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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
Endpoint summary
Administrative data
Description of key information
Oral administration of the test item to rats for a period of forty-two days for males and up to fifty-four days for females at dose levels of up to 1000 mg/kg/day resulted in treatment-related effects in males treated with 1000 and 350 mg/kg/day. No toxicologically significant effects were detected in females from any treatment groups. No clinically observable signs of toxicity were observed during the daily clinical observations and no toxicologically significant effects were observed during the weekly open field arena observations, the haematological parameters, or the blood chemical parameters. The effects detected in this study were considered not to represent an adverse health effect, therefore a NOAEL and a suitable high dose level for use on a twenty-eight day study was considered to be 1000 mg/kg/day.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Remarks:
- combined repeated dose and reproduction / developmental screening
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reason / purpose for cross-reference:
- read-across source
- 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
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- see "Details on results"
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- see "Details on results"
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- Mortality.
One male treated with 350 mg/kg/day was found dead on Day 35. One female
from this treatment group was also terminated early due to an unscheduled mating on Day 18.
There were no further unscheduled deaths during the study.
Clinical Signs.
No clinical signs of toxicity were detected.
Bodyweights.
No adverse effects on bodyweight development were detected.
Food Consumption and Food Efficiency.
No adverse effects on food consumption or food efficiency were detected.
Water Consumptions. No significant intergroup differences were detected.
No intergroup differences were detected.
Ophthalmoscopic Examination
Not examined.
Haematology.
No toxicologically significant effects were detected in the haematological parameters measured.
Blood Chemistry.
No toxicologically significant effects were detected in the blood chemical parameters measured.
Urinalysis.
Not examined.
Behavioural Assessment.
There were no treatment-related changes in the behavioural parameters measured.
Functional Performance Tests.
There were no treatment-related changes in functional performance.
Sensory Reactivity Assessments.
There were no treatment-related changes in sensory reactivity.
Necropsy.
The male treated with 350 mg/kg/day that was found dead on Day 35 had reddened lungs and fluid in the thoracic cavity.
Organ Weights.
No toxicologically significant effects were detected in the organ weights measured.
Histopathology - non-neoplastic.
The following treatment-related effects were detected:
LIVER: Centrilobular hepatocyte enlargement was seen in relation to treatment for males only treated with 1000 mg/kg/day.
Hepatocyte enlargement is commonly observed in the rodent liver following the administration of xenobiotics and, in the absence of associated inflammatory or degenerative changes, is generally considered to be adaptive in nature.
KIDNEY: A higher incidence of globular accumulations of eosinophilic material was observed in the tubular epithelium of males treated with 1000 or 350 mg/kg/day. A slightly higher incidence of the condition was also seen for males treated with 50 mg/kg/day compared with the control group, but this condition is seen occasionally as a spontaneous change and an effect of treatment at the low dose was not convincing. This finding is consistent with the presence of hydrocarbon nephropathy, which results from the excessive accumulation of α2-microglobulin in renal proximal tubular epithelial cells. α2-Microglobulin is found only in the proximal tubular epithelium of adult male rats.
HISTOPATHOLOGY: NEOPLASTIC (if applicable) Not applicable.
HISTORICAL CONTROL DATA (if applicable) Not applicable.
OTHER FINDINGS - 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: No adverse effects observed
- Key result
- Critical effects observed:
- no
- Conclusions:
- The oral administration of test material to rats by gavage, at dose levels of 1000, 350 and 50 mg/kg/day, resulted in treatment-related effects at 1000 and 350 mg/kg/day. These effects were considered not to represent an adverse effect of treatment, hence the NOAEL for systemic toxicity was considered to be 1000 mg/kg/day.
- Executive summary:
The study was designed to investigate the systemic toxicity and potential adverse effects of the test material on reproduction (including offspring development) and complies with the recommendations of the OECD Guidelines for Testing of Chemicals No. 422 “Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test” .
The test material was administered by gavage to three groups each of ten male and ten female Wistar Han™:HsdRccHan™:WIST strain rats, for up to fifty-four consecutive days (including a two week maturation phase, pairing, gestation and early lactation for females), at dose levels of 50, 350 and 1000 mg/kg/day. A control group of ten males and ten females was dosed with vehicle alone (Arachis oil BP).
Clinical signs, behavioural assessments, bodyweight development, food and water consumption were monitored during the study. Haematology and blood chemistry were evaluated prior to mating and at termination on five selected males and females from each dose group.
Pairing of animals within each dose group was undertaken on a one male: one female basis within each treatment group on Day 15 of the study, with females subsequently being allowed to litter and rear their offspring to Day 5 of lactation.
During the lactation phase, daily clinical observations were performed on all surviving offspring, together with litter size and offspring weights and assessment of surface righting reflex.
