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EC number: 218-792-3 | CAS number: 2235-46-3
- 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
Acute oral toxicity:
Acute oral toxicity dose (LD50) of target chemical N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3) was considered based on experimental study, the LD50 cut-off value was considered to be 5000 mg/kg in rats. The study concluded that the LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, N,N-diethyl-3-oxobutyramide cannot be classified for acute oral toxicity.
Acute Inhalation toxicity:
Acute Inhalation toxicity dose (LC50) for N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3) was considered based on data available for the structurally and functionally similar read across chemicals. The LC50 value is >5 mg/L. Thus, comparing this value with the criteria of CLP regulation, N,N-diethyl-3-oxobutyramide cannot be classified for acute inhalation toxicity.
Acute Dermal toxicity:
Acute Dermal toxicity dose (LD50) for N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3) was considered based on experimental study conducted on rats, the LD50 value considered to be >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, N,N-diethyl-3-oxobutyramide cannot be classified for acute dermal toxicity.
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:
- guideline study
- Justification for type of information:
- Data is from experimental report.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Principles of method if other than guideline:
- The aim of this study was to assess the toxicity potential of Diethylacetoacetamide (DEAAA) (CAS No. 2235-46-3) after single oral administration in Wistar Rats and an observation period of 14 days
- GLP compliance:
- yes
- Test type:
- acute toxic class method
- Limit test:
- yes
- Specific details on test material used for the study:
- - IUPAC Name: N,N-diethyl-3-oxobutyramide- InChI: 1S/C8H15NO2/c1-4-9(5-2)8(11)6-7(3)10/h4-6H2,1-3H3- Smiles: N(C(CC(C)=O)=O)(CC)CC- Molecular formula :C8H15NO2- Molecular weight :157.212 g/mol- Substance type:Organic- Physical state:Pale yellow clear liquid- Lot/batch No.: 31- Expiration date of the lot/batch: May 03, 2016
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS- Source: National Institute of Biosciences Pune- Females (if applicable) nulliparous and non-pregnant:yes- Age at study initiation: 9 - 12 weeks- Weight at study initiation: Minimum: 120 gm ;Maximum: 150 gm (Individual body weights were within ± 20 % prior to treatment after overnight fasting)- Fasting period before study: Rat were foasted overnight - Housing:Group of three animals were housed in polycarbonate cages (size 37 [cm] x 21 [cm], height 20 [cm])- Diet (e.g. ad libitum): All animals were provided conventional laboratory rodent diet, ad libitum- Water (e.g. ad libitum):Aqua guard filtered tap water was provided ad libitum via drinking bottles.- Acclimation period:Animal nos. 01-03 was acclimatized for 8 days, 04-06 for 11 days, 07-09 for 18 days and 10-12 for 8 days prior to administration of the test item. ENVIRONMENTAL CONDITIONS - Temperature (°C): Minimum: 19.30 °C; Maximum: 23.90 °C - Humidity (%): Minimum: 50.80%; Maximum: 66.50% - Air changes (per hr): More than 12 changes per hour - Photoperiod (hrs dark / hrs light): 12 hour light and 12 hour dark IN-LIFE DATES: From: November 09, 2015 To:December 22, 2015
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- VEHICLE - Concentration in vehicle: 300 mg/kg and 2000 mg/kg - Amount of vehicle (if gavage):10 ml/kg - Justification for choice of vehicle:Corn oil was selected as a vehicle based on solubility testing - Lot/batch no. (if required): MR301015 DOSAGE PREPARATION (if unusual):Vehicle (Corn oil) was added to the weighed quantity of test item (300 mg and 2000 mg) slowly and mixed well. Transferred the formulation to the measuring cylinder and made the final volume up to 10 ml. Hence, stock dose concentration was achieved as 30 mg/ml and 200 mg/ml. The test item was miscible in corn oil. The dosing solution was prepared freshly, shortly prior to dose administration. CLASS METHOD (if applicable) - Rationale for the selection of the starting dose:The starting dose level was that, which most likely to produce mortality in some of the dosed animals. The starting dose level was selected as 300 mg/kg body weight as no information was available to conduct the study.
- Doses:
- 300 and 2000 mg/kg bw
- No. of animals per sex per dose:
- Total = 12 Females (Group of 3 animals/dose)
- Control animals:
- not specified
- Details on study design:
- - Duration of observation period following administration: 14 days - Frequency of observations and weighing:After test item administration, individual animals were frequently observed at 30 minutes, 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all the animals were observed once a day during the 14 day observation period.All surviving animals were observed twice daily (morning and evening) for morbidity and mortality, throughout the acclimatization and study period.All the rats were weighed on days 0 (prior to dosing), 7 and 14. - Necropsy of survivors performed: yes - Other examinations performed: All the animals were observed for external and internal gross pathology.
