Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 205-516-1 | CAS number: 141-97-9
- 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
Key value for chemical safety assessment
Effects on fertility
Description of key information
Short description of key information:
The study was performed 1999 as
GLP-study according to OECD-guideline no. 421. The administration route
was oral gavage. Ten animals were treated per sex and dose groups
resulting in a total of 80 animals. Dose levels were 0, 50, 225 and 1000
mg/kg/day. There were no effects on clinical signs, mortality, body
weights, food consumption. There were minor effects in the highest dose
groups on reproduction. However, these findings were considered to be
not relevant and therefore, a NOEL of 1000 mg/kg/day was established.
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- November 1998 - June 1999
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Specific details on test material used for the study:
- - Name of test item in the report: Acetoacetic acid ethyl ester
- Appearance: colorless liquid - Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Deutschland GmbH, Sulzfeld/Germany
- Adaptation: 5 days
- Age at study initiation: 68-72 days
- Weight at study initiation: Males: 264-287 g; Females: 195-216 g
- Housing: single housing except mating period, where 1 male & 1 female was placed per cage - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- The test substance was suspended in tap water and was administered orally at a constant volume of 10 ml/kg b.w. 7 days per week during the following periods:
- males: 2 weeks prior to mating, during the mating period and approx. 2 weeks post mating at least until the minimum total dosing period of 28 days had been completed (up to and including the day before sacrifice).
- females: throughout the study beginning 2 weeks prior to mating and continuing up to, and including, day 3 post-partum or the day before sacrifice.
The control animals received 10 ml tap water/kg b.w./day in the same manner. The test substance preparations were freshly prepared every day. The daily dose of the test substance was adjusted to the animal's body weight daily. - Details on mating procedure:
- 4 groups of sexually mature male and female rats were randomly paired for mating. Mating was monogamous: 1 male and 1 female animal were placed in one cage during the dark period. The female was placed with the same male until pregnancy occurred or two weeks had elapsed. Each morning the females were examined for the presence of sperm. If findings were negative, mating was repeated. The day of conception (day 0 of pregnancy) was considered to be the day on which sperm was found. In case pairing was unsuccessful, re-mating of females with proven males of the same group was considered. This procedure was repeated until at least 8 pregnant dams were available for each group.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Stability/homogeinity was analyzed by gas chromatography (GC)
- Intrument: HP 5890 Series II (Hewlett-Packard)
- Autosampler: HP 7673 (Hewlett-Packard)
- Integrator: HP 3396 Series II linked to a host computer with Peak96 software (Hewlett-Packard)
- Column: HP-1 (100% methyl silicone), 25 m, 0.32 mm i.d., 0.52 pm film (Hewlett-Packard)
- Injector: 220°C
- Detector: FID, 280°C
- Oven: hold 50°C (2 min.), heat up to 150°C (20°C/min.), hold 150°C (2 min.)
- Carrier gas: Helium, 2.5 ml/min.
- Split: 51 ml/min.
- Septum purge: 2.6 ml/min.
- Retention times: Ethyl acetoacetate: approx. 4.7 min. / Internal standard: approx. 3.9 min.
The test item was found to be stable in the vehicle at room temperature. - Duration of treatment / exposure:
- The test substance was suspended in tap water and administered orally at a constant volume of 10 ml/kg b.w. 7 days per week during the following periods:
- males: 2 weeks prior to mating, during the mating period and approx. 2 weeks post mating at least until the minimum total dosing period of 28 days had been completed (up to and including the day before sacrifice).
- females: throughout the study beginning 2 weeks prior to mating and continuing up to, and including, day 3 post-partum or the day before sacrifice.
The control animals received 10 ml tap water/kg b.w./day in the same manner. The test substance preparations were freshly prepared every day. The daily dose of the test substance was adjusted to the animal's body weight daily. - Frequency of treatment:
- 7 days per week
- Details on study schedule:
- - Start of the study (adaptation period): November 25th, 1998
- 1st dosing: November 30th, 1998
- Study termination in-life phase males: December 28th, 1998 / females: January 21st, 1999 - Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 50 mg/kg bw/day (nominal)
- Dose / conc.:
- 225 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 80 animals were used in this study:
- control group (0 mg/kg/day): 10 animals/sex
- low dose group (50 mg/kg/day): 10 animals/sex
- mid dose group ( 225 mg/kg/day): 10 animals/sex
- high dose group (1000 mg/kg/day): 10 animals/sex - Control animals:
- yes, concurrent vehicle
- Details on study design:
- Rationale for dose selection was based on toxicological data already available for this substance.
- Positive control:
- no positive control tested
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: At least once daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: At least once daily
BODY WEIGHT: Yes
- Time schedule for examinations: At first day of dosing, weekly thereafter and at study termination.
