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EC number: 221-659-2 | CAS number: 3179-63-3
- 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
Endpoint summary
Administrative data
Description of key information
No repeated dose toxicity study is available for dimethylaminopropanol. Dimethylethanolamine (DMAE) is a structural analogue of dimethylaminopropanol and was used for read-across.
Repeated dose toxicity (vapour inhalation): Dimethylethanolamine: Acute, 2-week and 13-week Inhalation Toxicity Studies in Rats. Comparable to the OECD guideline 413 with concentrations tested of 8, 24 and 76 ppm (equivalent to 36, 108 and 325 mg/m³). The NOEC for local effects was 108 mg/m³ and the NOAEC for systemic effects was found to be greater than 325 mg/m³. [Klonne et al., 1987]
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- not reported, published 1987
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well documented publication which meets basic scientific principles.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- Deviations:
- not applicable
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Kingston, NY)
- Age at study initiation: approx. 9 weeks old.
- Weight at study initiation: 180 g for males and 130 g females
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum): Purina Certified Rodent Chow 5002, Ralston Purina Co., St. Louis, MO ad libitum except during exposures
- Water (e.g. ad libitum): yes, except during exposures
- Acclimation period: yes
ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- inhalation
- Type of inhalation exposure:
- not specified
- Vehicle:
- other: no data
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 4320-liter stainless-steel and glass chambers
- Method of holding animals in test chamber: not reported
- Source and rate of air: not reported
- Method of conditioning air: not reported
- System of generating particulates/aerosols: DMEA vapor was generated by metering the liquid into a heated, spiral-grooved evaporator with a countercurrent airstream, similar in design to the one used by Carpenter et al. (1975).
- Temperature, humidity, pressure in air chamber: 25°C and 46%,
- Air flow rate: 800-1000 liters/min
- Air change rate: not reported
- Method of particle size determination: not reported
- Treatment of exhaust air: not reported
TEST ATMOSPHERE
- Brief description of analytical method used: The CC column was a 5 ft X 1/4 in stainless-steel column packed with 20% SP-2100 on 80/ 100 mesh Supelcoport (Supelco, BeIlefonte, PA), maintained at 200°C.
- Samples taken from breathing zone: yes
VEHICLE (if applicable) no - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Chamber concentrations of DMEA were analyzed at approximately 40-min intervals with a Perkin-Elmer 3920B gas chromatograph (CC) equipped with a flame ionization detector. Chamber atmosphere samples were automatically injected into the GC with the use of a Perkin-Elmer environmental sampler.
- Duration of treatment / exposure:
- 13 wk
- Frequency of treatment:
- 6h/d, 5d/wk
- Remarks:
- Doses / Concentrations:
8, 24, 76 ppm
Basis:
analytical conc. - No. of animals per sex per dose:
- 20
- Control animals:
- yes
- Details on study design:
- 10 male rats were assigned to the control, middle and high concentration groups for possible ultrastructural evaluation of nerve tissue (not performed since no behavioral abnormalities or light microscopic lesions of nerve tissue were observed).
- Dose selection rationale: not reported
- Rationale for animal assignment (if not random): randomized
- Rationale for selecting satellite groups: to investigate recovery of effects of treatment
- Post-exposure recovery period in satellite groups: 5 week
One-half of all rats per sex per group were sacrificed after at least 2 days of exposure during the 14th week of the study; the remaining rats were sacrificed after 5 complete weeks of recovery. - Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations checked in table [No.3] were included.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: daily
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: were measured during the 16-hr urine collection period.
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION: were measured during the 16-hr urine collection period.
OPHTHALMOSCOPIC EXAMINATION: Yes, (evaluation of the eye with a light source and
magnifying lens)
- Time schedule for examinations: not reported
- Dose groups that were examined: not reported
HAEMATOLOGY: Yes
- Time schedule for collection of blood: made the morning following the last DMEA exposure day (except for recovery animals).
