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EC number: 249-079-5 | CAS number: 28553-12-0
- 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
Repeated dose toxicity: other routes
Administrative data
- Endpoint:
- repeated dose toxicity: other route
- Remarks:
- other: mice IP injection on days -5, 2, 9, and 16 of 18 day study
- Type of information:
- experimental study
- Adequacy of study:
- disregarded due to major methodological deficiencies
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Peer reviewed publication using non-guideline and non-GLP study design to examine the effects of intraperitoneal injection of DINP on atopic dermatitis-like skin lesions in NC/Nga mice.
Data source
Reference
- Reference Type:
- publication
- Title:
- Effects of diisononyl phthalate on atopic dermatitis in vivo and immunologic responses in vitro.
- Author:
- Koike E, Yanagisawa R, Sadakane K, Inoue K, Ichinose T, Takano H.
- Year:
- 2 010
- Bibliographic source:
- Environ Health Perspect
Materials and methods
- Principles of method if other than guideline:
- NC/Nga mice aged 7 weeks were treated with 0.15, 1.5, 15 or 150 mg/kg/day DINP on days -5, 2, 9, and 16 of the study. Five days following the first IP injection of DINP the mice were exposed to the allergen Dermatophagoides pteronyssinus via intradermal injection in the ventral side of the right ear every 2-3 days. The purpose of the experiment was to determine the effects of IP injection of DINP on atopic dermatitis-like skin lesions. The effects of DINP in vitro exposure on bone-marrow derived dendritic cells or splenocytes was evaluated.
- GLP compliance:
- not specified
Test material
- Reference substance name:
- DINP
- IUPAC Name:
- DINP
- Details on test material:
- DINP purchased from Wako Pure Chemical Industries, Osaka, Japan. Dermatophagoides pteronyssinus (Dp) purchased from Cosmo Bio LSL, Tokyo Japan. CAS or catalog number was not provided.
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- other: NC/Nga
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Japan
- Age at study initiation: 7 weeks and 11-15 weeks
- Weight at study initiation: 20-23 g at 7 weeks and 24-27 g at 11-15 weeks
- Fasting period before study: no
- Housing: no information
- Diet ad libitum: CE-2; Clea Japan Inc., Tokyo Japan)
- Water ad libitum: distilled
- Acclimation period: one week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-26
- Humidity (%): 40-69
- Air changes (per hr): no information
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: To: no information
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- olive oil
- Details on exposure:
- NC/Nga mice aged 7 weeks were IP injected with 0.15, 1.5, 15 or 150 mg/kg/day DINP dissolved in 0.1 ml olive oil on days -5, 2, 9, and 16 of the study. Five days following the first IP injection of DINP the mice were exposed to 5 ug of the allergen Dermatophagoides pteronyssinus dissolved in 10 ul saline via intradermal injection in the ventral side of the right ear on days 0, 3, 5, 8, 10, 12, 15, and 17 of the study.
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Study lasted 18 days.
- Frequency of treatment:
- DINP IP injection on days -5, 2, 9, and 16 of the study.
Dp injection on days 0, 3, 5, 8, 10, 12, 15, and 17 of the study.
In vitro exposure of DINP to differentiated bone marrow cells and splenocytes continuous for 24 hours.
In vitro exposure of DINP + Dp to differentiated bone marrow cells continuous for 72 hours.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
In vivo DINP concentrations 0.15, 1.5, 15 or 150 mg/kg/day.
Dp concentration 5 ug.
In vitro DINP concentration 0.1, 1, 10, and 100 uM.
- No. of animals per sex per dose:
- n=12 for ear thickness.
n=5 for histological changes, eosinophil infiltration, mast cell degranulation
n=3 for bone marrow derived cultures
n=3 for splenocytes - Control animals:
- yes, concurrent vehicle
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: No data
FOOD CONSUMPTION: No data
FOOD EFFICIENCY: No data
WATER CONSUMPTION: No data
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: No data
CLINICAL CHEMISTRY: Limited data
- Time schedule for collection of blood: Sampled by cardiac puncture 24 hours after last injection of Dp on day 18
- Animals fasted: No
- IgG, IgE and histamine levels were examined
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No
OTHER:
Histologic evaluation of the right ears
Ear thickness
Number of infiltrated eosinophils and mast cells
Degranulation of mast cells
Quantitation of cytokines and chemokines the ear tissue
Cytokine production of bone marrow cells
Cytokine and antigen stimulated proliferation of splenocytes
- Statistics:
- Significance of variation was determined by one-way analysis of variance or Kruskal-Wallis analysis. Differences were analyzed using Dunnett's or Steel multiple comparison test. p<0.05 was considered significant.
