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EC number: 404-800-4 | CAS number: 118832-72-7 IRGANOX L 118
- 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
Key value for chemical safety assessment
Genetic toxicity in vivo
Description of key information
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1989-07-04 to 1989-02-07
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: OECD guideline study, GLP
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OTS 798.5395 (In Vivo Mammalian Cytogenics Tests: Erythrocyte Micronucleus Assay)
- Qualifier:
- according to guideline
- Guideline:
- other: EEC (19 September 1984), Mutagenicity (Micronucleus Test). Official Journal of the European Communities No L 251 137-139.
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
- Species:
- hamster
- Strain:
- other: Cricetulus griseus
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: CIBA-GEIGY Tierfarm, Sisseln
- Weight at study initiation: females 31-34 g, males 30-35 g (tolerability test), females 21-31 g, males 22-34 g (mutagenicity test).
- Assigned to test groups randomly: yes
- Housing: Individually
- Diet: ad libitum (NAFAG No. 924)
- Water: tap water, ad libitum
- Acclimation period: At least 3 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15 - 23
- Humidity (%): 50 - 84
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: arachis oil
- Details on exposure:
- The preparation was administered orally to groups of 24 female and 24 male animals each in the negative and in the 5000 mg/kg bw dose group. The positive control group consisted of 8 female and 8 male animals. Treatment consisted of a single application. 16, 24 and 48 hours after application 8 female and 8 male animals per sampling time were sacrificed by dislocation of the cervical vertebrae.
- Duration of treatment / exposure:
- Single exposure
- Frequency of treatment:
- Once
- Post exposure period:
- 16, 24, 48 hrs
- Remarks:
- Doses / Concentrations:
5000 mg/kg bw
Basis:
nominal conc. - No. of animals per sex per dose:
- In the tolerability test: 2 females and 2 males
In the mutagenicity test: 24 females and 24 males in the treatment groups and in the negative control groups. 8 females and 8 males in the positive control group - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- yes (CPA; Cyclophosphamide)
- Tissues and cell types examined:
- Bone marrow was harvested from the shafts of both femurs with fetal calf serum. After centrifugation small drops of the sediment mixture were transferred on the end of a slide, spread out with the aid of a polished cover glass and air-dried. Within 24 hours, the slides were stained in undiluted May-Grünwald solution for 3 min then in May-Grünwald solution/water 1/1 for 2 min. After being rinsed in distilled water, the slides were left immersed in diluted Giemsa solution (16.6%), for 10 min. After rinsing with distilled water and air-drying, the slides were cleared in Xylene and mounted.
- Details of tissue and slide preparation:
- The slides of five animals from each sex showing the best differentiation between mature and polychromatic erythrocytes were selected for later scoring. The slides of five female and five male animals each of the negative control group and of the dosage group sacrificed at 16, 24 and 48 hours post treatment were examined. From the animals of the positive control group which were sacrificed 24 hours after application, the slides of five female and five male animals were scored. 1000 polychromatic erythrocytes per animal each were scored for the incidence of micronuclei. To determine the mitotic activity of the red compartment, the ratio of polychromatic to normochromatic erythrocytes was calculated for each animal by counting a total of 1000 erythrocytes. A low proportion of polychromatic erythrocytes is indicative for a mitosis inhibiting activity of the test substance.
- Evaluation criteria:
- - The quality of the slides must allow a clear differentiation between polychromatic and normochromatic erythrocytes.
- The result obtained with the positive control has to fulfill the criteria given for a positive response. - Statistics:
- The significance of difference was assessed by X2-test.
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
Three groups of four Chinese hamsters (two females and two males) are treated with three different doses, one receiving the maximum dose of 5000 mg/kg, or the highest applicable dose, and the other two doses of 1/5 and 1/25 of that amount respectively. The animals are treated with a single dose. The observation period corresponds to the interval between administration and sacrifice of the animals in the mutagenicity test, plus one day. In this experiment the dose of 5000 mg/kg was determined as the highest applicable in the mutagenicity assay
POSITIVE CONTROL
The positive control (cyclophosphamide, 64 mg/kg, sampling time 24 hours) yielded a marked increase of the percentage of micronucleated cells. Here the mean percentage of polychromatic erythrocytes with micronuclei was 1.00. In comparison with the negative control (0.08) this value is highly significant (p <0.05), confirming an appropriate sensitivity of the test system. - Conclusions:
- Interpretation of results (migrated information): negative
- Executive summary:
The test item was assessed in the micronucleus assay for its potential to induce micronuclei in polychromatic erythrocytes (PCE) in the bone marrow cells of the Chinese hamster. The test item was administered orally to groups of 24 female and 24 male animals at 0 (vehicle control) or 5000 mg/kg bw. 16, 24 and 48 hours after application 8 females and 8 males per sampling time were sacrificed and bone-marrow smears were prepared. There was no significant increase in the number of micronucleated polychromatic erythrocytes in the animals treated with the dose of 5000 mg/kg bw of the test item as compared with the negative control animals at all three sampling times. The positive control group (cyclophosphamide) consisted of 8 female and 8 male animals and showed the appropriate response, thus confirming sensitivity of the test system. In conclusion, it can be stated that during the study described and under the experimental conditions reported, the test item did not induce micronuclei as determined by the micronucleus test in the bone marrow cells of the Chinese hamster.
