Registration Dossier

Administrative data

Description of key information

Acute toxicity: oral:
A K2 acute oral toxicity test was performed in male and female Crl:COBS CD(SD)BR rats according to a guideline similar to OECD Guideline 401 (Huntsman, 1978). This study was selected as key study.
Acute toxicity: inhalation
No reliable acute inhalation test was available for DMDEE. Only a K4 study is available for acute inhalation tested in male and female Sprague Dawley rats (Huntsman, 1978). The test was performed according a guideline equivalent to OECD Guideline 403.
Acute toxicity: dermal
A K2 acute dermal test was performed in male and female New Zealand White rabbits according to a guideline similar to OECD Guideline 402 (Huntsman, 1978). This study was selected as key study.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
not indicated
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Well documented non-GLP study performed according to a guideline similar to OECD Guideline 401. Only two animals per sex per dose level are used (instead of 5).
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Only 2 animals per sex per dose level are used instead of 5.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
OTHER SPECIFICS:
- Name of test material (as cited in study report): Aus 0213 4236-14-4 Alkaline Corrosive Liquid N2 Pad Urethane Catalyst
- Appearance: orange liquid
Species:
rat
Strain:
other: Crl:COBS CD (SD) BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Young albino rats: Charles River CD Strain, Crl:COBS CD (SD) BR
- Source: Charles River Breeding Laboratories, Inc., Wilmington, Massachusetts 01887
- Age at study initiation: young rats
- Weight at study initiation: males 180-232 g (mean 205.2 g); females 164-220 g (mean 194.8 g)
- Fasting period before study: 24 hours before oral intubation
- Housing: Animals were housed in suspended, wire-mesh stock cages
- Diet (e.g. ad libitum): permitted a standard laboratory diet: Purina Rat Chow 5012, Ralstor, Purina Company, St. Louis, Missouri 63188 (ad libitum)
- Water (e.g. ad libitum): water was permitted ad libitum
- Acclimation period: at least 5 days

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
or undiluted
Details on oral exposure:
Form administered: As a 10.0% (w/v) aqueous solution at 118.5-400,0 mg/kg and undiluted at 1350 - 4556 mg/kg.
Selected groups of albino rats were administered test material at several dose levels. All doses were administered directly into the stomachs of the rats using a hypodermic syringe equipped with a ball-tipped intubating needle.
Doses:
118,5; 400; 1350; 2025; 3038; 4556 mg/kg bw
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
After oral administration of the test material, the rats were housed individually in suspended, wire-mesh cages and observed for the following 14 days. Initial and final body weights, mortalities and reactions were recorded. A necropsy examination was conducted on all animals.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 025 mg/kg bw
Based on:
test mat.
Remarks on result:
other: SD = +/- 237.6 mg/kg
Mortality:
118,5 mg/kg group: 0 /4 dead
400 mg/kg group: 0/4 dead
1350 mg/kg group: 0/4 dead
2025 mg/kg group: 2/4 dead (1 female between 6-22h and 1 female after 1.5 days)
3038 mg/kg group: 4/4 dead (1 male and 1 female between 6-22h, 1 male after 1 day, 1 female after 2 days)
4556 mg/kg group: 4/4 dead (2 males after 4.5 days, 2 females between 6-22h)
Clinical signs:
Diuresis was observed in the 4556 mg/kg dose group in 2 animals.
Hypoactivity, hyperirritability, lacrimation and tremors were observed in the 2025 and 3038 mg/kg dose group.
Hemorrhagic lacrimation was observed in the 2025 mg/kg dose group in 1 animal.
Loss of balance was observed in the 3038 mg/kg dose group in 1 animal.
Body weight:
No adverse effects noted.
Gross pathology:
At 2025 mg/kg bw moderate postmortem autolysis was observed in 2 females
At 3038 mg/kg bw moderate postmortem autolysis was observed in one male and one female and slightly pale spleen was observed in one male
At 4556 mg/kg bw moderate postmortem autolysis was observed in two females and advanced postmortem autolysis was observed in two males.
Other findings:
No data
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
In this study an acute oral LD50 value of 2025 mg/kg bw was determined in rats after exposure to the substance. Therefore, the substance is considered not to be classified according to CLP.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 025 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
not indicated
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Well-documented non-GLP study performed according to guideline similar to OECD Guideline 402. Only 2 animals per sex per dose level are used (instead of 5). Skin was abraded in half of the animals.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Only 2 instead of 5 animals per sex per dose level are used. Skin was abraded in half of the animals.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
OTHER SPECIFICS:
- Name of test material (as cited in study report): Aus 0213 4236-14-4 Alkaline Corrosive Liquid N2 Pad Urethane Catalyst
- Appearance: orange liquid
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Pel-Freez, Inc., USDA No. 71-B-16, Rogers, Arkansas 72756
- Age at study initiation: young adult albino rabbits: approximately 10 - 13 weeks of age
- Housing: The rabbits were housed in suspended, wire-bottomed steel cages
- Diet (e.g. ad libitum): The rabbit were maintained on a standard laboratory diet: Purina Rabbit Chow Special, 5340, Ralston Purina Company, St. Louis, Missouri, 63188
- Water (e.g. ad libitum): Water was offered ad libitum
- Acclimation period: All rabbits were kept under observation in the laboratory for at least 7 days prior to testing

