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EC number: 207-383-5 | CAS number: 466-99-9
- 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:
- fertility, other
- Remarks:
- Fertility and general reproduction toxicity study
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
Data source
Reference
- Reference Type:
- review article or handbook
- Title:
- PHARMACOLOGY/TOXICOLOGY NDA REVIEW AND EVALUATION
- Author:
- Thornton-Jones SR
- Year:
- 2 004
- Bibliographic source:
- NDA 21-044, DEPARTMENT OF HEALTH AND HUMAN SERVICES, PUBLIC HEALTH SERVICE, FOOD AND DRUG ADMINISTRATION CENTER FOR DRUG EVALUATION AND RESEARCH
Materials and methods
- GLP compliance:
- yes
Test material
- Reference substance name:
- Hydromorphone hydrochloride
- EC Number:
- 200-762-6
- EC Name:
- Hydromorphone hydrochloride
- Cas Number:
- 71-68-1
- Molecular formula:
- C17H19NO3.ClH
- IUPAC Name:
- Hydromorphone hydrochloride
1
Test animals
- Species:
- rat
- Strain:
- other: CD(SD)IGS BR VAF/Plus
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Details on mating procedure:
- - M/F ratio per cage: 1/1
- Length of cohabitation: 21 days
- Proof of pregnancy: vaginal plug / sperm in vaginal smear referred to as day 0 of pregnancy - Duration of treatment / exposure:
- 28 days before cohabitation (maximum 15 days) and continuing through the day before sacrifice (at least 10 weeks prior to sacrifice) - males
Once daily beginning 15 days before cohabitation and continuing through day 7 of pregnancy - females
- No. of animals per sex per dose:
- 25
- Control animals:
- yes
- Details on study design:
- - Dose selection rationale: doses selected based on previous oral (gavage) dose range-finding study
Examinations
- Parental animals: Observations and examinations:
- MORTALITY AND CLINICAL SIGNS: Yes
- Time schedule: twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: weekly and days 0, 3, 6, 7, 8, 10 and 13 of pregnancy (females)
FOOD CONSUMPTION: Yes
- Time schedule for examinations: weekly and days 0, 3, 6, 7, 8, 10 and 13 of pregnancy (females) - Oestrous cyclicity (parental animals):
- Examination of vaginal cytology for 14 days prior to dosing initiation, for 14 days beginning with day after first administration and then until spermatoza were observed in vaginal smear.
- Postmortem examinations (parental animals):
- GROSS NECROPSY
After cohabitation period - males
Day 13 pregnancy - females
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Description (incidence and severity):
- Excessive chewing, chromorhinorrhea, hyperactivity, chormodacryorrhea, misaligned incisors
- Description (incidence):
- One mid-dose male died on day 42
- Description (incidence and severity):
- Rats gained weight until 5 weeks after which weight loss occurred from weeks 5 to 6.
- Description (incidence and severity):
- Food consumption was reduced in males from the first week of dosing onward. In females, reduced consumption was observed in high dose females during the first week of gestation but was coparable to control animals during the second week after dosing.
Reproductive function / performance (P0)
- Description (incidence and severity):
- The number of eustrous stages per 14 days was comparable across the 4 dosage groups
- Description (incidence and severity):
- No effects on sperm motility, count and density.
- Description (incidence and severity):
- No effects on number of days cohabitation, number of rats mated, or number of pregnancies.
Details on results (P0)
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- < 0.5 other: mg/kg
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- clinical signs
- body weight and weight gain
- food consumption and compound intake
Target system / organ toxicity (P0)
- Critical effects observed:
- not specified
Results: F1 generation
General toxicity (F1)
- Description (incidence and severity):
- No dead feotuses.
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 5 other: mg/kg
- Based on:
- test mat.
- Sex:
- not specified
- Remarks on result:
- other: No test material-related effects were observed at the highest dose
Target system / organ toxicity (F1)
- Critical effects observed:
- no
Overall reproductive toxicity
- Reproductive effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- Administration of the test material resulted in adverse clinical signs at all doses, reduced body weight gain and the two highest doses and reduced food consumption at the highest dose. No test-material related effects on mating and fertility were observed. The NOAEL for maternal toxicity was < 0.5 mg/kg. The NOAEL for reproductive effects was 5 mg/kg.
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