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EC number: 276-696-7 | CAS number: 72490-01-8
- 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
![](https://poisoncentres.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 20 Apr 1987 to 17 Jun 1987
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 987
- Report date:
- 1987
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 412 (28-Day (Subacute) Inhalation Toxicity Study
- Version / remarks:
- May 1981
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Ethyl [2-(4-phenoxyphenoxy)ethyl]carbamate
- EC Number:
- 276-696-7
- EC Name:
- Ethyl [2-(4-phenoxyphenoxy)ethyl]carbamate
- Cas Number:
- 72490-01-8
- Molecular formula:
- C17 H19 N O4
- IUPAC Name:
- ethyl [2-(4-phenoxyphenoxy)ethyl]carbamate
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Remarks:
- KFM-Han
- Sex:
- male/female
Administration / exposure
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- nose only
- Vehicle:
- other: ethanol
- Mass median aerodynamic diameter (MMAD):
- 3 µm
- Geometric standard deviation (GSD):
- 1.9
- Duration of treatment / exposure:
- 6 hours/day
- Frequency of treatment:
- 5 days/week, total of 21 exposures
Doses / concentrationsopen allclose all
- Dose / conc.:
- 10 mg/m³ air (nominal)
- Remarks:
- Group 2: Low dose, equivalent to 11 mg/m³ air (actual concentration)
- Dose / conc.:
- 100 mg/m³ air (nominal)
- Remarks:
- Group 3: Mid dose, equivalent to 99 mg/m³ air (actual concentration)
- Dose / conc.:
- 1 000 mg/m³ air (nominal)
- Remarks:
- Group 4: High dose, equivalent to 1050 mg/m³ air (actual concentration)
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent no treatment
Results and discussion
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- Local
- Effect level:
- > 1 000 mg/m³ air (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- other: no local effects observed. Equivalent to 1050 mg/m³ air (actual concentration)
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- Systemic
- Effect level:
- 100 mg/m³ air (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical biochemistry
- food consumption and compound intake
- organ weights and organ / body weight ratios
- Remarks on result:
- other: Equivalent to 99 mg/m³ air (actual concentration)
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Any other information on results incl. tables
Exposure system monitoring
The particle size distribution determined using a Mercer Impactor. The mean (standard deviation) of the percentage of the aerosol sampled which was collected on the 3 µm (mass median aerodynamic diameter) stage or less was found to be 97.4 % (SD = 1.91).
The temperature and oxygen content measurements showed no unusual excursions. The humidity measurements were discontinued after two days due to the alcohol solvent affecting the sensor and thereby the humidity readings.
Mortality: All rats survived the study periods.
Clinical signs: No signs of toxicity were seen during the study.
Food consumption: Food was slightly in the high dose male animals at the end of the treatment period. The food consumption for all other groups were similar for the male and female animals.
Body weights: Body weight gains were slightly reduced in the high dose (group 4) male animals. This was noted as well in reduced terminal body in the group 4 males. The body weights for all other groups were similar for the male and female animals.
Ophthalmoscopy: No treatment-related effects were noted.
Haematology: The of haematological data indicated no changes of toxicological significance at the end of exposure for the treated groups, nor at the end of the treatment-free recovery period for group 4.
Treatment-unrelated: All differences in the results of the haematology parameters were considered to be incidental and of normal biological variation when compared to that of the controls.
Clinical biochemistry: For biochemical data no changes of toxicological significance were noted at the end of exposure for the treated groups; however a slightly increased potassium level (by 22%) and chloride level (by 5%) for males, and slightly increased albumin level (by 11 % and total protein level (by 9%) for females was noted for group 4 when compared to controls. These findings were considered to be of an adaptive nature due to the treatment and found to be reversible at the end of the treatment-free (recovery) period.
Treatment- unrelated: All other differences in the results of the clinical biochemistry parameters were considered to be incidental and of normal biological variation when compared to that of the controls.
Sacrifice and pathology:
Organ weight and organ weight ratios
The following statistically significant changes in absolute and relative organ weights noted in group 4 as compared to controls:
In males: Lungs displayed increased ratios in group 4. Liver displayed increased ratios in group 4.
In females: Liver displayed increased weights and ratios in group 4. Kidneys displayed increased ratios in group 4.
These changes were not considered to be of toxicological significance as there were no correlates of these changes with the histological and biochemical findings.
Macroscopic findings:The macroscopic findings recorded were unremarkable.
Microscopic findings: No treatment related microscopic findings were recorded.
The various spontaneous microscopic findings recorded are within the normal range observed at these ages and in this strain of rat. They may be attributed to sub-clinical illness, spontaneous congenital abnormalities or physiological status.
