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EC number: 203-933-3 | CAS number: 112-07-2
- 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:
- 1984
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with national standard methods with acceptable restrictions
- Remarks:
- Well documented publication which meets basic scientific principles and based on a GLP study.
Cross-reference
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- publication
- Title:
- Teratogenic evaluation of ethylene glycol monobutyl ether in Fischer 344 rats and new zealand white rabbits following inhalation exposure.
- Author:
- Tyl RW, Millicovsky G, Dodd DE, Pritts I, France KA and Fisher LC
- Year:
- 1 984
- Bibliographic source:
- Env. Health Perspect., 57, p47-68.
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 2-butoxyethanol
- EC Number:
- 203-905-0
- EC Name:
- 2-butoxyethanol
- Cas Number:
- 111-76-2
- Molecular formula:
- C6H14O2
- IUPAC Name:
- 2-butoxyethanol
- Details on test material:
- - Name of test material (as cited in study report):
- Source: Union Carbide Corporation
- Lot #45-235
- Analytical purity: 99.6 %, verified.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Hilltop Lab Animals Inc, Scottdale, PA
- Age at study initiation: 100 days on arrival
- Weight at study initiation: 185-203g
- Housing: stainless steel wire mesh cages
- Diet (ad libitum except during exposure): Ground rodent lab chow, certified, Ralston Purina Mills, RIchmond, IN
- Water (ad libitum except during exposure): tap
- Acclimation period: 2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature, Humidity, Air changes: recorded in source but not reported except for during exposures (see later)
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Glass and stainless steel 2.1x1x2.1(h)m, volume 4350l.
- Method of holding animals in test chamber: no restraint
- Air change rate: 14/hr
- Temperature, humidity, pressure in air chamber: measured 4x per exposure: temp 75.7-80.9F, humidity 33.9-49%
- System of generating vapour: Liquid metered from a piston pump into a heated glass evaporator. Temperature maintained at minimum required to vapourise liquid. Vapour carried to exposure chamber by conditioned air. Expected chamber concentration reached within 20mins of start of experiment.
- Treatment of exhaust air: filtered.
TEST ATMOSPHERE
- Brief description of analytical method used: GC with FID calibrated over expected concentration range. Sampling once per hour.
- Samples taken from breathing zone: yes. Vapour concentrations in breathing zone found variation of 1% - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- GC FID, once per hour during exposure period.
- Details on mating procedure:
- - Impregnation procedure: cohoused.
- If cohoused:
- M/F ratio per cage: 1:1
- Length of cohabitation: checked 2x day for copulation plugs
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy - Duration of treatment / exposure:
- GD 6-15.
- Frequency of treatment:
- 6hrs/day
- Duration of test:
- to GD 21
Doses / concentrationsopen allclose all
- Dose / conc.:
- 25 ppm (nominal)
- Remarks:
- 121mg/m3. 24-26ppm (analytical)
- Dose / conc.:
- 50 ppm (nominal)
- Remarks:
- 242mg/m3. 49-51ppm (analytical)
- Dose / conc.:
- 100 ppm (nominal)
- Remarks:
- 483mg/m3. 96-100ppm (analytical)
- Dose / conc.:
- 200 ppm (nominal)
- Remarks:
- 966mg/m3. 195-207ppm (analytical)
- No. of animals per sex per dose:
- 36 per dose group.
- Control animals:
- yes, sham-exposed
- Details on study design:
- no further information
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS, DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
- Time schedule for examinations: days gd 0, 6, 9, 12, 15, 21
FOOD CONSUMPTION and WATER CONSUMPTION: Yes
- days 0-3, 3-6, 6-9, 9-12, 12-15, 15-18, 18-21
POST-MORTEM EXAMINATIONS: Yes / No / No data
- Sacrifice on gestation day 21
- Organs examined: liver, kidney, thymus, spleen, uterus.
- haematologic analysis also carried out for erythrocyte count, haemoglobin and hematocrit. - 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 resorptions: Yes - Fetal examinations:
- - External examinations: Yes
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: Yes - Statistics:
- For continuous variables: comparison with control by Levene's test for equal variances, ANOVA and t test with Bonferroni probabilities. Non-parametric data compared using Kruskal-Wallis test followed by Mann-Whitney U test when appropriate. Incidence data compared using Fisher's exact test. Significance level of 0.05 used for all assessments.
- Indices:
- no data
- Historical control data:
- no data
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- The following were not seen in controls or low dose groups but were in >75% of dams at 200ppm: cold and pale extremities; tail tip discoloured, ulcerated missing.
The following were not seen in controls or low dose groups but were in up to 25% of dams at 100ppm and >75% of dams at 200ppm: stained urogenical area, fluid on tray (positive for occult blood), red fluid on tray.
The following was not seen in controls but with increasing incidence with dose: perioccular wetness.
The following was seen in controls but with increasing incidence at 100/200ppm: perinasal encrustation, urogenital wetness and encrustation, fur stained red - Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Dose-dependent maternal weight loss was observed at 200 ppm (GD 6-15) and 100 ppm (GD 6-9). Statistically significantly reduced weight gain was seen at 200ppm (GD 6-21) and 100ppm (GD6-15). Overall weight of the 100ppm dams was similar at the end of the study to controls but in the high dose animals was reduced by 11%. These reductions co-incided with the start of treatment.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Dose-dependent reduction of food consumption was observed at 200 ppm and 100 ppm (both GD 6-12). The GD 6-9 reduction at 200ppm was 80% with the animals almost stopping eating. The reduction at 100ppm over the same period was 25%. These reductions co-incided with the start of treatment. Overall food consumption during the treatment period was signficantly reduced by 43% at 200ppm and 13% at 100ppm compared to controls.
