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EC number: 203-846-0 | CAS number: 111-21-7
- 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://www.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Endpoint summary
Administrative data
Description of key information
Oral: NOAEL (rat) ≥ 796 (m) and 1195 (f) mg/kg bw/day (subchronic)
Inhalation: NOAEC (rat) ≥ 227 mg/m³ (subacute)
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with acceptable restrictions. Lack of test material details and no clinical biochemistry.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- lack of test material details and no clinical biochemistry
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 53 - 54 g
- Housing: 5 animals of the same sex per cage
- Diet: basal diet of ground Purina Laboratory Chow
- Water: ad libitum - Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- DIET PREPARATION
- Mixing appropriate amounts with: basal diet of ground Purina Laboratory chow - Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- daily, 7 days/week
- Remarks:
- Doses / Concentrations:
0.1, 1 %
Basis:
nominal in diet - Remarks:
- Doses / Concentrations:
25, 250 mg/rat/day
Basis:
nominal in diet - Remarks:
- Doses / Concentrations:
79.6, 796 mg/kg bw/day (males)
Basis:
other: mean dose value as calculated from the reported body weight and mean value per rat - Remarks:
- Doses / Concentrations:
119.5, 1195 mg/kg bw/day (females)
Basis:
other: mean dose value as calculated from the reported body weight and mean value per rat - No. of animals per sex per dose:
- 15
- Control animals:
- yes, concurrent no treatment
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION AND COMPOUND INTAKE:
- Food consumption for each group was recorded at approximately weekly intervals
DIET EFFICIENCY: Yes
- Body weight gain in g/food consumption in g per unit time (Day 0- 27; Day 28-60; Day 61-89 and Day 0-89) X 100 calculated as time-weighted averages from the consumption and body weight gain data were determined.
FEED EFFICIENCY: Yes
- Diet efficiency (Body weight gain in g/food consumption in g per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain) x 1.01 or x 1.001, respectively
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Day 47 and Day 89
- How many animals: 10 animals per sex from the high dose group and the control group were examined.
- Parameters checked: hematocrit, hemoglobin, white blood cell value and differential blood values
URINALYSIS: Yes
- Time schedule for collection of urine: Day 47 and Day 89
- How many animals: 5 animals per sex from the high dose group and the control group were examined.
- Parameters checked: pH value, specific gravity, albumin, sugar, occult blood, ketones and physical characteristics were examined. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes. Liver, kidneys, spleen, heart, brain, lungs and testes.
HISTOPATHOLOGY: Yes. Trachea, lung, heart, tongue, oesophagus, stomach, small and large intestine, liver, kidney, urinary bladder, pituitary, adrenal, pancreas, thyroid, parathyroid, testes, ovary and uterus, spleen, femoral bone marrow, cerebrum, cerebellum and eye. - Statistics:
- Mean values were calculated and the Students´s t-test was applied.
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- High dose group (males): reduced white blood cell value (non adverse)
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
One animal in low dose group was found dead on Day 85, no treatment related effect.
BODY WEIGHT AND WEIGHT GAIN
No effects were observed.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
No effects were observed.
FOOD EFFICIENCY
No effects were observed.
HAEMATOLOGY
No treatment related effects were observed. White blood cell counts of the control and high dose males were within the normal range. However, at the 5% significance level (Student t-test) the average white blood cell count of the treated group was significantly lower than the control at Day 47 and 89. According to the author, it appeared that the control average white blood cell count was probably high (see Table 2 under "Any other information on results incl. tables").
URINALYSIS
No effects were observed.
ORGAN WEIGHTS
No effects were observed.
GROSS PATHOLOGY
No effects were observed. One high-dose male had multiple, yellowish nodules characteristic of chronic murine pneumonia in all lobes of the lungs.
