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EC number: 939-718-2 | CAS number: 1474044-80-8
- 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
Endpoint summary
Administrative data
Description of key information
A combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test was conducted with Barium bis( di c8-c10, branched, c9 rich, alkylnaphthalene sulphonate) in rats by oral gavage. This GLP study followed the OECD 422 guideline. Dose levels were based on the results of a 10-day dose range finding study. The dose levels for this combined 28-day oral gavage study with reproduction/developmental toxicity screening test were selected to be 15, 50 and 150 mg/kg. This was based on an estimated purity of 90%. After completion of the testing, the substance was determined to be UVCB with a purity of 100%. Based on the UVCB purity, the doses are considered to be 17, 55 and 165 mg/kg/day.
After acclimatization, four groups of ten male and ten female Wistar Han rats were exposed by oral gavage to the test substance. Males were exposed for 29 days, i.e. 2 weeks prior to mating, during mating, and up to termination. Females were exposed for 42-55 days, i.e. during 2 weeks prior to mating, during mating, duringpost-coitum, and during at least 4 days of lactation.
Results/discussion
The lower motor activity of females at 150 mg/kg was temporary in nature since at commencement and the end of the measurement interval motor activity appeared similar to control levels. Moreover, the lower motor activity was not associated with concurrent changes in clinical appearance or changes during functional observation tests. Therefore, this change in motor activity was considered to be of no toxicological relevance.
Tubular crystals were noted in the kidneys of one male and one female at 150 mg/kg (up to slight degree).Crystal deposition can lead to obstructive nephropathy. In this study, this finding was accompanied in the female by tubular dilatation, epithelial hypertrophy and granular cast(s) (up to slight degree) in the immediate vicinity as tubular crystals were noted, and is suggestive for findings secondary to obstruction. Therefore, the presence of tubular crystals is considered to be adverse.
The increased severity of congestion/erythrophagocytosis in the mesenteric lymph nodes of females treated at 15 mg/kg, 50 mg/kg and 150 mg/kg (up to moderate degree, and corresponding to dark red foci/reddish discolouration of the mesenteric lymph node in some females at 15 and 150 mg/kg) was considered to be non-adverse given the absence of any other indicators of cellular damage, e.g. inflammation or necrosis. The increased incidence and severity of hyperplasia/hypertrophy of the follicular epithelium of the thyroid gland in females treated at 150 mg/kg was subtile in nature and occurred in the absence of a dose-related trend, and was therefore considered to be non-adverse.
There were no morphological findings in the reproductive organs of either sex which could be attributed to the test item.
No toxicologically significant changes were noted in any of the remaining parental parameters investigated in this study (i.e. clinical appearance, functional observations, body weight, food consumption, clinical laboratory investigations, macroscopic examination and organ weights).
Based on these results, the repeat dose No Observed Adverse Effect Level (NOAEL) is 50 mg/kg (55 mg/kg-as UVCB).
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:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 07 March 2012 to 11 June 2012 (end of in-life phase)
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP study with no significant deficiencies
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Source F0: Charles River Deutschland, Sulzfeld, Germany.
Age at start F0-treatment: Approximately 11 weeks.
Number of F0-animals: 40 females and 40 males.
Acclimatization F0: At least 5 days prior to start of treatment.
Health inspection F0: Upon receipt of the animals.
Identification F0: Earmark and tattoo.
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study. - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- Initial doses (0, 15, 50, 150 mg/kg respectively) were based on an estimated purity of 90%. After completion of the in-life phase the substance was classified as UVCB with a purity of 100%. Therefore, actual doses were 10% higher, i.e. 17, 55 and 165 mg/kg respectively.
Method: Oral gavage, using a plastic feeding tube. Formulations were placed on a magnetic stirrer during dosing.
Dose volume: 5 mL/kg body weight. Actual dose volumes were calculated according to the latest body weight.
Frequency: Once daily for 7 days per week, approximately the same time each day with a maximum of 6 hours difference between the earliest and latest dose. Animals were dosed up to the day prior to scheduled necropsy. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analyses were conducted according to a validated method (Project 498817). These analyses were conducted after the in-life phase as no suitable analytical method was available at an earlier stage. Samples of formulations were analyzed for homogeneity (highest and lowest concentration) and accuracy of preparation (all concentrations). Stability in vehicle over 6 hours at room temperature was also determined (highest and lowest concentration).
The accuracy of preparation was considered acceptable if the mean measured concentrations were 85-115% of the target concentration. Homogeneity was demonstrated if the coefficient of variation was ≤ 10%. Formulations were considered stable if the relative difference before and after storage was maximally 10%. - Duration of treatment / exposure:
- Males were exposed for 31 days, i.e. 2 weeks prior to mating, during mating, and up to the day prior to scheduled necropsy. Females were exposed for 41-52 days, i.e. during 2 weeks prior to mating, during mating, during post-coitum, and during at least 4 days of lactation (up to the day prior to scheduled necropsy). Female nos. 44 (Group 1), 65, (Group 3) and 77 (Group 4) were not dosed during littering.
