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EC number: 601-101-8 | CAS number: 111497-86-0
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 21 October 2015 - 09 May 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 016
- Report date:
- 2016
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- 2-Propenoic acid, (1-methyl-1,2-ethanediyl) bis[oxy(methyl-2,1-ethanediyl)] ester, reaction products with diethylamine
- EC Number:
- 601-101-8
- Cas Number:
- 111497-86-0
- Molecular formula:
- Molecular formula not available for this UVCB.
- IUPAC Name:
- 2-Propenoic acid, (1-methyl-1,2-ethanediyl) bis[oxy(methyl-2,1-ethanediyl)] ester, reaction products with diethylamine
- Test material form:
- liquid
1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL- Source and lot/batch No.of test material: JBLE0012T- Expiration date of the lot/batch: May 2016STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL- Storage condition of test material: Controlled room temperature protected from lightTREATMENT OF TEST MATERIAL PRIOR TO TESTING- Treatment of test material prior to testing: None
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS - Source: Charles River Laboratories, Sulzfeld, Germany - Age at study initiation: 11 weeks old at mating - Weight at study initiation: 197-233 g - Fasting period before study: - Housing: - Diet (e.g. ad libitum): ssniff SM R/M "Autoclavable Complete Feed for Rats and Mice - Breeding and Maintenance" - Water (e.g. ad libitum): tap water - Acclimation period: 5 days ENVIRONMENTAL CONDITIONS - Temperature (°C): 20.0 - 23.8°C - Humidity (%): 39-70% - Air changes (per hr): 15-20/hour - Photoperiod (hrs dark / hrs light):12 / 12 IN-LIFE DATES: From: 17 November 2015 To: 07 December 2015
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: VEHICLE - Justification for use and choice of vehicle (if other than water): corn oil - Lot/batch no. (if required): MKBQ9948V / MKBS6944V- 3 mL/kg
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analysis of test substance for concentration and/or homogeneity by validated GC method.Duplicate samples (top, middle and bottom samples) taken from the test formulation two times during the study (second and last weeks of treatment). One duplicate sample taken on each occasion from vehicle control for concentration measurement.
- Details on mating procedure:
- - Impregnation procedure: cohoused - If cohoused: - M/F ratio per cage: 1:1 - Length of cohabitation: 2 hours - Proof of pregnancy: vaginal plug / sperm in vaginal smear referred to as day 0 of pregnancy
- Duration of treatment / exposure:
- GD 6 to GD 19
- Frequency of treatment:
- Daily
- Duration of test:
- Until GD 20
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 24 mated females/group
- Control animals:
- yes
- Details on study design:
- - Dose selection rationale: based on available data, including an OECD 422 study
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes - Time schedule: Twice daily each day DETAILED CLINICAL OBSERVATIONS: Yes / No / No data - Time schedule: at the onset of treatment (GD 6) then weekly BODY WEIGHT: Yes - Time schedule for examinations: GD 0, 3, 6, 8, 10, 12, 14, 16, 18 and 20 FOOD CONSUMPTION: Yes - Time schedule: GD 0, 3, 6, 8, 10, 12, 14, 16, 18 and 20 POST-MORTEM EXAMINATIONS: Yes - Sacrifice on gestation day 20 - Organs examined: viscera, ovaries, uterus, OTHER:
- Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes Examinations included: - Gravid uterus weight: Yes - Number of corpora lutea: Yes - Number of implantations: Yes - Number of early resorptions: Yes - Number of late resorptions: Yes
- Fetal examinations:
- - External examinations: Yes: all per litter - Soft tissue examinations: Yes: half per litter - Skeletal examinations: Yes: half per litter - Head examinations: Yes:half per litter
- Statistics:
- SPSS PC+4.0
- Historical control data:
- Yes
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, non-treatment-related
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Statistically significantly decreased bodyweight and bodyweight gain were seen in the high dose group on several days/periods. However, the difference in terminal bodyweight and bodyweight gain during the study (GD 0 - 20) was less than 10%. Furthermore, the bodyweight loss duing the treatment period (GD 6 - 20) was not considered statistically significant. Therefore, these findings were not considered as clear treatment-related adverse effects. A similar but stronger effect was detected for the corrected terminal bodyweight, corrected bodyweight gain and corrected net bodyweight gain. The corrected bodyweight gain and corrected net bodyweight gain values were significantly lower compared to the control group (by 22 and 29%, respectively). These adverse effects were considered related to administration of the test substance.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- A slight effect on food consumption was observed for all test groups. Statistically significant decreased food consumption was seen for the high dose group.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
Maternal developmental toxicity
- Number of abortions:
- not examined
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- not examined
- 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 examined - Changes in number of pregnant:
- not examined
- Other effects:
- not examined
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed - Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- not examined
- Changes in litter size and weights:
- not examined
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Other effects:
- not examined
Effect levels (fetuses)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Remarks on result:
- other: Embryotoxicity
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Remarks on result:
- other: Foetotoxicity
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Remarks on result:
- other: Teratogenicity
Fetal abnormalities
- Key result
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Key result
- Developmental effects observed:
- no
Applicant's summary and conclusion
- Executive summary:
A study was conducted to assess the effect of amine synergist on the embryonic and fetal development of Hannover Wistar rats in their first pregnancy according to OECD Guideline 414, in compliance with GLP. Groups of 24 pregnant females were administered the substance diluted in corn oil (3 mL/kg) at 0, 100, 300 and 1000 mg/kg/day from Gestation Day 6 to 20. Cesarian sections, necrospy of dams and examinations of uterine content were performed on GD 20.