HISTOPATHOLOGY: NON-NEOPLASTIC
No adverse effects were observed. - Dose descriptor:
- NOAEL
- Effect level:
- >= 250 other: mg/rat/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: overall effects
- Dose descriptor:
- NOAEL
- Effect level:
- >= 796 mg/kg bw/day (nominal)
- Based on:
- other: mean dose value as calculated from the reported body weight and mean value per rat
- Sex:
- male
- Basis for effect level:
- other: overall effects
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 195 mg/kg bw/day (nominal)
- Based on:
- other: mean dose value as calculated from the reported body weight and mean value per rat
- Sex:
- female
- Basis for effect level:
- other: overall effects
- Critical effects observed:
- not specified
Reference
All animals exhibited varying, generally mild degree of chronic murine pneumonitis, with no discernable pattern of involment in different groups. Minimal focal chronic pyelonephritis was present in 2 animals in the high dose group and in one control animal one low dose group. There was no oxalate crystal precipitation in the kidneys of the test group animals or other evidence of nephrosis. Minimal focal chronic myocarditis was present in one animal each in the high dose and the control group. Squamous metaplasia of the epithelium of rare thyroid follicles was seen in two animas in each group. A parasitic worm was found within the colon of one control animal.
The abnormalities seen are typical of natural disease processes commonly found in laboratory rats. There is no morphologic evidence in the tissues examined of abnormality due to the experimental feeding program.
Table 1. Average Body Weights.
|
Group [% diet] |
|||||
Days on |
1 |
0.1 |
control |
1 |
0.1 |
control |
|
Males |
Females |
||||
0 |
56 |
50 |
54 |
53 |
53 |
55 |
7 |
99 |
86 |
96 |
92 |
88 |
93 |
14 |
150 |
138 |
147 |
130 |
127 |
129 |
20 |
200 |
187 |
202 |
166 |
158 |
163 |
27 |
250 |
235 |
251 |
184 |
176 |
185 |
34 |
303 |
280 |
292 |
209 |
202 |
210 |
40 |
343 |
320 |
332 |
226 |
217 |
225 |
47 |
361 |
345 |
342 |
235 |
228 |
233 |
53 |
400 |
377 |
382 |
244 |
241 |
242 |
60 |
408 |
394 |
386 |
258 |
253 |
260 |
64 |
427 |
404 |
414 |
257 |
254 |
261 |
70 |
432 |
419 |
428 |
263 |
263 |
268 |
76 |
462 |
440 |
454 |
273 |
271 |
279 |
82 |
472 |
442 |
464 |
279 |
284 |
284 |
89 |
476 |
462 |
465 |
280 |
280 |
284 |
Mean |
322.6 |
305.3 |
313.9 |
209.9 |
206.3 |
211.4 |
Mean over all Males/Females |
|
313.9 |
|
|
209.2 |
Table 2. Results of Hematology.
White blood cell value x 103 |
Group [% diet] |
|||
1 |
control |
1 |
control |
|
Males |
Females |
|||
Day 47 |
17.9 |
23.1 |
19.1 |
18.6 |
Day 89 |
16.4 |
21 |
15.4 |
12.9 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Quality of whole database:
- The available information comprises adequate, reliable (Klimisch score 2) and consistent studies, and is thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.6, of Regulation (EC) No 1907/2006.
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well documented study report which meets basic scientific principles. Lack of details on study design and test material.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
- Deviations:
- yes
- Remarks:
- lack of details on study design and test material
- GLP compliance:
- no
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: A&E Farms, Altamont, USA
- Diet: Purina Laboratory Chow, either ground or pelleted - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- clean air
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical glass inhalation chambers
- Source and rate of air: filtered air at 1 L/min through a 125 mL gas washing bottle fitted with a fritted cylinder and partially filled with the compound.
- System of generating vapour: The fritted cylinder broke up the air stream into small bubbles which rose through the column of the test material and assisted in vaporising the compound into the air stream. The gas washing bottle was placed in a water bath heated to 100 °C. The effluent air from the gas washing bottle was passed directly into the inhalation chamber.
TEST ATMOSPHERE
- Brief description of analytical method used: Samples were taken in methanol each day and analyzed by gas chromatography. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Concentrations were calculated on the basis of air flow and weight loss of compound and gas chromatography of air samples.