- Anaesthetic used for blood collection: Yes (methoxyflurane)
- Animals fasted: No
- How many animals: not reported
- Parameters checked in table [No.1] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: made the morning following the last DMEA exposure day (except for recovery animals).
- Animals fasted: No
- How many animals: not reported
- Parameters checked in table [No.2] were examined.
URINALYSIS: Yes
- Time schedule for collection of urine:during a 16-hr period prior to sacrifice from rats held in polycarbonate metabolism cages
- Metabolism cages used for collection of urine: Yes
- Animals fasted: No data
- Parameters examined: Semiquantitative measurements on urine: included pH, protein, bilirubin, urobilinogen, glucose, ketones, and blood. In addition, osmolality determinations (Cryomatic osmometer, Advanced Instruments, Inc., Needham Heights, MA) and microscopic evaluations of the urine sediment were performed.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: not reported
- Dose groups that were examined: not reported
- Battery of functions tested: sensory activity / grip strength / motor activity / other: see Table 3
OTHER: Organ weight determinations, gross pathologic examination, and blood and urine sample collections were made the morning following
the last DMEA exposure day (except for recovery animals). - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (see Table 4). Additional histopathologic examinations were performed on rats from the control and high exposure groups, with nasal turbinates also being evaluated for the middle exposure group rats. - Other examinations:
- Organ weights: brain, kidney, liver, lungs, testes, and adrenals.
- Statistics:
- Results of quantitative continuous variables were intercompared among the DMEA concentration levels and the control group by Bartlett’s homogeneity of variance (Sokal and Rohlf, 1969), analysis of variance (ANOVA), and Duncan’s multiple range test (Snedecor and Cochran, 1967). Duncan’s test was used when a significant F value from an ANOVA was observed. For heterogeneous group variances, the groups were compared by ANOVA for unequal variances (Brown and Forsythe, 1974) and either Student’s t test or Cochran’s t test (Snedecor and Cochran, 1967) was used. Corrected Bonferroni probabilities were used for t test comparisons (Miller, 1966). The fiducial limit of 0.05 (two-tailed) was used as the critical level of significance for all comparisons. For the calculation of the LC50, the method of Finney (1964) was used.
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- lower in 76 ppm-group, returned to control during the recovery period
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- corneal opacity which regressed during the night
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- nasal lesions
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No animals died during the study.
BODY WEIGHT AND WEIGHT GAIN
The body weight gains for both sexes of the 76 ppm group were statistically significantlly lower than control values for most of the latter half of the 13 week exposure regimen (Table 5). The body weight gain valuesfor the 76 ppm group returned to control values during the recovery period. There were no exposure-related alterations of body weight gain for rats exposed to 8 or 24 ppm of DMEA.
OPHTHALMOSCOPIC EXAMINATION
Corneal opacity occurred in the 24 and 76ppm groups at the end of the daily exposure, beginning approximately 2-3 weeks after initiation of exposures. The opacity regressed during the night-time nonexposure hours. There was also a moderate incidence (approximately 25%) of audible respiration in rats of the 76 ppm group.
HISTOPATHOLOGY: NON-NEOPLASTIC
Exposure related nasal lesions were observed histologically at the termination of exposures in both sexes of the 76 ppm group, bu were generally not observed in rats of the 24 ppm group (Table 6). The lesions were limited to the anterior nasal cavity and included squamous metaplasia, microcysts ((cystic intraepithelial glands) mucous cell hyperplasia of the respiratory epithelium, mild rhinitis, and atrosoluphy of the dorsal olfactory epithelium. The incidence and severity of these lesions were decreased at the end of the recovery period, indicating some degree of repair. Additionally, 4/ 10 males had laryngitis and two of these rats also had tracheitis. No similar lesions were found in female rats. Vacuolization of the corneal epithelium was
observed in 3/10 female rats of the 76 ppm group at the termination of exposures but not at the end of the recovery period. - Dose descriptor:
- NOEC
- Effect level:
- 24 ppm
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- histopathology: non-neoplastic
- Critical effects observed:
- not specified
- Conclusions:
- DMAE acts primarily as an ocular and upper respiratory tract irritant. 24 ppm is the NOEC.
