Registration Dossier

Administrative data

Description of key information

Oral LD50 (rat): 984 mg/kg bw (BASF 1980, equivalent or similar to OECD 401) 
Inhalation LC50 (rat): > 2.9 mg/L air (aerosol, 4h, BASF 1978), 20 - 26 mg/L (vapour, 3h, BASF 1980 + 1969)
Dermal LD50 (rabbit): > 200 mg/kg bw (BASF 1978, equivalent or similar to OECD 402), 672mg/kg (Patty 1962, secondary source)

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:
1979 - 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scientifically acceptable study report.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
Principles of method if other than guideline:
according to BASF-internal standard, see details in the section "Any other information on materials and methods incl. tables".
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hagemann, Germany
- Age at study initiation: Not specified
- Weight at study initiation: 280-180 g (males), 220-180 g (females)
- Fasting period before study: 15 h – 20 h before administration
- Housing: Not specified
- Diet: Standardized animal laboratory diet (Herilan mouse/rat/hamster maintenance diet supplied by H. Eggersmann KG, Germany)
- Water: Not specified
- Acclimation period: Not specified
- Date of first administration: May 11, 1979
- Date of last administration: June 20, 1979
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Form of administration: solution
- Concentration in vehicle (%, w/v): 6.81, 10.0, 14.7, 21.5 (to obtain 681, 1000, 1470, 2150 mg/kg)
- Amount of vehicle: 10 mL/kg per dosage
- Justification for choice of vehicle: solubility

MAXIMUM DOSE VOLUME APPLIED:
- Admin. vol. (mL/kg): 10
Doses:
681, 1000, 1470, 2150 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
Probit Analysis (Finney DJ, Cambridge University Press, 3rd ed., 1971)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
984 mg/kg bw
Based on:
test mat.
95% CL:
>= 805 - <= 1 197
Remarks on result:
other: Doses used for calculation: 691, 1000, 1470 mg/kg bw
Mortality:
Male animals: 681 and 1000 mg/kg: 1/5 after 14 days, 1470 and 2150 mg/kg: 5/5 after 14 days
Female animals: 681 mg/kg: 1/5 after 14 days; 1000 mg/kg: 2/5 after 14 days; 1470 and 2150 mg/kg: 5/5 after 14 days
Clinical signs:
Highest dose level: dyspnea, gasping, apathy, anomalous position, staggering, spastic gait, piloerection, cyanosis, ecsiccosis, poor general state
Body weight:
Mean body weights of male animals: beginning of study 24 g (50 and 200 mg/kg), after 13 days 31.6 g (50 mg/kg)
Mean body weights of female animals. beginning of study 22 g (50 and 200 mg/kg), after 13 days 25.4 g (50 mg/kg)
Gross pathology:
Animals that died: Heart: acute dilatation right-sided ; acute congestion; stomach: atonic, liquid blood-coloured contents, in the region of the glandular stomach severe diffuse reddening (corrosive gastritis); intestine: atonic, diarrheal contents, enteritis.
Sacrificed animals: No pathologic findings noted.

