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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
Key value for chemical safety assessment
Effects on fertility
Description of key information
Reproductive toxicity study
The data available for N,N-diethyl-3-oxobutanamide (2235-46-3)and structurally similar read across chemicals was reviewed to determine the reproductive toxicity.The NOAEL for reproductive toxicity was considered to be above 50-250mg/kg bw/day as No effects on reproductive parameters were observed .When male and female rats were treated with N,N-diethyl-3-oxobutanamide (2235-46-3).Thus, comparing this value with the criteria of CLP regulation N,N-diethyl-3-oxobutanamide (2235-46-3)not likely to classify as reproductive toxicant.
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- 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:
- Weight of evidence approach based on structurally similar chemicals
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: As mentioned below
- Principles of method if other than guideline:
- WoE report is based on two reproductive toxicity studies on rats Study 1&2.Reproductive and Developmental toxicity study of test material was performed on Sprague Dawley rats.
- GLP compliance:
- not specified
- Limit test:
- no
- Justification for study design:
- No data available
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- No data available
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No data available
- Route of administration:
- oral: feed
- Vehicle:
- not specified
- Details on exposure:
- No data available
- Details on mating procedure:
- No data available
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Study 1F0: 80 days before mating during mating, gestation, and lactation.F1: 93 days before mating during mating, gestation, and lactation.Study 214 days (from day 6 to day 20 p.c.)
- Frequency of treatment:
- daily
- Details on study schedule:
- No data available
- Remarks:
- Study 10, 500, 2,000, or 5,000 ppm ( 0, 25, 100, or 250 mg /kg/day)Study 20, 50,250,750 mg/kg bw/day
- No. of animals per sex per dose:
- Study 1Total:1120 mg/kg bw/day:28 male and 28 female 25 mg/kg bw/day:28 male and 28 female100 mg/kg bw/day:28 male and 28 female250mg/kg bw/day:28 male and 28 female
- Control animals:
- yes
- Details on study design:
- No data available
- Positive control:
- No data available
- Parental animals: Observations and examinations:
- Study 1&2Parental animals observation and examinationsCAGE SIDE OBSERVATIONS: yes DETAILED CLINICAL OBSERVATIONS: Yes Time schedule: twice daily BODY WEIGHT: YesTime schedule for examinations: twice dailyFOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): twice dailyFood consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: no Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data: No data availableWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data Time schedule for examinations:
- Oestrous cyclicity (parental animals):
- No data available
- Sperm parameters (parental animals):
- No data available
- Litter observations:
- Study 1The F1 and F2 litters were observed for number of live and stillborn pups, external anomalies, sex and body weight grouped by sex on lactation days 0, 4, 7, and 14, sex and individual body weights (only group weights reported) on lactation day 21, viability, and behavioral abnormalities at least twice daily during lactation.Study 2Pups were examined for external abnormalities.The number of viable and nonviable pups was recorded for each female. All pups were sexed and weighed individually
- Postmortem examinations (parental animals):
- Study 1&2Postmortem examinations (Parent Animal)SACRIFICE :yes GROSS NECROPSY: yes gross necropsy and histological examination of the ovaries, prostate, seminal vesicles, testes with epididymides, uterus, vagina, and all gross lesions were conducted in all parental rats HISTOPATHOLOGY / ORGAN WEIGHTSThe tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.: macroscopic examination was performed
- Postmortem examinations (offspring):
- Study 1&2SACRIFICE - The F1 offspring not selected as parental animals and all F2 offspring were sacrificed at ) on lactation day 21 days of age. - These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows: GROSS NECROPSY - Gross necropsy consisted of external and internal examinations ,sex and body weight HISTOPATHOLOGY / ORGAN WEIGTHS The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.
- Statistics:
- No data available
- Reproductive indices:
- No data available
- Offspring viability indices:
- No data available
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Study 1.Hair loss appeared to be more prominent in 250mg/kg dose group F0 females than in other groupsStudy 2.
