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EC number: 226-615-6 | CAS number: 5437-98-9
- 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
KEY STUDY (KEY_401_1997_Inveresk_14820), LD50 female rat (= most sensitive sex): 1755 mg/kg bw
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Well performed GLP and OECD guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Olac Ltd, Shaw's Farm, Blackthorn, Bicester
- Age at study initiation: 5-7 weeks old
- Weight at study initiation:
-- male , mean: 192 g
-- female, mean: 156 g
- Fasting period before study: overnight prior to dosing
- Housing: in suspended polypropylene cages with stainless steel grid tops and bottoms
- Diet (e.g. ad libitum): Rat and Mouse No. 1 Maintenance Diet, supplied by Special Diets Services, 1 Stepfield, Witham, Essex, CM8 3AD, ad libitum
- Water (e.g. ad libitum): Domestic mains quality drinking water, ad libitum
- Acclimation period: for at least 5 days prior to commencement of the study
ENVIRONMENTAL CONDITIONS
- Temperature (°C): maximum/minimum 20°C / 19°C
- Humidity (%): Although the mean humidity is outwith the range specified in the protocol, 55 % ± 15 %, it is considered not to have affected the outcome of the study.
- Air changes (per hr): 15-20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 h light/dark cycle - Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- 0.5%
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle:
Dose level / Conc.
1250 / 125 mg/ml
1500 / 150 mg/ml
1750 / 175 mg/ml
2000 / 200 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg bw - Doses:
- 1250, 1500, 1750 and 2000 mg/kg bw.
- No. of animals per sex per dose:
- 4 groups of 5 male and 5 female rats were dosed
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
-- Body weights were recorded weekly
-- Animals were observed daily up to 14 days
- Necropsy of survivors performed: yes
- Other examinations performed:
-- clinical signs: yes
-- body weight: yes
-- organ weights: no
-- necropsy: yes - Statistics:
- The intercept and slope values of the dose-response curve and hence the LD50, was estimated by applying the standard technique of maximum likelihood estimation to the probit model, as described in Finney (1971)
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 1 941 mg/kg bw
- Based on:
- test mat.
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 1 755 mg/kg bw
- Based on:
- test mat.
- Mortality:
- Dose / male / female
level
1250 / 0 of 5 / 0 of 5
1500 / 1 of 5 / 1 of 5
1750 / 1 of 5 / 1 of 5
2000 / 3 of 5 / 5 of 5 - Clinical signs:
- other: Clinical signs noted from Day 1 included ataxia, subdued behaviour, piloerection, prostration, tremors, hunched appearance, laboured breathing, increased salivation and a red discharge from the eyes and/or nose. Generally, the surviving animals recovered
- Gross pathology:
- None of the necropsy findings were considered to be related to treatment.
- Interpretation of results:
- Toxicity Category IV
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Under the conditions of the study, the median oral lethal doses (LD50s) for the test item in rats were estimated to be:
Males: 1941 mg/kg bw
Females: 1755 mg/kg bw
Males and Females: 1830 mg/kg bw
These findings meet criteria for a classification as acutely toxic according to REGULATION (EC) No 1272/2008:
Acute oral toxicity: Category 4 - Executive summary:
This study investigated the acute oral toxicity potential and median oral lethal dose (LD50) of the test substance, after a single oral gavage administration to rats.
In the study, 4 groups of 5 male and 5 female rats were dosed with 1250, 1500, 1750 and 2000 mg/kg bw. Dosing solutions were administered via oral gavage at a dose volume of 10 ml/kg bw. The vehicle was 0.5% Carboxymethylcellulose. The animals were observed daily for reaction to treatment for up to 14 days after dosing. Following premature death or sacrifice, on Day 15, the animals were subjected to necropsy. Body weights were recorded weekly.
At 1250 mg/kg bw there were no premature decedents, at 1500 mg/kg bw, one male was found dead on Day 2 and 1 female was killed humanely on Day 2. At 1750 mg/kg bw, one male and 1 female were found dead on Day 2 and at 2000 mg/kg bw, one male was found dead on Day 1, and another 2 males were killed humanely, one on Day 1 and another on Day 2, all 5 females were killed humanely, three on Day 1 and two on Day 2.