- Statistics:
- not specified
- Preliminary study:
- not specified
- Sex:
- female
- Dose descriptor:
- LD50 cut-off
- Effect level:
- 5 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No mortality was observed in animals treated with 300 and 2000 mg/kg body weight throughout the 14 days observation period
- Clinical signs:
- other: At 300 and 2000 mg/kg body weight, all the animals were observed normal throughout the experimental period
- Gross pathology:
- During external and internal gross necropsy examination, terminally sacrificed animals treated with 300 and 2000 mg/kg body weight showed no abnormalities
- Other findings:
- not specified
- Interpretation of results:
- other: Not classified
- Conclusions:
- The LD50 cut-off value was considered to be 5000 mg/kg bw, when female Wistar rats were treated with N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3) via oral gavage route.
- Executive summary:
Acute Oral Toxicity Study of N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3) was conducted as per OECD No. 423 on 12 female Wistar rats at the dose concentration of 300 and 2000 mg/kg bw. The animals were fasted for minimum 16-17.5 hours prior to dosing and for 4 hours post dosing, feed was withheld but drinking water provided ad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs.3 rats of the first group G1 were dosed with starting dose of 300 mg/kg body weight and the animals did not show any mortality. So another 3 animals of the same group G1 were dosed with 300 mg/kg body weight and no mortality was observed. Next, 3 animals of group G2 were dosed with 2000 mg/kg body weight and no mortality was observed. So, another 3 animals of the same group G2 were dosed with 2000 mg/kg body weight and no mortality was observed. Hence, further dosing was stopped.After test item administration, individual animals were frequently observed at 30 minutes, 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all the animals were observed once a day during the 14 day observation period. All surviving animals were observed twice daily (morning and evening) for morbidity and mortality, throughout the acclimatization and study period. All the rats were weighed on days 0 (prior to dosing), 7 and 14.All the animals were observed for external and internal gross pathology.No mortality was observed in animals treated with 300 and 2000 mg/kg body weight throughout the 14 days observation period. At 300 and 2000 mg/kg body weight, all the animals were observed normal throughout the experimental period.Mean body weight of all the animals treated with 300 and 2000 mg/kg body weight were observed with gain on day 7 and 14, as compared to day 0. During external and internal gross necropsy examination, terminally sacrificed animals treated with 300 and 2000 mg/kg body weight showed no abnormalities. Hence, The LD50 cut-off value was considered to be 5000 mg/kg bw, when female Wistar rats were treated with N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3) via oral gavage route.
Reference
Table 1: Individual Animal Body Weight (g) andBody Weight Changes(%)
Sex:Female
Animal No. | Group/ Dose (mg/kg body weight) |
| Body Weight (gram) | Body Weight Change (%) | |||
Dose Volume* (ml) | Day 0 | Day 7 | Day 14 | Day 0-7 | Day 0-14 | ||
01 | G1/ 300 | 1.5 | 145 | 163 | 198 | 12.41 | 36.55 |
02 | 1.5 | 150 | 168 | 200 | 12.00 | 33.33 | |
03 | 1.4 | 144 | 159 | 186 | 10.42 | 29.17 | |
04 | 1.3 | 134 | 159 | 182 | 18.66 | 35.82 | |
05 | 1.4 | 140 | 167 | 173 | 19.29 | 23.57 | |
06 | 1.3 | 132 | 155 | 181 | 17.42 | 37.12 | |
07 | G2/ 2000 | 1.2 | 120 | 143 | 192 | 19.17 | 60.00 |
08 | 1.4 | 142 | 177 | 210 | 24.65 | 47.89 | |
09 | 1.4 | 139 | 168 | 200 | 20.86 | 43.88 | |
10 | 1.4 | 136 | 156 | 178 | 14.71 | 30.88 | |
11 | 1.4 | 142 | 162 | 194 | 14.08 | 36.62 | |
12 | 1.4 | 139 | 155 | 171 | 11.51 | 23.02 |
*= Dose volume calculated based on day 0 body weight
Table 2: Summary of Animal Body Weight (g) and Body Weight Changes (%)
Sex:Female
Group/ Dose (mg/kg body weight) | Rats Body Weight (g) | Body Weight Changes (%) | ||||
Day 0 | Day 7 | Day 14 | 0-7 | 0-14 | ||
G1/ 300 | Mean | 140.83 | 161.83 | 186.67 | 15.03 | 32.59 |
SD | 6.88 | 5.08 | 10.46 | 3.85 | 5.30 | |
n | 6 | 6 | 6 | 6 | 6 | |
G2/ 2000 | Mean | 136.33 | 160.17 | 190.83 | 17.50 | 40.38 |