Extensive functional observations were performed on five selected males from each dose group after the completion of the mating phase, and for five selected parental females from each dose group on Day 4post partum.
Males were terminated on Day 43, followed by the termination of all surviving females and offspring on Day 5post partum. All animals were subjected to a gross necropsy examination and histopathological evaluation of selected tissues was performed.
Mortality.
One male treated with 350 mg/kg/day was found dead on Day 35. One female from this treatment group was also terminated early due to an unscheduled mating on Day 18.
There were no further unscheduled deaths during the study.
Clinical Observations.
No clinical signs of toxicity were detected.
Behavioural Assessment.
There were no treatment-related changes in the behavioural parameters measured.
Functional Performance Tests.
There were no treatment-related changes in functional performance.
Sensory Reactivity Assessments.
There were no treatment-related changes in sensory reactivity.
Bodyweight.
No adverse effects on bodyweight development were detected.
Food Consumption.
No adverse effects on food consumption or food efficiency were detected.
Water Consumption.
No intergroup differences were detected.
Haematology.
No toxicologically significant effects were detected in the haematological parameters measured.
Blood Chemistry.
No toxicologically significant effects were detected in the blood
chemical parameters measured.
Organ Weights.
No toxicologically significant effects were detected in the organ weights measured.
Necropsy.
The male treated with 350 mg/kg/day that was found dead on Day 35 had reddened lungs and fluid in the thoracic cavity.
Histopathology.
The following treatment-related effects were detected:
LIVER: Centrilobular hepatocyte enlargement was seen in relation to treatment for males only treated with 1000 mg/kg/day.
Hepatocyte enlargement is commonly observed in the rodent liver following the administration of xenobiotics and, in the absence of associated inflammatory or degenerative changes, is generally considered to be adaptive in nature.
KIDNEY: A higher incidence of globular accumulations of eosinophilic material was observed in the tubular epithelium of males treated with 1000 or 350 mg/kg/day. A slightly higher incidence of the condition was also seen for males treated with
50 mg/kg/day compared with the control group, but this condition is seen occasionally as a spontaneous change and an effect of treatment at the low dose was not convincing.
This finding is consistent with the presence of hydrocarbon nephropathy, which results from the excessive accumulation ofα2-microglobulin in renal proximal tubular epithelial cells.α2-Microglobulin is found only in the proximal tubular epithelium of adult male rats.
The oral administration of test material to rats by gavage, at dose levels of 1000, 350 and 50 mg/kg/day, resulted in treatment-related effects at 1000 and 350 mg/kg/day. These effects were considered not to represent an adverse effect of treatment, hence the 'No Observed Adverse Effect Level' (NOAEL) for systemic toxicity was considered to be 1000 mg/kg/day.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: dermal
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: dermal
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Oral administration of the test item to rats for a period of forty-two days for males and up to fifty-four days for females at dose levels of up to 1000 mg/kg/day resulted in treatment-related effects in males treated with 1000 and 350 mg/kg/day. No toxicologically significant effects were detected in females from any treatment groups. No clinically observable signs of toxicity were observed during the daily clinical observations and no toxicologically significant effects were observed during the weekly open field arena observations, the haematological parameters, or the blood chemical parameters.
Macroscopic findings did not reveal any effects considered to be attributable to treatment. Organ weight data however revealed increases in absolute and relative liver and kidney weight for males treated with 1000 and 350 mg/kg/day and microscopic examinations revealed treatment related effects in the liver and kidney for males treated with 1000 mg/kg/day. Centrilobular hepatocyte enlargement was evident however this is commonly observed in the rodent liver following the administration of xenobiotics and, in the absence of associated inflammatory or degenerative changes, is generally considered to be adaptive in nature.
A higher incidence of
globular accumulations of eosinophilic material in the tubular
epithelium was also detected. Accumulations of globular eosinophilic
material in the tubular epithelium is a well documented effect and are
peculiar to the male rat, which occurs in response to treatment with
certain hydrocarbons. Female rats and other species do not develop
“hydrocarbon nephropathy” and for this reason, the effect is not
indicative of a hazard to human health.
Centrilobular hepatocyte enlargement was seen in relation to treatment
for males only treated with 1000 mg/kg/day. Hepatocyte enlargement is
commonly observed in the rodent liver following the administration of
xenobiotics and, in the absence of associated inflammatory or
degenerative changes, is generally considered to be adaptive in nature.
The effects detected in this study were considered not to represent an adverse health effect, therefore a NOAEL and a suitable high dose level for use on a twenty-eight day study was considered to be 1000 mg/kg/day.
Justification for classification or non-classification
There are conclusive and sufficient data for classification of the substance with regard to repeated dose toxicity.
The test item is not classified for this endpoint in accordance with CLP Regulation (EC) No 1272/2008.
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