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Study 1.There were no chemical-related deaths during the studyStudy 2.1/24 females given 750 mg/kg/day found dead
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Study 1.Body weights of parental rats were lower in some of the 100mg/kg and 250 mg/kg dose groups at some points in the study, but the difference with controls was generally <10%.Study 2.Slight to markedly lower body weight gain at 250 and 750 mg/kg/day (statistically significant at 750 mg/kg/day, p<0.001) between Days 6 and 21 p.c. ; lower final body weight at 750 mg/kg/day (statistically significant, p<0.001).
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Study 1.Changes in food consumption tended to parallel the changes in body weight and were generally <10% different than controls.Study 2.Reduced food consumption at 250 and 750 mg/kg/day at initiation of the treatment period, persisting until Day 18 p.c. at 750 mg/kg/day.
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- Study 1.No treatment-related effects on reproduction or fertility were observed at any of the dose levels evaluated in this study.Study 2.Post implantation loss: slight to markedly higher at 250 and 750 mg/kg/day
- Dose descriptor:
- NOAEL
- Effect level:
- > 50 - < 250 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- mortality
- body weight and weight gain
- food consumption and compound intake
- reproductive performance
- Remarks on result:
- other: No treatment-related effects on reproduction or fertility were observed at any of the dose levels
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Study 1.Hair loss appeared to be more prominent in 250mg/kg dose group F1 females than in other groups
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- not specified
- Description (incidence and severity):
- Study 2.24/24, 21/24, 23/24 and 18/23 females with live fetuses at 0, 50, 250 and 750 mg/kg/day, respectively
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Study 1.reduced male and female F1 pup weights in the 250mg/kg dose group on lactation days 14 and 21Study 2.Fetal body weight/litter: statistically significantly lower at 750 mg/kg/day
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Study 1.F1 males showed mottled kidneys with incidences of 0/23, 2/23 (9%), 6/23 (26%), and 8/23 (35%) of the males (control and increasing dose groups). Microscopy revealed inflammation, hyaline droplet and granular cast formation, and regeneration of tubules.
- Gross pathological findings:
- not specified
- Description (incidence and severity):
- Study 2.malformations (anasarca, cleft palate, short trunk, anal atresia, short tail and/or acaudate) in 2 fetuses from 2/18 litters at 750 mg/kg/day
- Histopathological findings:
- not specified
- Other effects:
- not specified
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- > 50 - <= 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- viability
- clinical signs
- body weight and weight gain
- organ weights and organ / body weight ratios
- Remarks on result:
- other: overall no developmental toxic effects observed
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- mortality observed, treatment-related
- Description (incidence and severity):
- Decreased F2 pup viability in the 50mg/kg and 250mg/kg dose groups on postnatal day 4
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Reduced male and female F2 pup weights in the 250mg/kg bw dose group on lactation days 14 and 21
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings:
- not specified
- Other effects:
- not specified
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Dose descriptor:
- NOAEL
- Generation:
- F2
- Effect level:
- 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- viability
- mortality
- body weight and weight gain
- Remarks on result:
- other: overall no developmental toxic effects observed
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
- Relation to other toxic effects:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- No Observed Effect Level (NOEL) for reproductive toxicity was considered to be 250mg/kg/day, and NOAEL dose-level of 100 mg/kg/day was considered to be for developmental toxicity. When male and female Sprague Dawley rats were treated with N,N-diethyl-3-oxobutanamide (2235-46-3)orally.
- Executive summary:
Data available from different studies were reviewed to determine the reproductive toxicity of N,N-diethyl-3-oxobutanamide (2235-46-3).The studies are as mentioned below:
Study 1
A two-generation reproductive study of test material was performed in male and female Sprague-Dawley rats. Test material in dose concentration 0, 500, 2,000, or 5,000 ppm ( 0, 25, 100, or 250 mg /kg/day) were fed diets. The F0 parental generation consisted of 28 males and 28 females per group which were administered treated or control diet for at least 80 days prior to mating. Twenty-eight male and 28female offspring per group from the F1 generation were selected randomly to become the parents of the F2generation. These animals were treated for at least 93 days prior to mating. For both parental groups, treatment was continued through gestation and lactation. After weaning, 10 pups/sex/groups were subjected to gross necropsy. F0 females were killed after the selection of F1 parents. F1 females were sacrificed after weaning of their litters. The parameters were used to assess toxicity were twice daily observations for deaths and clinical signs, body weight, and food consumption (not measured during the mating periods). Additionally, gross necropsy and histological examination of the ovaries, prostate, seminal vesicles, testes with epididymides, uterus, vagina, and all gross lesions were conducted in all parental rats and 10 weanlings/sex/group in the control and 250mg/kg/daydose groups. Parameters used to assess developmental toxicity in the F1 and F2 litters included number of live and stillborn pups, external anomalies, sex and body weight grouped by sex on lactation days 0, 4, 7, and 14, sex and individual body weights (only group weights reported) on lactation day 21, viability, and behavioral abnormalities at least twice daily during lactation.