SD | 8.31 | 11.72 | 14.29 | 4.91 | 13.11 | |
n | 6 | 6 | 6 | 6 | 6 |
Keys:SD = Standard Deviation, n = Number of Animals
Table 3: Individual Animal Clinical Signs and Symptoms
Sex:Female
Animal No. | Group/ Dose (mg/kg body weight) | Hours (Day 0) | ||||
1/2 | 1 | 2 | 3 | 4 | ||
01 | G1/ 300 | 1 | 1 | 1 | 1 | 1 |
02 | 1 | 1 | 1 | 1 | 1 | |
03 | 1 | 1 | 1 | 1 | 1 | |
04 | 1 | 1 | 1 | 1 | 1 | |
05 | 1 | 1 | 1 | 1 | 1 | |
06 | 1 | 1 | 1 | 1 | 1 | |
07 | G2/ 2000 | 1 | 1 | 1 | 1 | 1 |
08 | 1 | 1 | 1 | 1 | 1 | |
09 | 1 | 1 | 1 | 1 | 1 | |
10 | 1 | 1 | 1 | 1 | 1 | |
11 | 1 | 1 | 1 | 1 | 1 | |
12 | 1 | 1 | 1 | 1 | 1 |
Key: 1 = Normal
Table 3: Individual Animal Clinical Signs and Symptoms (Continued)
Sex:Female
Animal No. | Group/ Dose (mg/kg body weight) | Days post dosing | |||||||||||||
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | ||
01 | G1/ 300 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
02 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
03 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
04 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
05 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
06 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
07 | G2/ 2000 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
08 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
09 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
10 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
11 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
12 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
Key: 1 = Normal
Table 4: Individual Animal Mortality Record
Sex:Female
Animal No. | Group/ Dose (mg/kg body weight) | Day of Observation (Day 0 to 14) | |
Morning Observation | Evening Observation | ||
01 | G1/ 300 | No mortality and morbidity | No mortality and morbidity |
02 | No mortality and morbidity | No mortality and morbidity | |
03 | No mortality and morbidity | No mortality and morbidity | |
04 | No mortality and morbidity | No mortality and morbidity | |
05 | No mortality and morbidity | No mortality and morbidity | |
06 | No mortality and morbidity | No mortality and morbidity | |
07 | G2/ 2000 | No mortality and morbidity | No mortality and morbidity |
08 | No mortality and morbidity | No mortality and morbidity | |
09 | No mortality and morbidity | No mortality and morbidity | |
10 | No mortality and morbidity | No mortality and morbidity | |
11 | No mortality and morbidity | No mortality and morbidity | |
12 | No mortality and morbidity | No mortality and morbidity |
Key:TS = Terminal Sacrifice
Table 5: Gross Necropsy Observation
Sex:Female
Animal No. | Group/ Dose (mg/kg body weight) | Mode of Death | Gross Observation | |
External | Internal | |||
01 | G1/ 300 | TS | No abnormality detected | No abnormality detected |
02 | TS | No abnormality detected | No abnormality detected | |
03 | TS | No abnormality detected | No abnormality detected | |
04 | TS | No abnormality detected | No abnormality detected | |
05 | TS | No abnormality detected | No abnormality detected | |
06 | TS | No abnormality detected | No abnormality detected | |
07 | G2/ 2000 | TS | No abnormality detected | No abnormality detected |
08 | TS | No abnormality detected | No abnormality detected | |
09 | TS | No abnormality detected | No abnormality detected | |
10 | TS | No abnormality detected | No abnormality detected | |
11 | TS | No abnormality detected | No abnormality detected | |
12 | TS | No abnormality detected | No abnormality detected |
Key : TS = Terminal Sacrifice
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 5 000 mg/kg bw
- Quality of whole database:
- Data is Klimisch 1 and from study report.
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Remarks:
- experimental data of read across substances
- Justification for type of information:
- Data for the target chemical is summarized based on the structurally and functionally similar read across chemicals.
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- according to guideline
- Guideline:
- other: As mentioned below
- Principles of method if other than guideline:
- WoE report is based on 2 acute inhalation toxicity studies as - WoE-2 and WoE-3. Acute Inhalation toxicity test was carried out to study the effects of the test chemicals on rodents.
