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EC number: 201-553-2 | CAS number: 84-69-5
- 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:
- two-generation reproductive toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Non guideline study. Available as a published report. Acceptable with restrictions.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 995
Materials and methods
- Principles of method if other than guideline:
- continuous breeding study
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Dibutyl phthalate
- EC Number:
- 201-557-4
- EC Name:
- Dibutyl phthalate
- Cas Number:
- 84-74-2
- IUPAC Name:
- dibutyl phthalate
- Details on test material:
- purchased material - analysis indicated purity of 98% or greater
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 Breeding Laboratories, Portage, MI
- Age at study initiation: 10-11 wk
- Housing: in breeding pairs
- Diet (e.g. ad libitum): NIH-07 Open Formula meal (Zeigler Brothers In., Gardners, PA), ad libitum
- Water (e.g. ad libitum): deionized water, ad libitum
- Acclimation period: 2-3 wk
Administration / exposure
- Route of administration:
- oral: feed
- Details on exposure:
- Continuous exposure to 1000, 5000 or 10000 ppm DIBP in diet over 5 litters and 2 generations
- Details on mating procedure:
- - M/F ratio per cage: 1:1
- Length of cohabitation (continuous breeding phase): 112 days
- Length of cohabitation (for second generation): 7 days
- Proof of pregnancy: sperm in vaginal smear - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- - Homogeneity: confirmed using HPLC (within 10% of nominal)
- Stability in diet: confirmed using GC-FID (stable for 1 week under animal room conditions) - Frequency of treatment:
- continuous, via feed
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0, 1000, 5000, 1000 ppm
Basis:
nominal in diet
- Remarks:
- Doses / Concentrations:
0, 52, 256, 509 mg/kg bw/d
Basis:
other: approx. amount ingested, males
- Remarks:
- Doses / Concentrations:
0, 80, 385, 794 mg/kg bw/d
Basis:
other: approx. amount ingested, females
- No. of animals per sex per dose:
- Continuous breeding study: 40 controls/sex; 20 test/sex
Two-generation phase: 20/sex - Control animals:
- yes, plain diet
- Details on study design:
- Male and female SD rats (F0) were housed in breeding pairs for 112 days for delivery of 5 litters
- individually housed for delivery of final litters while exposure continued.
Two-generation phase performed using final litters from continuous breeding phase:
- F1 pups exposed to DIBP (same level as received by parents) until sexual maturity achieved (approx. 77 d old)
- male and female pairs mated for 7 days while receiving treatment
- F1 females allowed to deliver F2 litters
Examinations
- Parental animals: Observations and examinations:
- - clinical signs
- body weight and feed consumption - Oestrous cyclicity (parental animals):
- Estrous cycle data collected for 12 d prior to necropsy:
- cycle length (days)
- estrous stages (as percentage of cycle) - Sperm parameters (parental animals):
- Sperm data collected at necropsy:
- spermatid heads (per g testis and per testis)
- epididymal sperm motility (%), concentration (per g), abnormal sperm (%) - Litter observations:
- - total and live pups per litter
- sex ratio
- pup body weight - Postmortem examinations (parental animals):
- - organ weights (F0 and F1)
- histopathology of selected tissues (F0 and F1) - Statistics:
- For normally distributed data, the Cochran-Armitage test used to assess any dose-trend effects present and chi-square or Fisher's exact test used for control versus treatment comparisons. Trend testing of results with skewed distributions used Jonckheere's test or Wilcoxon's test, while control versus test comaprisons were performed according to Shirley, Dunn or Mann and Whitney.
- Reproductive indices:
- - mating index
- pregnancy index
- fertility index
- dam weight at delivery
- days to litter
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- effects observed, treatment-related
- Reproductive performance:
- effects observed, treatment-related
Details on results (P0)
F1 adult mating index (30% of control), pregnancy index (5% of control) and fertility index (17% of control) were significantly decreased at 10000 ppm.
F1 spermatid heads were decreased significantly at 10000 ppm (47% reduction per g testis, 54% reduction per testis); epididymal spermatozoal concentration was decreased significantly at 10000 ppm (49% reduction per g cauda).
Mild to moderate degeneration of seminiferous tubules and interstital cell hyperplasia was present in 7-8 of 10 F1 males subject to microscopic examination from the 10000 ppm, with minimal or mild changes present in 1-2 of 10 males from the 5000 ppm group (absent from the 1000 ppm group).
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not examined
- Mortality / viability:
- not examined
- 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)
Effect levels (F1)
open allclose all
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 5 000 ppm (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: decreased spermatid heads in testis, decreased epididymal spermatozoal concentration
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 5 000 ppm (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: decreased mating index, pregnancy index and fertility index
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 1 000 ppm (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: degeneration of seminiferous tubules and interstital cell hyperplasia
Results: F2 generation
Effect levels (F2)
- Dose descriptor:
- LOAEL
- Generation:
- F2
- Effect level:
- 1 000 ppm (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: decreased pup weights
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Treatment with dibutyl phthalate over two generations was associated with reduced pregnancy and fertility indices, decreased pup weights, reductions in sperm and spermatid counts and degeneration of seminiferous tubules and interstital cell hyperplasia.
- Executive summary:
The effects of dibutyl phthalate on reproductive functions was examined in male and female SD rats. Animals were intially housed in breeding pairs as part of a continuous breeding study, with treatment extending to 112 days with delivery of 5 litters. A second generation was then mated using pups from the final litters of the continuous breeding phase, with animals receiving DIBP to sexual maturity (approx. 77 d old) after which they were mated. Dose levels of 0, 1000, 5000 or 10000 ppm DBP in diet were used, equivalent to received treatments of approx. 52, 256 or 509 mg/kg bw/d for males, and 80, 385 and 794 mg/kg bw/d for females. Pregnancy and fertility indices for F1 parents were statistically significantly lower for the 10000 ppm group, with live F2 pup weights significantly decreased at all dose levels. Decreased epididymal sperm count and testicular spermatid head count were apparent at 10000 ppm, with mild to moderate degeneration of seminiferous tubules and interstital cell hyperplasia present in the 5000 ppm and 10000 ppm F1 males. An overall LOAEL of 1000 ppm (52-80 mg/kg bw/d) was obtained for effects on pup weight, with a NOAEL of 1000 ppm (52 mg/kg bw/d) for microscopically detected changes in male gonadal tissue.
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