There were no chemical-related deaths during the study. Hair loss appeared to be more prominent in 250mg/kg /day dose group F0 and F1 females than in other groups. Body weights of parental rats were lower in some of the 100 mg/kg /day and 250mg/kg /day dose groups at some points in the study, but the difference with controls was generally <10%. Changes in food consumption tended to parallel the changes in body weight and were generally <10% different than controls. F1 males showed mottled kidneys with incidences of 0/23, 2/23 (9%), 6/23 (26%), and 8/23 (35%) of the males (control and increasing dose groups). Microscopy revealed inflammation, hyaline droplet and granular cast formation, and regeneration of tubules. No explicit information was provided in the review regarding the other organs examined. Neonatal toxicity as evidences by reduced pup sizes in both generations was noted for males and females250mg/kg /day groups on postnatal day 4 and reduced male and female F1 and F2 pup weights in the 250mg/kg /day dose group on lactation days 14 and 21.No treatment-related effects on reproduction or fertility were observed at any of the dose levels evaluated in this study. Hence No Observed Effect Level (NOEL) for reproductive toxicity was considered to be 250mg/kg/day, and NOAEL dose-level of 100 mg/kg/day was considered to be for developmental toxicity. When male and female Sprague Dawley rats were treated with test material orally.
Study 2
Reproductive and developmental toxicity study of test material was performed on female rats according OECD Guidelines for Testing of Chemicals; Methods No. 414. The test material in dose concentration0, 50,250,750 mg/kg bw/dayvia oral administration from day 6 to day 20 p.c. Clinical signs, Body weight and food consumption were noted. Pups were examined for external abnormalities. The number of viable and nonviable pups was recorded for each female. All pups were sexed and weighed individually. Clinical signs round back, emaciated appearance, piloerection , loud breathing, dyspnea, sneezing, reddish vaginal discharge, chromorhinorrhea and/or dacryhorrhea) in 1/24, 4/24 and 14/24 females given 50, 250 or 750 mg/kg/day, respectively. Ptyalism in 1/24 and 16/24 females given 250 or 750 mg/kg/day. 1/24 females given 750 mg/kg/day found dead. slight to markedly lower body weight gain at 250 and 750 mg/kg/day (statistically significant at 750 mg/kg/day, p<0.001) between Days 6 and 21 p.c. ; lower final body weight at 750 mg/kg/day (statistically significant, p<0.001). Reduced food consumption at 250 and 750 mg/kg/day at initiation of the treatment period, persisting until Day 18 p.c. at 750 mg/kg/day. Post implantation loss: slight to markedly higher at 250 and 750 mg/kg/day. Gravid uterus weight slight to markedly lower at 250 and 750 mg/kg/day. 24/24, 21/24, 23/24 and 18/23 females with live fetuses at 0, 50, 250 and 750 mg/kg/day, respectively. Fetal body weight/litter statistically significantly lower at 750 mg/kg/day. Malformations (anasarca, cleft palate, short trunk, anal atresia, short tail and/or acaudate) in 2 fetuses from 2/18 litters at 750 mg/kg/day were observed. HenceNo Observed Effect Level (NOEL) was considered to be 50mg/kg/day, and LOAEL dose-level of 250 mg/kg/day was considered to be for reproductive toxicity.When femalerats were treated withtest material orally.
