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EC number: 619-290-0 | CAS number: 97780-06-8
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- one-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 991
- Report date:
- 1991
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Groups of 16 male and 16 female Crl:CD®(SD}BR rats were fed for 90 days with diets that contained 0, 100, 1000 or 5000 ppm of the test substance to assess its subchronic toxicity. At these dietary levels, male rats received an average of 0, 7.3, 71, and 365 mg/kg/day of the test substance in the 0, 100, 1000 and 5000 ppm groups, respectively. For female rats, the average daily dose was 0, 9.5, 88, and 453 mg/kg/day in the 0, 100, 1000, and 5000 ppm groups, respectively.
After 90 days on test, six rats per group were used to conduct a one-generation reproduction study. Male and female rats continued to receive their respective treatment group’s diet throughout mating, gestation, and lactation. - GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Reference substance 002
- Cas Number:
- 97780-06-8
- Test material form:
- solid
- Details on test material:
- Purity: 96%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Crl:CD®(SD)BR
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- other: Certified Purina® Laboratory Chow #5002
- Details on exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Mixing appropriate amounts with (Type of food): Certified Purina® Laboratory Chow #5002
- Storage temperature of food: Refrigerated (temperature not stated in the report) - Details on mating procedure:
- - M/F ratio per cage: 1:1
- Length of cohabitation: 15 days
- Proof of pregnancy: Copulation plug
- After successful mating each pregnant female was caged (how): After the 15-day mating period, each female rat was housed individually in polypropylene cages with bed-o'cobs® cage bedding - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Approximately 50-gram samples were taken during the study from each treatment level (excluding control diet) and analyzed for the concentration, homogeneity, or stability of the test substance in the diet. Homogeneity was determined by collecting a sample from the top, middle, and bottom of the mixing vessel. Stability was determined by collecting four samples from the middle of the mixing vessel. One of the four samples was immediately frozen, the second was refrigerated for ten days, the third was stored at room temperature for 24 hours, and the fourth was stored at room temperature for ten days. Homogeneity and stability samples were taken at the start of the study. Homogeneity samples were also taken after one week on test when mixers were changed from the Stephan to the Hobart high-speed mixer. Samples to verify the concentration of the test substance in the diet were taken at the end of the 90-day feeding portion of the study.
Diet samples were analyzed for the test substance by reversed-phase liquid chromatography. The test substance was ultrasonically extracted (~ 1 hour) from diet samples (10.0 g) into methylene chloride. The 0 ppm sample was extracted with 50 mL of the solvent; 100, 1000 and 5000 ppm diet samples were extracted with 100 mL of methylene chloride. Extracts (~ 5 mL) were filtered through 0.45 µm filters. Filtered
extracts were then diluted 4:10 (100 ppm), 1:25 (1000 ppm) or 1:100 (5000 ppm). Aliquots (1.50 mL) of the filtered extract (0 ppm) or diluted extracts (100, 1000, 5000 ppm) were evaporated to dryness under nitrogen. The resulting residues were ultrasonically resuspended in acetonitrile (1.50 mL, 5-10 min).
Recovery efficiencies were determined at the 5000 ppm level by adding 50.0 mg of the test substance directly to control diet (10.0 g) and at the 100 ppm level by addition of a test substance stock solution (1.00 mL, 1000 µg/mL) to control diet (10.0 g).
The reference test compound (96% purity) was used to make calibration standards (2.0, 4.0, 6.0 µg/mL) for the creation of the standard curve. Quantitation was performed using linear regression analysis.
The dietary concentration of INA-7881 was determined by duplicate injection with a Hewlett Packard 1090a liquid
chromatograph. - Duration of treatment / exposure:
- 1 Generation
- Frequency of treatment:
- Daily
- Details on study schedule:
- Six designated rats in each test group were used to initiate a one-generation, one-litter reproduction substudy at the end of the 90-day feeding study. Throughout the reproduction substudy, all rats received their respective group's diet. Each female rat was housed with a randomly selected male rat from the same test group for a period of fifteen days. During the 15-day mating period, each female rat was checked daily for the presence of a copulation plug. After the 15-day mating period, each female rat was housed individually in polypropylene cages with bed-o'cobs® cage bedding. Six days later, female rats were examined at least twice daily for the birth of pups.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 100 ppm
- Dose / conc.:
- 1 000 ppm
- Dose / conc.:
- 5 000 ppm
- No. of animals per sex per dose:
- 6 males and 6 females
- Control animals:
- yes, plain diet
- Positive control:
- No
Examinations
- Parental animals: Observations and examinations:
- The male and female parent rats were sacrificed and discarded without pathological evaluation.
