Registration Dossier

Administrative data

Description of key information

Acute toxicity - oral: The oral LD50 in rats was determined to be 2885 mg/kg bw in a study conducted similarly to OECD guideline 401 (Mallory, 1993).

Acute toxicity - inhalation: No mortality occurred when rats were exposed to air  near-saturated with the test substance vapor for 8 hours (Bio/dynamics Inc., 1979). the LC50 is considered to be > 0.74 mg/L.

Acute toxicity - dermal: In a study conducted similarly to OECD guideline 402, the acute dermal LD50 was determined to be 2980 mg/kg bw in New Zealand White rabbits (Mallory, 1993).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1992-02-05 - 1992-03-11
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
Limited information on the test substance.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name as cited in study report: 6398-9-20
- Color: clear
- Storage: during storage no change in the physical state of test article
- Specific gravity: 0.948 g/mL
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Inc., Wilmington, Massachusetts, USA
- Age at study initiation: 6-10 weeks
- Weight at study initiation: 155-291 g (dose-range finder), 157-232 g (main test); weight variation in each sex did not exceed +/- 20%
- Fasting period before study: yes
- Housing: individually in stainless steel wire mesh cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30-70 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 4.22 ml/kg bw (based on max. dose level 4000 mg/kg bw and specific gravity 948 mg/ml)

DOSAGE PREPARATION (if unusual): test article was dosed as received using specific gravity calculations.

Doses:
0 (water), 2000, 2500, 3000, 4000 mg/kg bw
No. of animals per sex per dose:
5 substance exposed animals, 3 control animals
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations at 1h, 4h, 24h after dosing and once daily thereafter; body weights at 0h, 7d and 14d after exposure (or when found dead).
- Necropsy of survivors performed: yes
- Other examinations performed: toxicological effects, viability, gross necropsy, histopathology (of control and highest dose group)
Statistics:
LD50 calculations according to Litchfield and Wilcoxon.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 885.3 mg/kg bw
Based on:
test mat.
95% CL:
>= 2 400.7 - <= 3 467.7
Sex:
male
Dose descriptor:
LD50
Effect level:
2 922.1 mg/kg bw
Based on:
test mat.
95% CL:
>= 2 308.9 - <= 3 698.2
Sex:
female
Dose descriptor:
LD50
Effect level:
2 627.2 mg/kg bw
Based on:
test mat.
95% CL:
>= 2 157.7 - <= 3 198.8
Mortality:
No mortality in 6 control rats (3M/3F)
2000 mg/kg: 1/5 females
2500 mg/kg: 3/5 males and 2/5 females
3000 mg/kg: 1/5 males and 3/5 females
4000 mg/kg: 5/5 males and 5/5 females
All deads occurred on or 1 day after the day of exposure.
Clinical signs:
Decreased activity during the first few days after exposure only (only for substance exposed rats).
Dyspnea during the first few days after exposure only (in 2500-3000-4000 dosed rats)
Body weight:
No remarkable findings
Gross pathology:
In exposed animals that died during the study: distended stomach and intestines (all dose levels), dark or pale organs (3000 and 4000 mg/kg).
No visible lesions in control animals and all survivors.
Other findings:
No treatment related findings compared to control rats.
Interpretation of results:
not classified
Conclusions:
In view of the LD50 value of 2885 mg/kg bw in this rat study, the substance does not need to be classified for acute orale toxicity according to the CLP Regulation (EC)1272/2008.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
no data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Remarks:
No information on study design and methodology was presented.
Reason / purpose for cross-reference:
reference to other study
Qualifier:
no guideline followed
GLP compliance:
not specified
Test type:
other: Data not available
Limit test:
no
Specific details on test material used for the study:
No test item information provided
Species:
rat
Strain:
other: Albino (MR Wistar)
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
-Mean weight at study initiation:
0.59 g/kg: 150
1.18 g/kg: 152
2.35 g/kg: 150
4.70 g/kg: 150

- Fasting period before study: animals fasted for 24 hours were dosed with the test substance as received
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
animals fasted for 24 hours were dosed with the test substance as received
Doses:
0.59, 1.18, 2.35, 4.70 g/kg
No. of animals per sex per dose:
5 males/dose
Control animals:
no
Details on study design:
- Frequency of weighing: beginning and end of study
- Necropsy of survivors performed: yes
Statistics:
no information provided
Sex:
male
Dose descriptor:
LD50
Effect level:
1 660 mg/kg bw
Based on:
not specified
Remarks on result:
other: mean
Mortality:
Mortality
0.59 g/kg: 0/5
1.18 g/kg: 2/5
2.35 g/kg: 3/5
4.70 g/kg: 5/5