FOOD CONSUMPTION: Yes
- Food consumption for each animal determined: Weekly
WATER CONSUMPTION: Yes
- Time schedule for examinations: Daily monotoring of drinking water bottles
Individual animals were observed at least once daily for any signs of behavioural
changes, reaction to treatment or illness. In addition, the nature of the faeces was a checked daily.
Immediately after administration any signs of illness or reaction to treatment were
recorded. In case of changes the animals were observed until the symptoms disappeared.
In addition, animals were checked regularly throughout the working day
from 7.30 a.m. to 4.30 p.m..
On Saturdays and Sundays animals were checked regularly from 8.00 a.m. to 12.00
a.m. with a final check performed at approximately 4.00 p.m..
Dated and signed records of appearance, change and disappearance of clinical signs
were maintained on clinical history sheets for individual animals. - Oestrous cyclicity (parental animals):
- no details reported
- Sperm parameters (parental animals):
- no data
- Litter observations:
- The duration of gestation of the female rats was recorded and was calculated from day 0 of pregnancy. Each litter was examined as soon as possible after delivery to establish the number and sex of pups, stillbirths, live births, runts (pups that are significantly smaller than corresponding control pups) and the presence of gross abnormalities.
Live pups were counted and the sex was determined. The pups were weighed on days 1 and 4 post-partum. Any abnormal behaviour of the pups was recorded. - Postmortem examinations (parental animals):
- The male animals were sacrificed after a minimum total dosing period of 28 days if no longer needed for further mating. Dams with offspring were sacrificed on day 4 post-partum, or shortly thereafter. Females showing no evidence of copulation were sacrificed 24-26 days after the last day of the mating period. a At the time of sacrifice or death during the study, the adult animals were examined macroscopically for any abnormalities or pathological changes. Special attention was paid to the reproductive organs. The number of corpora lutea and implantation sites were recorded.
The testes and epididymides of all male adult animals were weighed. Dead pups and pups killed at day 4 post-partum, or shortly thereafter, were carefully examined externally for gross abnormalities. The ovaries, testes, epididymides, accessory sex organs and all organs showing macroscopic lesions of all adult animals were preserved. The testes and epididymides were preserved in Bouin's fixative; the remaining tissues were preserved in 7%
buffered formalin. - Postmortem examinations (offspring):
- see above
- Statistics:
- For all numerical values homogeneity of variances was tested using the Bartlett chisquare test. When the variances were homogeneous, the Dunnett test (p <= 0.01) was used to compare the experimental groups with the control group. In case of heterogeneity of variances, the Student's t-test was carried out, limit of significance was p <= 0.01. For the comparison of classification measurements the FISHER's exact test (n < 100) or chi 2-test with Yates' correction for continuity (n >= 100) (p <= 0.05 and p <= 0.01) were employed.
- Reproductive indices:
- For each group the following reproductive indices were determined: gestation index, fertility index females and males, pre-implantation loss, post-implantation loss. For each litter and group the following indices were determined: birth index, live birth index, viability index
- Offspring viability indices:
- Further checks were made early in each working day and again in the afternoon to look for dead or moribund animals. This would have allowed post mortem examinations to be carried out during the working period of that day. On Saturdays and Sundays a similar procedure was followed except that the final check was carried out at approximately mid-day.
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No substance-related behavioural changes were observed at 50, 225 or 1000 mg/kg b.w.
- Dermal irritation (if dermal study):
- not examined
- Description (incidence and severity):
- Oral study performed
- Mortality:
- no mortality observed
- Description (incidence):
- None of the low-, intermediate- and high-dosed male and female parent animals died prematurely.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Body weight remained within the normal range of the control animals at 50, 225 and 1000 mg/kg b.w.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No substance-related influence was noted on absolute and relative food consumption compared to the control at 50, 225 or 1000 mg/kg b.w.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Description (incidence and severity):
- Drinking water consumption was not influenced.
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- Was restricted to testicle, epididymis and ovary of the animals of the control group and the high dose level group (1000 mg/kg b.w.). The microscopic examination revealed no substance- related pathological findings.
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- effects observed, non-treatment-related
- Description (incidence and severity):
- In this particular case, one female treated with 1000 mg!kg bw had very poor reproductive performances: low number of corpora lutea and high postimplantation loss (44%). For all these reasons: 1) marginal effects not supported by statistical significance; 2) values in the
range of historical controls; 3) one female in the high dose group with poor reproductive performances, I suggest to reconsider the NOEL of this experiment. In conclusion, In conclusion, on the basis of the study, there no scientific reason to fix the NOEL for reproductive toxicity of Ethyl acetoacetate at 225 mg!kg bw. - Key result
- Dose descriptor:
- NOEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Key result
- Critical effects observed:
- no
- Clinical signs:
- not examined
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- not examined
- Body weight and weight changes:
- not examined
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- not examined
- Remarks on result:
- not measured/tested
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- 0 or 225 mg/kg b.w. did not influence the reproduction parameters of the rats. The post-implantation loss and viability index were similar to those of the control. The number of pups born was not effected, the pups developed normally. Body weight and sex ratio of the pups were not influenced. The pups did not show any substance-related pathological findings at external observation on lactation day 4.