- Executive summary:
In the 13-week sub-chronic study, F-344 rats were exposed to 0, 8, 24, or 76 ppm DMEA for 6 hr/day, 5 days/week for 13 weeks.The principal exposure-related changes were transient comeal opacity in the 24 and 76 ppm groups; decreased body weight gain for the 76 ppm group; and histopathologic lesions of the respiratory and olfactory epithelium of the anterior nasal cavity of the 76 ppm group and of the eye of several 76 ppm group females. Rats maintained for a 5-week recovery period only exhibited histological lesions of the nasal tissue, with the lesions being decreased in incidence and severity. DMEA acts primarily as an ocular and upper respiratory tract irritant and toxicant at vapor concentrations of 76 ppm, while 24 ppm or less produced no biologically significant toxicity in rats. Thus, 24 ppm was considered to be the no-observable-effect level.
Reference
TABLE 5 |
||||
Body Weight Gain for F-344 Rats Exposed to DMEA Vapor for 13 Weeks and Maintained for a 5-Week Recovery Perioda |
||||
Interval (weeks) |
Mean exposure concentration (ppm) |
|||
0 |
8 |
24 |
76 |
|
|
Males |
|||
8b |
108 ± 12.2 |
112 ± 8.6 |
113 ± 11.1 |
102 ± 8.0* |
14c |
154 ± 11.5 |
157 ± 9.9 |
157 ± 10.2 |
147 ± 10.6* |
19d |
167 ± 16.7 |
166 ± 7.1 |
172 ± 13.2 |
169 ± 9.2 |
|
Females |
|||
8 |
54 ± 4.7 |
53 ± 5.9 |
51 ± 5.0 |
49 ± 6.8** |
14 |
73 ± 5.4 |
70 ± 5.8 |
70 ± 6.3 |
64 ± 6.6** |
19 |
76 ± 6.8 |
73 ± 7.7 |
71 ± 5.1 |
71 ± 4.0 |
aValues represent mean ± SD. |
TABLE 6 |
||||||||||||
Incidence of Selected Nasal Tissue Histopathologic Lesions in F-344 Rats Exposed to DMEA Vapor for 2 or 13 Weeks and Sacrificed the Day after the Final Exposure |
||||||||||||
|
2-week studya |
13-week studyb |
||||||||||
Males |
Females |
Males |
Females |
|||||||||
DMEA concentration (ppm): |
0 |
98 |
288 |
0 |
98 |
288 |
0 |
24 |
76 |
0 |
24 |
76 |
Total No. examined |
10 |
10 |
7 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
Unremarkable |
10 |
1 |
0 |
9c |
5 |
0 |
9d |
8 |
0 |
9d |
8 |
1 |
Rhinitis |
0 |
5 |
6 |
0 |
5 |
7 |
0 |
2 |
0 |
0 |
2 |
7 |
Squamous metaplasia |
0 |
8 |
7 |
0 |
2 |
10 |
0 |
0 |
9 |
0 |
0 |
4 |
Epithelial erosion |
0 |
1 |
4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Mucosal ulceration |
0 |
4 |
6 |
0 |
2 |
8 |
0 |
0 |
0 |
0 |
0 |
0 |
Degeneration of olfactory mucosa/epithelium |
0 |
0 |
1 |
0 |
0 |
9 |
0 |
0 |
0 |
0 |
0 |
0 |
Degeneration of respiratory epithelium |
0 |
0 |
0 |
0 |
0 |
4 |
0 |
0 |
8 |
0 |
0 |
7 |
Atrophy of olfactory epithelium |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
10 |
0 |
0 |
3 |
Microcysts in respiratory epithelium |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
10 |
0 |
0 |
3 |
aAll animals of the 586 ppm group died on study and were not histologically evaluated. Incidence values in the table also do not include those four male rats of the 288 ppm group which died on study. |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEC
- 325 mg/m³
- Study duration:
- subchronic
- Species:
- rat
Repeated dose toxicity: inhalation - local effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- not reported, published 1987
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well documented publication which meets basic scientific principles.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- Deviations:
- not applicable
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Kingston, NY)
- Age at study initiation: approx. 9 weeks old.
