Registration Dossier

Administrative data

Description of key information

Oral (similar to OECD 401): LD50 (female)= 436 mg/kg bw, LD50 (male)= 866 mg/kg bw, LD50 (male/female)= 653 mg/kg bw
Inhalation (OECD 403): LC50 > 600 mg/m³ (maximum achivable concentration)
Dermal (similar to OECD 402): LD50 > 2000 mg/kg bw

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(1981)
Deviations:
yes
Remarks:
(no constant volume was applied)
Qualifier:
according to
Guideline:
other: OECD Short-Term and Long-Term Toxicology Groups Final Report (December 1979)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Industries
- Weight at study initiation: 250±40 g
- Fasting period before study: 16 h
- Housing: individually in conventional design stainless steel, wire mesh bottom cages
- Diet: Purina Rodent Chow, ad libitum
- Water: fresh water, ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
not specified (under controlled laboratory conditions)
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
250, 500, 1000, and 1600 mg/kg bw (based on the results of a screening test)
No. of animals per sex per dose:
5
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: frequently on the first day of dosing and twice a day thereafter (at least 4 h apart)
- Frequency of weighing: 24 h, 7 and 14 days after dosing
- Necropsy of survivors performed: yes
Statistics:
The oral median lethal dose, 95% confidence interval, and approximate slope of the dose response curve were calculated by a computerised version of Finney's (1972) Probit Method.
Sex:
female
Dose descriptor:
LD50
Effect level:
436 mg/kg bw
Based on:
test mat.
95% CL:
210 - 730
Remarks on result:
other: Deaths occurred in all dose groups in 1/5 females at 250 mg/kg bw, 3/5 females at 500 mg/kg bw, 5/5 females at 1000 mg/kg bw, and 5/5 females at 1600 mg/kg bw.
Sex:
male
Dose descriptor:
LD50
Effect level:
866 mg/kg bw
Based on:
test mat.
95% CL:
567 - 1 368
Remarks on result:
other: Deaths occurred in 1/5 males at 500 mg/kg bw, 3/5 males at 1000 mg/kg bw, and 5/5 males at 1600 mg/kg bw.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
653 mg/kg bw
Based on:
test mat.
95% CL:
447 - 892
Mortality:
Deaths occurred in all dose groups with 1/5 females at 250 mg/kg bw, 3/5 females and 1/5 males at 500 mg/kg bw, 5/5 females and 3/5 males at 1000 mg/kg bw and 5/5 males and females each at 1600 mg/kg bw. The females exhibited to be the more sensitive species. The deaths occurred within one and a half hours following dosage in all cases except three animals, which died several hours later.
Clinical signs:
Surviving animals appeared normal within 48 h. Generally, signs of toxicity exhibited by rats included extreme lethargy, ataxia, convulsions and coma.
Body weight:
Food consumption and body weight gains were slightly depressed during the first 24 h following treatment, but appeared normal during the remaining part of the study period.
Gross pathology:
Necropsy of animals that died during the study showed haemorrhagic condition of the gastrointestinal tract. However, terminal sacrifice of surviving animals did not reveal any compound related gross pathological alterations in the tissues and organs examined.
Interpretation of results:
other: CLP/EU GHS criteria are met, Category 4 classification required according to Regulations (EC) No 1272/2008
Conclusions:
The test item was investigated for acute oral toxicity in a study conducted similar to OECD 401, and in compliance with GLP. 5 Sprague Dawly rats per sex received single doses of of 250, 500, 1000, and 1600 mg/kg bw of the test material via gastrointestinal intubation. Deaths occurred in all dose groups with 1/5 females at 250 mg/kg bw, 3/5 females and 1/5 males at 500 mg/kg bw, 5/5 females and 3/5 males at 1000 mg/kg bw and 5/5 males and females each at 1600 mg/kg bw. Signs of toxicity exhibited by surviving rats included extreme lethargy, ataxia, convulsions and coma, but were resolved within 48 h. Food consumption and body weight gains were slightly depressed during the first 24 h following treatment, but appeared normal during the remaining part of the study period. Necropsy of animals that died during the study showed haemorrhagic condition of the gastrointestinal tract. However, terminal sacrifice of surviving animals did not reveal any compound related gross pathological alterations in the tissues and organs examined. Based on the outcome of the study, the LD50 value for males was calculated to be 866 mg/kg bw, whereas the LD50 value for females was determined to be 436 mg(kg bw. The combined LD50 value (male/female) was calculated to be 653 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
436 mg/kg bw
Quality of whole database:
The study was conducted similar to the appropriate guideline, and in compliance with GLP (RL2).

