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EC number: 248-948-6 | CAS number: 28299-41-4
- 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
Endpoint summary
Administrative data
Description of key information
10 male and female rats each were administered orally daily doses of the
test substance of 0 (control), 550, 1650 or 5000 ppm (ca. 0, 45, 132 or
425 mg/kg bw/d - male rats; ca. 0, 56, 174 or 604 mg/kg bw/d - female
rats) via diet for a period of 13 weeks. Mortality, clinical signs,
food/water intake, body weights were recorded and hematological,
clinical biochemistry determinations, and gross necropsy, histopathology
were performed.
Until the end of the study no difference in the appearance and the
behaviour of the treated and control animals was evident. Food and water
intake was not affected in any dose group. The body weight gain was
slightly decreased in male animals in the highest dose group (5000 ppm;
ca. 10%). The mortality was not affected in any dose group. No adverse
effects were evident from the hematological examinations at any dose
group. In the highest dose group the liver weights were increased, but
no histopathological findings of the liver or induction of cytochrom
P-450 or the N- and O-demethylases were observed. The pathological and
histopathological examinations revealed no damage on other organs or
tissues. Therefore no adverse effects up to and including 1650 ppm were
found.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: guideline study according OECD TG 408
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Principles of method if other than guideline:
- 10 male and female rats each were administered orally daily doses of the test substance of 0 (control), 550, 1650 or 5000 ppm (ca. 0, 45, 132 or 425 mg/kg bw/d - male rats; ca. 0, 56, 174 or 604 mg/kg bw/d - female rats) via diet. mortality, clinical signs, food/water intake, body weights were recorded and hematological, clinical biochemistry determinations, and gross necropsy, histopathology were performed
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Male + female Wister rats, SPF, at start of the experiment ca. 5-6 weeks old, average weight 77 g males, and 75 g females , husbandry: standardised conditions, single cage (makrolon type II).
- Route of administration:
- oral: feed
- Vehicle:
- other: Altromin flour
- Details on oral exposure:
- Feed and water were available ad-libitum.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Content of test substance and formulation was determined.
- Duration of treatment / exposure:
- 13 weeks.
- Frequency of treatment:
- Daily.
- Remarks:
- Doses / Concentrations:
550, 1650 resp. 5000 ppm
Basis:
nominal in diet - Remarks:
- Doses / Concentrations:
ca. 45, 132 or 425 mg/kg bw/d (male rats)
Basis:
nominal in diet - Remarks:
- Doses / Concentrations:
ca. 56, 174 or 604 mg/kg bw/d (female rats)
Basis:
nominal in diet - No. of animals per sex per dose:
- 10 males + 10 females/dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: no
- Positive control:
- no
- Observations and examinations performed and frequency:
- Animals were inspected twice daily (daily on weekends and holidays) and clinical signs recorded. ophthalmological examinations were done on 10 male and 10 female animals of the control and 5000 ppm group at the beginning and the end of the trial. body weight of the animals was determined before the test and weekly afterwards. food and water intake was determined weekly. laboratory tests on blood samples were accomplished after 1 and 3 months.
- Sacrifice and pathology:
- Animals were sacrificed after 3 months and organs/tissues dissected. Histopathology was carried out on the preserved organs and tissues.
- Other examinations:
- no further data
- Statistics:
- According Mann et al. (Ann. Math. Stat. 18, 50 (1947) and Wilcoxon (Biometrics 1, 80 (1948).
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Ophthalmological findings:
- effects observed, treatment-related
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 132 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Reduced body weight gain/ increased liver weights and influence on the metabolism of proteins
- Dose descriptor:
- NOAEL
- Effect level:
- 174 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: Increased liver weights and influence on the metabolism of proteins
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 425 mg/kg bw/day (nominal)
- System:
- hepatobiliary
- Organ:
- liver
- Treatment related:
- yes
- Dose response relationship:
- yes
- Executive summary:
Method: 10 male and female rats each were administered orally daily doses of the test substance of 0 (control), 550, 1650 or 5000 ppm (ca. 0, 45, 132 or 425 mg/kg bw/d - male rats; ca. 0, 56, 174 or 604 mg/kg bw/d - female rats) via diet. Mortality, clinical signs, food/water intake, body weights were recorded and hematological, clinical biochemistry determinations, and gross necropsy, histogpathylogy were performed.
Result: the NOAEL = 132 mg/kg bw/day (male rats), NOAEL = 174 mg/kg bw/day (female rats)
Reference: Kroetlinger, Schilde (Bayer AG), 1988
Reference
All dose groups: no changes of the hematological,
pathological-anatomic, histopathological or ophthalmologic parameters.
5000 ppm : in the males body weight gain reduced by ca. 10 %; in both
sexes liver weights were increased, but Cytochrome P-450 and N-
or O-Demethylases not induced;
Clinical-chemical investigations: indications of a treatment-related influence on the metabolism of proteins (increased content of albumin
and decreased content of globulin in the serum) and indications of a slight cholestasis (increased activities of the alkaline phosphatase in the plasma).
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 132 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- GLP guideline study
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Ditolyl ether was tolerated up to and including 1650 ppm when given via the feed without adverse symptoms.
Therefore is the NOAEL = 132 mg/kg bw/day (male rats) and the NOAEL = 174 mg/kg bw/day (female rats).
No studies for dermal or inhalative repeated dose are available - by oral application ditolyl ether is of low systemic toxicity. Furthermore, in the toxicokinetic studies with diphenylether - as a surrogate for ditolylether - was demonstrated to be quantitatively absorbed and eye irritation studies showed no potential for irritation of mucous membranes. Therefore, a repeated dose dermal or inhalative study is not required and cannot be justified either scientifically or in terms of animal welfare.
Justification for selection of repeated dose toxicity via oral
route - systemic effects endpoint:
13 w key study is used
Justification for classification or non-classification
A classification is not required as no serious or irreversible effects in an oral subchronic study were seen up to and including 1650 ppm (132 mg/kg bw/day).
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