- Frequency of treatment:
- Once daily
- Remarks:
- Doses / Concentrations:
Oral gavage in corn oil
Basis:
actual ingested - No. of animals per sex per dose:
- 10
- Details on study design:
- After acclimatization, four groups of ten male and ten female Wistar Han rats were exposed by oral
gavage to the test substance at 0, 15, 50 and 150 mg/kg. Males were exposed for 29 days, i.e. 2
weeks prior to mating, during mating, and up to termination. Females were exposed for 42-55 days,
i.e. during 2 weeks prior to mating, during mating, during post-coitum, and during at least 4 days of
lactation. - Positive control:
- No
- Observations and examinations performed and frequency:
- The following observations and examinations were evaluated: mortality / viability, clinical signs (daily),
functional observations and locomotor activity (Week 4 (males); end of lactation (females)), body
weight and food consumption (at least at weekly intervals), clinical pathology (Week 4 (males); end of
lactation (females)), macroscopy at termination, organ weights and histopathology on a selection of
tissues, and reproduction/developmental parameters, consisting of mating, fertility and conception
indices, precoital time, number of corpora lutea and implantation sites, gestation index and duration,
parturition, maternal care, sex ratio and early postnatal pup development (mortality, clinical signs,
body weights and macroscopy). Formulations were analyzed once during the study to assess
accuracy, homogeneity and stability. - Sacrifice and pathology:
- All males and the selected 5 females/group (see Allocation) were deprived of food overnight (with a
maximum of approximately 20 hours) prior to planned necropsy, but water was provided. Non-selected
females were not deprived of food.
Animals surviving to scheduled necropsy and the moribund animal were deeply anaesthetized using
isoflurane (Abbott B.V., Hoofddorp, The Netherlands) and subsequently exsanguinated.
All animals were subjected to macroscopic examination of the cranial, thoracic and abdominal tissues
and organs, with special attention being paid to the reproductive organs. Descriptions of all
macroscopic abnormalities were recorded.
The numbers of former implantation sites and corpora lutea were recorded for all paired females. - Statistics:
- The following statistical methods were used to analyze the data:
- If the variables could be assumed to follow a normal distribution, the Dunnett-test (many-to-
one t-test) based on a pooled variance estimate was applied for the comparison of the treated
groups and the control groups for each sex.
- The Steel-test (many-to-one rank test) was applied if the data could not be assumed to
follow a normal distribution.
- The Fisher Exact-test was applied to frequency data.
The following additional methods of statistical analysis were used:
Motor activity data was subjected to the Kruskal-Wallis nonparametric ANOVA test to
determine intergroup differences followed by the Wilcoxon test to compare the treated groups
to the control group.
All tests were two-sided and in all cases p < 0.05 was accepted as the lowest level of significance.
Group means were calculated for continuous data and medians were calculated for discrete data
(scores) in the summary tables. Test statistics were calculated on the basis of exact values for means
and pooled variances. Individual values, means and standard deviations may have been rounded off
before printing. Therefore, two groups may display the same printed means for a given parameter, yet
display different test statistics values. - 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:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- 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
- Description (incidence and severity):
- The lower motor activity of females at 150 mg/kg was temporary since at commencement and the end of the measurement interval motor activity appeared similar to control levels. Moreover, the lower motor activity was not associated with concurrent
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- .
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- Scattered effects but not apparent dose trend. See attached data tables.
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Tubular crystals were noted in the kidneys of one male and one female at 150 mg/kg (up to slight degree). This finding was accompanied in the female by tubular dilatation, epithelial hypertrophy and granular cast(s).
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
The lower motor activity of females at 150 mg/kg was temporary in nature since at commencement
and the end of the measurement interval motor activity appeared similar to control levels. Moreover,
the lower motor activity was not associated with concurrent changes in clinical appearance or changes
during functional observation tests. Therefore, this change in motor activity was considered to be of no
toxicological relevance.
Tubular crystals were noted in the kidneys of one male and one female at 150 mg/kg (up to slight
degree). Crystal deposition can lead to obstructive nephropathy. In this study, this finding was
accompanied in the female by tubular dilatation, epithelial hypertrophy and granular cast(s) (up to
slight degree) in the immediate vicinity as tubular crystals were noted, and is suggestive for findings
secondary to obstruction. Therefore, the presence of tubular crystals is considered to be adverse.
The increased severity of congestion/erythrophagocytosis in the mesenteric lymph nodes of females
treated at 15 mg/kg, 50 mg/kg and 150 mg/kg (up to moderate degree, and corresponding to dark red
foci/reddish discolouration of the mesenteric lymph node in some females at 15 and 150 mg/kg) was
considered to be non-adverse given the absence of any other indicators of cellular damage, e.g.
inflammation or necrosis. The increased incidence and severity of hyperplasia/hypertrophy of the
follicular epithelium of the thyroid gland in females treated at 150 mg/kg was subtle in nature and
occurred in the absence of a dose-related trend, and was therefore considered to be non-adverse.
There were no morphological findings in the reproductive organs of either sex which could be
attributed to the test item.
