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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 value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- - Rationale for reliability of the study report related to the source substance: Well performed OECD and GLP guideline study (original reliability: 1) - Read across hypothesis: 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. Therfore, it can be reasonably assumed, that acute toxicity, MetHb forming properties and the possible skin sensitizing potential of p-Acetoacetanisidide and o-Acetoacetanisidide are likely to be similar.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- other: CBA/CaOlaHsd
- Sex:
- female
- Details on test animals and environmental conditions:
- Number of animals for the pre-test (non-GLP): 2 females
Number of animals for the main study: 16 females
Number of animals per group: 4 females (nulliparous and non-pregnant)
Number of test groups: 3
Number of control (vehicle) group: 1
Age: 8 - 12 weeks (beginning of acclimatization)
Feed: pelleted standard diet, ad libitum
Water: tap water, ad libitum,
Environment: temperature: 22 + 3°C
relative humidity: approx. 30-80%
artificial light: 6.00 a.m. - 6.00 p.m. - Vehicle:
- dimethylformamide
- Concentration:
- 5.0, 10.0, 25.0 % (w/v)
- No. of animals per dose:
- 4
- Details on study design:
- Administration and exposure: For determination of the highest non-irritant and technically applicable test item concentration, a non-GLP pretest was performed on two mice with concentrations of 2.5, 5, 10, and 25 % (w/v). The top dose of the test item is the highest technically achievable concentration whilst avoiding systemic toxicity and excessive local irritation. Four female mice were treated with different concentrations of the test item and
vehicle alone by topical application at the dorsum of each ear lobe (left and right) on three consecutive days. Five days after the first topical application, the mice were intravenously injected into a tail vein with radio-labelled thymidine (3H-methyl thymidine). Five hours after intravenous injection, the mice were sacrificed and the draining auricular lymph nodes excised and pooled per group. Single cell suspensions of lymph node cells were prepared from pooled lymph nodes which were subsequently washed and incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of 3H-methyl thymidine measured in a ß-scintillation counter.
Data and Observations: The proliferative response of lymph node cells is expressed as the number of radioactive disintegrations per minute per lymph node and as the ratio of 3HTdR incorporated into lymph node cells of test lymph nodes relative to that recorded for control lymph nodes (stimulation index). In addition to the sensitising reactions the following observations and data were recorded: mortality/viability once daily, body weights prior to the first application and prior to necropsy, clinical signs (local/systemic) daily from start to the termination of in-life phase. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- A statistical analysis was conducted for assessment of the dose-response relationship, and the EC3 value was calculated according to the equation
EC3 = (a-c) [(3-d)/(b-d)] + c
where EC3 is the estimated concentration of the test item required to produce a 3-fold increase in draining lymph node cell proliferative activity; (a, b) and (c, d) are respectively the co-ordinates of the two pair of data lying immediately above and below the S.I. value of 3 on the local lymph node assay dose response plot. - Positive control results:
- Results of the Positive Control Study performed in April 2004
S.I of alpha-Hexylcinnamaldehyde
5 %: 1.9
10 %: 6.1
25 % : 11.5
EC3 = (a-c) [(3-d)/(b-d)] + c = 6.3% (w/v)
Results of the Positive Control GLP Study performed in October 2004
S.I of alpha-Hexylcinnamaldehyde
5 %: 2.0
10 %: 3.0
25 % : 4.9
EC3 = (a-c) [(3-d)/(b-d)] + c = 9.9 % (w/v) - Parameter:
- SI
- Remarks on result:
- other: 5.0 % (w/v): 0.94 10.0 % (w/v): 0.90 25.0 % (w/v): 1.16
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: 0 % (w/v): 3337 5.0 % (w/v): 3126 10.0 % (w/v): 2993 25.0 % (w/v): 3876
- Interpretation of results:
- not sensitising
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- The test item Acetoacet-o-Anisidide TTR was found to be not a skin sensitiser in this assay.
- Executive summary:
In the study the test item Acetoacet-o-Anisidide TTR dissolved in DMF was assessed for its possible contact allergenic potential in accordance with OECD test guideline 429, adopted 2002 -04 -24.
For this purpose a local lymph node assay was performed using test item concentrations of 5.0, 10.0, and 25.0 %.
The animals did not show any clinical signs during the course of the study and no cases of mortality observed.
In this study Stimulation Indices (S.I.) of 0.94, 0.90, 1.16 were determined with the test item at concentrations of 5.0, 10.0, and 25.0 % (w/v) in DMF.
The test item Acetoacet-o-Anisidide TTR was found to be not a skin sensitiser in this assay.
Reference
Calculation and Results of individual Data
Vehicle: DMF
Test item concentration % (w/v) | Group | Measurement DPM | Calculation | Result | ||
DPM-BG a) | number of lymph nodes | DPM per lymph node b) | S.I. | |||
- | BG I | 0.0 | - | - | - | - |
- | BG II | 0.0 | - | - | - | - |
- | CG I | 3336.7 | 3336.7 | 8 | 417.1 | |
5.0 | TG 2 | 3126.3 | 3126.3 | 8 | 390.8 | 0.94 |
10.0 | TG 3 | 2992.5 | 2992.5 | 8 | 374.1 | 0.90 |
25.0 | TG 4 | 3876.1 | 3876.1 | 8 | 484.5 | 1.16 |
BG = Background (1 ml 5% trichloroaceticacid) in duplicate
CG = Control Group
TG = Test Group
S.I. = Stimulation Index
a) = The mean value was taken from the figures BG I and BG II
b) = Since the lymph nodes of the animals of a dose group were pooled, DPM/node was determined by dividing the measured value by the number of lymph nodes pooled
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
Discussion of classification or non-classification
Testing of o-acetoacetanisidide for skin sensitising properties in the LLNA revealed negative results. Following read across principles p-acetoacetanisidide is predicted not to be a skin sensitizer.
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)
0.85
0.91
Water solubility
2.6 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
Migrated from Short description of key information:
Read across (RA_92-15-9_KEY_429_2004_RCC_850803) LLNA:
Stimulation Indices (S.I.) of 0.94, 0.90, 1.16 were below the threshold of >/= 3 for a positive result and thus lead to the conclusion "not sensitising".
Justification for selection of skin sensitisation endpoint:
most reliable study available from a substance with similar structure
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Stimulation Indices found were below 3 (threshold for a positive result >/= 3) and thus don't meet criteria for classification as skin sensitizing according to REGULATION (EC) No 1272/2008.
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