Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 482-140-6 | CAS number: 13641-96-8
- 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:
- supporting study
- Study period:
- 25 Mar - 19 Apr 2010
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 010
- Report date:
- 2010
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- other: Guidelines for the Testing of Chemicals Section 4: Health Effects (Ministry of Environmental Protection of People's Republic of China)
- Deviations:
- no
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Version / remarks:
- adopted in 2018
- Deviations:
- yes
- Remarks:
- There are major deviations from the current OECD guideline. For details, please refer to "Principles of method if other than guideline".
- Principles of method if other than guideline:
- Deviations from the current OECD 414 guideline included the following:
dams were exposed on gestation day 6-15, the thyroid gland was not weighed or histopathologically assessed, no thyroid hormone levels were measured, 1/3 fetuses from each litter were examined for soft tissue alterations and all fetuses per litter were examined for skeletal alterations, anogenital distance was not measured, no individual data or raw data was included in the study report, the developmental effects were not specified as variations and malformations and the study was not conducted according to GLP. - GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- -
- EC Number:
- 482-140-6
- EC Name:
- -
- Cas Number:
- 13641-96-8
- Molecular formula:
- Hill formula: C6 H7 N O3 CAS formula: C6 H7 N O3
- IUPAC Name:
- 2-isocyanatoethyl prop-2-enoate
- Test material form:
- liquid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Shanghai SLAC Laboratory Animal Co., Ltd., China
- Age at study initiation: 3 months
- Weight at study initiation: 269 - 339 g
- Housing: Animals were housed in animal barrier system.
- Diet: standard diet (Suzhou Shuangshi Laboratory Animal Feed Co., Ltd.), ad libitum
- Water: ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 25
- Humidity (%): 40 - 70
IN-LIFE DATES: From: 25 Mar 2010 To: 19 Apr 2010
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test article was mixed with corn oil. Animals were gavaged based on 10 mL/kg bw.
VEHICLE
- Justification for use and choice of vehicle: not provided
- Amount of vehicle (if gavage): 10 mg/kg bw - Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- not applicable
- Details on mating procedure:
- - Impregnation procedure: cohoused
- M/F ratio per cage: not provided
- Length of cohabitation: not provided
- Further matings after two unsuccessful attempts: no
- Proof of pregnancy: vaginal plug; referred to as Day 0 of pregnancy - Duration of treatment / exposure:
- Pregnant rats were administered the test substance by oral gavage from Day 6 to 15.
- Frequency of treatment:
- once daily
- Duration of test:
- until Day 20 of gestation
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0.88 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 4.4 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 22 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 20 pregnant female rats in the vehicle control group and 23 pregnant female rats per dose in the groups treated with the test substance.
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale:
The doses were selected based on the results of an acute oral toxicity study. Groups of 5 female rats were orally dosed with 21.5, 46.4, 100, 215 and 464 mg/kg bw. The test substance was dissolved in corn oil and applied with a dose volume of 10 mL/kg bw. Mortalities were observed as follows:
21.5 mg/kg bw: No deaths occurred.
46.4 mg/kg bw: 1/5 females
100 mg/kg bw: 2/5 females
215 mg/kg bw: 4/5 females
464 mg/kg bw: 5/5 females
Observed clinical signs were as follows:
21.5 mg/kg bw: No obvious clinical signs were observed.
46.4 mg/kg bw: Salivation, unresponsiveness, gait flabby, sternutation, and emiction incontinence were observed at the second day after dosing in 1/5 females.
100 mg/kg bw: Salivation, unresponsiveness, gait flabby, sternutation, and emiction incontinence were observed 10 min after dosing in 2/5 females.
215 mg/kg bw: Salivation, unresponsiveness, gait flabby, sternutation, and emiction incontinence were observed 10 min after dosing in 5/5 females, while one animal returned to normal 3 days after treatment.
464 mg/kg bw: Salivation, unresponsiveness, gait flabby, sternutation, and emiction incontinence were observed 10 min after dosing in 5/5 females.
Based on the mortalities, the LD50 value was calculated to be 110 (55 - 220) mg/kg bw for female rats.
Based in the results of this acute oral toxicity study, the three doses (0.88, 4.40 and 22.00 mg/kg bw/day) were selected for the teratogenicity study.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations checked: for general health condition
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations: Body weight was recorded on gestation Day 0, 5, 8, 11, 14, 17 and 20.