- GLP compliance:
- not specified
- Test type:
- other: not specified
- Limit test:
- no
- Specific details on test material used for the study:
- - IUPAC Name: N,N-diethyl-3-oxobutyramide- InChI: 1S/C8H15NO2/c1-4-9(5-2)8(11)6-7(3)10/h4-6H2,1-3H3- Smiles: N(C(CC(C)=O)=O)(CC)CC- Molecular formula :C8H15NO2- Molecular weight :157.212 g/mol- Substance type:Organic- Physical state:Pale yellow clear liquid
- Species:
- other: 1. mouse 2. rat
- Strain:
- other: 1. not specified 2. Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- 1. not specified2. TEST ANIMALS- Source: USAEHA's colony- Weight at study initiation: 107±15 gm- Housing: Rats were individually caged and placed in a Wahmann 225 L, dynamic airflow exposure chamber.- Diet (e.g. ad libitum): The laboratory diet for the rats was Formulab ChoW® No. 5008, ad libitum- Water (e.g. ad libitum): ad libitum
- Route of administration:
- other: 1. inhalation 2. inhalation: aerosol
- Type of inhalation exposure:
- other: 1. not specified 2. not specified
- Vehicle:
- other: 1. not specified 2. not specified
- Remark on MMAD/GSD:
- not specified
- Details on inhalation exposure:
- 1. not specified2. GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION - Exposure apparatus:Wahmann 225 L, dynamic airflow exposure chamber - Exposure chamber volume: 225 L - Method of holding animals in test chamber:Rats were individually caged and placed in chamber - Method of conditioning air:Chamber air was pulled through a glass fiber filter at approximately 2 liters per minute for 5 minutes. - System of generating particulates/aerosols:The test compound was dispersed into the chambers for 4 hours using a Collison Nebulizer - Method of particle size determination: particle-sizing determinations were impossible due to the speed of evaporation of the test compound from the Teflon-coated slides. - Temperature, humidity, pressure in air chamber: The rate of airflow through the chamber as well as temperature was monitored during the exposures. TEST ATMOSPHERE - Samples taken from breathing zone: yes, the actual concentration of test chemical in the animals' breathing zones was measured four times during each exposure (0.5, 1, 2, and 3 hours into the exposure).
- Analytical verification of test atmosphere concentrations:
- not specified
- Duration of exposure:
- 4 h
- Remarks on duration:
- not specified
- Concentrations:
- 1. 142000 mg/m³2. 3700, 4260, 5185, 5450, 5480, and 5950 mg/m3
- No. of animals per sex per dose:
- 1. not specified2. 10 rats/sex/dose
- Control animals:
- other: 1. not specified 2. Yes, 10 rats/sex/dose
- Details on study design:
- 1. not specified2. - Duration of observation period following administration: 14 days, rats were observed during the exposure and for 14 days post exposure.- Frequency of observations and weighing: Body weights were determined on the day of exposure and days 1, 3, 7, and 14 days post exposure.- Necropsy of survivors performed: yes, at the conclusion of each 14-day observation period, the surviving animals were sacrificed by decapitation and internal organs examined for gross abnormalities. Tissues exhibiting gross abnormalities were preserved for future histopathologic examination.
- Statistics:
- 1. not specified2. not specified
- Preliminary study:
- 1. not specified2. not specified
- Sex:
- not specified
- Dose descriptor:
- LC50
- Effect level:
- 142 000 mg/m³ air
- Based on:
- test mat.
- Remarks on result:
- other: 50% mortality was observed
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- 5 950 mg/m³ air (analytical)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Mortality:
- 1. 50% mortality was observed at 142000 mg/m³.2. Mortality was observed in animals as follows – At 3700 mg/m3 – 1 male and 1 female was died; At 4260 mg/m3 – No mortality was observedAt 5185 mg/m3 – 2 males and 1 female rat was died;At 5450 mg/m3 – 3 males and 2 females were died;At 5480 mg/m3 – 2 male and 4 females were died;At 5950 mg/m3 – 7 males and 8 females were died
- Clinical signs:
- other: 1. not specified2. not specified
- Body weight:
- 1. not specified2. Significant differences were found between the acute inhalation exposure rat and control rat body weights over the 14-day observation period.
- Gross pathology:
- 1. not specified2. No gross lesions attributable to the inhalation of the test chemical were detected in rats necropsied 14 days after the acute aerosol exposures. No chemically-induced histological lesions were recognized in the tissues microscopically examined.
- Other findings:
- 1. not specified2. not specified
- Interpretation of results:
- other: Not classified
- Conclusions:
- According to CLP regulation the test chemical Formaldehyde, oligomeric reaction products with phenol (CAS No. 9003-35-4) cannot be classified for acute inhalation toxicity, as the LC50 value is >5 mg/L (>5000 mg/m3) and in the range of >5000-7570 mg/m3.
