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EC number: 208-100-8 | CAS number: 509-60-4
- 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:
- reproductive toxicity, other
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- documentation insufficient for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- MATERNAL AND FOETAL DISTRIBUTION OF H3-DIHYDROMORPHINE IN THE TOLERANT AND NONTOLERANT RAT
- Author:
- Yeh SY & Woods LA
- Year:
- 1 970
- Bibliographic source:
- JOURNAL OP PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 174, No. 1: 9 – 13.
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Pregnant Sprague-Dawley female rats were made tolerant to the test material by initiating s.c. injections of 2 mg/kg (base) of drug, twice daily, 30 hours after breeding and increasing the dosage to 15 mg/kg. Control nontolerant pregnant animals were treated in an identical manner except that they were injected with saline. Foetuses were removed by caesarean section at intervals of one-half to four hours after s.c. injection of 7 mg/kg (base) of H3- test material to the maternal rat on the 21st day of gestation. Free and conjugated-levels of test material were assessed in maternal and foetal tissues and plasma.
- GLP compliance:
- no
- Limit test:
- no
Test material
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: Weighing 250 to 300 g.
- Diet: Ad libitum
- Water: Ad libitum
ENVIRONMENTAL CONDITIONS
- Maintained under constant environmental conditions.
Administration / exposure
- Route of administration:
- subcutaneous
- Vehicle:
- physiological saline
- Details on exposure:
- About 30 hours after breeding, the pregnant female rats were begun on s.c. injections (gluteal region), twice daily, of non-labelled test material HCl in saline. Two dosage regimens of test material were used. The first was 4 mg/kg (base) initially, increased by 4 mg/kg every 2 days to a final dosage of 28 mg/kg for the last 8 days. Because this regimen gave a small number of full-term pregnancies, a lower dosage of test material was used, initially 2 mg/kg and increased at 2-day intervals to 4, 7, 10 and 15 mg/kg, which was maintained for the last 12 days. The injection volume was 2 mL/kg. Control non-tolerant pregnant rats were injected with equal volumes of saline.
Analgesia after injection of 7 mg/kg of drug in both the control and tolerant pregnant animal groups on the 18th day of gestation was tested with the hot plate method and compared with the effect in non-pregnant female rats. The pregnant rats were injected s.c. with 7 mg/kg (base) of tritium-labelled test material between 12 and 16 hours after the last injection of test material on the 21st day of gestation. - Details on mating procedure:
- Males were mixed with females in a ratio of 1:3 in the evening, and the next morning the pregnant animals, confirmed by the vaginal smear test, were separated.
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 4 mg/kg (base) initially, increased by 4 mg/kg every 2 days to a final dosage of 28 mg/kg for the last 8 days.
2 mg/kg (base) initially, increased at 2-day intervals to 4, 7, 10 and 15 mg/kg, which was maintained for the last 12 days. - Frequency of treatment:
- 4 mg/kg (base) initially, increased by 4 mg/kg every 2 days to a final dosage of 28 mg/kg for the last 8 days.
2 mg/kg (base) initially, increased at 2-day intervals to 4, 7, 10 and 15 mg/kg, which was maintained for the last 12 days.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 28 other: mg/kg
- Remarks:
- 4 mg/kg (base) initially, increased by 4 mg/kg every 2 days to a final dosage of 28 mg/kg for the last 8 days.
- Dose / conc.:
- 15 other: mg/kg
- Remarks:
- 2 mg/kg (base) initially, increased at 2-day intervals to 4, 7, 10 and 15 mg/kg, which was maintained for the last 12 days.
- No. of animals per sex per dose:
- Not specified
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- None specified
Examinations
- Postmortem examinations (parental animals):
- At the time of sacrifice the animals were anesthetized with ether and the foetuses were delivered by caesarean section with extreme care to avoid contamination by radioactive fluids from the mother. Maternal blood was withdrawn from the abdominal aorta, and the maternal brain, liver, kidneys and about 4 square inches of skin of the injection site (including muscle) were removed, blotted dry, wrapped in aluminium foil and frozen. All samples were collected within 10 minutes after anesthetization.
- Postmortem examinations (offspring):
- The foetuses were wiped, counted and weighed. The blood of foetuses was collected through decapitation, with heparin being used as an anticoagulant, and the livers, kidneys and brains were removed and pooled for each litter. All samples were collected within 10 minutes after anesthetization.
- Statistics:
- Two-tailed t test was used to compare the mean concentration of the drug in the tissue at P < 0.05 level.
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- not examined
- Mortality:
- not examined
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The larger dose of test material administered chronically reduces gain of maternal body weight.
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- 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
- Other effects:
- not examined
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- effects observed, treatment-related
- Description (incidence and severity):
- The larger dose of test material administered chronically reduces the number of litters and gain of maternal body weight but has no effect on the foetal body weight and the number of foetuses per litter.
Effect levels (P0)
- Remarks on result:
- not measured/tested
Target system / organ toxicity (P0)
- Critical effects observed:
- not specified
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not examined
- Mortality / viability:
- not examined
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- The larger dose of test material administered had no effect on the foetal body weight.
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
- Other effects:
- not examined
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not examined
Details on results (F1)
Effect levels (F1)
- Remarks on result:
- not measured/tested
Applicant's summary and conclusion
- Conclusions:
- The larger dose of test material administered chronically reduces the number of litters and gain of maternal body weight but has no effect on the foetal body weight and the number of foetuses per litter.
- Executive summary:
Pregnant Sprague-Dawley female rats were made tolerant to the test material by initiating s.c. injections of 2 mg/kg (base) of drug, twice daily, 30 hours after breeding and increasing the dosage to 15 mg/kg. Control nontolerant pregnant animals were treated in an identical manner except that they were injected with saline. Foetuses were removed by caesarean section at intervals of one-half to four hours after s.c. injection of 7 mg/kg (base) of H3- test material to the maternal rat on the 21st day of gestation. Free and conjugated-levels of test material were assessed in maternal and foetal tissues and plasma.
The larger dose of test material administered chronically reduces the number of litters and gain of maternal body weight but had no effect on the foetal body weight and the number of foetuses per litter.
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