Based on the data available from different studies, N,N-diethyl-3-oxobutanamide (2235-46-3)did not showed reproductive toxicity at dose concentration below 250mg/kg bw/day . Hence the test chemical is not likely to classify as a reproductive toxicant as per the criteria mentioned in CLP regulation.
Reference
Body Weight (g) of Rats on Lactation Day 21 in a 2-Generation Reproductive Study
Doses (mg/kg/day) | 0 | 25 | 100 | 250 |
F1 male | 46.2±6.50a | 46.8 ±5.06 | 45.7 ±4.53 | 40.1 ±4.22b |
F1 female | 44.1 ±4.64 | 44.6 ±4.44 | 44.2 ±4.51 | 39 1± 4.60b |
F2 males | 50.4 ±4.31 | 49.4 ±6.07 | 47.9 ±4.02 | 44.5± 3.93b |
F2 Female | 47.3± 4.52 | 47.6 ± 5.35 | 44.1 ±7.50 | 42.3± 3.23b |
aMean±standard deviation.bp<0.01.
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 250 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Data is Klimicsh 2 and from authoritative database
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Reproductive toxicity study
Data available from different studies were reviewed to determine the reproductive toxicity of N,N-diethyl-3-oxobutanamide (2235-46-3).The studies are as mentioned below:
Study 1
A two-generation reproductive study of test material was performed in male and female Sprague-Dawley rats. Test material in dose concentration 0, 500, 2,000, or 5,000 ppm ( 0, 25, 100, or 250 mg /kg/day) were fed diets. The F0 parental generation consisted of 28 males and 28 females per group which were administered treated or control diet for at least 80 days prior to mating. Twenty-eight male and 28female offspring per group from the F1 generation were selected randomly to become the parents of the F2generation. These animals were treated for at least 93 days prior to mating. For both parental groups, treatment was continued through gestation and lactation. After weaning, 10 pups/sex/groups were subjected to gross necropsy. F0 females were killed after the selection of F1 parents. F1 females were sacrificed after weaning of their litters. The parameters were used to assess toxicity were twice daily observations for deaths and clinical signs, body weight, and food consumption (not measured during the mating periods). Additionally, gross necropsy and histological examination of the ovaries, prostate, seminal vesicles, testes with epididymides, uterus, vagina, and all gross lesions were conducted in all parental rats and 10 weanlings/sex/group in the control and 250mg/kg/daydose groups. Parameters used to assess developmental toxicity in the F1 and F2 litters included number of live and stillborn pups, external anomalies, sex and body weight grouped by sex on lactation days 0, 4, 7, and 14, sex and individual body weights (only group weights reported) on lactation day 21, viability, and behavioral abnormalities at least twice daily during lactation.
There were no chemical-related deaths during the study. Hair loss appeared to be more prominent in 250mg/kg /day dose group F0 and F1 females than in other groups. Body weights of parental rats were lower in some of the 100 mg/kg /day and 250mg/kg /day dose groups at some points in the study, but the difference with controls was generally <10%. Changes in food consumption tended to parallel the changes in body weight and were generally <10% different than controls. F1 males showed mottled kidneys with incidences of 0/23, 2/23 (9%), 6/23 (26%), and 8/23 (35%) of the males (control and increasing dose groups). Microscopy revealed inflammation, hyaline droplet and granular cast formation, and regeneration of tubules. No explicit information was provided in the review regarding the other organs examined. Neonatal toxicity as evidences by reduced pup sizes in both generations was noted for males and females250mg/kg /day groups on postnatal day 4 and reduced male and female F1 and F2 pup weights in the 250mg/kg /day dose group on lactation days 14 and 21.No treatment-related effects on reproduction or fertility were observed at any of the dose levels evaluated in this study. Hence No Observed Effect Level (NOEL) for reproductive toxicity was considered to be 250mg/kg/day, and NOAEL dose-level of 100 mg/kg/day was considered to be for developmental toxicity. When male and female Sprague Dawley rats were treated with test material orally.