Onset of death
1.18 g/kg: two deaths at 6-24 hours
2.35 g/kg: two dealth at 6-24 hours and 1 death at 2 days
4.70 g/kg: four deaths at 0-6 hours and 1 death at 6-24 hours


Body weight:
Mean body weight at termination
0.59 g/kg: 249
1.18 g/kg: 254
2.35 g/kg: 249
Gross pathology:
Survivors - normal
Other findings:
No signs of intoxication were observed
Interpretation of results:
sligthly toxic
Conclusions:
The test substance is considered to be slightly toxic by ingestion in single doses.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 885 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1979-01-17 - 1979-05-03
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
However, limited details were provided on exposure conditions (i.e., particle size determination), test substance (i.e., purity), and animal husbandry. Only one concentration was used and exposure was for 8 hours without a justification provided.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Limited details were provided on exposure conditions (i.e., particle size determination), test substance (i.e., purity), and animal husbandry. Only one concentration was used and exposure was for 8 hours without a justification provided.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name as cited in study report: Poly[oxy(methyl-1,2-ethanediyl)], alpha-(2-aminomethylethyl)-omega-(2-aminomethylethoxy)
- Substance type: active
- Color: clear, amber
- Lot: Jefferson chemical company, sample no. AVS-0381, 4236-10-20a, SPC no. 1575
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, Massachusetts
- Weight at study initiation: 209-254
- Other: The animals were observed prior to exposure to assure that they were free from abnormalities.


IN-LIFE DATES: From: 1979-01-17 To: 1979-01-31
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Remarks:
dry
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: A glass exposure chamber housed the animals.
- Exposure chamber volume: 26.5 liter
- Source and rate of air: 4.0 liters per minute
- Method of conditioning air: The test substance was placed in a 500 milliliter gas-washing bottle. Dry air, at the minimum chamber flow rate of 4.0 liters per minute, was passed through the test substance and the resultant vapor-laden air was directed, undiluted, into the exposure chamber housing the test animals.
- Temperature, humidity, pressure in air chamber: the chamber temperature during the exposure was 22 degrees C.
- Other: The flask containing the test substance, two glass tubes, and connectors were weighed before and after the exposure period. The difference in weight was equal to the amount of test substance volatilized during the exposure. The nominal concentration was calculated by dividing the weight loss by the total air flow through the chamber during the exposure period.



Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
ca. 8 h
Concentrations:
0.74 mg/L (1.42 grams of test substance delivered in a total volume of 1920 liters of dry air)
No. of animals per sex per dose:
5 animals per sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for abnormal signs were recorded at 15 minute intervals for the first hour of exposure, hourly for the remaining seven hours of the exposure, upon removal from the chamber, at one hour post-exposure, and daily thereafter for 14 days. Individual body weights were recorded on day 0 (prior to exposure) and on Days 1, 2, 4, 7 and 14 (terminus) for all animals.
- Necropsy of survivors performed: yes; On Day 14 all animals were sacrificed (ethyl ether) and gross necropsy examinations were performed.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 0.74 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
8 h
Remarks on result:
other: No mortality was observed at 0.74 mg/L
Mortality:
No mortalities occurred.
Clinical signs:
other: No abnormalities were observed in any animals during the exposure. Upon removal from the chamber, one animal was observed to have dry rales. At one-hour post-exposure dry rales was noted again in the same animal. During the 14-day observation period dr
Body weight:
Individual body weight data showed normal weight gains in all animals except one male, which showed a somewhat depressed weight gain pattern.
Gross pathology:
Necropsy examinations revealed lung discoloration in nine of ten animals and kidney discoloration in six of ten animals. The frequency of lung and kidney discoloration was higher than that normally observed in Sprague-Dawley rats in this type of exposure and may have been indicative of a response to the exposure.
Interpretation of results:
study cannot be used for classification
Conclusions:
The acute inhalation toxicity of the test substance was evaluated in male and female rats. The LC50 was determined to be >0.74 mg/L.
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
no data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: No information on study design and methodology was presented.
Reason / purpose for cross-reference:
reference to other study
Qualifier:
no guideline available
GLP compliance:
not specified
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
No test item information provided
Species:
rat
Strain:
other: albino (MR Wistar)
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Mean weight at study initiation: 168
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
air
Details on inhalation exposure:
Animals were exposed to air near-saturated with vapor of the test substance for 7 hours at 25 °C.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
7 h
Concentrations:
Animals were exposed to air near-saturated with vapor of the test substance.
No. of animals per sex per dose:
10 animals/dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days (or other?) no data
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: limited data
Preliminary study:
No animals died after receiving a 7 hr exposure to near-saturated vapor at 25 °C. 0/10 animals died. Discomfort, irritation, dyspnea were observed within 15 minutes. Moderate skin irritation was seen within 30 minutes followed by a decrease in motor activity. Rapid recovery following exposure. Gross autopsy was normal.
Mortality:
0/10
Clinical signs:
other: Discomfort, irritation, dyspnea within 15 minutes. Moderate skin irritation within 30 minutes followed by decrease in motor activity. Rapid recovery following exposure.
Body weight:
Mean body weight at termination 310
Gross pathology:
Normal
Interpretation of results:
relatively harmless
Conclusions:
The rats exhibited discomfort, irritation, dyspnea within 15 minutes of inhalation exposure to the test substance. Moderate skin irritation was present within 30 minutes, followed by a decrease in motor activity. Rapid recovery following exposure.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
740 mg/m³