- Duration of treatment / exposure:
- 29 days
- Frequency of treatment:
- 6 h/day, 5 days/week
- Remarks:
- Doses / Concentrations:
saturated atmosphere range 97.7 - 183.9 ppm
Basis:
nominal conc. - Remarks:
- Doses / Concentrations:
saturated atmosphere range 877 - 1759 mg/m³
Basis:
other: nominal conc. as calculated from range 0.877 - 1.759 mg/L - Remarks:
- Doses / Concentrations:
saturated atmosphere range 8.8 - 23.7 ppm
Basis:
analytical conc. - Remarks:
- Doses / Concentrations:
saturated atmosphere range 80 - 227 mg/m³
Basis:
other: analytical conc. as calculated from range 0.08 - 0.227 mg/L - No. of animals per sex per dose:
- 6
- Control animals:
- yes
- Observations and examinations performed and frequency:
- BODY WEIGHT: Yes
HAEMATOLOGY: Yes
- Time schedule for collection of blood: prior to the first exposure and following the 20th exposure
- Parameters checked: haemoglobin, cell volume, white cell count and differential - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes. Liver, kidneys, spleen, heart, brain, lungs and testes.
HISTOPATHOLOGY: Yes. Trachea, lung, heart, tongue, oesophagus, stomach, small and large intestine, liver, kidney, urinary bladder, pituitary, adrenal, pancreas, thyroid, parathyroid, testes, ovary and uterus, spleen, femoral bone marrow, cerebrum, cerebellum and eye. - Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- slight lacrimation and yellow tinged fur (non adverse)
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- slight lacrimation and yellow tinged fur (non adverse)
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- treatment group: slighlty impaired BW gain
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No animals died during the study period. Slight lacrimation in the treatment and control group was observed throughout each exposure and on the seventh exposure it was noted that the experimental animals´ fur was becoming tinged with yellow.
BODY WEIGHT AND WEIGHT GAIN
Body weight gain in the treatment group was slightly reduced in comparison to the control group.
HAEMATOLOGY
No effects on haematological parameter observed.
GROSS PATHOLOGY
No gross lesions at necropsy in all animals. No evidence was seen of irritant effects on the upper respiratory tract, eyes or nose.
HISTOPATHOLOGY
The experimental and control groups showed the common chronic murine pneumonitis and both groups seemed to be equally affected. There was no evidence of chemical pneumonitis nor of the presence of any unabsorbed foreign substance in the alveoli.
OTHER FINDINGS
The analytical concentrations were about ten times lower than the calculated concentrations. Therefore, 26 g of hair of the test animals was analysed and 23.8 mg of the test compound could be extracted. - Dose descriptor:
- NOEC
- Effect level:
- >= 227 mg/m³ air (analytical)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: overall effects
- Dose descriptor:
- NOEC
- Effect level:
- >= 23.7 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: overall effects
- Critical effects observed:
- not specified
Reference
Table 1. Results of haematology (mean out of 6 animals).
|
Haemoglobin |
Cell volume |
White blood cell count |
Pre-exposure |
|
||
Treatment group |
15.8 |
49.3 |
18.48 |
Control group |
15.4 |
49.3 |
23.97 |
Post-exposure |
|
||
Treatment group |
19.2 |
49.2 |
21.92 |
Control group |
19.5 |
50.2 |
24.53 |
Table 2. Chamber concentrations.
Method |
Range [ppm] |
Mean [ppm] |
Standard deviation |
Number of observations |
Calculated weight |
91.7-183.9 |
137.7 |
26.4 |
22 |
Gas chromatography |
8.8-23.7 |
* |
3.6 |
27 |
*: unreadable in study report
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Quality of whole database:
- The available information comprises an adequate and reliable study (Klimisch score 2), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.6, of Regulation (EC) No 1907/2006.
Repeated dose toxicity: inhalation - local effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well documented study report which meets basic scientific principles. Lack of details on study design and test material.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
- Deviations:
- yes
- Remarks:
- lack of details on study design and test material
- GLP compliance:
- no
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: A&E Farms, Altamont, USA
- Diet: Purina Laboratory Chow, either ground or pelleted - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- clean air
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical glass inhalation chambers
- Source and rate of air: filtered air at 1 L/min through a 125 mL gas washing bottle fitted with a fritted cylinder and partially filled with the compound.
