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EC number: 221-882-5 | CAS number: 3268-49-3
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1997-10-06 to 1999-09-22
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 999
- Report date:
- 1999
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.3600 (Inhalation Developmental Toxicity Screen)
- Version / remarks:
- adopted 27 Sep 1985
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Version / remarks:
- adopted 212 May 1981
- Deviations:
- yes
- Remarks:
- particle sizes not given, MMAD not determined
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 3-(methylthio)propionaldehyde
- EC Number:
- 221-882-5
- EC Name:
- 3-(methylthio)propionaldehyde
- Cas Number:
- 3268-49-3
- Molecular formula:
- C4H8OS
- IUPAC Name:
- 3-(methylthio)propionaldehyde
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: CD (Sprague-Dawley derived)
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Kingston, New York, USA
- Age at study initiation: 64 - 72 days
- Weight at study initiation: 192 - 250 g (mean: 209.6 g)
- Housing: individually in suspended stainless steel wire mesh cages
- Diet: Certified Rodent Diet, No. 5002 (PMI Feeds, Inc., St. Louis, Missouri) ad libitum
- Water: facility water, provided to the animals via an automated watering system, ad libitum
- Acclimation period: at least 3 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21- 23
- Humidity (%): 32 - 72
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 17 Oct 1997 To: 07 Nov 1997
Administration / exposure
- Route of administration:
- inhalation
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- air
- Details on exposure:
- The test material was administered as a vapor in the breathing air of the animals.
- Analytical verification of doses or concentrations:
- yes
- Details on mating procedure:
- - Impregnation procedure: All females were purchased timed pregnant.
- Duration of treatment / exposure:
- 6 h
- Frequency of treatment:
- 6 h/day during Day 6 - 16 of gestation
- Duration of test:
- Gestation Days 6 - 20
Doses / concentrationsopen allclose all
- Dose / conc.:
- 10 ppm (nominal)
- Remarks:
- corresponding to 0.043 mg/L air or 43.0 mg/m3 air (corresponding to an analytical concentration of 9.87 ± 1.3 ppm, 0.0425 mg/L air or 42.5 mg/m3 air)
- Dose / conc.:
- 65 ppm (nominal)
- Remarks:
- corresponding to 0.28 mg/L air or 279.8 mg/m3 air (corresponding to an analytical concentration of 58.3 ± 7.2 ppm, 0.251 mg/L air or 251.0 mg/m3 air)
- Dose / conc.:
- 125 ppm (nominal)
- Remarks:
- corresponding to 0.538 mg/L air or 538.1 mg/m3 air (corresponding to an analytical concentration of 127.8 ± 18 ppm, 0.55 mg/L air or 550.1 mg/m3 air)
- No. of animals per sex per dose:
- 24
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Dose levels were selected based on the results of a pilot inhalation developmental toxicity study.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- In chamber observations: All animals were observed as a group at least once during each exposure for appearance, activity or other unusual findings.
- Cage side observations: All animals were observed at least twice daily for mortality, general appearance and signs of severe toxic or pharmacologic effects.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: during treatment interval pre- and postexposure on Days 4, daily on study Days 6 - 16 and on Day 20 of gestation.
- The observations included: general condition, skin and fur, eyes, nose, oral cavity, abdomen and external genitalia as well as evaluations of respiration. Unusual behavior was also recorded. During the treatment period, these examinations were performed both pre- and post-exposure.
BODY WEIGHT: Yes
- Time schedule for examinations: on Days 4, 6, 9, 12, 16, 18 and 20 of gestation. Day 0 gestation body weights were provided by the supplier
FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
Food consumption was recorded for each female during the following intervals of gestation: Days 4-6, 6-9, 9-12, 12-16, 16-18, and 18-20.