Dose formulations were analysed for test substance concentration twice during the treatment period using a validated GC method. Parameters monitored during the study included mortality and clinical observations, body weight, body weight gain and individual food consumtion. Maternal reproductive parameters associated with uterine examination were evaluated, and the foetuses were weighed ande xamined for external, visceral and skeletal abnormalities. Placentas were examined macroscopically. The number of confirmed pregnant, evaluated dams in the dose groups treated was 24 in the control group and 23, 24 and 24 in the low, mid and high dose groups, respectively.
All formulations were within the range of 92 to 107% of nominal concentration an were found to be homogenous. No test item was detected in the control samples. Based on these results, test item formulations were considered suitable for the study purposes. There was no unscheduled mortality or treatment related clinical signs in the study. Statistically significantly decreased body weight or body weight gain values were observed for the High dose group (100 mg/kg bw/day) on several days / periods. However, the difference in the terminal body weight and the body weight gain during the study (GD0-20) was less than 10%. Furthermore the body weight loss during the treatment period GD6-20) was not considered statistically significant. Therefore these findings were not considered as a clear test item related adverse effect. A similar but stronger effect was detected for the corrected terminal body weight, corrected body weight gain and corrected net body weight gain. The corrected body weight gain and corrected net body weight gain values were significantly lower compared to the control group (by 22% and 29% respectively). These adverse effects were considered related to the administration of the test item. A slight effect on the food consumtpion was observed in the study for all test groups. Additionally, statistically significant decreased food consumption was observed for the high dose group. There were no toxicologically significant differences, or test item related-changes in the reproductive parameters examined in the conditions of this study. The number of corpora lutea, implantation sites and pre-implantation loss mean values were comparable to the control for the test item treated groups at all dose levels. There were no effects on the early and late embryonic loss, post-implantation (total resorption, including the early and late embryonic loss) or total intrauterine mortality in the test item-related dams. No remarkable internal or external observations were recorded for any pregnant animals during necropsy. No abnormalities were observed on the placentas in any examined groups. The mean number of viable foetuses in all test item treated groups as well as their sex distribution were comparable with the control.
The weight of foetuses in the low, mid and high dose groups did not differ significantly from the control mean, when evaluated by both litter mean and group mean.
The number of body weight retarded foetuses in the test item treated groups was lower than in the control group. All abnormalities observed at external, visceral or skeletal examination in this study were considered as incidental findings, which were also observed in the concurrent study control group. The findinds lauid within historical control (HC) data or were considered to be spontaneous events unrelated to treatment.
In conclusion, when administered daily by oral gavage to pregnant Hannover Wistar rats from gestation days GD 6 to 19, amine synergist caused a slight maternal body weight and food intake effect in the high dose group, demonstrating an adequate but relatively minor maternal toxicity. There was no evidence of any adverse maternal effects in the mid and low dose groups. There were no toxicologically significant differences, or test item related-changes in the reproductive parameters examined in the conditions of this study. No foetal effects were seen at external, visceral and/or skeletal examination of foetuses in the study which could be related to the test item administration. The following NOAELs were derived (Hargitai, 2016):
NOAELmaternal toxicity:300 mg/kg bw/day
NOAELembryotoxicity:1000 mg/kg bw/day
NOAEL foetotoxicity: 1000 mg/kg bw/day
NOAELteratogenicity: 1000 mg/kg bw/day
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