- System of generating vapour: The fritted cylinder broke up the air stream into small bubbles which rose through the column of the test material and assisted in vaporising the compound into the air stream. The gas washing bottle was placed in a water bath heated to 100 °C. The effluent air from the gas washing bottle was passed directly into the inhalation chamber.
TEST ATMOSPHERE
- Brief description of analytical method used: Samples were taken in methanol each day and analyzed by gas chromatography. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Concentrations were calculated on the basis of air flow and weight loss of compound and gas chromatography of air samples.
- Duration of treatment / exposure:
- 29 days
- Frequency of treatment:
- 6 h/day, 5 days/week
- Remarks:
- Doses / Concentrations:
saturated atmosphere range 97.7 - 183.9 ppm
Basis:
nominal conc. - Remarks:
- Doses / Concentrations:
saturated atmosphere range 877 - 1759 mg/m³
Basis:
other: nominal conc. as calculated from range 0.877 - 1.759 mg/L - Remarks:
- Doses / Concentrations:
saturated atmosphere range 8.8 - 23.7 ppm
Basis:
analytical conc. - Remarks:
- Doses / Concentrations:
saturated atmosphere range 80 - 227 mg/m³
Basis:
other: analytical conc. as calculated from range 0.08 - 0.227 mg/L - No. of animals per sex per dose:
- 6
- Control animals:
- yes
- Observations and examinations performed and frequency:
- BODY WEIGHT: Yes
HAEMATOLOGY: Yes
- Time schedule for collection of blood: prior to the first exposure and following the 20th exposure
- Parameters checked: haemoglobin, cell volume, white cell count and differential - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes. Liver, kidneys, spleen, heart, brain, lungs and testes.
HISTOPATHOLOGY: Yes. Trachea, lung, heart, tongue, oesophagus, stomach, small and large intestine, liver, kidney, urinary bladder, pituitary, adrenal, pancreas, thyroid, parathyroid, testes, ovary and uterus, spleen, femoral bone marrow, cerebrum, cerebellum and eye. - Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- slight lacrimation and yellow tinged fur (non adverse)
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- slight lacrimation and yellow tinged fur (non adverse)
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- treatment group: slighlty impaired BW gain
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No animals died during the study period. Slight lacrimation in the treatment and control group was observed throughout each exposure and on the seventh exposure it was noted that the experimental animals´ fur was becoming tinged with yellow.
BODY WEIGHT AND WEIGHT GAIN
Body weight gain in the treatment group was slightly reduced in comparison to the control group.
HAEMATOLOGY
No effects on haematological parameter observed.
GROSS PATHOLOGY
No gross lesions at necropsy in all animals. No evidence was seen of irritant effects on the upper respiratory tract, eyes or nose.
HISTOPATHOLOGY
The experimental and control groups showed the common chronic murine pneumonitis and both groups seemed to be equally affected. There was no evidence of chemical pneumonitis nor of the presence of any unabsorbed foreign substance in the alveoli.
OTHER FINDINGS
The analytical concentrations were about ten times lower than the calculated concentrations. Therefore, 26 g of hair of the test animals was analysed and 23.8 mg of the test compound could be extracted. - Dose descriptor:
- NOEC
- Effect level:
- >= 227 mg/m³ air (analytical)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: overall effects
- Dose descriptor:
- NOEC
- Effect level:
- >= 23.7 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: overall effects
- Critical effects observed:
- not specified
Reference
Table 1. Results of haematology (mean out of 6 animals).
|
Haemoglobin |
Cell volume |
White blood cell count |
Pre-exposure |
|
||
Treatment group |
15.8 |
49.3 |
18.48 |
Control group |
15.4 |
49.3 |
23.97 |
Post-exposure |
|
||
Treatment group |
19.2 |
49.2 |
21.92 |
Control group |
19.5 |
50.2 |
24.53 |
Table 2. Chamber concentrations.
