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EC number: 202-086-7 | CAS number: 91-64-5
- 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:
- screening for reproductive / developmental toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 981
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The purpose of this study, performed at the Huntingdon Research Centre, England, was to dtermine a suitable high dietary level of Coumarin, a food and cosmetic flavouring substance, for a long-term feeding study in rats following in utero exposure.
The high dietary level used in this study was based on findings by Griepentrog.
Treatment commenced on 1 February 1980 and ended on 16 May 1980.
This report contains all data generated during the study. - GLP compliance:
- not specified
Test material
- Reference substance name:
- Coumarin
- EC Number:
- 202-086-7
- EC Name:
- Coumarin
- Cas Number:
- 91-64-5
- Molecular formula:
- C9H6O2
- IUPAC Name:
- 2H-chromen-2-one
- Test material form:
- other: crystalline
- Details on test material:
- -Substance type: pure substance
-Physical state: White crystalline powder
-Lot/batch No: CA 78300/01
-Storage condition of test material: room tempeature
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Test animals
-Source: Charles River Laboratories, Portage, USA
-Age at arrival: 8 weeks
-Weight at study initiation: 50g
-Diet: Free access to Spratts Laboratory Animals Diet No.2( treated with the appropriate level of coumarin)
-Water: Free access to tap water
-Acclimation: The acclimation period is 7 days.
Environmental conditions:
-Temperature: 22℃
- Humidity: 50%
- Lighting control: 12 hours light and 12 hours dark per 24 hours.
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- Coumarin was administered by admixture with the diet. The required dietary concentrations were obtained by the dilution of premix prepared each
week. Control animals received normal(untreated) diet. - Details on mating procedure:
- -Impregnation procedure: cohoused
-M/F ratio per cage: 1:2
-Length of cohabitation: 20days - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data. The doses were calculated based on the group mean food consumption
- Duration of treatment / exposure:
- Total duration of treatment 15 weeks
- Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0 ppm
Basis:
nominal in diet
control
- Remarks:
- Doses / Concentrations:
3000 ppm
Basis:
nominal in diet
- Remarks:
- Doses / Concentrations:
3000/5000 ppm
Basis:
nominal in diet
- Remarks:
- Doses / Concentrations:
5000 ppm
Basis:
nominal in diet
- No. of animals per sex per dose:
- 8 males plus 16 females per dose
- Control animals:
- yes, concurrent no treatment
- Positive control:
- None
Examinations
- Parental animals: Observations and examinations:
- Detailed clinical observation:
Any reaction to treatment exhibited by the rats was recorded daily as to type, duration and animal affected.
Body weight: the weight of each rat was recorded one week before the commencement of treatment and at twice intervals thereafter.
Food consumption: The quantity of food consumed by each cage of rats was recorded and the group mean weekly intake per rat calculated. - Oestrous cyclicity (parental animals):
- None
- Sperm parameters (parental animals):
- None
- Litter observations:
- Litter weight change:
Pups were weighed in total litters at birth, and at 4,7,11,14,18 and 21 days post partum.
Litter size
At birth, and at 4,7,11,14,18 and 21days, mean values were determined for both the total number of young and the number of viable and dead young. - Postmortem examinations (parental animals):
- None
- Postmortem examinations (offspring):
- None
- Statistics:
- Statistical analysis of data for adults involved on the study was not attempted, as it was considered that bodyweight and food consumption data clearly indicated an effect. Statistical significance of intergroup differences occurring among the pups and litters was assessed using the Kruskal-Wallis test, excluding from the test group 3(3000/5000ppm coumarin) as this group was already sufficiently different from the norm to detract from the accuracy of the method.
- Reproductive indices:
- No. females mated
No. females not pregnant - Offspring viability indices:
- The following reproductive parameters were evaluated statistically:
Viable litters at Day 21 post partum
Mortality during days 0-21
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
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Organ weight findings including organ / body weight ratios:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Other effects:
- effects observed, treatment-related
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- not examined
Details on results (P0)
Mortality: There was no adult mortality during the study.
Food consumption: Probably as a result of unpalatability, food consumption of males and females was reduced in all groups of treated adult rats.
Bodyweight gain: Associated with the effect on food intake, growth of males and females of all adult treated groups was severely impaired. This effect was most marked among rats exposed to Coumarin at 5000 ppm or 3000/5000 ppm.
Efficiency of food utilisation: The efficiency of food utilisation of all groups of treated adult rats was markedly inferior to that of the controls .
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- > 333 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: Based on no of mated/ pregnant
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
Details on results (F1)
Mean litter size at birth: The mean litter sizes of rats receiving 3000 or 5000 ppm (but not 3000/5000 ppm) were marginally lower than those of the controls.
Bodyweight gain of pups: The growth of pups of all treated groups was severely retarded by exposure to Coumarin.
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Growth and development of pups of all treated groups was markedly inferior to that of the controls. It’s considered that such a retardation of growth would result in a pup population which, if used for a long-term study, would show survival characteristics that would not be comparable to those of the controls.
It’s therefore concluded that none of the levels used in this study are suitable for use in an in utero derivation programme for long-term study. It’s considered that a suitable high dietary level for such a study design would be lower than 3000 ppm coumarin. - Executive summary:
Introduction:
The purpose of this study, performed at the Huntingdon Research Centre, England, was to determine a suitable high dietary level of coumarin, a food and cosmetic flavouring substance, for a long-term feeding study in rats following in utero exposure.
The high dietary level used in this study was based on findings by Griepentrog(Griepentrog, F., (1973) Toxicology, 1, 93-102)
This report contains all data generated during the study.
Results: Growth and development of pups of all treated groups was markedly inferior to that of the controls. It's considered that such a retardation of growth would result in a pup population which, if used for a long-term study, would show survival characteristics that would not be comparable to those of the controls.
It's therefore concluded that none of the levels used in this study are suitable for use in an in utero derivation programme for long-term study. It's considered that a suitable high dietary level for such a study design would be lower than 3000 ppm coumarin.
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