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1992-04-22 to 1992-07-09
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
Limited information on the test substance available.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name as cited in study report: 6398-9-20
- Lot/Batch number: 6398-9-20
- Color: clear
- Storage: during storage no change in physical state of the test article
- specific gravity: 0.948 g/ml
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Denver, PA, USA
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 2233 - 3574 g
- Fasting period before study: no, not applicable
- Housing: individually in cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 30-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: no data
- % coverage: at least 10% of the body surface was cleared
- Type of wrap if used: rubber dam and an elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): control: 5.6-7.3 ml water; 500 mg/kg dose: 1.3-1.9 ml test substance; 2000 mg/kg dose: 5.4-7.5 ml; 3200 mg/kg dose: 9.7-11.4 ml; 4000 mg/kg dose: 9.4-12.2 ml.
- Constant volume or concentration used: no

Duration of exposure:
24 hours
Doses:
0 (water), 500, 2000, 3200, 4000 mg/kg bw
No. of animals per sex per dose:
5 in substance-treated groups and 3 in controls.
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations once daily; body weights at 0h, 7d and 14d after exposure (or when found dead).
- Necropsy of survivors performed: yes
- Other examinations performed: toxicological effects, viability, gross necropsy, histopathology (of control and highest dose group)
Statistics:
Method of Litchfield & Wilcoxon.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 979.7 mg/kg bw
Based on:
test mat.
95% CL:
>= 993.8 - <= 8 934.1
Sex:
male
Dose descriptor:
LD50
Effect level:
2 979.7 mg/kg bw
Based on:
test mat.
95% CL:
>= 2 037.4 - <= 4 357.9
Sex:
female
Dose descriptor:
LD50
Effect level:
2 979.7 mg/kg bw
Based on:
test mat.
95% CL:
>= 2 037.4 - <= 4 357.9
Mortality:
Control: no mortality
500 mg/kg: no mortality
2000 mg/kg: no mortality
3200 mg/kg: 4/5 females and 4/5 males died during the first 3 days
4000 mg/kg: all animals died within 2 days.
Clinical signs:
Decreased activity, abnormal gait, abnormal stance, dyspnea, body drop, prostration in 2000-3200-4000 mg/kg dose animals.
No clinical signs in control animals and in 500 mg/kg dose animals.
Necrosis of the skin at the application site was observed in all animals exposed to the test substance.
Body weight:
No significant effects compared to controls.
Gross pathology:
Animals that died during the study: discolored thymus and liver, prominent lobular pattern throughout the liver.
Survivors: no relevant effects.
Other findings:
Histopathology: no treatment related effects.
Interpretation of results:
not classified
Conclusions:
In view of the LD50 value of 2980 mg/kg bw in this rabbit study, the substance does not need to be classified for acute dermal toxicity according to the CLP Regulation (EC) 1272/2008.
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
no data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: No information on study design and methodology was presented.
Qualifier:
no guideline available
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
No test item information provided
Species:
rabbit
Strain:
other: albino
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
-Mean weight at study initiation:
DOSE: Weight (g)
0.29 g/kg: 3.25
0.59 g/kg: 3.00
1.18 g/kg: 2.84
2.35 g/kg: 2.89
Type of coverage:
occlusive
Vehicle:
not specified
Details on dermal exposure:
TEST SITE
- Type of wrap if used: impervious cuff