FOOD CONSUMPTION AND COMPOUND INTAKE: No
WATER CONSUMPTION AND COMPOUND INTAKE: No
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20 by CO2
- Organs examined: uterus - 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
- Number of dead/live fetuses: Yes - Blood sampling:
- - Plasma: No
- Serum: No - Fetal examinations:
- - External examinations: Yes: all fetuses
- Soft tissue examinations: Yes, approximately 1/3 of the fetuses
- Skeletal examinations: Yes: approximately 2/3 of the fetuses
- Head examinations: No
- Anogenital distance of all live rodent pups: No
- Other: Sex, body weight, body length and tail length of live fetuses were recorded. 1/3 of the fetuses from each litter was taken and fixed in Bouin's solution for 2 weeks. Subsequently, the splanchnic malformations of fetus was examined. For the other 2/3 fetuses from each litter, the skin, organs and fat tissue were removed from the body. The skeleton was fixed in 90% ethanol solution at least 12 h and then put in 1% sodium hydroxide solution 3 - 5 days until the muscle became transparent and skeleton muscle could be clearly observed. The skeleton was stained with alizarin red solution until skeleton became red and then changed to transparent solution I for 1 - 2 days, followed by transparent solution II for 1 - 2 days. In the end skeleton was changed to transparent solution III for 1 - 2 days and after the skeleton had been stained red and the colour on the soft tissue faded, the sample was put into glycerol and skeletal malformations was examined. - Statistics:
- All ratios were analyzed by chi-square test. Study measurements were analyzed by ANOVA or nonparametric statistics. Fetus body length, tail length and body weight were compared by t test. The data of fetuses was analyzed in the unit of litter.
- Indices:
- No indices were calculated.
- Historical control data:
- Historical control data were not provided.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No abnormalities were detected in the female rats during the study.
- Dermal irritation (if dermal study):
- not examined
- Description (incidence and severity):
- not applicable
- Mortality:
- no mortality observed
- Description (incidence):
- No deaths occurred in any group during the study.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- 0.88 mg/kg bw/day: No body weight changes were observed when compared to the control group.
4.40 mg/kg bw/day: No body weight changes were observed when compared to the control group.
22.00 mg/kg bw/day: The body weights of the pregnant rats were reduced during Day 8 until 20 compared to the control animals. The reduction in body weight reached statistical significance on day 20 compared to the control group (approximately -4%).
For detail, please refer to the attached background material 1. - Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Endocrine findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- There were no statistically significant differences in uterus weight in any of the treatment group when compared to the control group. For detail, please refer to the attached background material 2.
- Gross pathological findings:
- not examined
- 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
- Description (incidence and severity):
- No statistically significant differences in the number of blastocyst implantation was observed in any of the treatment groups when compared to the control group.
For detail, please refer to the attached background material 2. - Total litter losses by resorption:
- not specified
- Early or late resorptions:
- no effects observed
- Description (incidence and severity):
- There was no statistically significant difference in the number of absorbed of fetuses in any treatment group when compared to the control group.
For detail, please refer to the attached background material 2. - Dead fetuses:
- no effects observed
- Description (incidence and severity):
- There was no statistically significant difference in the number of dead fetuses in any treatment group when compared to the control group.
For detail, please refer to the attached background material 2. - Changes in pregnancy duration:
- not examined
- Changes in number of pregnant:
- no effects observed
- Description (incidence and severity):
- The study was conducted with pregnant rats (23 females in the treatment groups and 20 females in the control group). Therefore, no differences in the number of pregnant rats was observed.
For detail, please refer to the attached background material 2. - Other effects:
- no effects observed
- Description (incidence and severity):
- Corpus lutea:
There was no statistically significant difference in the number of corpus lutea in females of any treatment group when compared to the control group.
For detail, please refer to the attached background material 2.
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Remarks:
- systemic toxicity
- Effect level:
- 4.4 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: No adverse effects observed at this dose level.
- Dose descriptor:
- LOAEL
- Remarks:
- systemic toxicity
- Effect level:
- 22 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- Dose descriptor:
- NOAEL
- Remarks:
- maternal developmental toxicity
- Effect level:
- 22 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: No adverse effects in regard to maternal developmental toxicity observed up to the highest dose tested.
Maternal abnormalities
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- There was no statistically significant difference in the fetal body weights of the treatment groups when compared to the control group. For detail, please refer to the attached background material 2.
- Reduction in number of live offspring:
- no effects observed
- Description (incidence and severity):
- There was no statistically significant difference in the number of live fetuses of any treatment group when compared to the control group.
For detail, please refer to the attached background material 2. - Changes in sex ratio:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The sex ration male:female was 100:80, 100:91, 100:96 and 100:105 in the control, low-, mid- and high dose group, respectively. The difference is not considered to be treatment-related as the largest difference was observed in the control group.
For detail, please refer to the attached background material 2. - Changes in litter size and weights:
- not examined
- Anogenital distance of all rodent fetuses:
- not examined
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Description (incidence and severity):
- No external malformations were observed in any of the treatment group. For detail, please refer to the attached background material 3.
- Skeletal malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- Observed skeletal malformations were as follows:
Control: 5/169 (2.96%) rib malformations, 84/169 (49.70%) sternum ossification, rudimentary or not ossified and 4/169 (2.37%) thoracic vertebra malformation
0.88 mg/kg bw/day: 10/179 (5.59%) rib malformations, 91/179 (50.84%) sternum ossification, rudimentary or not ossified and 1/179 (0.56%) thoracic vertebra malformation
4.40 mg/kg bw/day: 10/186 (5.37%) rib malformations, 99/186 (53.23%) sternum ossification, rudimentary or not ossified and 7/186 (3.76%) thoracic vertebra malformation
22.00 mg/kg bw/day: 17/179 (9.50%) rib malformations, 125/179 (69.83%) sternum ossification, rudimentary or not ossified and 17/179 (9.50%) thoracic vertebra malformation
For detail, please refer to the attached background material 3.