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION AND COMPOUND INTAKE: No
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation Day 20
- Organs examined: uterus and ovaries - 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
- Other: Number of live and dead fetuses - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter
- Head examinations: No - Statistics:
- Means and standard deviations were calculated for continuous data (body weight, body weight change, food consumption, number of corpora lutea, uterine implantation data, implantation loss, number of male/female fetuses, percentage of fetuses per litter, fetal weight). All statistical tests were conducted at the 5% and 1%, two-sided risk levels. In addition, multiple group analysis was performed when more than one treated group was compared to control. Statistical evaluation of equality of means were made by the appropriate one way analysis of variance (ANOVA) technique, followed by a multiple comparison procedure, if needed. If ANOVA showed no difference, no additional comparisons were made. If ANOVA was significant, Dunnett's test was used to determine which data, if any, differed from the control. Incidence data (mortality and pregnancy rate, incidence of litters containing fetuses with malformations or variations) was performed when more than one group was compared to control. In this case, a Fisher Exact Test with Bonferonni correction was performed to identify differences between the groups.
- Indices:
- Pre-implantation loss = ((number of corpora lutea - number of implantations) / number of corpora lutea) x 100
Post-implantation loss = ((number of early and late resorptions and dead fetuses) / number of implantation sites) x 100 - Historical control data:
- Please refer to Table No. 1 under "Any other information on materials and methods incl. tables"
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- During exposure: In the 125 ppm group, the most frequently seen in-chamber observations were lacrimation, labored breathing and closed eyes. These findings were considered treatment-related. Other less frequently seen in-chamber observations in this group included mucoid nasal discharge, salivation, chromodacryorrhea and brown ano-genital staining. The latter observations were observed in a few animals only and not attributed to treatment. There were no remarkable observations at 10 and 65 ppm.
Post-exposure: Yellow (urinary) and/or brown staining of the anogenital area and ventral surface were observed at all treatment levels. The incidence was dose-related and attributed to treatment. Findings were observed in a single low dose (10 ppm) animal (on two occasions), in 7of 24 mid dose (65 ppm) animals and in all 24 high dose (125 ppm) animals. These findings were seen as early as Day 8 of gestation and continued to be seen in several animals to Day 20 of gestation. Severity was generally slight to moderate in all groups. In addition, animals of the high dose group (125 ppm) had red/brown stainings on the face and snout, which was considered to be treatment-related. For details please refer to Table 1 under “Any other information on results incl. tables”. - Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Dose related decreases in body weight gain were observed during the treatment period (please refer to Tables 2 and 3 under “Any other information on results incl. tables”). At 10 ppm, mean body weight gains over the treatment period (Days 6-16 of gestation) were only slightly lower than body weight gains of the controls (57 vs. 64 g) and the mean body weights at study termination was within 2% of the mean control weights. Mean body weight gain during Days 6-20 of gestation were slightly, but significantly lower than controls (40 vs. 52 g), which was attributed to heavier gravid uterine weight seen in this group when compared to control data.
At 65 ppm, mean body weight gain was significantly decreased during gestation Days 6-16 (55 vs. 64 g), and over the gestation period Day 6-20 (52 vs. 41 g) when compared to control animals. At study termination, the mean body weights for the group were 4% lower than the mean control weight.
At 125 ppm, mean body weight gains from gestation Days 6-9, gestation Days 6-16 and gestation Days 9-20 were significantly reduced when compared to control animals. At study termination, the mean body weight gain was 8% lower than the mean control weight. The findings were considered treatment-related, as a clear dose-response relationship was evident. Findings in the high dose group were considered to be of toxicological significance. - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Food consumption patterns during gestation in the treated groups were consistent with body weight patterns. Dose-related decreases, relative to control values, occurred for food consumption measured either as total food intake (grams of food/day) or food intake adjusted for body weight (grams of food/kilogram of body weight/day). Statistically significant differences from concurrent control values occurred at a single interval (Days 12-16) for the 10 ppm group, at two intervals (Days 9-12 and 12-16) for the 65 ppm group and at all intervals (Days 6-9, 9-12, 12-16) during the treatment period for the 125 ppm group (please refer to Table 5 under “Any other information on results incl. tables”). The findings in the high dose group were attributed to treatment and considered as toxicologically relevant.