TEST MATERIAL
- Concentration (if solution):
0.29 g/kg
0.59 g/kg
1.18 g/kg
2.35 g/kg
Duration of exposure:
24 hours - continuous
Doses:
0.29, 0.59, 1.18, 2.35 g/kg
No. of animals per sex per dose:
5 animals/dose
Control animals:
not specified
Details on study design:
- Frequency of weighing: at beginning and end of study
Statistics:
no information was provided
Sex:
male
Dose descriptor:
LD50
Effect level:
760 other: mg/kg
Based on:
not specified
Remarks on result:
other: mean
Mortality:
Mortality
0.29 g/kg: 1/5
0.59 g/kg: 0/5
1.18 g/kg: 5/5
2.35 g/kg: 5/5


Onset of death
0.29 g/kg: one death at 6-24 hours
0.59 g/kg: N./A
1.18 g/kg: five deaths at 6-24 hours
2.35 g/kg: five deaths at 6-24 hours
Clinical signs:
Signs of intoxication: Diarrhea, exudate around mouth and nose, hind leg weakness.

Onset of signs
0.29 g/kg: 1 death at 6-24 hours
0.59 g/kg: N/A
1.18 g/kg: five animals at 6-24 hours with signs/death
2.35 g/kg: five animals at 6-24 hours with signs/death
Body weight:
Mean body weight at end of study
0.29 g/kg: 3.28
0.59 g/kg: 3.11
1.18 g/kg: N/A
2.35 g/kg: N/A
Gross pathology:
animals at 0.59 g/kg dose appeared normal
Other findings:
Signs of intoxication: Diarrhea, exudate around mouth and nose, hind leg weakness.
Interpretation of results:
other: corrosive
Conclusions:
The test substance is corrosive to the skin of the rabbit. Therefore, precautions should be observed to prevent skin contact with the product.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 980 mg/kg bw

Additional information

Acute toxicity studies of sufficient quality and conducted in methods comparable to OECD guidelines were available for oral, dermal, and inhalation routes of exposure to the test substance.

Acute toxicity: oral

The acute oral study was conducted using methods comparable to OECD guideline 401 (Mallory, 1993). Groups of 5 male and 5 female rats received an oral dose of test substance by gavage at 2000, 2500, 3000 and 4000 mg/kg bw, and the acute oral LD50 was determined to be 2885 mg/kg bw (combined sexes). Lower LD50 values were found in other studies which were assigned either not reliable (Klimisch 3) or not assignable (Klimisch 4). In these older studies, the used methods were poorly described. Furthermore, no constant dosing volume was applied, which could be the cause of the higher mortality.

Acute toxicity: dermal

In the acute dermal study conducted using methods similar to OECD guideline 402, groups of 5 male and 5 female New Zealand White rabbits were exposed to the test substance for 24 hours occlusively at 500, 2000, 3200 and 4000 mg/kg bw (Mallory, 1993). The acute dermal LD50 was determined to be 2980 mg/kg bw (combined sexes). Lower LD50 values were found in other studies which were assigned either not reliable (Klimisch 3) or not assignable (Klimisch 4). In these older studies, the used methods were poorly described. Furthermore, no constant dosing volume was applied, which could be the cause of the higher mortality.

Acute toxicity: inhalation

In the acute inhalation study conducted using methods similar to OECD guideline 403, groups of rats were exposed to air nearly saturated with the test substance vapor for 8 hours (Bio/dynamics Inc., 1979). The nominal concentration was calculated to be 0.74 mg/L (740 mg/m3). No mortality occurred during the 14 day observation period. LC50 was considered thus > 0.74 mg/L.

Justification for classification or non-classification

The oral LD50 of 2885 mg/kg falls outside the hazard categories for acute oral toxicity, and therefore no classification is warranted for the oral route.

The dermal LD50 of 2980 mg/kg falls outside the hazard categories for acute dermal toxicity, and therefore no classification is warranted for the dermal route.

The inhalatory LC50 is set at greater than 740 mg/m³, as it is based on one dose tested only. Therefore, no conclusion can be made on the classification.