At 1000 mg/kg b. w. the number of pups at birth and during the 4-day lactation period was slightly decreased compared to the control correlating with the reduced number of implants. Hence the mean post-implantation loss was increased to 13.2% (control: 5.9%) and the mean birth index and live birth index (both: 86.8%) were decreased compared to the control indices (both: 94.1 %). However, the mean viability index (97 .6%) was in the range of the control (93. 7%). Further differences observed in comparison to the control are without any biological relevance. - Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
- Other effects:
- not examined
- Behaviour (functional findings):
- not examined
- Developmental immunotoxicity:
- not examined
- Key result
- Dose descriptor:
- NOEL
- Generation:
- F1
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Critical effects observed:
- no
- Clinical signs:
- not examined
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- not examined
- Body weight and weight changes:
- not examined
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
- Other effects:
- not examined
- Behaviour (functional findings):
- not examined
- Developmental immunotoxicity:
- not examined
- Remarks on result:
- not measured/tested
- Key result
- Reproductive effects observed:
- no
- Lowest effective dose / conc.:
- 1 000 mg/kg bw/day
- Treatment related:
- no
- Conclusions:
- Under the present test conditions, the NOEL (no-observed-effect level) of Ethyl acetoacetate was found to be 1000 mg/kg b.w./day.
- Executive summary:
The study was performed 1999 as GLP-study according to OECD-guideline no. 421. The administration route was oral gavage. Ten animals were treated per sex and dose groups resulting in a total of 80 animals. Dose levels were 0, 50, 225 and 1000 mg/kg/day. There were no effects on clinical signs, mortality, body weights, food consumption. There were minor effects in the highest dose groups on reproduction. However, these findings were considered to be not relevant and therefore, a NOEL of 1000 mg/kg/day was established.
Reference
none
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Justification for selection of Effect on fertility via oral route: Guideline study; Klimisch 1
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Effects on developmental toxicity
Description of key information
The developmental toxicity study requirement according to REACH Annex IX was waived based on a weight of evidence approach, based on the following information:
1. a reproduction/developmental toxicity screening test of Ethyl acetoacetate according to OECD 421 by oral administration to Sprague-Dawley rats did not reveal significant substance-related effects. There were minor findings in the highest dose groups on reproduction only, however, these findings were considered to be not relevant and therefore, a NOEL of 1000 mg/kg/day was established in this study
2. read-across to Ethyl acetate, a chemical with similar chemical structure as Ethyl acetoacetate. A review of the available toxicity and toxicokinetic data showed, that both substances have a comparable toxicity profile. In a guideline repeated dose inhalation study with histopathology of reproductive organs and evaluation of sperm parameters, rats were exposed to doses of 750 and 1500 ppm. Analysis of sperm parameters and histopathological evaluation of male and female reproductive organs was included in a subchronic inhalation toxicity study of ethyl acetate. 13 -week exposures up to 1500 ppm ethyl acetate had no effect on sperm number, motility or morphology; and there were no test substance-related pathology finding in reproductive tissues examined microscopically. The NOAEL was considered to be 1500 ppm.
3. read-across to Methyl acetate, a chemical with similar chemical structure as Methyl acetoacetate. A review of the available toxicity and toxicokinetic data showed, that both substances have a comparable toxicity profile. Toxicity data for Methyl acetate were also previously reviewed by the European Chemicals Bureau and reported in the "European Union Risk Assessment Report: Methyl acetate / Vol. 34". According to a comprehensive compilation of data from several experimental studies after peer-review, it was concluded, that Methyl acetate is not considered to produce developmental toxicity / teratogenicity.
References:
- European Union Risk Assessment Report: Methyl acetate (CAS No: 79 -20 -9 / EINECS No: 201 -185 -2), Vol. 34, 2003
- ECHA-CHEM (http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances): Ethyl acetate (EC No. 205-500-4 / CAS-No 141-78-6)
Link to relevant study records
- Endpoint:
- developmental toxicity
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Species:
- rat
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
Reference
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no study available (further information necessary)
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Based on the data available the substance is not classified or labeled according to Directive 67/548/EEC (DSD) or Regulation 1272/2008/EC (CLP).
Additional information
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.