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EC number: 209-143-5 | CAS number: 556-88-7
- 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 insect germ cell study: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- March 1985 - December 1985
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 988
- Report date:
- 1988
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5275 (Sex-linked Recessive Lethal Test in Drosophila melanogaster)
- Deviations:
- yes
- Remarks:
- 1. CS males were dosed in conc. based on results of preliminary study. 2. Tot. number flies in test and in control group was less than 8000. 3. DMSO as a solvent was avoided as recomm. by the EPA. These deviations had no effect on the outcome of the study
- GLP compliance:
- yes
- Type of assay:
- Drosophila SLRL assay
Test material
- Reference substance name:
- 1-nitroguanidine
- EC Number:
- 209-143-5
- EC Name:
- 1-nitroguanidine
- Cas Number:
- 556-88-7
- Molecular formula:
- CH4N4O2
- IUPAC Name:
- N-nitroguanidine
- Reference substance name:
- Sodium sulphate
- EC Number:
- 231-820-9
- EC Name:
- Sodium sulphate
- Cas Number:
- 7757-82-6
- Molecular formula:
- Na2O4S
- IUPAC Name:
- disodium sulfate
- Reference substance name:
- Sodium nitrate
- EC Number:
- 231-554-3
- EC Name:
- Sodium nitrate
- Cas Number:
- 7631-99-4
- Molecular formula:
- HNO3.Na
- IUPAC Name:
- sodium nitrate
- Reference substance name:
- 4,6-diamino-1,3,5-triazin-2(1H)-one
- EC Number:
- 211-455-1
- EC Name:
- 4,6-diamino-1,3,5-triazin-2(1H)-one
- Cas Number:
- 645-92-1
- Molecular formula:
- C3H5N5O
- IUPAC Name:
- 4,6-diamino-1,3,5-triazin-2(1H)-one
- Reference substance name:
- 6-amino-1,3,5-triazine-2,4(1H,3H)-dione
- EC Number:
- 211-456-7
- EC Name:
- 6-amino-1,3,5-triazine-2,4(1H,3H)-dione
- Cas Number:
- 645-93-2
- Molecular formula:
- C3H4N4O2
- IUPAC Name:
- 6-amino-1,3,5-triazine-2,4(1H,3H)-dione
- Test material form:
- solid: particulate/powder
Constituent 1
impurity 1
impurity 2
impurity 3
impurity 4
- Specific details on test material used for the study:
- Test substance supplier Aunflower AAP
Test animals
- Species:
- Drosophila melanogaster
- Strain:
- other: Canton-S (CS), wild-type stock and Basc, laboratory stock
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: insectary of Letterman Army Institute of Research; the original stock colonies were obtained from the Mid-American Drosophila stock center, Bowling Green State University, Bowling Green, Ohio
- Housing: all insect colonies were reared in polypropylene bottles; those selected for SLRL testing were housed in glass vials
- Diet (e.g. ad libitum): standard medium consisiting of cornmeal (NSCO Chemicals), unsulphured molasses (Ingredient Technology Corp.), Yeast (Nabisco Brands, Inc.), and nutrient agar (Moorhead & Co., Inc.)
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 2 °C
- Humidity (%): 57 +/- 8%
- Photoperiod (hrs dark/hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- - solution of 1% fructose in water was found to be an appropriate vehicle for the nitroguanidine
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
- The solubility of nitroguanidine in water is relatively high compared to that of most explosives. Preliminary studies were conducted to test potentila dosages for toxicity to flies and their ability to feed and digest nitroguanidine in an appropriate medium
- A feeding solution vehicle of 1.0% fructose in deionized water was selected for the study - Duration of treatment / exposure:
- 72 h
- Frequency of treatment:
- Dosing was continous for 72 h. Flies were transferred every 24 hours to vials containing fresh compound solutions
- Post exposure period:
- 8 days
Doses / concentrations
- Remarks:
- Doses / Concentrations:
2.08 µg/ml - 20.8 µg/ml
Basis:
nominal conc.
- No. of animals per sex per dose:
- 25 surviving CS males (wild type) were selected after feeding on the dosing solution and were scored by mating with Basc virgin females (ratio males:females = 1:3). At days 1,4, 6, and 8 after dosing the CS male was transferred to successive groups of 3 Basc virgin females. 4 replicates
Total number of test flies examined in the test group was 6913, for the negative control group, the number of flies was 7328. - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- - 1.0 mM ethylmethane sulfonate solution formulated with 1.0% fructose in water
Examinations
- Tissues and cell types examined:
- x-chromosomes
- Details of tissue and slide preparation:
- no details reported
- Evaluation criteria:
- - Scoring of the mutants resulting from positive control exposure was based on mating 5 CS males in the same manner as males treated with the test compound (4 replicates).
- After sufficient numbers of flies had emerged, a maximum of 25 (minimum of 5) kidney-shaped red-eyed F1 females were selected at random and mated with their sibling white-body, bar-shaped, apricot-eyed males.
- After 2 to 3 weeks the F2 progeny were examined and scored for the absence of round, red-eyed males, which would indicate that a lethal mutation had taken place in the treated male.
