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EC number: 273-729-7 | CAS number: 69012-29-9 By-product from the production of ferronickel from a complex ore. Consists primarily of oxides of aluminum, iron, magnesium and silicon.
- 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:
- multi-generation reproductive toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Study was performed before EU/OECD protocol establishment and no guideline is mentioned. Data on reproductive and developmental toxicity for slags, ferronickel-manufg. is not available for the whole substance. Until a relevant study is performed on slags, ferronickel-manufg., it was attempted to identify possible adverse effects based on data for its recognised constituents, even though the results cannot be applied directly, due to the way the constituents are bound in the matrix of the substance and are not as bioavailable as the free substances that are examined. So, the results must be taken into consideration with care.
Data source
Reference
- Reference Type:
- publication
- Title:
- Potential toxicity of iron overload in successive generations of rats
- Author:
- R.O. Fisch,M.D., A.S. Deinard, M.D., L.J. Disch, B.A., and W. Krivit
- Year:
- 1 975
- Bibliographic source:
- The American Journal of Clinical Nutrition 28: 136-139
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- No guideline mentioned in the study.
- GLP compliance:
- no
- Remarks:
- Study was performed before the establishment of GLP
- Limit test:
- no
Test material
- Reference substance name:
- Iron
- EC Number:
- 231-096-4
- EC Name:
- Iron
- Cas Number:
- 7439-89-6
- Molecular formula:
- Fe
- IUPAC Name:
- iron
- Details on test material:
- No further details
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- 6-week-old Sprague-Dawley rats, fed on Purina Chow.
Administration / exposure
- Route of administration:
- intramuscular
- Type of inhalation exposure (if applicable):
- other: not applicable
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- The experimental 16 females were given parenteral iron (Imferon: 20 mg/kg) by intramuscular injection according to the following schedule:
7 & 8-week old: 1 injection of 20mg/kg per week
9 &10-week old: 2 injections of 20mg/kg per week
11 & 12-week old: 3 injections of 20mg/kg per week
The total amount of iron given was approximately 62-72 mg/animal during the 6-week period of injections. Following the last injection at 1 2 weeks of age, the treated females received no iron for 1 week, following which they and the control females were allowed to mate with the males. During pregnancy, no female received iron injections. - Details on mating procedure:
- After the last injection on the females were 12 weeks old, followed 1 week without iron supplementation and then they were allowed to mate with the males. When the offspring was 6 weeks old random separation and repetition of the experiment until fourth generation was performed. Interbreeding was carefully avoided.
- Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- not applicable
- Duration of treatment / exposure:
- 6-week period of injections, until the animals were 12 weeks of age.
- Frequency of treatment:
- 7 & 8-week old: 1 injection of 20mg/kg per week
9 &10-week old: 2 injections of 20mg/kg per week
11 & 12-week old: 3 injections of 20mg/kg per week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
between 62 and 72 mg/animal during the 6-week injection period
Basis:
other: actual injected
- No. of animals per sex per dose:
- 16 animals in the first generation (G-1)
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- After the last group of females (G-4) delivered their offspring (G-5), every other female and all of her offspring were sacrificed within 12 hours of birth (Fig. 1). In all, eight treated females and their 72 offspring, as well as four control females and their 49 offspring, were sacrificed. This occurred, in general, immediately after birth and always by 12 hours of age. The sacrificed animals were assayed for total body iron content. Seven experimental females and their 62 offspring, as well as two control females and their 1 3 offspring, were allowed to live to 6 weeks of age (one female died during labor), at which time both females and offspring were weighed.
- Positive control:
- No
Examinations
- Parental animals: Observations and examinations:
- Iron assay performed in triplicate on each adult rat that was sacrificed.
Growth, as measured by weight, was also examined. - Oestrous cyclicity (parental animals):
- no data
- Sperm parameters (parental animals):
- no data
- Litter observations:
- No differences in litter size between test group and control group.
- Postmortem examinations (parental animals):
- Iron assay. See "postmortem examinations (Offspring) for details. In this case, the initial digestion was done in 300 ml of distilled water and I liter of concentrated nitric acid. The “whole-rat” solution of this digest was filtered and diluted to 2 liters. Two-milliliter aliquots were then treated as described above. The iron assay for each of the adult rats was done in triplicate.
- Postmortem examinations (offspring):
- Iron assay. The cadaver of each newborn rat was sectioned and dried at 110 C overnight. The dried tissue was weighed and digested in 3 ml of distilled water and 10 ml of concentrated nitric acid (redistilled by C. F. Smith Chemical Co., Columbus, Ohio). The resulting solution was gently boiled until clear and allowed to cool. The solid lipid layer that formed was removed by filtration through iron-free glass wool. Additional concentrated
nitric acid was used to rinse the lipid solids and bring the total sample volume to 25 ml. A 2-ml aliquot of the “whole-rat” solution and 10 ml of concentrated nitric acid were further digested by boiling to one-third original volume. At this point, another 10 ml of concentrated nitric acid were added and the solution was redigested. The remaining liquid was made up to a volume of 10 ml with concentrated nitric acid and its iron concentration was determined on an atomic absorption spectrophotometer using a Fischer iron standard (1-7 ppm) and concentrated nitric acid as a blank. - Statistics:
- The test of the reproducibility of iron determination was done on three different days on the offspring animals. The mean coefficient of variance (CV = 100SD/’X) was 6.6%. When this assay method was applied to situations where known concentrations of iron were present, the average percent recovery of iron was 85%.
- Reproductive indices:
- no information
- Offspring viability indices:
- No differences in litter size was observed.
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- increased body weight in iron-treated females
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- increased body weight in iron-treated females
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- Test substance intake: total body iron of adult females was significantly higher in test group
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
Effect levels (P0)
- Dose descriptor:
- LOAEC
- Effect level:
- > 62 - < 72 other: mg/animal
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: The only observable effects were on the weight of the mothers, which was greater for the test group. No differences were observed in the litter size.
- Remarks on result:
- other: Generation: 1st generation (parent) (migrated information)
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- no effects observed
- Description (incidence and severity):
- offspring reproduced normally
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- nothing observable
- Histopathological findings:
- not examined
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The toxicity of iron overload on successive generations was tested in female rats from generation 1 to generation 5 included. Test group received a total amount of 62-72 mg/animal during a 6 week period of dosing parenterally. This route was chosen because iron given orally is absorbed in limited quantities. When the offspring was 6 weeks old random separation and repetition of the experiment until fourth generation was performed. Mothers and offspring were examined for iron body burden, litter size and litter postnatal development. Mother weight was higher in the iron-treated females but no differences in litter size (viability of offspring) were noted. It can be concluded that iron overload did not affect fertility of female rats in subsequent generations
- Executive summary:
The toxicity of iron overload on successive generations was tested in female rats from generation 1 to generation 5 included. Test group received a total amount of 62-72 mg/animal during a 6 week period of dosing parenterally. This route was chosen because iron given orally is absorbed in limited quantities. When the offspring was 6 weeks old random separation and repetition of the experiment until fourth generation was performed. Mothers and offspring wereexamined for iron body burden, litter size and litter postnatal development. Mother weight was higher in the iron-treated females but no differences in litter size (viability of offspring) were noted. It can be concluded that iron overload did not affect fertility of female rats in subsequent generations
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