- Executive summary:
Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the acute oral toxicity of the test chemical N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3). The studies are as mentioned below:
1. Acute inhalation toxicity study of test chemical was conducted in mice at the dose concentration of 142000 mg/m3. 50% mortality was observed at 142000 mg/m³. Hence, LC50 value was considered to be 142000 mg/m3, when mice were treated with test chemical by inhalation route.
2. Acute inhalation toxicity study of test chemical was conducted in male and female Sprague-Dawley albino rats at the dose concentration of 3700, 4260, 5185, 5450, 5480, and 5950 mg/m3. Rats were individually caged and placed in a Wahmann 225 L, dynamic airflow exposure chamber. The test compound was dispersed into the chambers for 4 hours using a Collison Nebulizer. Rats were observed during the exposure and for 14 days post exposure. Body weights were determined on the day of exposure and days 1, 3, 7, and 14 days post exposure. At the conclusion of each 14-day observation period, the surviving animals were sacrificed by decapitation and internal organs examined for gross abnormalities. Tissues exhibiting gross abnormalities were preserved for future histopathologic examination. The concentrations for the acute aerosol exposures were measured analytically. Mortality was observed in animals as follows – At 3700 mg/m3 – 1 male and 1 female was died; At 4260 mg/m3 – No mortality was observed; At 5185 mg/m3 – 2 males and 1 female rat was died; At 5450 mg/m3 – 3 males and 2 females were died; At 5480 mg/m3 – 2 male and 4 females were died; At 5950 mg/m3 – 7 males and 8 females were died. Significant differences were found between the acute inhalation exposure rat and control rat body weights over the 14-day observation period. No gross lesions attributable to the inhalation of the test chemical were detected in rats necropsied 14 days after the acute aerosol exposures. No chemically-induced histological lesions were recognized in the tissues microscopically examined. Hence, LC50 value was considered to be 5950 mg/m³, when male and female Sprague-Dawley albino rats were treated with test chemical by inhalation route via aerosol for 4 hour exposure.
Thus, based on the above studies on N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3) and it’s structurally and functionally read across substances, it can be concluded that LC50 value is >5 mg/L. Thus, comparing this value with the criteria of CLP regulation, N,N-diethyl-3-oxobutyramide cannot be classified for acute inhalation toxicity.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LC50
- Value:
- 142 000 mg/m³ air
- Quality of whole database:
- Data is Klimisch 2 and from authoritative database.
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- Data is from experimental report.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Principles of method if other than guideline:
- The aim of this study was to assess the dermal toxicity of Diethylacetoacetamide (DEAAA) (CAS No. 2235-46-3) after single dose application by dermal route in Wistar rats and 14 day observation period.
- GLP compliance:
- yes
- Test type:
- other: Acute Dermal Toxicity
- Limit test:
- yes
- Specific details on test material used for the study:
- - IUPAC Name: N,N-diethyl-3-oxobutyramide- InChI: 1S/C8H15NO2/c1-4-9(5-2)8(11)6-7(3)10/h4-6H2,1-3H3- Smiles: N(C(CC(C)=O)=O)(CC)CC- Molecular formula :C8H15NO2- Molecular weight :157.212 g/mol- Substance type:Organic- Physical state:Pale yellow clear liquid
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS- Source: In-House Bred- Females (if applicable) nulliparous and non-pregnant: yes- Age at study initiation: young adult animals - Weight at study initiation: Male:Minimum: 214 g and Maximum: 235 g; Female:Minimum: 229 g and Maximum: 259 g - Housing:The animals were housed individually in polycarbonate cages (size 37 [cm] x 21 [cm], height 20 [cm]).- Diet (e.g. ad libitum): All animals were provided conventional laboratory rodent diet, ad libitum. - Water (e.g. ad libitum):Aqua guard filtered tap water was provided via drinking bottles, ad libitum - Acclimation period:All animals were acclimatized to the test conditions for 6 days prior to application of the test item. ENVIRONMENTAL CONDITIONS - Temperature (°C): Minimum: 19.40 °C; Maximum: 23.60 °C - Humidity (%): Minimum: 43.30%; Maximum: 68.10% - Air changes (per hr): More than 12 changes per hour - Photoperiod (hrs dark / hrs light): 12 hour light and 12 hour dark IN-LIFE DATES: From: December 08, 2015 To:December 28, 2015
- Type of coverage:
- occlusive
- Vehicle:
- not specified
- Details on dermal exposure:
- TEST SITE - Area of exposure: clipped dorsal area of rat skin - % coverage: greater than 10% body surface area - Type of wrap if used: Test item was held in contact with the skin with a porous gauze dressing (Approx. 10% of body surface area of rat) and non-irritating tape REMOVAL OF TEST SUBSTANCE - Washing (if done): test item was removed by using distilled water - Time after start of exposure:24-hour
- Duration of exposure:
- 24-hour
- Doses:
- 2000 mg/kg bw
- No. of animals per sex per dose:
- Total = 10 (Five per sex)
- Control animals:
- not specified
- Details on study design:
- - Duration of observation period following administration: 14 days - Frequency of observations and weighing:After test item administration, individual animals were frequently observed at 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all animals were observed once a day during the 14 day observation period for clinical signs. All animals were observed for Local signs/skin reactions (in common with clinical signs) once daily and for mortality and morbidity twice daily.All rats were weighed on days 0 (prior to dosing), 7 and 14. - Necropsy of survivors performed: yes, at the end of 14 day observation period, all the surviving rats were euthanized by overdose of CO2 and subjected to gross pathology examination, for external and internal observations.