- Weight at study initiation: 180 g for males and 130 g females
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum): Purina Certified Rodent Chow 5002, Ralston Purina Co., St. Louis, MO ad libitum except during exposures
- Water (e.g. ad libitum): yes, except during exposures
- Acclimation period: yes
ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- inhalation
- Type of inhalation exposure:
- not specified
- Vehicle:
- other: no data
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 4320-liter stainless-steel and glass chambers
- Method of holding animals in test chamber: not reported
- Source and rate of air: not reported
- Method of conditioning air: not reported
- System of generating particulates/aerosols: DMEA vapor was generated by metering the liquid into a heated, spiral-grooved evaporator with a countercurrent airstream, similar in design to the one used by Carpenter et al. (1975).
- Temperature, humidity, pressure in air chamber: 25°C and 46%,
- Air flow rate: 800-1000 liters/min
- Air change rate: not reported
- Method of particle size determination: not reported
- Treatment of exhaust air: not reported
TEST ATMOSPHERE
- Brief description of analytical method used: The CC column was a 5 ft X 1/4 in stainless-steel column packed with 20% SP-2100 on 80/ 100 mesh Supelcoport (Supelco, BeIlefonte, PA), maintained at 200°C.
- Samples taken from breathing zone: yes
VEHICLE (if applicable) no - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Chamber concentrations of DMEA were analyzed at approximately 40-min intervals with a Perkin-Elmer 3920B gas chromatograph (CC) equipped with a flame ionization detector. Chamber atmosphere samples were automatically injected into the GC with the use of a Perkin-Elmer environmental sampler.
- Duration of treatment / exposure:
- 13 wk
- Frequency of treatment:
- 6h/d, 5d/wk
- Remarks:
- Doses / Concentrations:
8, 24, 76 ppm
Basis:
analytical conc. - No. of animals per sex per dose:
- 20
- Control animals:
- yes
- Details on study design:
- 10 male rats were assigned to the control, middle and high concentration groups for possible ultrastructural evaluation of nerve tissue (not performed since no behavioral abnormalities or light microscopic lesions of nerve tissue were observed).
- Dose selection rationale: not reported
- Rationale for animal assignment (if not random): randomized
- Rationale for selecting satellite groups: to investigate recovery of effects of treatment
- Post-exposure recovery period in satellite groups: 5 week
One-half of all rats per sex per group were sacrificed after at least 2 days of exposure during the 14th week of the study; the remaining rats were sacrificed after 5 complete weeks of recovery. - Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations checked in table [No.3] were included.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: daily
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: were measured during the 16-hr urine collection period.
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION: were measured during the 16-hr urine collection period.
OPHTHALMOSCOPIC EXAMINATION: Yes, (evaluation of the eye with a light source and
magnifying lens)
- Time schedule for examinations: not reported
- Dose groups that were examined: not reported
HAEMATOLOGY: Yes
- Time schedule for collection of blood: made the morning following the last DMEA exposure day (except for recovery animals).
- Anaesthetic used for blood collection: Yes (methoxyflurane)
- Animals fasted: No
- How many animals: not reported
- Parameters checked in table [No.1] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: made the morning following the last DMEA exposure day (except for recovery animals).
- Animals fasted: No
- How many animals: not reported
- Parameters checked in table [No.2] were examined.