Table 1 Overview of results
Dose (mg/m3) |
1.5 |
1.5 |
11 |
11 |
99 |
99 |
1050 |
1050 |
dr |
|
m |
f |
m |
f |
m |
f |
m |
f |
|
Mortality |
none |
|
|||||||
Clinical signs |
No treatment-related findings |
|
|||||||
Body Weight |
|
|
|
|
|
|
d |
|
|
Food consumption |
|
|
|
|
|
|
d |
|
|
Ophthalmoscopy |
No treatment-related findings |
|
|||||||
Haematology |
|
|
|
|
|
|
|
|
|
haemoglobin |
|
|
|
|
|
|
|
ic |
|
Clin. Chemistry |
|
|
|
|
|
|
|
|
|
bilirubin, total |
|
|
|
|
|
|
dc |
|
|
potassium |
|
|
|
|
|
|
ic |
|
|
chloride |
|
|
|
|
|
|
ic |
|
|
albumin |
|
|
|
|
|
|
|
ic |
|
protein, total |
|
|
|
|
|
|
|
ic |
|
calcium |
|
|
|
|
|
|
dc |
|
|
urea |
|
|
|
|
|
dc |
|
|
|
sodium |
|
|
|
|
|
dc |
|
|
|
Organ weights |
|
|
|
|
|
|
|
|
|
lungs |
|
|
|
|
|
|
icr |
|
|
liver |
|
|
|
|
|
|
icr |
ica,r |
|
testes |
|
|
|
|
|
|
icr |
|
|
kidneys |
|
|
|
|
|
|
|
icr |
|
adrenal |
|
|
|
|
|
dca,r |
|
|
|
Pathology |
|
|
|
|
|
|
|
|
|
Macroscopy |
No treatment-related findings |
|
|||||||
Microscopy |
No treatment-related findings |
|
dr dose related
dc/ic statistically significantly decreased/increased compared to the controls
d/i decreased/increased, but not statistically significantly compared to the controls
aabsolute organ weight
rrelative organ weight
Applicant's summary and conclusion
- Conclusions:
- Based on increased liver and kidney weights and clinical biochemical findings, the systemic NOAEL is set at 99 mg/m3. Since no adverse local effects were observed, the local NOAEL is set at >1050 mg/m3.
- Executive summary:
The study was performed in accordance with OECD TG 412 and in compliance with GLP. Four groups of Wistar, KFM-Han rats, each containing 5 males and 5 females, inhaled 1.5, 11, 99 or 1050 mg/m3 test substance using ethanol as vehicle. The exposure was 6 hours per day for 5 days per week for 29 days. The mean particle size of the aerosol sampled which was 3 µm and the GSD 1.9 μm. No mortality occurred. No clinical or ocular abnormalities were observed. Body weight gain was decreased in males at 1050 mg/m3 (terminal body weight 93 % of control) at the end of the exposure period. Also a decrease in food consumption was observed in these males. At haematology, haemoglobin was slightly, but significantly decreased at 1050 mg/m3 in females (94 % of control). Clinical biochemistry investigations showed a dose-dependent and significant decrease in total bilirubin (72 % of control) and a dose-dependent and significant increase in potassium and chloride (122 % and 105 % of control, respectively) in the highest dosed males. Increased potassium may indicate kidney insufficiency. Calcium was slightly but significantly decreased in these males (97 % of control). In the females, urea was significantly decreased at the 99 mg/m3 dose (78 % of control) and sodium was slightly but significantly decreased at the highest dose (99 % of control). Albumin and total protein were both significantly increased at the highest dose level (111 % and 109 % of control, respectively). In the recovery groups, all values were normal again. Relative weights of the lungs, liver and testis were significantly increased in males of the highest dose group (116 %, 114 % and 116 %, respectively). In females of the highest dose group, absolute and relative liver weight were significantly increased (127 % and 134 %, respectively). Relative kidney weight was significantly increased (116 %) at the highest dose. Absolute and relative adrenals weight were significantly decreased (both 81 %) at 99 mg/m3. However, in the absence of any decreases at the high dose level this finding was considered not toxicologically relevant. Changes in relative testes and lung weight might be due to decreased terminal body weight. Macroscopically and microscopically no treatment-related effects were observed. Males of the control group and the 1050 mg/m3 dose group showed similar histopathological findings, namely bronchial associated lymphoid tissue hyperplasia (2/5 and 1/5, resp.) and interstitial pneumonitis (5/5 and 4/5, resp.) of the lungs, and mononuclear inflammatory cell foci (3/5 and 1/5, resp.) of the liver. Females of both the control group and the 1050 mg/m3 dose group showed nephrocalcinosis of the kidneys. Based on increased liver and kidney weights and clinical biochemical findings, the systemic NOAEL is set at 99 mg/m3. Since no adverse local effects were observed, the local NOAEL is set at >1050 mg/m3.
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