- Statistics:
- No statistical analysis was performed for LD50 calculation since the study was terminated with limit test.
- Preliminary study:
- not specified
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: No mortality was observed
- Mortality:
- No mortality was observed at limit dose of 2000 mg/kg body weight during the 14 day observation period.
- Clinical signs:
- other: At 2000 mg/kg, all the animals were observed normal throughout the experimental period.
- Gross pathology:
- The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality.
- Other findings:
- not specified
- Interpretation of results:
- other: Not classified
- Conclusions:
- The LD50 was considered to be >2000 mg/kg bw, when male and female Wistar rats were treated with N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3) by dermal application.
- Executive summary:
Acute Dermal Toxicity Study was conducted using N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3) as per OECD No.402 in 10 male and female healthy young adult Wistar rats which were randomly selected and used for conducting acute dermal toxicity study at the concentration of 2000 mg/kg bw. Rats free from injury and irritation of skin were selected for the study. 24 hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight based on the test item density (0.98475) and latest body weight was applied by single dermal application and observed for 14 days after treatment. On test day 0, test item was applied directly on the intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area. This porous gauze dressing was covered with a non-irritating tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed.The animals were observed daily for mortality and clinical signs, during the acclimatization period and post dosing till the termination. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1, 14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs / Skin reactions were observed daily from test days 1-14. Body weights were recorded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically.No mortality was observed in any animal till the end of the experimental period.At 2000 mg/kg, all the animals were observed normal throughout the experimental period. Mean body weight was observed with gain on day 7 and 14 of male and female animals, as compared to day 0. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality. Hence, LD50 was considered to be >2000 mg/kg bw, when male and female Wistar rats were treated with N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3) by dermal application.
Reference
Table 1: Dose Volume (ml), Individual Animal Body Weight (g) andBody Weight Changes(%)
Dose:2000 mg/ kg bodyweight Group:G1 Density:0.98475
Animal No. | Sex | Dose Volume* (ml) | Body Weight (gram) | Body Weight Change (%) | |||
Day 0 | Day 7 | Day 14 | Day 0-7 | Day 0-14 | |||
01 | Male | 0.44 | 219 | 235 | 259 | 7.31 | 18.26 |
02 | 0.43 | 214 | 229 | 251 | 7.01 | 17.29 | |
03 | 0.48 | 235 | 246 | 267 | 4.68 | 13.62 | |
04 | 0.45 | 221 | 245 | 278 | 10.86 | 25.79 | |
05 | 0.43 | 214 | 239 | 266 | 11.68 | 24.30 | |
06 | Female | 0.51 | 252 | 256 | 263 | 1.59 | 4.37 |
07 | 0.52 | 258 | 270 | 281 | 4.65 | 8.91 | |
08 | 0.51 | 249 | 256 | 264 | 2.81 | 6.02 | |
09 | 0.53 | 259 | 276 | 285 | 6.56 | 10.04 | |
10 | 0.47 | 229 | 238 | 249 | 3.93 | 8.73 |
Key: * = based on the test item density and day 0 body weight
Table 2:Summaryof Animal Body Weight (g) and Body Weight Changes (%)
Dose: 2000 mg/kg body weight Group: G1
Sex | Body Weight (gram) | Body Weight Changes (%) | ||||
Day 0 | Day 7 | Day 14 | Day 0-7 | Day 0-14 | ||
Male | Mean | 220.60 | 238.80 | 264.20 | 8.31 | 19.85 |
SD | 8.62 | 7.09 | 10.03 | 2.90 | 5.07 | |
n | 5 | 5 | 5 | 5 | 5 | |
Female | Mean | 249.40 | 259.20 | 268.40 | 3.91 | 7.62 |
SD | 12.14 | 14.74 | 14.66 | 1.88 | 2.34 | |
n | 5 | 5 | 5 | 5 | 5 |
Keys: SD= Standard deviation, n = Number of animals
Table 3: Individual Animal Clinical Signs and Symptoms
Dose:2000 mg/kg body weight Group:G1
Animal No. | Sex | Hour(s) - Day 0 | Day(s) | |||||||||
1 | 2 | 3 | 4 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | ||
01 | Male | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
02 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
03 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
04 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
05 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
06 | Female | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
07 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
08 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
09 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
10 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