URINALYSIS: Yes
- Time schedule for collection of urine:during a 16-hr period prior to sacrifice from rats held in polycarbonate metabolism cages
- Metabolism cages used for collection of urine: Yes
- Animals fasted: No data
- Parameters examined: Semiquantitative measurements on urine: included pH, protein, bilirubin, urobilinogen, glucose, ketones, and blood. In addition, osmolality determinations (Cryomatic osmometer, Advanced Instruments, Inc., Needham Heights, MA) and microscopic evaluations of the urine sediment were performed.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: not reported
- Dose groups that were examined: not reported
- Battery of functions tested: sensory activity / grip strength / motor activity / other: see Table 3
OTHER: Organ weight determinations, gross pathologic examination, and blood and urine sample collections were made the morning following
the last DMEA exposure day (except for recovery animals). - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (see Table 4). Additional histopathologic examinations were performed on rats from the control and high exposure groups, with nasal turbinates also being evaluated for the middle exposure group rats. - Other examinations:
- Organ weights: brain, kidney, liver, lungs, testes, and adrenals.
- Statistics:
- Results of quantitative continuous variables were intercompared among the DMEA concentration levels and the control group by Bartlett’s homogeneity of variance (Sokal and Rohlf, 1969), analysis of variance (ANOVA), and Duncan’s multiple range test (Snedecor and Cochran, 1967). Duncan’s test was used when a significant F value from an ANOVA was observed. For heterogeneous group variances, the groups were compared by ANOVA for unequal variances (Brown and Forsythe, 1974) and either Student’s t test or Cochran’s t test (Snedecor and Cochran, 1967) was used. Corrected Bonferroni probabilities were used for t test comparisons (Miller, 1966). The fiducial limit of 0.05 (two-tailed) was used as the critical level of significance for all comparisons. For the calculation of the LC50, the method of Finney (1964) was used.
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- lower in 76 ppm-group, returned to control during the recovery period
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- corneal opacity which regressed during the night
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- nasal lesions
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No animals died during the study.
BODY WEIGHT AND WEIGHT GAIN
The body weight gains for both sexes of the 76 ppm group were statistically significantlly lower than control values for most of the latter half of the 13 week exposure regimen (Table 5). The body weight gain valuesfor the 76 ppm group returned to control values during the recovery period. There were no exposure-related alterations of body weight gain for rats exposed to 8 or 24 ppm of DMEA.
OPHTHALMOSCOPIC EXAMINATION
Corneal opacity occurred in the 24 and 76ppm groups at the end of the daily exposure, beginning approximately 2-3 weeks after initiation of exposures. The opacity regressed during the night-time nonexposure hours. There was also a moderate incidence (approximately 25%) of audible respiration in rats of the 76 ppm group.
HISTOPATHOLOGY: NON-NEOPLASTIC
Exposure related nasal lesions were observed histologically at the termination of exposures in both sexes of the 76 ppm group, bu were generally not observed in rats of the 24 ppm group (Table 6). The lesions were limited to the anterior nasal cavity and included squamous metaplasia, microcysts ((cystic intraepithelial glands) mucous cell hyperplasia of the respiratory epithelium, mild rhinitis, and atrosoluphy of the dorsal olfactory epithelium. The incidence and severity of these lesions were decreased at the end of the recovery period, indicating some degree of repair. Additionally, 4/ 10 males had laryngitis and two of these rats also had tracheitis. No similar lesions were found in female rats. Vacuolization of the corneal epithelium was
observed in 3/10 female rats of the 76 ppm group at the termination of exposures but not at the end of the recovery period. - Dose descriptor:
- NOEC
- Effect level:
- 24 ppm
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- histopathology: non-neoplastic
- Critical effects observed:
- not specified
- Conclusions:
- DMAE acts primarily as an ocular and upper respiratory tract irritant. 24 ppm is the NOEC.
- Executive summary:
In the 13-week sub-chronic study, F-344 rats were exposed to 0, 8, 24, or 76 ppm DMEA for 6 hr/day, 5 days/week for 13 weeks.The principal exposure-related changes were transient comeal opacity in the 24 and 76 ppm groups; decreased body weight gain for the 76 ppm group; and histopathologic lesions of the respiratory and olfactory epithelium of the anterior nasal cavity of the 76 ppm group and of the eye of several 76 ppm group females. Rats maintained for a 5-week recovery period only exhibited histological lesions of the nasal tissue, with the lesions being decreased in incidence and severity. DMEA acts primarily as an ocular and upper respiratory tract irritant and toxicant at vapor concentrations of 76 ppm, while 24 ppm or less produced no biologically significant toxicity in rats. Thus, 24 ppm was considered to be the no-observable-effect level.