Reference
Experimental Result
Sacrifice | Treatment | Sex | polychromatic erythrocytes (average) |
normochromatic erythrocytes (average) |
ratio of p / n erythrocytes |
number of polychromatic erythrocytes with micronuclei (average) |
% of polychromatic erythrocytes with micronuclei (average) |
16 h | Control | female | 510 | 490 | 1 | 0.6 | 0.06 |
male | 603 | 397 | 1.5 | 0 | 0 | ||
5000 mg/kg | female | 548 | 452 | 1.2 | 0.6 | 0.06 | |
male | 632 | 368 | 1.7 | 0.8 | 0.08 | ||
24 h | Control | female | 512 | 488 | 1 | 1 | 0.1 |
male | 573 | 427 | 1.3 | 0.6 | 0.06 | ||
5000 mg/kg | female | 544 | 456 | 1.2 | 0.4 | 0.04 | |
male | 657 | 343 | 1.9 | 0.4 | 0.04 | ||
48 h | Control | female | 581 | 419 | 1.4 | 0.6 | 0.06 |
male | 648 | 352 | 1.8 | 0.2 | 0.02 | ||
5000 mg/kg | female | 485 | 515 | 0.9 | 0.8 | 0.08 | |
male | 605 | 395 | 1.5 | 0.4 | 0.04 | ||
Positive Control |
|||||||
48 h | Control | female | 512 | 488 | 1 | 1 | 0.1 |
male | 573 | 427 | 1.3 | 0.6 | 0.06 | ||
64 mg/kg | female | 523 | 477 | 1.1 | 12.6 | 1.26 | |
male | 581 | 419 | 1.4 | 7.4 | 0.74 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
In vitro
Ames test:
A Salmonella typhimurium/Escherichia coli reverse mutation assay was carried out according to OECD Guideline 471 and in compliance with GLP principles (CIBA-GEIGY, 1988). In the presence and absence of rat liver S-9-microsomal activation system and at concentrations of 5-5000 μg per plate, S. typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538 as well as E. coli strain WP2uvrA were tested for the induction of base-pair substitutions or frameshift mutations. No evidence of a mutagenic potential was observed. No cytotoxicity was noted up to the highest dose tested. The positive controls induced the appropriate responses. Based on the results of these experiments and on standard evaluation criteria, it is concluded that the test article and its metabolites did not induce gene mutations in the strains of S. typhimurium and E. coli used.
HPRT Test:
In a GLP-compliant genotoxicity study according to OECD guideline 476 the test item was assessed for its potential to induce gene mutations at the HPRT locus using V79 cells of the Chinese hamster (Harlan, 2013). The study was performed in two independent experiments, using identical experimental procedures. In the first experiment the treatment period was 4 hours with and without metabolic activation. The second experiment was performed with a treatment time of 4 hours with and 24 hours without metabolic activation. The concentration range of the main experiments was limited by phase separation of the test item. The test item was dissolved in DMSO. The tested concentrations in the main experiment ranged from 1.9 to 150 µg/ml. Phase separation occurred in both main experiments at 50.0 µg/mL and above with and without metabolic activation. No relevant cytotoxic effects indicated by a relative cloning efficiency I or cell density below 50% in both parallel cultures occurred in experiment I and II up to the maximum concentration with and without metabolic activation following 4 and 24 hours treatment. No relevant and reproducible increase in mutant colony numbers/106cells was observed in the main experiments up to the maximum concentration. The mutation frequency did not exceed the historical range of solvent controls. In conclusion it can be stated that under the experimental conditions reported the test item did not induce gene mutations at the HPRT locus in V79 cells and is therefore considered to be non-mutagenic in this HPRT assay.
In vivo
Micronucleus test:
In an in vivo micronucleus test (Ciba-Geigy, 1989) performed according to OECD test guideline 474 and in compliance to GLP, the test article was investigated for its potential to induce micronuclei in polychromatic erythrocytes (PCE) in the bone marrow cells of Chinese hamsters. The test item was administered orally to groups of 24 female and 24 male animals at 5000 mg/kg body weight. The positive control group (cyclophosphamide) consisted of 8 female and 8 male animals. 16, 24 and 48 hours after application 8 females and 8 males per sampling time were sacrificed and bone-marrow smears were prepared. No statistically significant increase in the number of micronucleated polychromatic erythrocytes compared to the negative control animals were observed at all three sampling times. The respective "positive control" experiment with cyclophosphamide (64 mg/kg) yielded an average of 1.00% polychromatic erythrocytes with micronuclei. This is significantly different from the controls (0.08%) treated with the vehicle (arachis oil) alone. It is concluded that under the conditions of this experiment, no evidence of mutagenic effects was obtained in Chinese hamsters and the test substance is therefore considered to be non clastogenic.
Justification for selection of genetic toxicity endpoint
GLP compliant in vivo study following OECD guidelines
Justification for classification or non-classification
Dangerous Substance Directive (67/548/EEC)
The available experimental test data is reliable and suitable for the purpose of classification under Directive 67/548/EEC. Based on the present data, classification for genotoxicity is not warranted.
Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008
The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the present data, classification for genotoxicity is not warranted.
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