Animal No. | Sex | Day(s) | ||||||
8 | 9 | 10 | 11 | 12 | 13 | 14 | ||
01 | Male | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
02 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
03 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
04 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
05 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
06 | Female | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
07 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
08 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
09 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
10 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
Key: 1 = Normal
Table 4: Individual Animal Mortality Record
Dose:2000 mg/kg body weight Group:G1
Animal No. | Sex | Days of Observation (0 to 14) | |
Morning Observations | Evening Observations | ||
01 | Male | No mortality and morbidity | No mortality and morbidity |
02 | No mortality and morbidity | No mortality and morbidity | |
03 | No mortality and morbidity | No mortality and morbidity | |
04 | No mortality and morbidity | No mortality and morbidity | |
05 | No mortality and morbidity | No mortality and morbidity | |
06 | Female | No mortality and morbidity | No mortality and morbidity |
07 | No mortality and morbidity | No mortality and morbidity | |
08 | No mortality and morbidity | No mortality and morbidity | |
09 | No mortality and morbidity | No mortality and morbidity | |
10 | No mortality and morbidity | No mortality and morbidity |
Table 5: GrossNecropsyObservation
Dose:2000 mg/kg body weight Group:G1 Mode of Death:Terminal Sacrifice
Animal No. | Sex | Gross Observation | |
External | Internal | ||
01 | Male | No abnormality detected | No abnormality detected |
02 | No abnormality detected | No abnormality detected | |
03 | No abnormality detected | No abnormality detected | |
04 | No abnormality detected | No abnormality detected | |
05 | No abnormality detected | No abnormality detected | |
06 | Female | No abnormality detected | No abnormality detected |
07 | No abnormality detected | No abnormality detected | |
08 | No abnormality detected | No abnormality detected | |
09 | No abnormality detected | No abnormality detected | |
10 | No abnormality detected | No abnormality detected |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- Data is Klimisch 1 and from experimental report.
Additional information
Acute oral toxicity:
In different experimental studies, N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for N,N-diethyl-3-oxobutyramide. The studies are summarized as below –
Acute Oral Toxicity Study of N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3) was conducted as per OECD No. 423 on 12 female Wistar rats at the dose concentration of 300
and 2000 mg/kg bw. The animals were fasted for minimum 16-17.5 hours prior to dosing and for 4 hours post dosing, feed was withheld but drinking water provided ad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs.3 rats of the first group G1 were dosed with starting dose of 300 mg/kg body weight and the animals did not show any mortality. So another 3 animals of the same group G1 were dosed with 300 mg/kg body weight and no mortality was observed. Next, 3 animals of group G2 were dosed with 2000 mg/kg body weight and no mortality was observed. So, another 3 animals of the same group G2 were dosed with 2000 mg/kg body weight and no mortality was observed. Hence, further dosing was stopped.After test item administration, individual animals were frequently observed at 30 minutes, 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all the animals were observed once a day during the 14 day observation period. All surviving animals were observed twice daily (morning and evening) for morbidity and mortality, throughout the acclimatization and study period. All the rats were weighed on days 0 (prior to dosing), 7 and 14.All the animals were observed for external and internal gross pathology.No mortality was observed in animals treated with 300 and 2000 mg/kg body weight throughout the 14 days observation period. At 300 and 2000 mg/kg body weight, all the animals were observed normal throughout the experimental period.Mean body weight of all the animals treated with 300 and 2000 mg/kg body weight were observed with gain on day 7 and 14, as compared to day 0. During external and internal gross necropsy examination, terminally sacrificed animals treated with 300 and 2000 mg/kg body weight showed no abnormalities. Hence, The LD50 cut-off value was considered to be 5000 mg/kg bw, when female Wistar rats were treated with N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3) via oral gavage route.
