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EC number: 700-954-4 | CAS number: 1338-23-4
- 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
Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- sub-chronic toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- disregarded due to major methodological deficiencies
- Study period:
- 1987-07-06 to 1987-10-07
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- significant methodological deficiencies
- Remarks:
- no positive control, no OECD and EU guideline was followed; no GLP stated
Data source
Reference
- Reference Type:
- secondary source
- Title:
- Unnamed
- Year:
- 1 993
- Report date:
- 1993
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- NA
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 2-[(2-hydroperoxybutan-2-yl)peroxy]butane-2-peroxol; butane-2,2-diperoxol
- EC Number:
- 700-954-4
- Cas Number:
- 1338-23-4
- Molecular formula:
- Mixture of C4H10O4 and C8H18O6
- IUPAC Name:
- 2-[(2-hydroperoxybutan-2-yl)peroxy]butane-2-peroxol; butane-2,2-diperoxol
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: F344/N
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Taconic farms, Germantown, NY
- Age at study initiation: 6 weeks
- Housing: individually
- Diet (e.g. ad libitum): NIH-07 Open Formula Pellets (Zeigler Brothers, Inc, Gardners, PA) ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 4 weeks
ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 23.89 °C
- Humidity: 31 -72 %
- Air changes (per hr): 12 to more than 20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours per day
Administration / exposure
- Type of coverage:
- not specified
- Vehicle:
- other: DMP
- Details on exposure:
- Methyl-ethylketone peroxide in DMP was diluted with DMP to achieve 0.3, 1.0, 3.0, 10.0, and 30.0% (w/w) solutions. Groups of 10 animals were dosed at a volume of 0.3 mL per rat.
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- once a day for 5 days per week, except holidays, for a total of 13 weeks, plus 2 consecutive dose days
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 other: mg/animal
- Remarks:
- untreated and DMP control
- Dose / conc.:
- 1.07 other: mg/animal
- Dose / conc.:
- 3.57 other: mg/animal
- Dose / conc.:
- 10.7 other: mg/animal
- Dose / conc.:
- 35.7 other: mg/animal
- Dose / conc.:
- 107 other: mg/animal
- No. of animals per sex per dose:
- 10
- Control animals:
- yes
- Details on study design:
- Doses for the 13-week studies were based on the results of the 2-week studies (doses of 0, 50.6, 101.3, 202.5, 405 or 810 mg MEKP/kg body weight). In the 13-week studies, methyl-ethylketone peroxide in DMP was diluted with DMP to achieve 0.3, 1.0, 3.0, 10.0 and 30.0% (w/w) solutions. All groups were dosed at a volume of 0.3 mL per rat. Methyl-ethylketone peroxide was administered topically to the clipped dorsal skin of rats.
- Positive control:
- no positive control
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS:No data
DETAILED CLINICAL OBSERVATIONS:No data
DERMAL IRRITATION (if dermal study): Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION: No data
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: No data
CLINICAL CHEMISTRY:No data
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: No data - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Other examinations:
- - Vaginal cytology and sperm morphology evaluations were performed on rats during the 13-week studies.
- Sperm motility was evaluated at necropsy. - Statistics:
- Two approaches were employed to assess the significance of pairwise comparisons between dosed and control groups in the analysis of continuous variables. Organ and body weight dat, which are approximately normally distributed, were analyzed using the parametric multiple comparisons procedures of Williams (1971, 1972) and Dunnett (1955). Data that typically have skewed distributions were analyzed using the nonparametric multiple comparisons methods of Shirley (1977) or Dunn (1964). Jonckheere`s test (Jonckheere,1954) used to assess the significance of dose-response trends and to determine whether a trend-sensitive test (Williams, Shirley) was more appropriate for pairwise comparisons than a test capable of detecting departures from monotonic dose response (Dunnett, Dunn). If the P-value from Jonckheere`s test was greater than or equal to 0.10, Dunn`s or Dunnett`s test was used rather than Shirley`s or Williams`test.
The outlier test of Dixon and Massey (1951) was employed to detect extreme values. No value selected by outlier test was eliminated unless it was at least twice the next largest value or at most half of the next smallest value. The extreme values chosen by the statistical test were subject to approval by NTP personnel. In addition, values indicated by the laboratory report as being inadequate due to technical problems were eliminated from the analysis.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Three females in the high-dose (107 mg/animal) group died or were killed moribund during week 1 of the study. All animals in the 35.7 mg/animal group and all remaining animals in the 107 mg/animal group were killed during week 8 due to the severity of the skin lesions at the site of methyl-ethylketone peroxide application.
- Dermal irritation:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Three females in the high-dose (107 mg/animal) group died or were killed moribund during week 1 of the study. All animals in the 35.7 mg/animal group and all remaining animals in the 107 mg/animal group were killed during week 8 due to the severity of the skin lesions at the site of methyl-ethylketone peroxide application.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- The mean final body weight and mean body weight gain for untreated controls were greater than the corresponding values for DMP controls.
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- There were statistically significant increases in the relative weights of several organs, primarily in males in the 10.7 mg/animal group.
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Additional observations in many of the early-death rats receiving 107 mg/animal were "scar tissue" at the application site and enlarged spleens. In those animals that survived for 13 weeks, significant necropsy observations were limited to thick, crusty skin at the application site in serveral animals from the 10.7 mg/animal group. Necrosis varied in severity from diffuse involvement of both dermis and epidermis at higher concentrations to focal ulcerations of the epidermis, which occurred more frequently in the 10.7 mg/animal group. An associated inflammatory reaction consisted of both surface exudation and dermal inflammation. Typically, a coagulum of surface exudate containg serous fluid and neutrophils was seen overlying denuded or regenerative areas, with necrotic skin tissue admixed in more severe cases. The dermal reaction was subjacent to ulcerated, sloughed, or regenerateted epidermis and was collectively termed "chronic-active" to be inclusive of varied patterns, including primarily neutrophilic, fibrovascular, granulomatous, or fibrotic reactions.
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- < 1.07 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: local tissue damage
Target system / organ toxicity
- Key result
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- None of those studies are suitable for risk assessment of systemic toxicity after dermal contact, as severe local tissue (skin) damage was noted due methyl-ethylketone peroxide`s corrosively.
- Executive summary:
Methyl-ethylketone peroxide (in DMP) was tested in two dermal 90-day repeated dose toxicity studies to mice and rats (Reliability: 3). None of those studies are suitable for risk assessment of systemic toxicity after dermal contact, as severe local tissue (skin) damage was noted due methyl-ethylketone peroxide`s corrosively. Consequently, systemic toxicity after dermal application is extrapolated from oral studies by route to route extrapolation according to the guidance documents. Performing of repeated dermal toxicity studies is not in line with animal welfare ideas. Therefore a new 90 day oral toxicity study is proposed to gain more information on the repeated dose toxicity of methyl-ethylketone peroxide.
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