- Food efficiency:
- no effects observed
- 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:
- no effects observed
- 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:
- no effects observed
- 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
- Changes in number of pregnant:
- not examined
- Other effects:
- not examined
Effect levels (maternal animals)
open allclose all
- Key result
- Dose descriptor:
- LOAEC
- Remarks:
- systemic
- Effect level:
- 127.8 ppm (analytical)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- clinical signs
- food consumption and compound intake
- Remarks on result:
- other: corresponding to 0.55 mg/L air or 550.1 mg/m3 air
- Key result
- Dose descriptor:
- NOAEC
- Remarks:
- systemic
- Effect level:
- 58.3 ppm (analytical)
- Based on:
- test mat.
- Basis for effect level:
- other: no adverse effect observed
- Remarks on result:
- other: corresponding to 0.251 mg/L air or 251.0 mg/m3 air
- Key result
- Dose descriptor:
- NOAEC
- Remarks:
- fertility
- Effect level:
- 127.8 ppm (analytical)
- Based on:
- test mat.
- Basis for effect level:
- other: no adverse effect observed
- Remarks on result:
- other: corresponding to 0.55 mg/L air or 550.1 mg/m3 air
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- 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
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEC
- Remarks:
- developmental
- Effect level:
- 127.8 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effect observed
- Remarks on result:
- other: corresponding to 0.55 mg/L air or 550.1 mg/m3 air
Fetal abnormalities
- Key result
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Key result
- Developmental effects observed:
- no
Any other information on results incl. tables
Table 1: Clinical findings post exposure (frequency/animals)
Group | 1 | 2 | 3 | 4 |
Concentration (ppm) | 0 | 10 | 65 | 125 |
General Appearance | ||||
Necrotic tip of tail | 0/0 | 0/0 | 0/0 | 8/1 |
Dermal findings | ||||
Brown stains facial | 0/0 | 0/0 | 0/0 | 5/1 |
Ano-genital stains | 9/6 | 19/9 | 43/15 | 164/23 |
Red stains facial | 0/0 | 5/3 | 15/9 | 51/16 |
Ocular findings | ||||
Chromodacryorrhea - unilateral | 1/1 | 1/1 | 3/2 | 3/3 |
Chromodacryorrhea - bilateral | 0/0 | 0/0 | 0/0 | 5/2 |
Lacrimation - unilateral | 1/1 | 0/0 | 3/1 | 10/5 |
Lacrimation - bilateral | 0/0 | 1/1 | 0/0 | 22/8 |
Oral/Buccal findings | ||||
Nasal discharge - clear | 0/0 | 0/0 | 0/0 | 2/2 |
Excessive salivation | 0/0 | 0/0 | 0/0 | 1/1 |
Table 2: Mean body weight dams
Group | 1 | 2 | 3 | 4 |
Concentration (ppm) | 0 | 10 | 65 | 125 |
Day | ||||
0 | 211 ± 12.5 | 212 ± 11.5 | 209 ± 12.2 | 210 ± 15.9 |
4 | 235 ± 13.5 | 235 ± 14.5 | 234 ± 12.5 | 234 ± 15.9 |
6 | 254 ± 16.2 | 254 ± 14.9 | 253 ± 14.1 | 250 ± 17.3 |
9 | 268 ± 17.6 | 266 ± 18.1 | 264 ± 13.9 | 250 ± 16.4** |
12 | 289 ± 20.1 | 281 ± 21.3 | 279 ± 13.6 | 265 ± 17.1** |
16 | 319 ± 22.9 | 311 ± 23.1 | 308 ± 15.3 | 290 ± 19.2** |