The above experimental study is further supported by the study mentioned in publication, handbook, authoritative database and secondary source for the target chemical N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3). Acute oral toxicity study was conducted in groups of 5 male Carworth–Wistar rats at the dose concentration of 4760 (3390-6680) mg/kg bw. The doses are different in logarithmic order by a factor of 2. The test chemical was given undiluted via oral gavage route. After administration of the substance, the animals became 14 days long observed. The statistically probable ste LD50 value and its confidence interval according to the method of Thompson (Bacteriol Rev.11, 1947, p.115) using of the Tables of Weil (Biometrics 8, 1952, p. 249). 50% mortality was observed at 4760 mg/kg bw. Therefore, LD50 value was considered to be 4760 mg/kg bw, with 95% confidence limit of 3390-6680 mg/kg bw, when groups of 5 male Carworth–Wistar rats were treated with N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3) via oral gavage route.
Thus, based on the above studies on N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3), it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, N,N-diethyl-3-oxobutyramide cannot be classified for acute oral toxicity.
Acute Inhalation Toxicity:
Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the acute oral toxicity of the test chemical N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3). The studies are as mentioned below:
1. Acute inhalation toxicity study of test chemical was conducted in mice at the dose concentration of 142000 mg/m3. 50% mortality was observed at 142000 mg/m³. Hence, LC50 value was considered to be 142000 mg/m3, when mice were treated with test chemical by inhalation route.
2. Acute inhalation toxicity study of test chemical was conducted in male and female Sprague-Dawley albino rats at the dose concentration of 3700, 4260, 5185, 5450, 5480, and 5950 mg/m3. Rats were individually caged and placed in a Wahmann 225 L, dynamic airflow exposure chamber. The test compound was dispersed into the chambers for 4 hours using a Collison Nebulizer. Rats were observed during the exposure and for 14 days post exposure. Body weights were determined on the day of exposure and days 1, 3, 7, and 14 days post exposure. At the conclusion of each 14-day observation period, the surviving animals were sacrificed by decapitation and internal organs examined for gross abnormalities. Tissues exhibiting gross abnormalities were preserved for future histopathologic examination. The concentrations for the acute aerosol exposures were measured analytically. Mortality was observed in animals as follows – At 3700 mg/m3 – 1 male and 1 female was died; At 4260 mg/m3 – No mortality was observed; At 5185 mg/m3 – 2 males and 1 female rat was died; At 5450 mg/m3 – 3 males and 2 females were died; At 5480 mg/m3 – 2 male and 4 females were died; At 5950 mg/m3 – 7 males and 8 females were died. Significant differences were found between the acute inhalation exposure rat and control rat body weights over the 14-day observation period. No gross lesions attributable to the inhalation of the test chemical were detected in rats necropsied 14 days after the acute aerosol exposures. No chemically-induced histological lesions were recognized in the tissues microscopically examined. Hence, LC50 value was considered to be 5950 mg/m³, when male and female Sprague-Dawley albino rats were treated with test chemical by inhalation route via aerosol for 4 hour exposure.
Thus, based on the above studies on N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3) and it’s structurally and functionally read across substances, it can be concluded that LC50 value is >5 mg/L. Thus, comparing this value with the criteria of CLP regulation, N,N-diethyl-3-oxobutyramide cannot be classified for acute inhalation toxicity.
Acute Dermal toxicity:
Acute Dermal Toxicity Study was conducted using N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3) as per OECD No.402 in 10 male and female healthy young adult Wistar rats which were randomly selected and used for conducting acute dermal toxicity study at the concentration of 2000 mg/kg bw. Rats free from injury and irritation of skin were selected for the study. 24 hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight based on the test item density (0.98475) and latest body weight was applied by single dermal application and observed for 14 days after treatment. On test day 0, test item was applied directly on the intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area. This porous gauze dressing was covered with a non-irritating tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed.The animals were observed daily for mortality and clinical signs, during the acclimatization period and post dosing till the termination. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1, 14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs / Skin reactions were observed daily from test days 1-14. Body weights were recorded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically.No mortality was observed in any animal till the end of the experimental period.At 2000 mg/kg, all the animals were observed normal throughout the experimental period. Mean body weight was observed with gain on day 7 and 14 of male and female animals, as compared to day 0. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality. Hence, LD50 was considered to be >2000 mg/kg bw, when male and female Wistar rats were treated with N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3) by dermal application. Thus, comparing this value with the criteria of CLP regulation, N,N-diethyl-3-oxobutyramide cannot be classified for acute dermal toxicity.
Justification for classification or non-classification
Based on the above experimental studies on N,N-diethyl-3-oxobutyramide (CAS no: 2235-46-3) and it’s structurally and functionally read across substances, it can be concluded that LD50 value is >2000 mg/kg bw for acute oral and dermal toxicity; and LC50 value is >5 mg/L for acute inhalation toxicity. Thus, comparing these values with the criteria of CLP regulation, N,N-diethyl-3-oxobutyramide cannot be classified for acute oral, dermal and inhalation toxicity.
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