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EC number: 700-041-0 | CAS number: -
- 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

Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2002
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with national standard methods with acceptable restrictions
- Justification for type of information:
- Read across, see declaration
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 002
- Report date:
- 2002
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: internal protocol
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- (2S)-2-[(4R)-2-Oxo-4-propyl-1-pyrrolidinyl]butanamide
- Cas Number:
- 357336-20-0
- Molecular formula:
- C11H20N2O2
- IUPAC Name:
- (2S)-2-[(4R)-2-Oxo-4-propyl-1-pyrrolidinyl]butanamide
- Test material form:
- solid: particulate/powder
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: suspension in the vehicle l% (w/v) methylcellulose 400cps in sterile pyrogen free water (water for irrigation).
- Details on exposure:
- The females were dosed twice daily at least 6 hours apart, by oral gavage, from Days 6 to 17 of pregnantcy, inclusive, and received half the daily dose at each administration. The administration was conducted using rubber catheters and disposable plastic syringes. A standard dose volume of 5 mL/kg bodyweight/sub-dose (10 mL/kg bodyweight/day) was given. The dose volume given to each animal was adjusted daily according to the daily bodyweight and dosing was conducted at approximately the same time each day.
- Duration of treatment / exposure:
- Days 6 to 17 of pregnant y
- Frequency of treatment:
- The females were dosed twice daily at least 6 hours apart
Doses / concentrationsopen allclose all
- Dose / conc.:
- 150 mg/kg bw/day (nominal)
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Dose / conc.:
- 600 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 6
- Control animals:
- yes, concurrent vehicle
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- The observations did not persist into the post-dosing period.
There were no clinical signs recorded in the groups receiving 150 or 300 mg/kg/day. - Mortality:
- no mortality observed
- Description (incidence):
- There were no premature deaths during the study.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- here was a dosage-related increase in bodyweight gain, relative to Controls, between Days 6 and 7 of pregnancy (corresponding to Days 1 and 2 of dosing). This change achieved a statistical significance at 300 and 600 mg/kg/day (see Text Table 1). From Day 8 of pregnancy, the maternal bodyweight gain became similar between the Control group and groups receiving ucb 34714. Overall, at the end of the dosing period (Day 18 of pregnancy), there was no noteworthy difference in bodyweight gain between the Control group and groups receiving ucb 34714
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- here was a slight, statistically significant reduction (-9%, relative to Controls) in mean food consumption in the group receiving 600 mg/kg/day, over the period of Days 6 to 9 of pregnancy (corresponding to Days 1 to 4 of dosing) .From Day 9 and until Day 17 of pregnancy, there was no noteworthy difference between the Control group and groups receiving ucb 34714. After cessation of dosing, the food consumption was slightly increased between Days 17 and 20 (approximately +8V0, relative to Controls) in the groups that had received 300 or 600 mg/kg/day. These changes are summarised in Text Table 2. There was no effect of treatment on food consumption in females receiving 150 mg/kg/day.
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Description (incidence and severity):
- There was no effect of maternal treatment on the mean number of corpora Iutea or implantations, the extent of post-implantation losses or the number of live foetuses per female in any of the groups receiving ucb 34714 when compared with the Controls.
- Pre- and post-implantation loss:
- effects observed, treatment-related
- Description (incidence and severity):
- There was no effect of maternal treatment on the mean number of corpora Iutea or implantations, the extent of post-implantation losses or the number of live foetuses per female in any of the groups receiving ucb 34714 when compared with the Controls.
There was a slight increase in the mean percent pre-implantation loss in the group receiving 600 mg/kg/day (13%), when compared with the Controls (9.3%). This was considered to be due to one female (number 75) which had a very high pre-implantation loss. - Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- not examined
- Changes in pregnancy duration:
- not examined
- Changes in number of pregnant:
- not examined
- Other effects:
- not examined
- Details on maternal toxic effects:
- In the main study groups, there were four females receiving 150 mg/kg/day which were not pregnant at necropsy (numbers 27, 34, 46 and 47). All other main study females were pregnant with live foetuses. In the satellite groups for toxicokinetic evaluation, one female. receiving 300 mg/kg/day (number 11O)and one receiving 600 mg/kg/day (number 126) were not pregnant at necropsy. All other satellite females were pregnant at necropsy.
There was no effect of maternal treatment on the mean number of corpora Iutea or implantations, the extent of post-implantation losses or the number of live foetuses per female in any of the groups receiving ucb 34714 when compared with the Controls.
There was a slight increase in the mean percent pre-implantation loss in the group receiving 600 mg/kg/day (13%), when compared with the Controls (9.3%). This was considered to be due to one female (number 75) which had a very high pre-implantation loss.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 300 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- clinical signs
Maternal abnormalities
- Key result
- Abnormalities:
- not specified
Results (fetuses)
- Fetal body weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There was no effect of maternal treatment on the mean foetal, placental or gravid uterus weights or on the percentage of male foetuses in any of the groups receiving ucb 34714 when compared with the Controls.
n the group receiving 600 mg/kg/day there were four foetuses with major abnormalities, compared with no major abnormalities in the Control group. Two of these four abnormal foetuses were from the same litter (female number 75, that had macroscopic findings in the kidneys and a high pre-implantation loss) and had major abnormalities consisting of absent kidneys in one foetus, small kidneys and absence of a uterine horn in the other.