Method |
Range [ppm] |
Mean [ppm] |
Standard deviation |
Number of observations |
Calculated weight |
91.7-183.9 |
137.7 |
26.4 |
22 |
Gas chromatography |
8.8-23.7 |
* |
3.6 |
27 |
*: unreadable in study report
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Quality of whole database:
- The available information comprises an adequate and reliable study (Klimisch score 2), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.6, of Regulation (EC) No 1907/2006.
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Subacute toxicity: oral
A subacute study was performed as a limit test, administrating 7232 mg/kg bw/day 2,2'-[ethane-1,2-diylbis(oxy)]bisethyl diacetate to a group of 10 rats via gavage, 5 days/week within 23 days (Raleigh, 1984b).
In the study, 3/10 animals were killed by mechanical intubation accidents and 2/10 animals died after the 7th and 1/10 died following the 13th administration. No marked consistent changes in the blood values were reported. During gross pathology and histopathological examination, there were signs of minimal chronic murine pneumonitis in the 3 rats that succumbed. The 4 animals that were sacrificed at the end of the study showed mild to moderate hydropic degeneration of the liver. No evidence of “Glycol toxicity” in the form of nephrosis or calcium oxalate crystal deposition in the kidney tubules was observed in the test animals.
Subchronic toxicity: oral
A subchronic study with 2,2'-[ethane-1,2-diylbis(oxy)]bisethyl diacetate similar to OECD guideline 408 is available (Raleigh, 1984a). 2,2'-[ethane-1,2-diylbis(oxy)]bisethyl diacetate was administered to groups of 15 Sprague-Dawley rats at doses of 0.1, 1 % in the diet (corresponding to calculated concentrations of 79.6, 796 mg/kg bw/day (m) and 119.5, 1195 mg/kg bw/day (f)), 7 days/week for 13 weeks. A concurrent negative control group receiving the diet only was included in the testing.
In the study, no test substance related mortality occurred and no signs of systemic toxicity were observed. In addition, no effects on body weight gain, food consumption, organ weights, haematological parameters and urinalysis were observed. During gross pathology and histopathological examination, no test substance related changes were apparent. There was no oxalate crystal precipitation in the kidneys of the test group animals or other evidence of nephrosis.
Thus, the resulting NOAEL for repeated dose toxicity is greater than the highest applied dose of 1% in the diet corresponding to 796 mg/kg bw/day (m) and 1195 mg/kg bw/day (f).
Subacute toxicity: inhalation
2,2'-[ethane-1,2-diylbis(oxy)]bisethyl diacetate was tested in a subacute toxicity study via the inhalation route (Raleigh, 1984c). The study was performed as a limit test, at a saturated atmosphere ranging from 80 - 227 mg/m³ to a group of 6 male rats, 6 h/day, 5 days/week for 29 days.
No mortality was observed during the study period. Slight lacrimation in the treatment and control group was observed throughout each exposure and on the 7th exposure it was noted that the experimental animals´ fur was becoming tinged with yellow. Body weight gain in the treatment group was slightly reduced in comparison to the control group. No effects on haematological parameter and no changes during gross pathology were observed. No evidence was seen of irritant effects on the upper respiratory tract, eyes or nose. Histopathology showed no evidence of chemical pneumonitis or of the presence of any unabsorbed foreign substance in the alveoli.
Thus, the resulting NOEC for repeated dose toxicity via inhalation is greater than the highest administered dose of 277 mg/m³ air.
Conclusions for repeated dose toxicity
In summary, one subchronic repeated dose toxicity study via the oral route showed no adverse systemic effects resulting in a NOAEL greater than the highest applied dose of NOAEL of 796 mg/kg bw/day (m) and 1195 mg/kg bw/day (f) in rats.
One subacute repeated dose toxicity study via the inhalation route showed no adverse systemic effects resulting in a NOEC greater than the highest applied dose of 277 mg/m³ air in male rats.
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The selected study is the most adequate and reliable study with the longest duration and the lowest dose descriptor.
Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
There is only one study available.
Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
There is only one study available.
Justification for classification or non-classification
The available data on the repeated dose toxicity of 2,2'-[ethane-1,2-diylbis(oxy)]bisethyl diacetate (CAS 111-21-7) do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and the data are therefore conclusive but not sufficient for classification.
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