In an acute oral toxicity study according to an internal BASF method (BASF, 1980), Sprague Dawley rats were given a single oral dose of the test substance diluted in water at 681, 1000, 1470 or 2150 mg/kg bw. Animals were then observed for mortality and for clinical symptoms of toxicity for 14 days. All animals were subjected to necropsy. As clinical signs dyspnea, gasping, apathy, anomalous position, staggering, spastic gait, piloerection, cyanosis, ecsiccosis, and poor general state were noticed at the highest dose level. The oral LD50 was estimated as 984 mg/kg bw. This acute oral study is classified as acceptable. It satisfies the guideline requirement for an acute oral study according to OECD 401 in principle.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1969
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scientifically acceptable study report.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
Principles of method if other than guideline:
according to BASF-internal standard, see details in the section "Any other information on materials and methods incl. tables".
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Gassner
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
suspension, emulsion with Traganth, Cremophor EL
Details on oral exposure:
The test substance was administered in concentrations of 2, 20 or 30% (v/v).
Doses:
200, 1600, 1800, 2000, 2500, 3200, 6400 mm3/kg
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
ca. 1 508 mg/kg bw
Based on:
test mat.
Remarks on result:
other: extrapolated from original value, test substance density: 0.815
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
ca. 1 850 other: mm3/kg
Based on:
test mat.
Remarks on result:
other: original value
Mortality:
200 mm3/kg: 0/20 after 7 days;
1600 mm3/kg: 1/20 after 7 days;
1800 mm3/kg: 8/20 after 7 days;
2000 mm3/kg: 15/20 after 7 days;
2500, 3200 and 6400 mm3/kg: 20/20 after 7 days
Clinical signs:
Dyspnea, apathy, crusty eyes and rhinarium.
Gross pathology:
Animals died: Slightly bloody-serous blurred snouts, atony of the intestine, suspicion of petechial bleedings of the mucosa of the stomach.
Animals sacrificed: No organ findings reported.
Other findings:
Animals of the lowest dosing group (200 mm3/kg) showed no symptoms.

In this study (BASF, 1969), test groups consisting of 10 animals were treated by single gavage application with an aqueous solution of the test substance. The animals were each observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 14 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observation period also were subjected to necropsy. The LD50 value of ca. 1508 mg/kg bw was estimated on the basis of the observed mortalities. The study was conducted according to an internal BASF method which in principle is comparable to the OECD Guideline 401.

Executive summary:

In an acute oral toxicity study according to an internal BASF method (BASF AG, 1969), Gassner rats were given a single oral dose of the test substance diluted in water at 200, 1600, 1800, 2000, 2500, 3200, 6400 mm3/kg; concentrations of 2, 20 or 30% (v/v) were applied. Animals were then observed for mortality and for clinical symptoms of toxicity for 14 days. All animals were subjected to necropsy. As clinical signs dyspnea, apathy, crusty eyes and rhinarium were noticed. The oral LD50 was deemed as appr. 1508 mg/kg bw (original value: appr. 1850 mm3/kg). This acute oral study is classified as acceptable. It satisfies the guideline requirement for an acute oral study accordingto OECD 401 in principle.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
984 mg/kg bw
Quality of whole database:
Estimated Klimisch Rating: 2

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:
weight of evidence
Study period:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scientifically acceptable study report.
Principles of method if other than guideline:
according to BASF-internal standard
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: MUS RATTUS, Brunnthal, Germany (SPF breeding)
- Age at study initiation: Not reported
- Weight at study initiation: 185 +/- 15 g
- Fasting period before study: Not reported
- Housing: Not reported
- Diet: Herilan MRH of H. EGGERSMANN KG, Rinteln/Weser, Germany, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: Not reported
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Whole-body inhalation system (groups of 5 animals are placed in wire cages which are located in a glass-steel inhalation chamber)
- Exposure chamber volume: V= 200 L
- Method of holding animals in test chamber: Wire cages
- Source and rate of air: Generator system: Continuous infusion pump UNITA I (BRAUN, Germany)
- Method of conditioning air: By means of a continuous infusion pump, constant amounts of the test substance were supplied to an evaporator heated to 75°C. The vapours that were formed were mixed with a flow of fresh air and passed into the inhalation chamber.
- System of generating particulates/aerosols: Glass evaporator with thermostat (BASF)
- Method of particle size determination: No further data
- Treatment of exhaust air: No further data
- Temperature, humidity, pressure in air chamber: No further data

TEST ATMOSPHERE
- Brief description of analytical method used: Gaschromatography
- Samples taken from breathing zone: yes (4 mm probe)
- Pressure ratio: By means of an exhaust air system, the pressure ratios in the inhalation system were adjusted in such a way that there was a pressure slightly below the atmospheric pressure (negative pressure). The inhalation mixture was offered to the animals for inhalation for 4 hours.

