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EC number: 202-267-0 | CAS number: 93-68-5
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Remarks:
- combined repeated dose and reproduction / developmental screening
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1999
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: The study was conducted and reported according to the OECD combined repeat dose and reproductive/developmental toxicity test 422 and principles of GLP.
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 003
- Report date:
- 2003
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 2'-methylacetoacetanilide
- EC Number:
- 202-267-0
- EC Name:
- 2'-methylacetoacetanilide
- Cas Number:
- 93-68-5
- Molecular formula:
- C11H13NO2
- IUPAC Name:
- N-(2-methylphenyl)-3-oxobutanamide
- Details on test material:
- TS: Mitsuboshi Chemical Co., Ltd.
Purity: 99.9%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ORGANISMS
Age: 9 weeks for male, 8 weeks for female
Weight at initiation: 343-391 g for male, 211-241 g for female
Number of animals: 10 per sex per dose
Pellet food and water: free take
MATING PROCEDURE
one by one in each cage
(All of those 10 pairs had finished mating by Day 4.)
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: 1% Methylcellulose water solution
- Details on oral exposure:
- ADMINISTRATION
Vehicle: 1% methylcellulose water solution, 0.5mL/100g body weight
Type of administration: gavage, once a day
Duration of administration:
male; 44 days (including 14 days before mating)
female: 41-45 days (from 14 days before mating to 3 days after
parturition) - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- no data available.
- Duration of treatment / exposure:
- males: 44days, females: from 14days before mating to Day 3 of lactation
(41 - 45days) - Frequency of treatment:
- one administration per day
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 8, 25, 80, 250 mg/kg/day
Basis:
other: 1% Methylcellulose water solution
- No. of animals per sex per dose:
- 10 animals per sex per dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- AAOT was administered to Sprague-Dawley rats (10/sex/dose) at doses of 0, 8, 25, 80, 250 mg/kg/day
by oral gavage. The dosing period was 44 days for males and 41 - 45 days (including 14 days before mating
and 3 days after pregnancy) for females. - Positive control:
- No data available.
Examinations
- Observations and examinations performed and frequency:
- CLINICAL OBSERVATIONS AND FREQUENCY
Clinical signs and mortality: every day
Body weight: once a week, and the time of termination
Food consumption: at every body weight check (24hr consumption)
Water consumption: not checked - Sacrifice and pathology:
- Organs: by male after extraction of blood, and by female at day 4 after (estimated) pregnant;
for weight check; brain, liver, kidney, spleen, heart, thymus, thyroid, pituitary, adrenals, testes and epididymides
for observation; above mentioned ones plus, lung, stomach, bladder,
medulla, spinal cord, sciatic nerve, etc. - Other examinations:
- HISTOPATHOLOGICAL OBSERVATIONS
Urinalysis: by male at Day 39 - 43; pH, blood, protein, ketones, bilirubin, urobilinogen, specific gravity, deposit and appearance
Hematology: by male at day 45 (stopped feeding at 17:00 on the day before terminal kill); erythrocyte count, hemoglobin, hematocrit, MCV,
MCH, mean corpuscular hemoglobin(MCHC), leukocyte count, platelet count, reticulocyte count, Heinz-body and methemoglobin
Blood biochemical: Same sample as hematology was used.; total protein, albumin, albumin/globulin(A/G) ratio, glucose, triglyceride,
total cholesterol, total bilirubin, nitrogen of urea, creatinine, GOT, GPT, gamma-GTP, lactate dehydrogenase(LDH),
alkaline phosphatase, cholin esterase, calcium, phosphate, sodium and potassium - Statistics:
- No data available.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No change in mortality and behavior were observed in any groups
- Mortality:
- no mortality observed
- Description (incidence):
- No change in mortality and behavior were observed in any groups
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No toxicological effect was observed in any groups
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No toxicological effect was observed in any groups
- Food efficiency:
- not examined
- Description (incidence and severity):
- No findings
- Water consumption and compound intake (if drinking water study):
- not examined
- Description (incidence and severity):
- not checked
- Ophthalmological findings:
- not examined
- Description (incidence and severity):
- not checked
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- see table under section "any other information on results inc. tables"
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- see table under section "any other information on results inc. tables"
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Male: Increases of specific gravity was observed in 250mg/kg group. It's likely within normal range, and no related change was observed in another check items.
- Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- no findings
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- see table under section "any other information on results inc. tables"
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- see table under section "any other information on results inc. tables"
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- see table under section "any other information on results inc. tables"
- Histopathological findings: neoplastic:
- no effects observed
- Description (incidence and severity):
- No findings
- Details on results:
- In the 250 mg/kg/day group the following effects were observed: decreases of erythrocyte count, hemoglobin concentration
and hematocrit value in males; increases of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH),
reticulocyte count, methemoglobin concentration, bilirubin and potassium in males; increase of pituitary weight in males;
increases of weight of spleen, weight of liver, extramedullary hematopoiesis and congestion in spleen in both sexes; and
blackening of spleen and hemosiderin deposit in liver and spleen in both sexes.
In the 80 mg/kg/day group the following effects were observed: decrease of erythrocyte count and increases of MCV and
bilirubin in male; increase of congestion in spleen in female; and blackening of spleen and hemosiderin deposit in liver and spleen in both sexes.
No changes in mortality, behavior or toxic effect on the body weight and food consumption were observed in any groups.
Increase of specific gravity of urine was observed in males of the 250 mg/kg group. However no related changes were observed in other findings.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 25 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: see 'Remark'
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
HEMATOLOGICAL AND BLOOD CHEMICAL FINDINGS IN MAL
Dose (mg/kg/day) |
0 |
8 |
25 |
80 |
250 |
erythrocyte count: mean corpuscular volume (MCV): hemoglobin concentration: hematocrit value: mean corpuscular hemoglobin (MCH): reticulocyte count: methemoglobin concentration: Heinz-body in erythrocytes: bilirubin: potassium: |
-
- - -
- - - - - - |
-
- - -
- - - - - - |
-
- - -
- - - - - - |
D
I - -
- - - - - - |
D
I D D
I I I O I I |
-: normal or nothing, I: increased, D: decreased, O: observed
HISTOPATHOLOGICAL FINDINGS, ETC. IN MALE
Dose (mg/kg/day) |
0 |
8 |
25 |
80 |
250 |
blackening of spleen: enlargement of spleen: weight of spleen: weight of pituitary: weight of liver: hemosiderin deposit in liver and spleen: extramedullary hematopoiesis: congestion in spleen: eosinophilic body in tuble of kidneys: |
- - - - -
- - -
- |
- - - - -
- - -
- |
- - - - -
- - -
- |
O I - - -
O - -
- |
O - I I -
O I I
I |
-: normal or nothing, I: increased, D: decreased, O: observed
HISTOPATHOLOGICAL FINDINGS, ETC. IN FEMALE
Dose (mg/kg/day) |
0 |
8 |
25 |
80 |
250 |
blackening of spleen: enlargement of spleen: weight of spleen: weight of pituitary: weight of liver: hemosiderin deposit in liver and spleen: extramedullary hematopoiesis: congestion in spleen: eosinophilic body in tuble of kidneys: |
- - - - -
- - -
- |
- - - - -
- - -
- |
- - - - -
- - -
- |
O - - - -
O - I
- |
O O I - I
O I I
- |
-: normal or nothing, I: increased, D: decreased, O: observed
Applicant's summary and conclusion
- Conclusions:
- Toxicological effects and the target organs are hemolytic anemia and the related changes on the blood, spleen, liver and kidney,
including male kidney (increasing of eosinophilic bodies) and female liver (increasing of the weight).
The NOAEL for repeat dose toxicity to rats is 25 mg/kg/day in both sexes. - Executive summary:
The Combined Repeat Dose and Reproduction/Developmental Toxicity Screening Test (MHW Japan 1999b) was well conducted according to OECD TG422, following GLP and published in the OECD SIDS Dossier in year 2003.
The test results are described as follows. AAOT was administered to Sprague-Dawley rats (10/sex/dose) at doses of 0, 8, 25, 80, 250 mg/kg/day by oral gavage. The dosing period was 44 days for males and 41 - 45 days (including 14 days before mating and 3 days after pregnancy) for females.
The blood findings in males in the 250 mg/kg/day group were: decreases of erythrocyte count, hemoglobin concentration and hematocrit value, also increases of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), reticulocyte count, methemoglobin concentration, bilirubin and potassium. Other findings in the 250 mg/kg/day group were: increase of pituitary weight in males; increases of weight of spleen, weight of liver, extramedullary hematopoiesis and congestion in spleen, also blackening of spleen and hemosiderin deposit in liver and spleen in both sexes. The blood findings in males in the 80 mg/kg/day group were: decrease of erythrocyte count and increase of MCV and bilirubin. Other findings in the 80 mg/kg/day group were: increase of congestion in spleen in females, blackening of spleen and hemosiderin deposit in liver and spleen in both sexes. In all dose groups up to 250 mg/kg/day, no changes in mortality, behavior or toxic effects on the body weight and food consumption were observed in any sexes. No toxic effects were observed in any dose groups up to 25 mg/kg/day.
The NOAEL for repeat dose toxicity to rats is 25 mg/kg/day in both sexes.
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