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EC number: 480-340-8 | 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- other: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Justification for Read Across is given in Section 13 of IUCLID.
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 999
- Reference Type:
- secondary source
- Title:
- Unnamed
- Year:
- 2 004
- Reference Type:
- secondary source
- Title:
- Micronucleated Erythrocyte Frequency in Peripheral Blood of B6C3F1 Mice from Short-Term, Prechronic, and Chronic Studies of the NTP Carcinogenesis Bioassay Program
- Author:
- Witt, K.L., Knapton, A., Wehr, C.M., Hook, G.J., Mirsalis, J., Shelby, M.D., and MacGregor, J.T.
- Year:
- 2 000
- Bibliographic source:
- Environ. Mol. Mutagen. 36, 163-194.
Materials and methods
- Principles of method if other than guideline:
- The frequency of micronucleated erythrocytes in peripheral blood samples from 13-weeks dermal exposure of B6C3F1 mice to the substance was assessed. The protocol followed was the one described in MacGregor, J.T.et al.1990.
MacGregor, J.T., Wehr, C.M., Henika, P.R., and Shelby, M.D. (1990). The in vivo erythrocyte micronucleus test: Measurement at steady state increases assay efficiency and permits integration with toxicity studies. Fundam. Appl. Toxicol. 14, 513-522. - GLP compliance:
- yes
- Remarks:
- Food and Drug Administration Good Laboratory Practice Regulations (21 CFR, Part 58)
- Type of assay:
- other: Mammalian Erythrocyte Micronucleus assay
Test material
- Reference substance name:
- 2,2',2''-nitrilotriethanol
- EC Number:
- 203-049-8
- EC Name:
- 2,2',2''-nitrilotriethanol
- Cas Number:
- 102-71-6
- Molecular formula:
- C6H15NO3
- IUPAC Name:
- 2,2',2''-Nitrilotriethanol
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- B6C3F1
- Details on species / strain selection:
- Mice provide a convenient model for these studies because, unlike rats, mice do not selectively remove micronucleated cells from the peripheral circulation. Therefore, the frequency of micronucleated cells in the circulating blood of mice would be expected to closely reflect the frequency in bone marrow, and unlike bone marrow sampling, repeated peripheral blood measurements can be made, without disturbing the physiology of the animals, by sampling a few microliters of blood at a time.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Simonsen Laboratories (Gilroy, CA).
- Age at study initiation: 6 weeks old.
- Housing: individually in Polycarbonate (Lab Products, Inc., Garfield, NJ) cages, equipped with Beta-Chips hardwood chips (Northeastern Products, Inc., Warrensburg, NY) (changed weekly). Cage filters: DuPont 2024 spun-bonded polyester filter (Snow Filtration Co Cincinnati, OH), changed every 2 weeks. Stainless steel racks were used and were changed every 2 weeks.
- Diet: NIH-07 open formula pelleted diet (Zeigler Brothers, Inc.,Gardners, PA), available ad libitum, changed weekly
- Water: tap water (City of Columbus municipal supply) via automatic watering system (Edstrom Industries, Waterford, WI), available ad libitum.
- Acclimation period: 11-14 days.
- Other: five male and six female mice were randomly selected for parasite evaluation and gross observation for evidence of disease. At the beginning of quarantine and at the beginning and the end of the studies, serologic analyses were performed on five male and five female and mice using the protocols of the NTP Sentinel Animal Program.
ENVIRONMENTAL CONDITIONS
- Temperature: 20.0 - 23.9 °C.
- Humidity: 35 - 65 %.
- Air changes: 15 changes per hour.
- Photoperiod: 12 hrs dark / 12 hrs light.
- Other: fluorescent light was used.
Administration / exposure
- Route of administration:
- dermal
- Vehicle:
- - Vehicle/solvent used: acetone. Except for the highest dose, which was applied neat, all doses were administered in acetone.
- Justification for choice of solvent/vehicle: acetone is miscible with the test material and because acetone rapidly evaporates.
- Amount of vehicle: dose volumes were adjusted weekly, if necessary, according to the average body weights of the dosed groups. - Details on exposure:
- TEST SITE
- Area of exposure: the area extending from the animal’s mid-back to the dorsal intrascapular region; the site of application was clipped weekly during the studies.