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- 24 hours prior to the dermal applications, the backs of the rabbits were clipped free of hair with electric clippers. The animals were then returned to their cages to await testing on the following day. The 24-hour waiting period allowed recovery of the stratum corneum from the disturbance which accompanied the close-clipping procedure and permitted healing of any microscopic abrasians possibly produced during the process. At the end of the 24-hour recovery period, just prior to the application of the test material, the clipped test skin site of one half of the animals was abraded (with a slightly bent tip of a hypodermic needle) by making a series of parallel, epidermal abrasions, every 2 or 3 centimeters longitudinally. These abrasions were made sufficiently deep to penetrate the stratum corneum, but not to disturb the derma.
- Area of exposure: backs of the rabbits
- % coverage: 30% of the total body surface area
- Type of wrap if used: The test site was covered by wrapping the trunk of each animal with an impervious plastic sleeve which was securely taped in place. This plastic wrap insured close contact of the epidermis and the test material. To prevent oral ingestion of the test material, each animal was fitted with a lightweight, flexible plastic collar which was worn throughout the observation period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test material remained in contact with the skin for 24 hours. At the end of this period, the plastic sheeting was taken off and all removable residual test material was washed off with warm tap water.
Duration of exposure:
24 hours
Doses:
1350, 2025, 3038 and 4556 mg/kg bw
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
One hour after test material removal, the test skin sites were examined for local skin reactions. Observations for mortality and behavioral abnormalities were made daily for a total of 14 days following the dermal exposure. Initial, 7- and 14-day body weights were recorded. In addition, local skin reactions were evaluated at 7 and 14 days. A necropsy examination was conducted on all animals.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 038 mg/kg bw
Based on:
test mat.
Remarks on result:
other: SD = +/- 356.4 mg/kg
Mortality:
1350 mg/kg group: 0/4 dead
2025 mg/kg group: 0/4 dead
3038 mg/kg group: 2/4 dead (both exposed to intact skin)
4556 mg/kg group: 4/4 dead
Clinical signs:
Adverse body effects, varying in degree of severity, were noted in several of the animals at 7 and 14 days. The test material was slightly irritating to the skin of the albino rabbit. Skin reactions at 24 hours were characterized by barely perceptible to pale red erythema and slight edema. Desquamation was observed at the test skin sites of most of the surviving animals at 7 and 14 days.
Hypoactivity was observed in the 1350, 2025 and 4556 mg/kg dose group
Hyperirritability was observed in all dose groups
Diarrhea, slight miosis, hindquarter paralysis and emaciation were observed in the 3038 mg/kg dose group
Loss of righting and tremors were observed in the 4556 mg/kg dose group
Body weight:
No data
Gross pathology:
1350 mg/kg dose group: jejunum distended with gas; perineum stained with urine in one male
2025 mg/kg dose group: perineum stained with feces in one male
3038 mg/kg dose group: moderate postmortem autolysis in one male and perineum stained with feces; emaciation; moderate postmortem autolysis
4556 mg/kg dose group: Diffuse yellow discoloration of all lobes of the liver; hemorrhagic-like foci (1 mm) within mucosa of glandular region of the stomach in one male and hemorrhagic-like foci (1-3 mm) within the mucosa of the stomach in one female.
Other findings:
No data
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
In this study an acute dermal LD50 value of 3038 mg/kg bw was determined in rabbits after exposure to the test substance. Therefore, the substance is considered not to be classified.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
3 038 mg/kg bw

Additional information

Acute toxicity: oral

Huntsman (1978) investigated the acute oral toxicity via gavage of 118.5, 400, 1350, 2025, 3038 and 4556 mg/kg bw test substance in 4 Crl:COBS CD (SD) BR male/female rats. After 14 days of observation, mortality has been observed: 2025 mg/kg group: 2/4 dead (1 female between 6-22h and 1 female after 1.5 days), 3038 mg/kg group: 4/4 dead (1 male and 1 female between 6-22h, 1 male after 1 day, 1 female after 2 days), 4556 mg/kg group: 4/4 dead (2 males after 4.5 days, 2 females between 6-22h). The acute oral LD50 was determined to be 2025 mg/kg bw. This study is designated as key study. In addition, two supporting K1 and K4 studies reported a LD50 value of > 2000 mg/kg bw and 2.83 mL/kg bw (3000 mg/kg bw), respectively.

Acute toxicity: inhalation

No reliable studies were available for the inhalation route. A waiver statement was added and justified as following: next to the oral route of exposure, for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route (REACH Regulation, column 2 adaptation of Annex VIII). For this substance, a key study is available for the dermal route of exposure. Therefore, an acute inhalation toxicity study should not be performed.

Acute toxicity: dermal

Huntsman (1978) investigated acute dermal toxicity of the test substance in 4 New Zealand White male/female rabbits after 24 hours of exposure to respectively 1350, 2025, 3038 and 4556 mg/kg bw. No mortality was observed at 1350 or 2025 mg/kg bw/d. In the 3038 mg/kg bw 2 animals out of 4 died. All animals (4/4) died in the 4556 mg/kg bw dosing group. Therefore, after 14 days of observation, an LD50 value of 3038 mg/kg bw was reported. This study is designated as key study. In addition, a supporting K4 study reported a LD50 value of 0,704 mL/kg bw (746 mg/kg bw).

Justification for classification or non-classification

Based on the available data and according to the criteria of the CLP Regulation, the test substance should not be classified as acute toxic via the oral and dermal route. No data were available to decide on the classification via the inhalation route.