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- Dose-dependent reduction of water consumption was observed at 200 ppm, primarily over the period GD6-9, where it reduced by 66%. These reductions co-incided with the start of treatment. Overall water consumption during the treatment period was signficantly reduced by 14% compared to controls.
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Haematological findings from blood samples taken at necropsy on GD21 (six days after the last exposure) showed signs of haemolytic anaemia for treatment with 100 ppm 2-butoxyethanol and higher. At 200ppm there was a significant reduction in RBC (-8%) and an significant increase in hemoglobin (+14%) and hematocrit (+20%.) RBC was also reduced at 100ppm (-9%). Mean corpuscular volume was significantly enlarged at 100 and 200ppm (+11 % and +30% respectively), hemoglobin per cell was increased (+11% at 100ppm, +25% at 200ppm) and mean corpuscular hemoglobin content also increased at both dose levels relative to controls by a small (<5%) but significant amount.
- Description (incidence and severity):
- Evidence of haematuria from 100 ppm
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Absolute and relative organ weight reductions were seen at 200ppm. Absolute and relative spleen weight increased (+19% and +24% respectively) and relative kidney weight increase (+9%) compared to controls. Gravid uterine weight was significantly reduced (-43%)
- Gross pathological findings:
- not examined
Maternal developmental toxicity
- Pre- and post-implantation loss:
- effects observed, treatment-related
- Description (incidence and severity):
- Significant reduction in the number of viable implants in 200ppm dose group only (reduced by half compared to other dose groups and control) Pre-implantation loss was elevated but not significantly.
- Total litter losses by resorption:
- effects observed, treatment-related
- Description (incidence and severity):
- Significant increase in number of litters totally resorbed in highest dose group (9 versus none in controls and 100ppm dose group)
- Early or late resorptions:
- effects observed, treatment-related
- Description (incidence and severity):
- Significant number of embryonic resorptions at 200ppm (2.8 versus effectively zero in all other groups including control)
- Dead fetuses:
- effects observed, treatment-related
- Description (incidence and severity):
- Significant increase at 200ppm only. (50% versus ~5% rate in all other dose groups and control).
- Changes in pregnancy duration:
- no effects observed
- Changes in number of pregnant:
- no effects observed
- Details on maternal toxic effects:
- Maternal toxicity was observed in a dose-related incidence during the exposure period,
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- 50 ppm
- Basis for effect level:
- body weight and weight gain
- clinical signs
- food consumption and compound intake
- haematology
Maternal abnormalities
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Reduction in number of live offspring:
- effects observed, treatment-related
- Description (incidence and severity):
- Reduction by approaching 50% at 200ppm compared to other dose levels and controls
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Description (incidence and severity):
- Total number of malformations: control 0, 25ppm 1, 50ppm 1, 100ppm 0, 200ppm 0.
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- Total number of malformations: control 0, 25ppm 3, 50ppm 0, 100ppm 0, 200ppm 1.
Evidence for retarded skeletal ossifications were seen at 100ppm and 200ppm. Exposure to 200 ppm was also associated with a significant increase in the number of litters with one or more foetuses with unossified skeletal elements and poorly ossified skeletal elements (anterior arch of atlas, cervical centra 5 and 6 and forelimb proximal phalanges) and poorly ossified skeletal elements (cervical arches and sternebrae 1, 3, 4 and 6). Primarily because the skeletal elements were poorly ossified there was a decreased incidence of bilobed cervical centra 5 and 6 and bilobed thoracic centra 9 and 13. There was also a decreased incidence of poorly ossified hindlimb proximal phalanges. At 100 ppm, the number of litters with one or more foetuses with unossified cervical centrum 6 was significantly increased and, because fewer also showed ossification of cervical centrum 5, the number bilobed was significantly decreased. No significant differences were observed for other aspects of skeletal ossification. - Visceral malformations:
- no effects observed
- Description (incidence and severity):
- Total number of malformations: control 1, 25ppm 1, 50ppm 2, 100ppm 2, 200ppm 3.
- Details on embryotoxic / teratogenic effects:
- There were no statistical significant increases in incidences of external, visceral, skeletal, or total malformations associated with exposure to 2-butoxyethanol.
Effect levels (fetuses)
- Dose descriptor:
- NOAEC
- Effect level:
- 50 ppm (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: delayed ossification
- Remarks on result:
- other: delay likely to be secondary to maternal toxicity
Fetal abnormalities
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Developmental effects observed:
- yes
- Lowest effective dose / conc.:
- 100 ppm (nominal)
- Treatment related:
- yes
- Relation to maternal toxicity:
- developmental effects as a secondary non-specific consequence of maternal toxicity effects
- Dose response relationship:
- yes
- Relevant for humans:
- no
Any other information on results incl. tables
No adverse reproductive or developmental effects were observed in animals exposed to 25 ppm or 50 ppm.
Applicant's summary and conclusion
- Conclusions:
- 2-butoxyethanol is not a developmental toxicant. Developmental effects seen are secondary to maternal toxicity.
- Executive summary:
In a GLP developmental toxicity study, pregnant rats were exposed to 2 -butoxyethanol vapour at concentrations up to 200ppm during GD6 -15. The results indicated that exposures from 100ppm upwards caused marked maternal toxicity, manifest by haemotoxicity and erduced body weight gain and food consumption. Exposures of 200ppm produced embryotoxicity, manifest as as increased resorptions and decreased viable implants per litter) and fetotoxicity (retardations in skeletal ossification). There was no evidence of teratogenicity. The developmental effects appear to be secondary to maternal toxicity.
Synopsis
NOAEC (maternal) =50ppm
NOAEC (ebryotoxicity, fetotoxicity) =100ppm
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