DOSING SOLUTIONS: periodic analyses of dose formulations of the substance were conducted by the study laboratory and the analytical chemistry laboratory with gas chromatography. The dose formulations were analyzed at the beginning, midpoint, and end of the studies; animal-room samples of the same dose formulations were also analyzed. All dose formulations and animal-room samples were within 10 % of the target concentrations. - Duration of treatment / exposure:
- 5 days per week, for 13 weeks
- Frequency of treatment:
- once per day.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 1 000 mg/kg bw/day
- Dose / conc.:
- 2 000 mg/kg bw/day
- Dose / conc.:
- 4 000 mg/kg bw/day
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- none
Examinations
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: doses for the 13-week study were based on the results of 14- and 16-day comparative studies in which the B6C3F1 mice received the substance by the dermal route in acetone. The results of the dermal studies included skin irritation of a severity that limited the highest dose for the 13-week studies to 4000 mg/kg for mice.
TREATMENT AND SAMPLING TIMES: peripheral blood samples were obtained from male and female B6C3F mice from the ventral tail vessel at the end of the 13-week exposure study.
DETAILS OF SLIDE PREPARATION: smears were immediately prepared and fixed in absolute methanol (for approximately 2 min) and were later stained with a chromatin-specific fluorescent dye mixture of Hoechst 33258/pyronin Y double fluorescent stain, using Sorensen’s M/ 15 phosphate buffer. Then they were coded.
METHOD OF ANALYSIS: slides were randomized and scored at 630 X magnification under oil immersion. They were scanned to determine the frequency of micronuclei in 2000 polychromatic erythrocytes (PCEs) and 10000 normochromatic erythrocytes (NCEs) in each animal per dose group. In addition, the percentage of polychromatic erythrocytes among 10000 erythrocytes was determined as a measure of bone marrow toxicity. Log transformation of the NCE data, testing for normality by the Shapiro-Wilk test, and testing for heterogeneity of variance by Cochran’s test were performed before statistical analyses. - Evaluation criteria:
- In the micronucleus test, an individual trial is considered positive if the trend test P value is less than or equal to 0.025 or if the P value for any single dosed group is less than or equal to 0.025 divided by the number of dosed groups. A final call of positive for micronucleus induction is preferably based on reproducibly positive trials.
Ultimately, the final call is determined by the scientific staff after considering the results of statistical analyses, the reproducibility of any effects observed, and the magnitudes of those effects. - Statistics:
- - The frequency of micronucleated cells among NCEs was analyzed by analysis of variance using the SAS GLM procedure.
- The frequency of micronucleated cells among NCEs was analyzed by a statistical software package that tested for increasing trend over dose groups with a one-tailed Cochran-Armitage trend test, followed by pairwise comparisons between each dosed group and the control group.
- In the presence of excess binomial variation, as detected by a binomial dispersion test, the binomial variance of the Cochran-Armitage test was adjusted upward in proportion to the excess variation.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- treatment-related decreases in sorbitol dehydrogenase activities in all dosed groups (males, females); significant increase in absolute kidney and liver weights of males and females of the highest groups.
- Vehicle controls validity:
- not specified
- Negative controls validity:
- not examined
- Positive controls validity:
- not examined
- Additional information on results:
- No significant increases in the frequencies of micronucleated NCEs or PCEs were observed at any dose tested.
The percentages of polychromatic erythrocytes in the dosed groups were similar to those in the vehicle control groups, indicating an absence of bone marrow toxicity.
Any other information on results incl. tables
The Frequency of Micronuclei in Peripheral Blood Erythrocytes of mice following treatment with the test material by dermal Application for 13 Weeks is presented in the table below. The following data are a combination of results from the current study and from data presented in NTP report, 2004.
10000 NCEs (normochromatic erythrocytes) and 2000 PCEs (polychromatic erythrocytes) were scored per animal.
Table: Frequency of micronuclei in peripheral blood erythrocytes.