The two remaining abnormal foetuses were from two different litters (female numbers 84 and 94) and major abnormalities consisted of bifid sternum for one foetus and transposition of the aortic and pulmonary arch for the other.
In the groups receiving 150 or 300 mg/kg/day there were single incidence of foetuses with major abnormalities, malrotated hind-limb at 150 and absent kidney at 300mg/kg/day.
There were no treatment-related increases in the incidence of specific minor abnormalities or variants in any group receiving ucb 34714. - Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- no effects observed
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Other effects:
- no effects observed
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 600 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- fetal/pup body weight changes
Fetal abnormalities
- Key result
- Abnormalities:
- effects observed, non-treatment-related
Overall developmental toxicity
- Key result
- Developmental effects observed:
- yes
- Lowest effective dose / conc.:
- 600 mg/kg bw/day (nominal)
- Treatment related:
- no
- Relation to maternal toxicity:
- developmental effects as a secondary non-specific consequence of maternal toxicity effects
- Dose response relationship:
- no
- Relevant for humans:
- yes
Applicant's summary and conclusion
- Conclusions:
- Pregnant females receiving oral doses of 150,300 or 600 mg/kg/day ucb 34714 as two equal daily sub-doses given 6 hours apart during the period of organogenesis, were continuously exposed to the parent compound at all dose levels. After 12 days of treatment, the extent of exposure and trough plasma concentrations (Czdh)were lower than on Day 1. Following single or repeated administration, the rate and extent of exposure increased less than proportionally with the increase in dose. However, the trough plasma levels increased more than proportionally with the increase in dose.
The high dose of 600 mg/kg/day induced clinical signs in the dams (post-dosing salivation and partially closed eyes) as well as a reduction in food consumption during the early stage of pregnancy. There were no noteworthy effects in the darns at the lower doses of 150 or 300 mg/kg/day. The treatment did not induce any effect on pregnancy data or on foetal development.
From the results obtained on this study the maternal ‘No Adverse Effect Level’ (NOAEL) was considered to be 300 mg/kg/day. The foetal/developmental ‘No Adverse Effect Level’ was considered to be 600 mglkgiday. - Executive summary:
Pregnant females receiving oral doses of 150, 300 or 600 mg/kg/day ucb 34714 during organogenesis were continuously exposed to the parent compound at all dose levels. After single and repeated administration of ucb 34714, the rate (Cmax) and extent (AUC (0-24h)) of exposure increased slightly less than proportionally to the dose. This could be related to a dose-dependent limitation in absorption and is consistent with previous reported data from the 4-week toxicity study (7). However, the trough plasma levels (CzJh) increased more than proportionally with the dose. After 12 days administration, the extent of exposure and trough plasma concentrations were lower than on Day 1. These observations, which are also consistent with previous data in non-pregnant rats (7), are possibly related to an increase in the metabolic clearance of ucb 34714.
At 600 mg/kg/day noteworthy maternal effects consisted of salivation and partially closed eyes in all females and a transient decrease in food consumption at the beginning of the treatment period. Salivation occurred immediately after dosing whereas partially closed eyes occurred between 1.25 and 1.5 hours post-dosing. The group mean food consumption was decreased by 9% relative to the Controls during the first three days of the dosing period. During the remaining dosing period, the food consumption was similar between the Control group and the group receiving 600 mg/kg/day. The overall bodyweight gain for the treatment period at 600 mg/kg/day was similar to that of the Controls. The only notable change consisted of a slight and transient increase in bodyweight gain, relative to Controls, between Days 6 and 7 of pregnancy.
At 300 mg/kg/day, the only notable maternal effect was a slight and transient increase in bodyweight gain between Days 6 and 7 of pregnancy. From Day 8, however, the bodyweight gain in this group was similar to that of the Controls. There were no maternal effects at 150 mglkglday.
There were four females receiving 150 mg/kg/day which were found to be not pregnant at necropsy. However, since there was no corresponding decrease in the pregnancy rate in females receiving higher dose levels and all other pregnancy parameters of the group receiving 150 m~kg/day were comparable to the Controls, this was considered not to be related to treatment.
At 600 mg/kg/day, four foetuses presented major abnormalities. However, two of these four abnormal foetuses were from the same litter (female 75) and the findings in both of these foetuses were similar in nature. Female 75 also had a relatively high pre-implantation loss and an abnormal kidney at necropsy. In view of the clustering of the abnormalities in this litter and their similar nature they were considered not to be related to treatment. The major abnormalities in the two remaining foetuses in this group and the two foetuses at lower dose levels (one in each of the groups receiving 150 or 300 mg/kg/day) were disparate in nature and were within the historical control ranges for these abnormalities. Therefore the incidence of major abnormalities in all groups were considered to be unrelated to treatment with ucb 34714.
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