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The study was conducted according to the appropriate guideline, but not in compliance with GLP. No information is given on the test material purity, the analytical verification of the test concentration, and the method of generating the vapour or aerosol.
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
(1981)
Deviations:
no
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratory
- Weight at study initiation: approximately 230 g
- Fasting period before study: no
- Housing: in satndard stainless steel, wire mesh bottom cages of conventional design during acclimatisation period, and in special stainless steel cages during experiment and subsequent observation period
- Diet: Purina Rodent Chow, ad libitum (except during exposure)
- Water: ad libitum (except during exposure)
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- not specified (under controlled laboratory conditions)
Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
clean air
Remarks:
(filtered with hepa and charcoal filters)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel and glass exposure chamber
- Exposure chamber volume: 450 l
- Method of holding animals in test chamber: in special stainless steel cages
- Source and rate of air: dynamic airflow (16-19 air changes per hour); supplied by a heating, ventilation, and air conditioning system, which filtered the air and controlled temperature and humidity
- System of generating particulates/aerosols: not specified
- Method of particle size determination: no data
- Treatment of exhaust air: filtered by a hepa filter, charcoal filter, and water scrubber
- Temperature, humidity, pressure in air chamber: 69±2°F (19.44-21.67°C), 43±3% humidity

TEST ATMOSPHERE
- Brief description of analytical method used: no data
- Samples taken from breathing zone: no data
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
0.6 mg/l target concentration (highest concentration that was able to be generated with the test equipment)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: frequently during exposure and daily during the week days of the post-exposure period
- Frequency of weighing: after 7 and 14 days
- Necropsy of survivors performed: yes (complete gross pathological examination on all major tissues and organs, with special attention was paid to the lung and trachea)
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 600 mg/m³ air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: highest concentration that was able to be generated with the test equipment
Mortality:
No mortality occurrend throughout the study period.
Clinical signs:
other: No clinical signs were reported.
Body weight:
There was no effect on the body weights observed throughout the study period.
Gross pathology:
There were no apparent abnormalities of major organs and tissues observed at the time of necropsy.
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
The test item was investigated for acute inhalation toxicity in a study conducted according to the OECD test guideline 403. Following 4 h of exposure, there was no toxicity observed in neither males nor females at 600 mg/m³, which was the highest concentration that was able to be generated with the test equipment. Thus, the LC50 value was set at >600 mg/m³.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
600 mg/m³
Quality of whole database:
The study was conducted according to the appropriate guideline, but not in compliance with GLP (RL2).

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
Deviations:
no
Qualifier:
according to
Guideline:
other: OECD Short-Term and Long-Term Toxicology Groups Final Report (December 1979)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: approximately 2.5 kg
- Housing: individually in clean, stainless steel cages
- Diet: standard Purina Rabbit Chow, ad libitum
- Water: fresh water, ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
not specified (temperature, humidity and light controlled room)
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal body surface area of the trunk
- % coverage: approximately 10
- Type of wrap if used: semiocclusively with a cotton cloth bandage taped to the hair