- Confirmation of a lethal mutation was obtained by conducting an F3 cross from each vial scored as a lethal mutation - Statistics:
- The testing was designed to examine approx. 2500 X-chromosomes in each of 4 replications, thereby yielding a total of 8000 to 10000 X-chromosomes for examination. Vials without F2 progeny or fewer than 5 progeny (F2) were scored as failures. The BMDP (Biomedical Programs) computer package was used to perform the analyses. Based on the number of lethal and nonlethal offspring for each male, by combining all replicates, the mutation frequency of nitroguanidine was compared to that of the control by Fisher's exact test for each of the four broods seperately and for the combined broods. All statistical tests were conducted at the 0.05 level of significance.
Results and discussion
Test results
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF DEFINITIVE STUDY
The frequencies of spontaneous mutation for nitroguanidine and the negative control were 0.188% and 0.096% based on 6913 and 7318 X-chromosomes, respectively. The mutation frequencies for the positive control, 1 mM ethylmethane sulfonate, was 17.8%. The mutation frequencies for each compound are presented in table 1. The mutation frequencies for each brood for nitroguanidine and the negative control are presented in table 2. No significant difference was detected between the mutation frequency of the negative control and the nitroguanidine with the Fisher's exact test (p = 0.1799). Also, no significant differences were detected between the negative control and the nitroguanidine for the data of broods 1, 2, 3, and 4 (table 2).
Any other information on results incl. tables
Table 1: Percent mutation frequencies in the Sex-linked Recessive Lethal Assay of nitroguanidine*
Compound |
1 |
2 |
3 |
4 |
Total Mutations |
Percent Mutations |
Nitroguanidine |
0/1115 |
5/1231 |
4/2352 |
4/2215 |
13/6913 |
0.188 |
Negative Control |
1/1481 |
1/1529 |
3/2155 |
2/2153 |
7/7318 |
0.096 |
Positive Control |
36/166 |
39/284 |
56/395 |
70/284 |
201/1129 |
17.80 |
* Data are recorded as number of SLRL events/numbers of X-chromosomes tested
Nitroguanidine: 25 maleDrosophila melanogenasterflies(CS strain) formed the P generation
Negative Control: 25 maleDrosophila melanogenasterflies(CS strain) formed the P generation
Positive Control: 5 maleDrosophila melanogenasterflies(CS strain) formed the P generation
Table 2: Fisher’s Exact Test for Significance of the difference between nitroguanidine and negative control in Sex-Linked Recessive Lethal Assay
|
Brood number |
|||
Compound |
1 |
2 |
3 |
4 |
Nitroguanidine |
3/2055 |
3/1815 |
5/1727 |
2/1316 |
Negative Control |
2/2094 |
2/1901 |
1/1844 |
2/1479 |
Positive Control |
44/336 |
88/291 |
63/316 |
6/186 |
p values |
0.6845 |
0.6805 |
0.1138 |
1.0000 |
Nitroguanidine: Nitroguanidine was dissolved in a 1% fructose solution in deionized water. Date are from 25 male Drosophila melanogenaster flies (CS strain) x 4 replicates mated with 3 Basc strain female flies each.
Negative Control: 1% fructose solution in deionized water. Date are from 25 Drosophila melanogenaster flies (CS strain) x 4 replicates mated with 3 Basc strain female flies each.
Positive Control: 1 mM ethylmethane sulfonate and 1% fructose in deionized water. Date are from 5 Drosophila melanogenaster flies (CS strain) x 4 replicates mated with 3 Basc strain female flies each.
Applicant's summary and conclusion
- Conclusions:
- Nitroguanidine was non-mutagenic following 72-hour feeding exposure to concentrations of nitroguanidine ranging from 2.08 µg/ml to 20.8 µg/ml.
- Executive summary:
The objective of this study was to evaluate the mutagenic potential of nitroguanidine in the Drosophila melanogenaster Sex-Linked Recessive Lethal Assay.
Nitroguanidine has been reported to produce significant damage in Chinese hamster fibroblasts (see IUCLID 7.6.1, "556-88-7_Nitroguanidin_chromosome_tests_hamster_cells_1976.pdf").
However, studies from this laboratory have indicated, that nitroguanidine is not mutagenic in the mouse lymphoma forward mutation assay (see IUCLID 7.6.1, "556-88-7_Nitroguanidin_mutagenic_potential_mouse_lymphoma_1987.pdf"), the Chinese hamster ovary sister chromatid exchange assay (see IUCLID 7.6.1, "556-88-7_Nitroguanidin_genetic_toxicology_1988.pdf"), or in the Ames Salmonella / mammalian microsome assay (see IUCLID 7.6.1, "556-88-7_Nitroguanidin_genetic_toxicology_ames_test_1988.pdf").
The results of this study confirm in an in vivo model for genetic toxicity the previous findings that nitroguanidine has no mutagenic potential at doses which approach the limits of solubility in the appropriate test systems.
The results of this study indicate that nitroguanidine is not mutagenic when evaluated in the Drosophila melanogenaster Sex-Linked Recessive Lethal Assay.following 72-hour feeding exposure to concentrations of nitroguanidine ranging from 2.08 µg/ml to 20.8 µg/ml.
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