- Litter observations:
- Live and dead pups in each litter were counted as soon as possible after delivery was completed. Four days after birth:
• live pups were counted,
• the litter was weighed,
• ten pups, with an equal number of male and female pups where possible, were selected on the basis of their being representative of the
general health of their litter. Extra pups were sacrificed and discarded without pathological evaluation.
• litters of less than ten pups were not reduced, and
• reduced litters were weighed.
Twelve days after birth, live pups were counted. Twenty-one days after birth (weaning), each pup was sexed, weighed, sacrificed and discarded without pathological examination. - Postmortem examinations (parental animals):
- The male and female parent rats were sacrificed and discarded without pathological evaluation.
- Postmortem examinations (offspring):
- Twenty-one days after birth (weaning), each pup was sexed, weighed, sacrificed and discarded without pathological examination.
- Statistics:
- The Fisher's Exact, Kruskal-Wallis, and/or Mann-Whitney U tests were used to evaluate measures of reproduction and lactation performance. Statistically significant differences were judged at the p < 0.05 probability level.
- Reproductive indices:
- Indices of reproduction were calculated on a per litter basis for female rats bearing litters with at least one live pup. The percentage was calculated for each litter and the average percentage for each group is reported. The following formulas were used:
Fertility Index (%) = Number females bearing litters/Number of females mated x 100
Gestation Index (%) = Number of females bearing litters with at least one live pup/Number of females bearing litters x 100 - Offspring viability indices:
- Number of Pups Born Alive (%) = Total number of pups born alive/Total number of pups born x 100
0-4 Day Viability Index (%) = Total number of pups alive at 4 days postnatal (prior to litter reduction)/Total number of pups born alive x 100
1-4 Day Viability Index (%) = Total number of pups alive at 4 days postnatal (prior to litter reduction)/Total number of pups 1 day postnatal x 100
Lactation Index (%) = Total number of pups alive at weaning (21 days postnatal)/Total number of pups alive after litter reduction (4 days postnatal) x 100
Litter Survival (%) = Number of litters at weaning/Number of litters delivered x 100
Average # of Pups/litter = Total number of pups born alive/Total number of litters delivered
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The mean body weight of dams in the high-dose group was greater than the control group (320 g in the control group and 336.6 g in the high-dose group). Although these changes were statistically significant, they were considered not to be biologically relevant or compound related.
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- Concentration 0 100 ppm 1000 ppm 5000 ppm
Fertility Index 100% 83.3% 83.3% 83.3%
Gestation Index 100% 100% 100% 100%
% Pups born alive/Litter 100% 95% 100% 95.4%
0-4 Day Viability Index/Litter 98.3% 92.7% 91.3% 100%
1-4 Day Viability Index/Litter 100% 98.5% 97.6% 100%
Lactation Index/Litter 100% 100% 98.0% 100%
Litter survival 100% 100% 100% 100%
Mean number of pups/litter at:
Concentration 0 100 ppm 1000 ppm 5000 ppm
Birth (Total) 9.5 13.2 14.6 12.8
Birth (Alive) 9.5 12.6 14.6 12.2
24 Hours 9.3 12.0 13.6 12.2
Day 4 9.3 11.8 13.2 12.2
Day 4 after reduction 7.8 9.4 10.0 8.4
Day 12 7.8 9.4 10.0 8.4
Day 21 7.8 9.4 9.8 7.4
Number of males 4.5 5.2 5.8 4.4
Number of females 3.3 4.2 4.0 4.0
Effect levels (P0)
- Dose descriptor:
- NOEL
- Effect level:
- 5 000 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No compound-related effects were noted in the one-generation reproduction study. Therefore, the no-observable-effect level (NOEL) was 5000 ppm., the highest dose tested.
Applicant's summary and conclusion
- Conclusions:
- No compound-related effects were noted in the one-generation reproduction study. Therefore, the no-observable-effect level (NOEL) was 5000 ppm, the highest dose tested.
- Executive summary:
Groups of 16 male and 16 female Crl:CD®(SD)BR rats were fed for 90 days with diets that contained 0, 100, 1000 or 5000 ppm of the test substance to assess its subchronic toxicity. At these dietary levels, male rats received an average of 0, 7.3, 71, and 365 mg/kg/day of the test substance in the 0, 100, 1000 and 5000 ppm groups, respectively. For female rats, the average daily dose was 0, 9.5, 88, and 453 mg/kg/day in the 0, 100, 1000, and 5000 ppm groups, respectively. After 90 days on test, six rats per group were used to conduct a one-generation reproduction study. Male and female rats continued to receive their respective treatment group’s diet throughout mating, gestation, and lactation.
No compound-related effects were noted. Therefore, the no-observable-effect level (NOEL) was 5000 ppm, the highest dose tested.
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