No toxicologically significant changes were noted in any of the remaining parental parameters
investigated in this study (i.e. clinical appearance, functional observations, body weight, food
consumption, clinical laboratory investigations, macroscopic examination and organ weights).- Dose descriptor:
- NOAEL
- Effect level:
- 55 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- histopathology: non-neoplastic
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 150 mg/kg bw/day (actual dose received)
- System:
- urinary
- Organ:
- kidney
- Treatment related:
- yes
- Conclusions:
- Based on these results, the No Observed Adverse Effect Levels (NOAEL) for Parental animals is 50 mg/kg (55 mg/kg as UVCB)
- Executive summary:
A combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test was conducted with Barium bis( di c8-c10, branched, c9 rich, alkylnaphthalene sulphonate) in rats by oral gavage. This GLP study followed the OECD 422 guideline. Dose levels were based on the results of a 10-day dose range finding study. The dose levels for this combined 28-day oral gavage study with reproduction/developmental toxicity screening test were selected to be 15, 50 and 150 mg/kg. This was based on an estimated purity of 90%. After completion of the testing, the substance was determined to be UVCB with a purity of 100%. Based on the UVCB purity, the doses are considered to be 17, 55 and 165 mg/kg/day.
After acclimatization, four groups of ten male and ten female Wistar Han rats were exposed by oral gavage to the test substance. Males were exposed for 29 days, i.e. 2 weeks prior to mating, during mating, and up to termination. Females were exposed for 42-55 days, i.e. during 2 weeks prior to mating, during mating, duringpost-coitum, and during at least 4 days of lactation.
Results/discussion
The lower motor activity of females at 150 mg/kg was temporary in nature since at commencement and the end of the measurement interval motor activity appeared similar to control levels. Moreover, the lower motor activity was not associated with concurrent changes in clinical appearance or changes during functional observation tests. Therefore, this change in motor activity was considered to be of no toxicological relevance.
Tubular crystals were noted in the kidneys of one male and one female at 150 mg/kg (up to slight degree).Crystal deposition can lead to obstructive nephropathy. In this study, this finding was accompanied in the female by tubular dilatation, epithelial hypertrophy and granular cast(s) (up to slight degree) in the immediate vicinity as tubular crystals were noted, and is suggestive for findings secondary to obstruction. Therefore, the presence of tubular crystals is considered to be adverse.
The increased severity of congestion/erythrophagocytosis in the mesenteric lymph nodes of females treated at 15 mg/kg, 50 mg/kg and 150 mg/kg (up to moderate degree, and corresponding to dark red foci/reddish discolouration of the mesenteric lymph node in some females at 15 and 150 mg/kg) was considered to be non-adverse given the absence of any other indicators of cellular damage, e.g. inflammation or necrosis. The increased incidence and severity of hyperplasia/hypertrophy of the follicular epithelium of the thyroid gland in females treated at 150 mg/kg was subtile in nature and occurred in the absence of a dose-related trend, and was therefore considered to be non-adverse.
There were no morphological findings in the reproductive organs of either sex which could be attributed to the test item.
No toxicologically significant changes were noted in any of the remaining parental parameters investigated in this study (i.e. clinical appearance, functional observations, body weight, food consumption, clinical laboratory investigations, macroscopic examination and organ weights).
Based on these results, the repeat dose No Observed Adverse Effect Level (NOAEL) is 50 mg/kg (55 mg/kg - as UVCB).
Reference
The concentrations analysed in the formulations of Group 2 (15 mg/kg) and Group 3 (50 mg/kg) were in agreement with target concentrations (i.e. mean accuracies between 90% and 110%). For the formulation of Group 4 (150 mg/kg)
prepared for use during treatment, the mean accuracy was below the target concentration (i.e. 89% of target).
No test substance was detected in the Group 1 (control, 0 mg/kg) formulation.
The formulation of Group 2 was homogeneous (i.e. coefficient of variation ≤ 10%). The formulation of Group 4 showed a coefficient of variation exceeding 10% (i.e. 16%) and was therefore not homogeneous. The level of inhomogeneity measured for Group 4 formulations was similar to that observed for procedural recovery samples prepared at a slightly higher concentration level.
Formulations appeared visually homogenous.
Formulations at the entire range were stable when stored at room temperature under normal laboratory light conditions for at least 6 hours.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 55 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Results are from a GLP OECD 422 study and are judged reliable.
- System:
- urinary
- Organ:
- kidney
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
Justification for classification or non-classification
Although the NOAEL in the repeated dose toxicity study was set to 55 mg/kg bw/d, the adverse effects seen (tubular crystals in kidneys) at the high dose group in this study (150 mg/kg bw/d) were very weak and not too pronounced and only observed in one male and one female animal (i.e. in 2.5% of test animals - 40 animals per sex were used). Therefore, a classification for repeated dose toxicity is not proposed Therefore, no classification for repeated dose toxicity / specific target organ toxicity, repeat exposuire according to CLP (Regulation EC No 1272/2008) is proposed.
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