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

TEST MATERIAL
- Amount applied: 2000 mg/kg bw
- Constant volume or concentration used: no
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: frequently after dosing and twice daily thereafter
- Frequency of weighing: on days 7 and 14
- Necropsy of survivors performed: yes (complete gross necropsy)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed throughout the study period.
Clinical signs:
No behavioural effects were observed throughout the study period.
Body weight:
No obvious effect on body weights and food consumption were noted throughout the study period.
Gross pathology:
There were no test article related alterations noted at gross necropsy at study termination.
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
The test item was investigated for acute dermal toxicity in a limit test conducted similar to OECD 402, and in compliance with GLP. 5 New Zealand White rabbits per sex received a single dose of the test material at a dose of 2000 mg/kg bw. No mortality occurred and no signs of systemic toxicity were noted throughout the study period. Gross necropsy revealed no substance-related findings. Thus, the LD50 value for acute dermal toxicity was set at >2000 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The study was conducted similar to the appropriate guideline, and in compliance with GLP (RL2).

Additional information

Acute toxicity: oral

The test item was investigated for acute oral toxicity in a study conducted similar to OECD 401, and in compliance with GLP (Dow Corning Corporation, 1981a). 5 Sprague Dawly rats per sex received single doses of of 250, 500, 1000, and 1600 mg/kg bw of the test material via gastrointestinal intubation. Deaths occurred in all dose groups with 1/5 females at 250 mg/kg bw, 3/5 females and 1/5 males at 500 mg/kg bw, 5/5 females and 3/5 males at 1000 mg/kg bw and 5/5 males and females each at 1600 mg/kg bw. The females exhibited to be the more sensitive species. The deaths occurred within one and a half hours following dosage in all cases except three animals, which died several hours later. Signs of toxicity exhibited by suviving rats included extreme lethargy, ataxia, convulsions and coma, but were resolved within 48 h. Food consumption and body weight gains were slightly depressed during the first 24 h following treatment, but appeared normal during the remaining part of the study period. Necropsy of animals that died during the study showed haemorrhagic condition of the gastrointestinal tract. However, terminal sacrifice of surviving animals did not reveal any compound related gross pathological alterations in the tissues and organs examined. Based on the outcome of the study, the LD50 value for males was calculated to be 866 mg/kg bw, whereas the LD50 value for females was determined to be 436 mg/kg bw. The combined LD50 value (male/female) was calculated to be 653 mg/kg bw.

Acute toxicity: inhalation

The key study for acute inhalation toxicity was carried out according to OECD test guideline 403, but not in compliance with GLP. The study reports the LC50 value of >0.6 mg/l air in response to the exposure to N-[3-(dimethoxymethylsilyl)-2-methylpropyl]ethylenediamine in rat (Dow Corning Corporation, 1986). 5 Wistar rats per sex were treated in a limit test with the maximum achivable concentration of 0.6 mg/l (600 mg/m³) for 4 h. No mortality occurred throughout the study period and no clinical signs were reported. There was no effect on the body weights observed throughout the study period and there were no apparent abnormalities of major organs and tissues observed at the time of necropsy.

Acute toxicity: dermal

The test item was investigated for acute dermal toxicity in a limit test conducted similar to OECD 402, and in compliance with GLP (Dow Corning Corporation, 1981b). 5 New Zealand White rabbits per sex received a single dose of 2000 mg/kg bw of the neat test material for 24 h. No mortality occurred and no signs of systemic toxicity were noted during the 14 -day observation period. The animals gained weight as expected and no effect on food consumption was observed throughout the study period. Gross necropsy revealed no substance-related findings at study termination. Thus, the LD50 value for acute dermal toxicity was set at >2000 mg/kg bw.

Justification for classification or non-classification

The available data is reliable and suitable for classification. Based on this data, the submission substance meets the criteria for classification for acute oral toxicity (Xn, R22) according to 67/584/EEC and (Cat 4, H302) according to EC/1272/2008. Classification for acute dermal and acute inhalation toxicity according to 67/584/EEC and EC/1272/2008 is not warranted.