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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
Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- 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:
- study report
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2013
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- yes
- Remarks:
- some minor deviations
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distilled, oligomerisation products with 1-chloro-2,3-epoxypropane
- Cas Number:
- 68413-24-1
- Molecular formula:
- C24H36O2
- IUPAC Name:
- Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distilled, oligomerisation products with 1-chloro-2,3-epoxypropane
- Test material form:
- liquid
- Details on test material:
- - Name of test material (as cited in study report): CARDOLITE NC-513
- Physical state: liquid
- Batch no.: GH-0129
- Expiry date: 13.07.2014
- Storage condition of test material: room temperature 20 ± 5 °C, keep away from humidity
- Other: the test item was previously considered as 'Cashew, nutshell liq., oligomeric reaction products with 1-chloro-2,3-epoxypropane' (EC number 500-210-7).
1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River, Sandhofer Weg 7 97633 Sulzfeld, Germany
- Age at study initiation: 11-12 weeks
- Weight at study initiation: 259 g – 296 g (males); 173 g – 196 g (females) (at acclimatisation)
- Fasting period before study: no information
- Housing: Clean conventional housing
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6-9 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 10 cycles/hour
- Photoperiod (hrs dark / hrs light): 12h/12h
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
VEHICLE
- Justification for use and choice of vehicle (if other than water): The test item is not soluble in water in concentrations necessitated for this study. Formulations prepared with the vehicle are suitable for oral administration as it is the anticipated route of human exposure to the test item.
- Concentration in vehicle:
- Amount of vehicle (if gavage): Treatment volume was 5 mL/kg body weight in all groups
- Lot/batch no. (if required): N83746634 - Details on mating procedure:
- - Proof of pregnancy: vaginal plug and sperm in vaginal smear
- M/F ratio per cage: 1/1
- After successful mating each pregnant female was caged (how): single - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- males: 48 -61 days
females: >= 46 days - Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 250 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 62.5 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Remarks:
- Control
- No. of animals per sex per dose:
- 12
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: preliminary study
- Positive control:
- none
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice a day
- Cage side observations: Viability and mortality
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: at least once weekly
OTHER: see study record under 'Repeated dose toxicity' - Sperm parameters (parental animals):
- Parameters examined in male parental generation:
testis weight, epididymis weight - Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, weight gain
GROSS EXAMINATION OF DEAD PUPS: no - Postmortem examinations (parental animals):
- Sacrifice: Animals were euthanised when found to be moribund or when the adequate number of litters according to guideline OECD 422 was achieved. All animals were sacrificed humanely by asphyxiation in a CO2 atmosphere.
Organ weights: The body weight of all animals killed at the end of the treatment period was recorded before sacrifice, and the organs specified in the Tissue Procedure Table were weighed wet as soon as possible after dissection. The ratio of organ weight to body weight (recorded immediately before sacrifice) was calculated.
Macroscopic post-mortem examination: A complete macroscopic post-mortem examination was performed on all study animals. This included examination of the external surfaces, all orifices, the cranial cavity, the external surfaces of the brain and spinal cord, the thoracic, abdominal and pelvic cavities with their associated organs and tissues and the neck with its associated organs and tissues.
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Mild discomfort throughout the whole application period was observed for the animals treated with the high and the medium dose of the test item (wiping of nose and mouth through the cage bedding, salivation after application, bleeding of mucous membranes at nose and mouth, respirators sounds). Moreover, some male animals of the high dose group became lethargic after application of the test item on individual days. A biological and particularly toxicological relevance of these observations could not be excluded.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Regarding the body weight and the body weight gain, no significant differences were observed between all test item treated animals (male and female) and their respective vehicle control animals. Occasional differences observed for the females were assumed to be of natural origin based on the pregnancy status of the animals.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- Regarding the body weight and the body weight gain, no significant differences were observed between all test item treated animals (male and female) and their respective vehicle control animals. Occasional differences observed for the females were assumed to be of natural origin based on the pregnancy status of the animals.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Description (incidence and severity):
- Regarding the body weight and the body weight gain, no significant differences were observed between all test item treated animals (male and female) and their respective vehicle control animals. Occasional differences observed for the females were assumed to be of natural origin based on the pregnancy status of the animals.
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- No relevant test item induced effects on any haematology or clinical biochemistry parameter
could be detected - Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- No relevant test item induced effects on any haematology or clinical biochemistry parameter
could be detected - Endocrine findings:
- not examined
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- No alterations regarding general behaviour of the rats were observed during in-life phase
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- The type, incidence and severity of all microscopic findings observed did not indicate a relationship to the treatment with the test item. The repeated oral administration of the test item did not produce any evidence of pathomorphological findings that are considered to be due to a toxic effect of the test item.
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
Details on results (P0)
For females of the high dose group (1000 mg/kg bw) ovary weight was increased.