No statistically significant differences in skeletal malformations were observed in fetuses treated with 0.88 or 4.40 mg/kg bw/day compared to the control group. In the high dose group, the fetus ratio of rib malformations and sternum ossification rudimentary or not ossified and thoracic vertebra malformation and total skeletal malformations were higher than in the control group. The type of rib and thoracic vertebra malformations were not specified, and no individual data was given. Furthermore, variations and malformations were not listed separately and therefore it is possible that variations (structural change considered to have little or no detrimental effect; maybe transient and may occur relatively frequently in the control population) were presented as malformations (structural change considered detrimental to the animal and is usually rare). The control group prevalence was high and no historical control data range was included. There was no clear dose-response for either the rib malformation or thoracic vertebra malformations and the incidence of sternum ossification rudimentary or not ossified was very high in the control, which would lead towards a conclusion that this effect was a variation rather than a malformation. Furthermore, the acute oral toxicity study performed as a dose-range finder showed the LD50 value was 55 – 220 mg/kg bw, with severe adverse effects and mortality observed from 46.6 mg/kg bw. The highest dose group in the developmental toxicity study was approximately half of the dose that caused mortality in the range-finding study. Therefore, it is likely that the dams were systemically affected by the test substance and the observed effects on the offspring are considered to be secondary to the maternal systemic effects. - Visceral malformations:
- no effects observed
- Description (incidence and severity):
- No splanchnic malformations were observed in the treatment groups. For detail, please refer to the attached background material 3.
- Other effects:
- no effects observed
- Description (incidence and severity):
- Fetus body length:
There was no statistically significant difference in the body length of fetuses of any treatment group when compared to the control group.
Fetus tail length:
There was no statistically significant difference in the tail length of fetuses of any treatment group when compared to the control group.
For detail, please refer to the attached background material 2.
Effect levels (fetuses)
open allclose all
- Dose descriptor:
- NOAEL
- Remarks:
- developmental toxicity
- Effect level:
- 4.4 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed at this dose level.
- Dose descriptor:
- LOAEL
- Remarks:
- developmental toxicity
- Effect level:
- 22 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- skeletal malformations
- Remarks on result:
- other: adverse effects observed were secondary to maternal systemic toxicity.
Fetal abnormalities
- Abnormalities:
- effects observed, treatment-related
- Localisation:
- skeletal: sternum
- skeletal: rib
- skeletal: vertebra
- Description (incidence and severity):
- Increased incidences of rib malformations, sternum ossification rudimentary or not ossified and thoracic vertebra malformations.
Overall developmental toxicity
- Developmental effects observed:
- yes
- Lowest effective dose / conc.:
- 22 mg/kg bw/day
- Treatment related:
- yes
- Relation to maternal toxicity:
- developmental effects as a secondary non-specific consequence of maternal toxicity effects
- Dose response relationship:
- no
- Relevant for humans:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The study was conducted according to the Guidelines for the testing of chemicals section 4: Health Effects (Ministry of Environmental Protection of People's Republic of China) and comparable to OECD guideline 414 under non-GLP conditions. There were major deviations from the current OECD guideline: dams were exposed on gestation Day 6-15, the thyroid gland was not weighed or histopathologically assessed, no thyroid hormone levels were measured, 1/3 fetuses from each litter were examined for soft tissue alterations and all fetuses per litter were examined for skeletal alterations, anogenital distance was not measured, no individual data or raw data was included in the study report, and the developmental effects were not specified as variations and malformations. Under the conditions of this study, the maternal NOAEL for general toxicity was 4.40 mg/kg bw/day based on a statistically significant reduction in body weight. The fetal developmental NOAEL was 4.40 mg/kg bw/day. At 22.00 mg/kg bw/day, statistically significantly increased incidences of rib malformations, sternum ossification rudimentary or not ossified and thoracic vertebra malformations were observed compared to the control animals. However, variations and malformations were not listed separately and therefore it is possible that variations were presented as malformations. The type of variations/malformation was not specified. The control group prevalence was high and no historical control data range was included. There was no clear dose-response for either the rib malformation or thoracic vertebra malformations and the incidence of sternum ossification rudimentary or not ossified was very high in the control, which would lead towards a conclusion that this effect was a variation rather than a malformation. Furthermore, the acute oral toxicity study performed as a dose-range finder showed the LD50 value was 55 – 220 mg/kg bw, with severe adverse effects and mortality observed from 46.6 mg/kg bw. The highest dose group in the developmental toxicity study was approximately half of the dose that caused mortality in the range-finding study. Therefore, it is likely that the dams were systemically affected by the test substance and the observed effects on the offspring are considered to be secondary to the maternal systemic effects.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.