Study 2
Reproductive and developmental toxicity study of test material was performed on female rats according OECD Guidelines for Testing of Chemicals; Methods No. 414. The test material in dose concentration0, 50,250,750 mg/kg bw/dayvia oral administration from day 6 to day 20 p.c. Clinical signs, Body weight and food consumption were noted. Pups were examined for external abnormalities. The number of viable and nonviable pups was recorded for each female. All pups were sexed and weighed individually. Clinical signs round back, emaciated appearance, piloerection , loud breathing, dyspnea, sneezing, reddish vaginal discharge, chromorhinorrhea and/or dacryhorrhea) in 1/24, 4/24 and 14/24 females given 50, 250 or 750 mg/kg/day, respectively. Ptyalism in 1/24 and 16/24 females given 250 or 750 mg/kg/day. 1/24 females given 750 mg/kg/day found dead. slight to markedly lower body weight gain at 250 and 750 mg/kg/day (statistically significant at 750 mg/kg/day, p<0.001) between Days 6 and 21 p.c. ; lower final body weight at 750 mg/kg/day (statistically significant, p<0.001). Reduced food consumption at 250 and 750 mg/kg/day at initiation of the treatment period, persisting until Day 18 p.c. at 750 mg/kg/day. Post implantation loss: slight to markedly higher at 250 and 750 mg/kg/day. Gravid uterus weight slight to markedly lower at 250 and 750 mg/kg/day. 24/24, 21/24, 23/24 and 18/23 females with live fetuses at 0, 50, 250 and 750 mg/kg/day, respectively. Fetal body weight/litter statistically significantly lower at 750 mg/kg/day. Malformations (anasarca, cleft palate, short trunk, anal atresia, short tail and/or acaudate) in 2 fetuses from 2/18 litters at 750 mg/kg/day were observed. HenceNo Observed Effect Level (NOEL) was considered to be 50mg/kg/day, and LOAEL dose-level of 250 mg/kg/day was considered to be for reproductive toxicity.When femalerats were treated withtest material orally.
Based on the data available from different studies, N,N-diethyl-3-oxobutanamide (2235-46-3)did not showed reproductive toxicity at dose concentration below 250mg/kg bw/day . Hence the test chemical is not likely to classify as a reproductive toxicant as per the criteria mentioned in CLP regulation.
Effects on developmental toxicity
Description of key information
Developmental toxicity study
The data available for N,N-diethyl-3-oxobutanamide (2235-46-3)andstructurally similarread across chemicals was reviewed to determine the developmental toxicity.The NOAEL for reproductive toxicity was considered to be above 50-250mg/kg bw/day as No effects on reproductive parameters were observed .When male and female rats were treated with
N,N-diethyl-3-oxobutanamide (2235-46-3).
Thus, comparing this value with the criteria of CLP regulation N,N-diethyl-3-oxobutanamide (2235-46-3) not likely to classify as reproductive toxicant.
Link to relevant study records
- Endpoint:
- developmental toxicity
- 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:
- Weight of evidence approach based on structurally similar chemicals
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: As mentioned below
- Principles of method if other than guideline:
- WoE report is based on two developmental toxicity studies on rats Study 1&2 .Developmental toxicity study of test material was performed on female CD rats.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- other: CD
- Details on test animals or test system and environmental conditions:
- No data available
- Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- No data available
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- mated female used
- Duration of treatment / exposure:
- Study 1.14 days (from days 6 to 15 of gestation)Study 2.14 days (from day 6 to day 20 p.c.)