Clinical signs noted from Day 1 included ataxia, subdued behaviour, piloerection, prostration, tremors, hunched appearance, laboured breathing, increased salivation and a red discharge from the eyes and/or nose. Generally, the surviving animals recovered by Day 4.
Body weight performance was considered to have been satisfactory.
None of the necropsy findings were considered to be related to treatment.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 1 755 mg/kg bw
- Quality of whole database:
- reliable
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Discussion of classification or non-classification
Testing of p-acetoacetanisidide for acute oral toxicity revealed an LD50 value of 1755 mg/kg bw. Acetoacetanisidid congeners are suspected to form methemoglobin in man. The absence of definite indications for MetHb formation in this study might be attributed to the relative insensitivity of the rat to methemoglobinaemia inducing toxicants as compared to cat or man. Therefore and following precautionary principles p-acetoacetanisidide is assumed to be a MetHb forming agent in man.
Read across hypothesis / justification
The purpose of this assessment is to provide justification for read across in order to predict the skin sensitizing potential and MetHb forming properties of the target substance p-acetoacetanisidide (5437-98-9) based on available date coming from the source substances o-acetoacetanisidide (92-15-9).
Source and target substance are position isomeric acetoacetanisidides without any other structural differences. Both substances are characterized by similar physical-chemical properties and available data show a consistent toxicity profile. Therefore, it can reasonably be assumed, that acute toxicity, MetHb forming properties and the possible skin sensitizing potential of p-acetoacetanisidide and o-acetoacetanisidide are likely to be similar.
Data Matrix
|
Target Chemical |
Source Chemical |
CAS # |
5437-98-9 |
92-15-9 |
CHEMICAL NAME |
p-acetoacetanisidide |
o-acetoacetanisidide |
Other name |
4'-methoxyacetoacetanilide N-Acetoacetyl-p-anisidine |
2’-methoxyacetoacetanilide N-Acetoacetyl-o-anisidine |
Structure |
Not displayed |
Not displayed |
Physical and chemical properties |
|
|
Purity |
99.4 % |
99.86 % (w/w) |
Physical state |
solid |
solid |
Melting point |
116°C |
82°C |
Decomposition Temp. |
>450°C |
>450°C |
Density |
1.242 g/cm3 |
1.31 g/cm3 |
Vapour pressure (calculate) |
< 0.001 Pa at 20°C |
0.000036 Pa at 20°C |
Log Pow (at 23°C) |
|
0.91 |
Water solubility |
0.1 – 1 g/L |
3.24 g/L |
Solubility in organic solvents (n-octanol) |
> 1 g/L |
> 1 g/L |
Solubility in organic solvents (DMSO) |
> 1 g/L |
> 1 g/L |
Environmental fate and pathways |
|
|
Biodegradation |
OECD Guideline 302 B: > 97 % after 20 days |
OECD Guideline 301 F: Readily biodegradable after 28 days |
Ecotoxicological Information |
|
|
Acute toxicity fish |
LC50: 331.7 mg/L LC0: 220.0 mg/L LC100: 500.0 mg/L |
LC50: 332 mg/L LC0: 220 mg/L LC100: 500 mg/L |
Toxicological Information |
|
|
Acute Toxicity, oral, rat |
LD50: 1755 mg/kg bw |
LD50: 1535 mg/kg bw |
Acute Toxicity, oral, cat |
Read across prediction: MetHb formation |
MetHb formation |
Skin irritation |
Not irritating |
Not irritating |
Eye irritation |
Not irritating |
Not irritating |
Skin sensitization (LLNA) |
Read across prediction: Not sensitising |
Not sensitising |
Genetic toxicity in vitro (AMES) |
negative |
negative |
Justification for selection of acute toxicity – oral endpoint
Most reliable study available
Justification for classification or non-classification
The LD50 value of 1755 mg/kg bw meets criteria for classification as acutely toxic Cat 4 according to REGULATION (EC) No 1272/2008.
Since formation of methemoglobin in humans is assumed and systemic availability for all three exposure routs is not unlikely a classification as Cat 4, H302/H312/332 irrespective of the routes tested is warranted.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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