18 | 349 ± 28.7 | 338 ± 25.8 | 334 ± 20.8 | 319 ± 23.0** |
20 | 381 ± 31.0 | 373 ± 27.0 | 367 ± 25.1 | 349 ± 28.6** |
** = p < 0.01
Table 3: Body weight gains
Group | 1 | 2 | 3 | 4 |
Concentration (ppm) | 0 | 10 | 65 | 125 |
Days 0-4 | 24 ± 4.4 | 23 ± 8.0 | 24 ± 5.3 | 23 ± 6.3 |
Days 0-6 | 19 ± 5.6 | 19 ± 6.7 | 19 ± 5.9 | 17 ± 4.9 |
Days 6-9 | 14 ± 4.5 | 13 ± 4.9 | 11 ± 4.1 | 0 ± 6.3 ** |
Days 9-12 | 20 ± 6.0 | 14 ± 8.8 | 15 ± 6.8 | 15 ± 5.5 |
Days 12-16 | 30 ± 10.2 | 30 ± 10.4 | 29 ± 9.1 | 25 ± 8.3 |
Days 6-16 | 64 ± 12.6 | 57 ± 10.4 | 55 ± 7.0* | 40 ± 11.6** |
Days 16-20 | 63 ± 12.5 | 62 ± 6.6 | 59 ± 12.7 | 59 ± 12.6 |
* = p< 0.05, ** = p< 0.01
Table 4:
Net body weight change minus gravid uterine weight at termination (terminal body weight minus day 6 body weight minus uterine weight)
Control | 10 ppm | 65 ppm | 125 ppm |
52 ± 12.7 | 40 ± 11.4* | 41 ± 13.6* | 28 ± 9.7** |
* = p< 0.05, ** = p< 0.01
Table 5: Mean food consumption
Group | 1 | 2 | 3 | 4 |
Concentration (ppm) | 0 | 10 | 65 | 125 |
Food consumption data in g/animal/day | ||||
Days 4-6 | 23 ± 2.4 | 23 ± 2.4 | 23 ± 2.1 | 22 ± 2.2 |
Days 6-9 | 23 ± 2.8 | 22 ± 2.1 | 22 ± 1.8 | 16 ± 2.5** |
Days 9-12 | 25 ± 2.8 | 23 ± 2.3 | 22 ± 2.6** | 20 ± 2.2** |
Days 12-16 | 26 ± 3.3 | 23 ± 2.4** | 22 ± 2.3** | 20 ± 2.6** |
Days 16-18 | 30 ± 4.0 | 27 ± 4.4 | 26 ± 4.3 | 31 ± 16.3 |
Days 18-20 | 28 ± 2.9 | 27 ± 2.0 | 27 ± 2.6 | 26 ± 2.8* |
Food consumption data in g/kg/day | ||||
Days 4-6 | 99± 8.4 | 97 ± 9.3 | 97 ± 7.5 | 94 ± 7.5 |
Days 6-9 | 90 ± 8.8 | 88 ± 5.4 | 87 ± 5.7 | 66 ± 11.0** |
Days 9-12 | 92 ± 7.9 | 87 ± 6.1 | 84 ± 8.2** | 79 ± 7.8** |
Days 12-16 | 89 ± 8.3 | 81 ± 8.8* | 79 ± 8.3** | 75 ± 9.6** |
Days 16-18 | 95 ± 8.2 | 86 ± 11.9 | 85 ± 12.8 | 105 ± 54.0 |
Days 18-20 | 81 ± 7.7 | 80 ± 6.7 | 81 ± 7.9 | 80 ± 8.8 |
Table 6: Fetal body weights
Control | 10 ppm | 65 ppm | 125 ppm | |
males | 4.1 ± 0.22 | 4.2 ± 0.25 | 4.4 ± 0.77 | 4.1 ± 0.40 |
females | 4.0 ± 0.25 | 4.1 ± 0.20 | 4.2 ± 0.75 | 3.9 ± 0.43 |
litter | 4.0 ± 0.21 | 4.2 ± 0.23 | 4.3 ± 0.74 | 4.0 ± 0.40 |
The concentrations of acrolein in the inhalation chambers for the 4 dose groups were 0, below detection limit, 1.19 ppm and 2.34 ppm (2.8 and 5.5 mg/m3). Actual concentration of test substance was only between 30 and 50% of nominal, no explanation given by the authors.
Applicant's summary and conclusion
- Conclusions:
- Maternal toxicity was noted at 127.8 ppm (corresponding to 0.55 mg/L air or 550.1 mg/m3 air), thus a LOAEC for systemic toxicity was derived to be 127.8 ppm (corresponding to 0.55 mg/L air or 550.1 mg/m3 air). The NOAEC for systemic toxicity was 58.3 ppm, corresponding to 0.251 mg/L air or 251.0 mg/m3 air. As the test item showed no adverse effects on fetal development, the NOAEC developmental was derived to be 127.8 ppm (corresponding to 0.55 mg/L air or 550.1 mg/m3 air). No teratogenic effects were observed at any dose level.
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