- Frequency of treatment:
- daily
- Duration of test:
- No data available
- Remarks:
- Study 1.0, 125, 250or 750 mg/kg/dayStudy 20, 50,250,750 mg/kg bw/day
- No. of animals per sex per dose:
- Study 1.Total:1000 mg/kg bw/day:25 females 125 mg/kg bw/day:25 females 250mg/kg bw/day:25 females 750mg/kg bw/day: 25 females
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data available
- Maternal examinations:
- Study 1& 2Parental animals observation and examinationsCAGE SIDE OBSERVATIONS: yes DETAILED CLINICAL OBSERVATIONS: Yes Time schedule: BODY WEIGHT: YesTime schedule for examinations: FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): yes Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: no Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data: No data availableWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data Time schedule for examinations: OTHER:
- Ovaries and uterine content:
- Study 1& 2The ovaries and uterine content was examined after termination: Yes Examinations included: - Gravid uterus weight: Yes - Number of corpora lutea: No data - Number of implantations: No data - Number of early resorptions: No data - Number of late resorptions: No data - Other:
- Fetal examinations:
- Study 1& 2- External examinations: Yes: all per litter - Soft tissue examinations: Yes: all per litter - Skeletal examinations: Yes: all per litter - Head examinations: No data
- Statistics:
- No data available
- Indices:
- No data available
- Historical control data:
- No data available
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Study 1.Clinical signs such as hypoactivity, ataxia, decreased muscle tone, foot splay, perinasal encrustation, and perioral wetness were observed; some of these signs were suggestive of neurotoxicity in this dose group because none of these signs were seen in the controls. Some of these clinical signs were seen only sporadically in the other treated groups. Study 2.Clinical signs round back, emaciated appearance, piloerection , loud breathing, dyspnea, sneezing, reddish vaginal discharge, chromorhinorrhea and/or dacryhorrhea) in 1/24, 4/24 and 14/24 females given 50, 250 or 750 mg/kg/day, respectively. Ptyalism in 1/24 and 16/24 females given 250 or 750 mg/kg/day.
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Study 1.In the 750mg/kg /day dose group dams, there was an increase in mortality rateStudy 2.1/24 females given 750 mg/kg/day found dead
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Study 1.In the 750mg/kg /day dose group dams, there was an a reduction in body weight gain Study 2.Slight to markedly lower body weight gain at 250 and 750 mg/kg/day (statistically significant at 750 mg/kg/day, p<0.001) between Days 6 and 21 p.c. ; lower final body weight at 750 mg/kg/day (statistically significant, p<0.001).
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Study 1.In the 750mg/kg /day dose group dams, there was an a reduction in food consumptionStudy 2.Reduced food consumption at 250 and 750 mg/kg/day at initiation of the treatment period, persisting until Day 18 p.c. at 750 mg/kg/day.
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Study 1.an increase in mean liver weights.Study 2.Gravid uterus weight slight to markedly lower at 250 and 750 mg/kg/day.
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- effects observed, treatment-related
- Description (incidence and severity):
- Study 1.A slight increase in percent post-implantation loss was seen in the 750mg/kg/day dose groupStudy 2.Post implantation loss: slight to markedly higher at 250 and 750 mg/kg/day
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not specified
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified - Changes in number of pregnant:
- not specified
- Other effects:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- > 50 - <= 250 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- clinical signs
- food consumption and compound intake
- mortality
- organ weights and organ / body weight ratios
- pre and post implantation loss
- Remarks on result:
- other: overall no toxic effects observed
- Abnormalities:
- not specified
- Localisation:
- not specified
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Study 1.a statistically-significant decrease in mean fetal body weight/litter was seen in the 750mg/kg /day dose group Study 2.Fetal body weight/litter: statistically significantly lower at 750 mg/kg/day
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified - Reduction in number of live offspring:
- effects observed, treatment-related
- Description (incidence and severity):
- Study 2.24/24, 21/24, 23/24 and 18/23 females with live fetuses at 0, 50, 250 and 750 mg/kg/day, respectively.
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- not specified
- External malformations:
- no effects observed
- Description (incidence and severity):
- Study 1.The incidence of external variations and/or malformations were comparable in the control and treatment groups
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- Study 1.The incidence of skeletal variations and/or malformations were comparable in the control and treatment groupsStudy 2..malformations (anasarca, cleft palate, short trunk, anal atresia, short tail and/or acaudate) in 2 fetuses from 2/18 litters at 750 mg/kg/day
- Visceral malformations:
- no effects observed
- Description (incidence and severity):
- Study 1.The incidence of visceral variations and/or malformations were comparable in the control and treatment groups
- Other effects:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- > 50 - <= 250 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- reduction in number of live offspring
- external malformations
- skeletal malformations
- visceral malformations
- Remarks on result:
- other: overall no developmental toxic effects observed
- Abnormalities:
- not specified
- Localisation:
- other: not specified
- Developmental effects observed:
- not specified
- Treatment related:
- not specified
- Relation to maternal toxicity:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- No Observed Effect Level (NOEL) for developmental toxicity was considered to be above 50-250mg/kg/day, When female rats were treated with N,N-diethyl-3-oxobutanamide (2235-46-3) orally.