Dose (mg/kg) |
Number of mice with erythrocytes scored |
Micronucleated NCEs/ 1000 NCEsa |
p valueb | Micronucleated PCEs /1000 cellsa |
PCEs (%) |
|
Male | vehicle control |
10 | 1.75 ± 0.20 | 2.13 ± 0.40 | 2.2 | |
1000 | 10 | 1.88 ± 0.17 | 0.3138 | 1.04 ± 0.36 | 2.2 | |
2000 | 10 | 1.36 ± 0.10 | 0.9350 | 2.41 ± 0.40 | 2.4 | |
4000 | 10 | 1.90 ± 0.30 | 0.3047 | 2.00 ± 0.48 | 2.1 | |
P=0.420c | ||||||
Female | vehicle control |
10 | 1.16 ± 0.12 | 2.06 ± 0.35 | 2.1 | |
1000 | 10 | 1.20 ± 0.08 | 0.3890 | 1.60 ± 0.34 | 2.2 | |
2000 | 10 | 1.08 ± 0.12 | 0.7393 | 2.38 ± 0.43 | 2.2 | |
4000 | 10 | 0.99 ± 0.11 | 0.8813 | 2.12 ± 0.39 | 2.0 | |
P=0 .925 |
a = Data are presented as mean ± standard error.
b = Pairwise comparison with the vehicle controls, significant at P ≤0.008.
c = Significance of micronucleated NCEs/1000 NCEs tested by the one-tailed trend test, significant at P ≤ 0.025.
Toxicity of animals
- The final mean body weight and weight gain of males in the 250 mg/kg group were less than those of the vehicle controls.
- Clinical findings were observed only in mice in the 4000 mg/kg groups and included scaliness, irritation, and discoloration at the site of test material application for males and females and skin erosion at this site in one male.
- Serum sorbitol dehydrogenase activity was significantly lower in comparison with the vehicle control; treatment-related decreases in sorbitol dehydrogenase activities occurred in all dosed groups of males and females.
- Differences in other hematology and clinical chemistry parameters were minimal or transient and were not considered to be biologically relevant.
- The absolute kidney and liver weights of males and females in the 4000 mg/kg groups were significantly greater than those of the vehicle controls; relative kidney weights of males administered 1000 mg/kg or greater and of all dosed groups of females were also greater than those of the vehicle controls. The absolute and relative spleen weights of females in the 4000 mg/kg group were significantly greater than those of the vehicle controls. Males administered 4000 mg/kg had a greater relative heart weight than the vehicle controls.
- At necropsy, the skin of males and females administered 4000 mg/kg was crusted (7/10 males 4/10 females) and white (1/10 males, 8/10 females), scaly (1/10 males), or both (5/10 males, 2/10 females) at the site of application. One female in the 2000 mg/kg group also had crusted skin. Minimal epidermal thickening (acanthosis), up to twice the normal thickness, occurred in nearly all dosed animals and in one vehicle control female; the severity of acanthosis was greater in the 4000 mg/kg groups than in the lower dose groups. Chronic active inflammation occurred in the 4000 mg/kg groups and in one female in the 2000 mg/kg group, with some animals having erosion, inflammation, or both. In these animals, the underlying dermis was often thickened by chronic active inflammation, including fibrosis.
Applicant's summary and conclusion
- Conclusions:
- No significant increases in the frequencies of micronucleated NCEs or PCEs at any dose tested were observed.
- Executive summary:
The substance was evaluated for its potential to induce formation of micronucleated polychromatic erythrocytes in the peripheral blood of mice. For this reason 10 male and 10 female B6C3F1 mice were dermally exposed to three concentrations of the substance (at 1000, 2000 and 4000 mg/kg) per day, for 5 days, for 13 weeks. After the exposure period, peripheral blood samples were taken from the ventral tail vessel of the mice. The smears were fixed in absolute methanol, they were stained, fixed and coded. 10000 NCEs (normochromatic erythrocytes) and 2000 PCEs (polychromatic erythrocytes) were scored for micronuclei per animal per dose group.
No significant increases in the frequencies of micronucleated NCEs or PCEs were observed at any dose tested.
The substance is considered as not mutagenic under the test conditions.
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