Effect levels (P0)
open allclose all
- Dose descriptor:
- NOAEL
- Remarks:
- systemic
- Effect level:
- 250 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- organ weights and organ / body weight ratios
- Dose descriptor:
- NOAEL
- Remarks:
- reproduction
- Effect level:
- >= 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other:
- Remarks on result:
- other: No adverse effects observed
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- mortality observed, treatment-related
- Description (incidence and severity):
- A statistical significant decrease in the amount of pups born alive was detected for the animals of the high and medium dose groups
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
Details on results (F1)
No further abnormalities were detected during gestation and lactation phase. In summary, an increase in pre- implantation losses and a corresponding decrease in the amount of pups born alive was detected in all dose groups compared to the vehicle control group. However, pup growth and development, as far as monitored, was normal for all test item treated animals when compared to the vehicle control animals. No further differences were observed regarding reproduction success (achievement and duration of pregnancy, post- implantation losses, survival rate of pups, development of pups) for all test item treated animals when compared to the vehicle control animals. In the absence of another test item related effect the reduced amount of live born could not be rated as clear evidence for a toxic effect. Nonetheless, a test item related effect could not be excluded.
Effect levels (F1)
open allclose all
- Dose descriptor:
- NOAEL
- Remarks:
- Development
- Generation:
- F1
- Effect level:
- >= 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- other: Pup growth and development (day 0 and day 4 post-partum) were normal for all test item treated animals when compared to the vehicle control animals
- Dose descriptor:
- NOAEL
- Remarks:
- Embryo-/fetotoxicity
- Generation:
- F1
- Effect level:
- 62.5 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: number of pups born alive
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of the present study, CARDOLITE NC-513 did not cause toxic changes and did not influence male and female reproductive performance (gonad function, mating behavior, conception, pregnancy, parturition) in parental male and female Wistar rats after repeated dose oral administration at 62.5, 250 or 1000 mg/kg bw/day.
The number of pups born alive was lower with respect to control at 250 and 1000 mg/kg bw/day.
Based on these observations the No Observed Adverse Effect Levels (NOAEL) were determined as follows:
NOAEL (F0 systemic) females/males: 250 mg/kg bw/day
NOAEL (F0 reproduction) females/males: >=1000 mg/kg bw/day
NOAEL (F1 embryo-/fetotoxicity) 62.5 mg/kg bw/day
NOAEL (F1 development): >=1000 mg/kg bw/day (pup growth and development (day 0 and day 4 post-partum) were normal for all test item treated animals when compared to the vehicle control animals) - Executive summary:
In a GLP-study according to OECD Tes Guideline 422 the toxic effects of the test item CARDOLITE NC-513 at doses of 62.5, 250 and 1000 mg/kg body weight on the subacute toxicity and the development and reproduction of Wistar rats after oral administration were under examination.The substance was at least applied for 46 days daily to rats of both sexes. The following observations were made.
General and detailed clinical signs:
Mild discomfort throughout the whole application period was observed for the animals treated with the high and the medium dose of the test item (wiping of nose and mouth through the cage bedding, salivation after application, bleeding of mucous membranes at nose and mouth, respirators sounds). Moreover, some male animals of the high dose group became lethargic after application of the test item on individual days. A biological and particularly toxicological relevance of these observations could not be excluded.
Body weight, food and water consumption: Regarding the body weight and the body weight gain, no significant differences were observed between all test item treated animals (male and female) and their respective vehicle control animals. Occasional differences observed for the females were assumed to be of natural origin based on the pregnancy status of the animals.
No test item related tendencies regarding food and water consumption of all test item treated animals (male and female) could be observed throughout the whole study phase when compared to their respective vehicle control animals. All fluctuations observed were most likely of natural origin.
Haematology and clinical biochemistry: no effects
Reproduction and Development:
A statistical significant decrease in the amount of pups born alive was detected for the animals of the high and medium dose groups. This was not statistically significant for the animals of the low dose group. The increase in pre-implantation losses was not significant for any dose group. Pup growth and development (day 0 and day 4 post-partum) were normal for all test item treated animals when compared to the vehicle control animals. No further findings regarding reproduction success (achievement and duration of pregnancy, post- implantation losses, survival rate of pups, development of pups) were observed in animals of any test item treated group when compared to the vehicle control group.
Necropsy:
The determination of organ weights, as part of the necropsy, showed a statistically significant increase of the liver weight (male; absolute and relative), a statistically significant decrease of the prostate weight (absolute and relative), a statistically significant increase of the brain weight (female; absolute), and a statistically significant weight increase of the right ovary (absolute and relative) within the animals treated with the high dose of the test item. However, the changed organ weights were not accompanied by structural changes (see below 'Histology'). Moreover, with increasing dose levels the amount of male animals having slightly developed mammary glands declined. Besides some further individual findings, heterogeneously distributed over all dose groups, no further apparent observations were made that could be related to the administration of the test item.
Histology: no effects
Based on these observations the No Observed Adverse Effect Levels (NOAEL) were determined as follows:
NOAEL (F0 systemic) females/males: 250 mg/kg bw/day
NOAEL (F0 reproduction) females/males: >=1000 mg/kg bw/day
NOAEL (F1 embryo-/fetotoxicity) 62.5 mg/kg bw/day
NOAEL (F1 development): >=1000 mg/kg bw/day (pup growth and development (day 0 and day 4 post-partum) were normal for all test item treated animals when compared to the vehicle control animals)
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