/prostate/testes or ovaries/uterus, esophagus, eyes (if grossly abnormal), femur (including marrow), heart, ileum, jejunum, kidneys, liver, lungs and mainstem bronchi, mammary gland, mandibular and mesenteric lymph nodes, nasal cavity and turbinates, pancreas, parathyroid glands, pituitary gland, preputial or clitoral glands, rectum, salivary glands, skin, spinal cord and sciatic nerve (if neurologic signs present), spleen, forestomach and glandular stomach, thymus, thyroid gland, trachea, urinary bladder, zymbal glands, and all gross lesions and tissue masses including regional lymph nodes. A complete histopathologic examination was conducted on all rats and mice from the control and 10% dose groups. Liver was examined from male rats in all other dose groups, and histologic sections of gross lesions were examined from all rats. - Statistics:
- Body weight and organ weight data were statistically analyzed within each sex by one-way Analysis of Variance tests, followed by Dunnett's t-test if pair-wise comparisons were indicated (p < 0.05)(Dunnett, 1955).
Results and discussion
Results of examinations
- 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):
- No deviations from expected food consumption/compound intake was observed.
- Food efficiency:
- not specified
- Description (incidence and severity):
- No description of caloric breakdown by dose.
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- In males, a statistically significant decrease in MCV in the 10% group was found, but was not biologically significant. Minor effects: in males of the 10% group at day 90, a slight decrease in MCH along with a transient decrease in MCHC in the 10% group males at day 21. At 90 days, the platelet count in males of the 1.25, 5 and 10% groups was significantly increased. These variations were evaluated as not biologically significant by the study authors.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- In males and females, a dose-related increase in serum alkaline phosphatase activity was found at days 5, 21 and 90. At days 5, 21 and 90, in males and females, there was a consistent dose-related increase in serum alkaline phosphatase activity in the 5 and 10% groups. Total bile acids were also statistically significantly elevated in males of the 5 and 10% groups at 5, 21 and 90 days. This is likely an adaptation to increased absorption and metabolism of lipids from the intestinal tract.
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Absolute liver weight and liver-to-body weight ratio were statistically significantly increased in male rats receiving 10% castor oil. Relative heart ratios were increased in some doses but not in a dose-related manner; as absolute heart weights were not increased, they were not considered treatment related.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No gross pathologic lesions noted.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- No histopathologic lesions in liver or any other organ.
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
- Description (incidence and severity):
- Reproductive function endpoints; slight decrease in epididymal weight (<10% in magnitude). This is not considered evidence of reproductive toxicity.
- Details on results:
- No toxicologically relevant adverse effects were observed in any treatment group.
In males in the highest dose group (10%), there was a statistically significant decrease in MCV ; this was not considered biologically significant. Also in this group, there was a slight decrease in MCH and the MCHC was transiently decreased at day 21. Other minor effects were observed in hematologic parameters: at 90 days, the platelet count in males of the 1.25, 5 and 10% groups was significantly increased. These variations were evaluated as not biologically significant by the study authors.
Serum alkaline phosphatase activity was increased in a treatment- and dose-related manner at days 5, 21 and 90, in both males and females in the 5 and 10% groups. Total bile acids were also statistically significantly elevated in males of the 5 and 10% groups at 5, 21 and 90 days. This is likely an adaptation to increased absorption and metabolism of lipids from the intestinal tract.
Absolute liver weight and liver-to-body ratio were increased in male rats at the high dose (10%). In males, there was a slight decrease in epididymal weight (< 10%) in the middle and high dose groups, but this was not dose-related. It is concluded that there was little or no evidence of any reproductive toxicity associated with castor oil exposure.
Histological examination revealed an absence of compound related lesions in any organ or tissue of rat exposed to castor oil in the diet.
The NOAEL was determined by the authors to be 10% in the diet, equivalent in females to 5725 mg/kg bw/d, and in males to 5835 mg/kg bw/d.
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 5 725 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Remarks:
- No adverse effects at the highest dose (10% in the diet, 5725 mg/kg bw/d in females (actual), 5835 mg/kg bw/d in males (actual)
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Any other information on results incl. tables
There were no observed loose or wet feces associated with castor oil intake in rats, likely due to its presence in food ingested over a relatively prolonged time period. Survival, food consumption, and body weights in treated animals were comparable to those of controls. Changes in serum liver enzyme levels reflect metabolic adaptation to the high lipid diet ingested. There were no gross or histopathologic lesions associated with the liver changes, nor were there any compound-related morphologic changes in any organ examined. The administration of diets containing up to 10% castor oil was not associated with toxicity to any specific organ, organ system or tissue, under the conditions of this study.
TABLE 3 |
Survival and Average Food Feed Studies of Castor Oil |
and |
Compound |
Consumption |
of F344/N |
Rats |
in |
the |
13-Week |
|||||||
|
Dose |
|
Mean |
BodyWeight |
(grams) |
Final Weight Relative to Controls (%) |
FeedConsumption |
|
|
Compound Consumption |
|
|||||
(% in feed) |
Survival |
(a) |
Initial |
Final |
|
|
Change |
(b) |
|
(c) |
||||||
MALE 0 0.62 1.25 2.5 5.0 10.0
FEMALE 0 0.62 1.25 2.5 5.0 10.0 |
10/10 10/10 10/10 10/10 10/10 10/10
10/10 10/10 10/10 10/10 10/10 10/10 |
|
132 130 126 131 131 129
108 108 107 109 110 108 |
364 346 359 356 351 353
208 202 205 202 206 197 |
|
233 216 233 226 220 224
100 95 97 93 96 89 |
95.0 98.6 97.8 96.4 97.0
97.1 98.6 97.1 99.0 94.7 |
|
65 65 65 63 61 58
64 65 64 63 61 57 |
|
|
|
0 404 809 1583 3067 5835
0 401 797 1569 3045 5725 |
|
||
(a) (b) (c) |
Number surviving/number initially in group. Averagegrams food consumed per kg body weight per day. Average mg compound consumed per kg body weight per day. |
|
|
|
|
|
|
|
|
Applicant's summary and conclusion
- Conclusions:
- The administration of diets containing up to 10% (w/w) of castor oil to F344 rats for 13 weeks was not associated with toxicity to any specific organ, organ system or tissue under the conditions of this study. The NOAEL is greater than 10%, equivalent to 5725 mg/kg bw/d in females and 5835 mg/kg bw/d in males (actual). The read-across approach from castor oil is acceptable for the purposes of classification and labelling, and filling registration data requirements.
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.
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