Reference
TABLE 5 |
||||
Body Weight Gain for F-344 Rats Exposed to DMEA Vapor for 13 Weeks and Maintained for a 5-Week Recovery Perioda |
||||
Interval (weeks) |
Mean exposure concentration (ppm) |
|||
0 |
8 |
24 |
76 |
|
|
Males |
|||
8b |
108 ± 12.2 |
112 ± 8.6 |
113 ± 11.1 |
102 ± 8.0* |
14c |
154 ± 11.5 |
157 ± 9.9 |
157 ± 10.2 |
147 ± 10.6* |
19d |
167 ± 16.7 |
166 ± 7.1 |
172 ± 13.2 |
169 ± 9.2 |
|
Females |
|||
8 |
54 ± 4.7 |
53 ± 5.9 |
51 ± 5.0 |
49 ± 6.8** |
14 |
73 ± 5.4 |
70 ± 5.8 |
70 ± 6.3 |
64 ± 6.6** |
19 |
76 ± 6.8 |
73 ± 7.7 |
71 ± 5.1 |
71 ± 4.0 |
aValues represent mean ± SD. |
TABLE 6 |
||||||||||||
Incidence of Selected Nasal Tissue Histopathologic Lesions in F-344 Rats Exposed to DMEA Vapor for 2 or 13 Weeks and Sacrificed the Day after the Final Exposure |
||||||||||||
|
2-week studya |
13-week studyb |
||||||||||
Males |
Females |
Males |
Females |
|||||||||
DMEA concentration (ppm): |
0 |
98 |
288 |
0 |
98 |
288 |
0 |
24 |
76 |
0 |
24 |
76 |
Total No. examined |
10 |
10 |
7 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
Unremarkable |
10 |
1 |
0 |
9c |
5 |
0 |
9d |
8 |
0 |
9d |
8 |
1 |
Rhinitis |
0 |
5 |
6 |
0 |
5 |
7 |
0 |
2 |
0 |
0 |
2 |
7 |
Squamous metaplasia |
0 |
8 |
7 |
0 |
2 |
10 |
0 |
0 |
9 |
0 |
0 |
4 |
Epithelial erosion |
0 |
1 |
4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Mucosal ulceration |
0 |
4 |
6 |
0 |
2 |
8 |
0 |
0 |
0 |
0 |
0 |
0 |
Degeneration of olfactory mucosa/epithelium |
0 |
0 |
1 |
0 |
0 |
9 |
0 |
0 |
0 |
0 |
0 |
0 |
Degeneration of respiratory epithelium |
0 |
0 |
0 |
0 |
0 |
4 |
0 |
0 |
8 |
0 |
0 |
7 |
Atrophy of olfactory epithelium |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
10 |
0 |
0 |
3 |
Microcysts in respiratory epithelium |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
10 |
0 |
0 |
3 |
aAll animals of the 586 ppm group died on study and were not histologically evaluated. Incidence values in the table also do not include those four male rats of the 288 ppm group which died on study. |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEC
- 108 mg/m³
- Study duration:
- subchronic
- Species:
- rat
Repeated dose toxicity: dermal - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: dermal
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: dermal
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
No repeated dose toxicity study is available for dimethylaminopropanol. Dimethylethanolamine (DMAE, CAS 108-01-0) is a structural analogue of dimethylaminopropanol and was used as read-across. In the two-week inhalation study (Klonne et al., 1987), rats exposed to higher concentrations of DMAE vapour (98, 288 and 586 ppm) during an 11-day period exhibited severe signs of respiratory and ocular irritation (except the 98 ppm group). All animals of the 586 ppm group and 4 of 15 male rats of the 288 ppm group died. Body weight values for the 288 ppm group were reduced to about 75% of preexposure values, while the 98 ppm group gained 35% less weight than controls. Statistically significant differences in clinical pathology parameters (288 ppm group) and in organ weight values (288 and 98 ppm groups) probably resulted from the decreased food consumption and not from specific target organ toxicity. In the groups evaluated histologically (the 98 and 288 ppm groups) the eye and nasal mucosa were the primary target organs.