- Executive summary:
Data available from different studies were reviewed to determine thedevelopmental toxicityof N,N-diethyl-3-oxobutanamide (2235-46-3).The studies are as mentioned below:
Study 1
Developmental toxicity study of test material was performed on mated female CD rats. Undiluted test material in dose concentration0, 125, 250, or 750 mg/kg/day were administered via oral gavage route from days 6 to 15 of gestation.Control animals received corn oil .Twenty-five mated female rats per group were used in study. Clinical signs, body weights, food consumption, maternal liver and gravid uterine weights, maternal ovarian and uterine examination were noted. fetal external examinations and internal soft-tissue and skeletal examinations were carried out.In the 750mg/kg/day dose dams clinical signs such as hypoactivity, ataxia, decreased muscle tone, foot splay, perinasal encrustation, and perioral wetness were observed; some of these signs were suggestive of neurotoxicity in this dose group because none of these signs were seen in the controls. Some of these clinical signs were seen only sporadically in the other treated groups. In the high-dose dams, there was an increase in mortality rate, a reduction in body weight gain and food consumption, and an increase in mean liver weights. A slight increase in percent post-implantation loss was seen in the 750mg/kg/day dose group and a statistically-significant decrease in mean fetal body weight/litter was seen in the 750mg/kg/day dose group. No additional compound-related effects were found.The incidence of external, visceral, and skeletalvariations and/or malformations were comparable in the control and treatment groups. HenceNo Observed Effect Level (NOEL) for developmental toxicity was considered to be 250mg/kg/day,When femaleCD rats were treated withtest material orally.
Study 2
Developmental toxicity study of test material was performed on female rats according OECDGuidelines for Testing of Chemicals; Methods No. 414. The test material in dose concentration0, 50,250,750 mg/kg bw/dayvia oral administration fromday 6 to day 20 p.c.Clinical signs,Body weight and food consumptionwere noted.Pups were examined for external abnormalities. The number of viable and nonviable pups was recorded for each female. All pups were sexed and weighed individually.Clinical signs round back, emaciated appearance, piloerection , loud breathing, dyspnea, sneezing, reddish vaginal discharge, chromorhinorrhea and/or dacryhorrhea) in 1/24, 4/24 and 14/24 females given 50, 250 or 750 mg/kg/day, respectively. Ptyalism in 1/24 and 16/24 females given 250 or 750 mg/kg/day. 1/24 females given 750 mg/kg/day found dead. slight to markedly lower body weight gain at 250 and 750 mg/kg/day (statistically significant at 750 mg/kg/day, p<0.001) between Days 6 and 21 p.c. ; lower final body weight at 750 mg/kg/day (statistically significant, p<0.001). Reduced food consumption at 250 and 750 mg/kg/day at initiation of the treatment period, persisting until Day 18 p.c. at 750 mg/kg/day. Post implantation loss: slight to markedly higher at 250 and 750 mg/kg/day. Gravid uterus weight slight to markedly lower at 250 and 750 mg/kg/day. 24/24, 21/24, 23/24 and 18/23 females with live fetuses at 0, 50, 250 and 750 mg/kg/day, respectively. Fetal body weight/litter statistically significantly lower at 750 mg/kg/day. Malformations (anasarca, cleft palate, short trunk, anal atresia, short tail and/or acaudate) in 2 fetuses from 2/18 litters at 750 mg/kg/day were observed. HenceNo Observed Effect Level (NOEL) was considered to be 50mg/kg/day for developmental toxicity.When femalerats were treated withtest materialorally.
Based on the data available from different studies, N,N-diethyl-3-oxobutanamide (2235-46-3)did not showeddevelopmental toxicity at dose concentration below 250mg/kg bw/day . Hence the test chemical is not likely to classify as a reproductive toxicant as per the criteria mentioned in CLP regulation.