Results and discussion
Effect levels
open allclose all
- Dose descriptor:
- LOEL
- Effect level:
- 15 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Remarks:
- DINP + Dp
- Sex:
- male
- Basis for effect level:
- other: Ear thinkness significantly increased. The authors noted that it was not dose dependent. The high dose 150 mg/kg/day was not significantly different.
- Dose descriptor:
- LOEL
- Effect level:
- 0.15 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Remarks:
- DINP + Dp
- Sex:
- male
- Basis for effect level:
- other: Decrease in expression of Eeotaxin and eotaxin-2
- Dose descriptor:
- NOEL
- Effect level:
- >= 150 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Remarks:
- DINP + Dp
- Sex:
- male
- Basis for effect level:
- other: infiltration of eosinophils
- Dose descriptor:
- NOEL
- Effect level:
- >= 150 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Remarks:
- DINP + Dp
- Sex:
- male
- Basis for effect level:
- other: Mast cell degranulation
- Dose descriptor:
- NOEL
- Effect level:
- >= 150 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Remarks:
- DINP + Dp
- Sex:
- male
- Basis for effect level:
- other: No effect on expression of IL-4, IL-5, IL-13, INF-gamma
- Dose descriptor:
- NOEL
- Effect level:
- >= 150 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Remarks:
- DINP + Dp
- Sex:
- male
- Basis for effect level:
- other: IgG and IgE levels
- Dose descriptor:
- NOEL
- Effect level:
- >= 100 other: uM
- Based on:
- test mat.
- Remarks:
- DINP
- Sex:
- not specified
- Basis for effect level:
- other: No effect on INF-gamma and IL-17 production in the cocultures of T cells and bone marrow cells.
- Dose descriptor:
- LOEL
- Effect level:
- 100 other: uM
- Based on:
- test mat.
- Remarks:
- DINP
- Sex:
- not specified
- Basis for effect level:
- other: Increase in Th2 chemokines TARC/CCL17 and MDC/CCL22 from bone marrow cells and an increase in CCR7 positive cells following in vitro exposure
- Dose descriptor:
- LOEL
- Effect level:
- 10 other: uM
- Based on:
- test mat.
- Remarks:
- DINP
- Sex:
- not specified
- Basis for effect level:
- other: Increase in CXCR4 positive bone marrow cells following in vitro exposure
- Dose descriptor:
- LOEL
- Effect level:
- 0.1 other: uM
- Based on:
- test mat.
- Remarks:
- DINP
- Sex:
- not specified
- Basis for effect level:
- other: MHCII positive bone marrow cells following in vitro exposure
- Dose descriptor:
- LOEL
- Effect level:
- 1 other: uM
- Based on:
- test mat.
- Remarks:
- DINP
- Sex:
- not specified
- Basis for effect level:
- other: Increase in CD86 positive bone marrow cells following in vitro exposure.
- Dose descriptor:
- LOEL
- Effect level:
- 1 other: uM
- Based on:
- test mat.
- Remarks:
- DINP
- Sex:
- not specified
- Basis for effect level:
- other: Increase in Dp-specific antigen presenting activity measured as cell proliferation.
- Dose descriptor:
- LOEL
- Effect level:
- 10 other: uM
- Based on:
- test mat.
- Remarks:
- DINP
- Sex:
- not specified
- Basis for effect level:
- other: Increase in IL-4 production in splenocytes following in vitro exposure
- Dose descriptor:
- LOEL
- Effect level:
- 0.001 other:
- Based on:
- test mat.
- Remarks:
- DINP
- Sex:
- not specified
- Basis for effect level:
- other: Increase in proliferation of splenocytes following in vitro exposure to DINP in the presence of Dp
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- DINP did not cause a dose dependent aggravation of AD-like skin lesions related to Do in NC/Nga mice. In vitro exposure to DINP enhanced the Th2 responses through activation of bone marrow cells and splenocytes although, this response occured at very high doses (100uM) or did not follow a clear dose response.
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