In the 13-week sub-chronic study, F-344 rats were exposed to 0, 8, 24, or 76 ppm DMEA for 6 hr/day, 5 days/week for 13 weeks (Klonne et al., 1987). No animals died during the study. The body weight gains for both sexes of the 76 ppm group were significantly lower than control values for most of the latter half of the 13-week exposure time. The body weight gain values for the 76 ppm group returned to control values during the recovery period. There were no expossure-related body weight gain effects for rats exposed to 8 or 24 ppm of DMEA. There were no exposure-related effects on the neurobehavioral, food and water consumption, hematologic, serum chemistry, or urinalysis evaluations, on organ weights, or on the gross appearance of organs. Exposure-related nasal lesions were observed histologically at the termination of exposures in both sexes of the 76 ppm group, but were generally not observed in rats of the 24 ppm group. The lesions were limited to the anterior nasal cavity and included squamous metaplasia, microcysts and mucous cell hyperplasia of the respiratory epithelium, mild rhinitis and atrophy of the dorsal olfactory epithelium. The incidence and severity of these lesions were decreased at the end of the recovery period, indicating some degree of repair. Additionally, 4/10 males had laryngitis and two of these rats also had tracheitis. No similar lesions were found in female rats. Vacuolization of the corneal epithelium was observed in 3/10 female rats of the 76 ppm group at the termination of exposures but not at the end of the recovery period. Corneal opacity occurred in the 24 and 76 ppm groups at the end of the daily exposure, beginning approximately 2-3 weeks after initiation of exposures. The opacity regressed during the night-time nonexposure hours. There was also a moderate incidence (approximately 25%) of audible respiration in rats of the 76 ppm group.
Justification for selection of repeated dose toxicity via oral
route - systemic effects endpoint:
Due to the corrosive effects caused by dimethylaminopropanol,
long-term oral application of the test substance is not reasonable
(aspects of animal welfare). Moreover, there are valid data available
from a subchronic inhalation study with dimethylethanolamine (DMAE, read
across, CAS 108-01-0) (Klonne et al., 1987), which allows assessment of
an oral exposure level by extrapolation procedure.
Justification for selection of repeated dose toxicity inhalation -
systemic effects endpoint:
NOAEC was calculated using the following equation: c [mg/m3] = (c
[ppm] x molecular weight) : 24.1
with molecular weight = 103.16 g/mol (dimethylaminopropanol)
Justification for selection of repeated dose toxicity inhalation -
local effects endpoint:
NOAEC was calculated using the following equation: c [mg/m3] = (c
[ppm] x molecular weight) : 24.1
with molecular weight = 103.16 g/mol (dimethylaminopropanol)
Justification for selection of repeated dose toxicity dermal -
systemic effects endpoint:
In the irritation studies, dimethylaminopropanol showed corrosive
effects on skin which were irreversible during the examination period.
Hence, long-term dermal testing is not reasonable (aspects of animal
welfare). Moreover, there are valid data available from a subchronic
inhalation study with dimethylethanolamine (DMEA, read across, CAS
108-01-0) (Klonne et al., 1987), which allows to assess dermal exposure
level by extrapolation procedure.
Justification for selection of repeated dose toxicity dermal - local
effects endpoint:
Dimethylaminopropanol was found to be corrosive to the rabbit skin
under occlusive conditions. Dermal application for 15 min caused
necrosis, while a 20-hour exposure induced necrosis and severe erythema
and edema after 24 hours. After 8 days, strong/movable necrosis was
observed. For further details refer also to IUCLID chapter 7.3.
Justification for classification or non-classification
Classification is not warranted according to the criteria of EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.
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