Reference
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 50 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is Klimicsh 2 and from authoritative database
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Developmental toxicitystudy
Data available from different studies were reviewed to determine thedevelopmental toxicityof N,N-diethyl-3-oxobutanamide (2235-46-3).The studies are as mentioned below:
Study 1
Developmental toxicity study of test material was performed on mated female CD rats. Undiluted test material in dose concentration0, 125, 250, or 750 mg/kg/day were administered via oral gavage route from days 6 to 15 of gestation.Control animals received corn oil .Twenty-five mated female rats per group were used in study. Clinical signs, body weights, food consumption, maternal liver and gravid uterine weights, maternal ovarian and uterine examination were noted. fetal external examinations and internal soft-tissue and skeletal examinations were carried out.In the 750mg/kg/day dose dams clinical signs such as hypoactivity, ataxia, decreased muscle tone, foot splay, perinasal encrustation, and perioral wetness were observed; some of these signs were suggestive of neurotoxicity in this dose group because none of these signs were seen in the controls. Some of these clinical signs were seen only sporadically in the other treated groups. In the high-dose dams, there was an increase in mortality rate, a reduction in body weight gain and food consumption, and an increase in mean liver weights. A slight increase in percent post-implantation loss was seen in the 750mg/kg/day dose group and a statistically-significant decrease in mean fetal body weight/litter was seen in the 750mg/kg/day dose group. No additional compound-related effects were found.The incidence of external, visceral, and skeletalvariations and/or malformations were comparable in the control and treatment groups. HenceNo Observed Effect Level (NOEL) for developmental toxicity was considered to be 250mg/kg/day,When femaleCD rats were treated withtest materialorally.
Study 2
Developmental toxicity study of test material was performed on female rats according OECDGuidelines for Testing of Chemicals; Methods No. 414. The test material in dose concentration0, 50,250,750 mg/kg bw/dayvia oral administration fromday 6 to day 20 p.c.Clinical signs,Body weight and food consumptionwere noted.Pups were examined for external abnormalities. The number of viable and nonviable pups was recorded for each female. All pups were sexed and weighed individually.Clinical signs round back, emaciated appearance, piloerection , loud breathing, dyspnea, sneezing, reddish vaginal discharge, chromorhinorrhea and/or dacryhorrhea) in 1/24, 4/24 and 14/24 females given 50, 250 or 750 mg/kg/day, respectively. Ptyalism in 1/24 and 16/24 females given 250 or 750 mg/kg/day. 1/24 females given 750 mg/kg/day found dead. slight to markedly lower body weight gain at 250 and 750 mg/kg/day (statistically significant at 750 mg/kg/day, p<0.001) between Days 6 and 21 p.c. ; lower final body weight at 750 mg/kg/day (statistically significant, p<0.001). Reduced food consumption at 250 and 750 mg/kg/day at initiation of the treatment period, persisting until Day 18 p.c. at 750 mg/kg/day. Post implantation loss: slight to markedly higher at 250 and 750 mg/kg/day. Gravid uterus weight slight to markedly lower at 250 and 750 mg/kg/day. 24/24, 21/24, 23/24 and 18/23 females with live fetuses at 0, 50, 250 and 750 mg/kg/day, respectively. Fetal body weight/litter statistically significantly lower at 750 mg/kg/day. Malformations (anasarca, cleft palate, short trunk, anal atresia, short tail and/or acaudate) in 2 fetuses from 2/18 litters at 750 mg/kg/day were observed. HenceNo Observed Effect Level (NOEL) was considered to be 50mg/kg/day for developmental toxicity.When femalerats were treated withtest material orally.
Based on the data available from different studies, N,N-diethyl-3-oxobutanamide (2235-46-3)did not showeddevelopmental toxicity at dose concentration below 250mg/kg bw/day . Hence the test chemical is not likely to classify as a reproductive toxicant as per the criteria mentioned in CLP regulation.
Justification for classification or non-classification
Thus, comparing this value with the criteria of CLP regulation N,N-diethyl-3-oxobutanamide (2235-46-3)not likely to classify as reproductive and developmental toxicant.
Additional information
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