VEHICLE
- Composition of vehicle: fresh air
- Concentration of test material in vehicle: technical maximal attainable concentration
- Justification of choice of vehicle: volatility of test substance

TEST ATMOSPHERE
- Particle size distribution: No data available
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): No data available
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gaschromatography (HP5040 A)
Duration of exposure:
4 h
Concentrations:
2.35; 2.5 mg/L (analytical concentrations)
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: technical maximal attainable concentration
Mortality:
1/10 (2.5 mg/L) after 1 day
0/10 (2.35 mg/L)
Clinical signs:
other: Intermittently resp. irregular breathing, eyelid closure, clotty fur, long-legged and staggering gait, ruffled fur. After 4 resp. 5 days no findings.
Body weight:
2.5 mg/L: mean body weight before study start 177.5 g, after 14 days 223.5 g
2.35 mg/L: mean body weight before study start 177.5 g, after 14 days 233.5 g
Gross pathology:
Sacrificed animals: heart: dilatation of the atrium, acute congestive hyperemia; liver: slightly pale-grey
Animal that died: nothing abnormal detected.
Other findings:
Dosing group 1:
Nominal concentration: 9.78 mg/L, analytical conc. 2.5 mg/L

Dosing group 2:
Nominal concentration: 2.35 mg/L, analytical conc. 9.07 mg/L
Executive summary:

In an acute inhalation study according to BASF-internal standard (BASF1980), the test substance was tested in 20 rats (10 animals per sex) at the technical maximal attainable concentration. The analytical concentrations were 2.35 and 2.5 mg/L. As clinical signs irregular breathing, eyelid closure, clotty fur, long-legged and staggering gait, and ruffled fur were observed up to max. 5 days after study beginning.One animal died after 1 day (2.5 mg/L), necropsy revealed no irregular findings. In sacrificed animals, observations were: heart: dilatation of the atrium, acute congestive hyperemia; liver: slightly pale-grey.The LC50 (4h) was deemed as > 2.5 mg/L (> 530 ppm).

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scientifically acceptable study report.
Principles of method if other than guideline:
according to BASF-internal standard
GLP compliance:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: MUS RATTUS, Brunnthal, Germany (SPF breeding)
- Age at study initiation: Not reported
- Weight at study initiation: Mean body weight of male animals: 204 g; mean body weight of female animal: 203 g
- Fasting period before study: Not reported
- Housing: Not reported
- Diet: Herilan MRH feed of H. EGGERSMANN KG, Rinteln/Weser, Germany, ad libitum (during the post-exposure observation period)
- Water: Tap water, ad libitum (during the post-exposure observation period)
- Acclimation period: Not reported
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose-only inhalation system (BUNDSCHUH, Griesheim, Germany)
- Exposure chamber volume: No further data
- Method of holding animals in test chamber: No further data
- Source and rate of air: UNITA I (BRAUN, Melsungen, Germany)
- Method of conditioning air: Mixing with test substance by UNITA I (BRAUN, Melsungen, Germany)
- System of generating particulates/aerosols: Twin-component nozzle
- Method of particle size determination: No further data
- Treatment of exhaust air: No further data
- Temperature, humidity, pressure in air chamber: No further data

TEST ATMOSPHERE
- Gaschromatography
- Samples taken from breathing zone: yes (7mm probe)

VEHICLE
- Composition of vehicle: fresh air
- Concentration of test material in vehicle: technical maximal attainable concentration
- Justification of choice of vehicle: volatility of test substance

TEST ATMOSPHERE
- Particle size distribution: No data available
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): No data available
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gaschromatography
Duration of exposure:
4 h
Concentrations:
Nominal concentrations: 3.67, 7.34 mg/L;
Analytical concentrations: 1.6, 2.9 mg/L;
one concentration allows a no effect level to be determined (0 mortality).
No. of animals per sex per dose:
10
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.9 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: analytical concentration
Mortality:
none
Clinical signs:
other: attemptions to escape, reddenish nasal secretion, accelerated breathing. The animals were without findings within 1 - 4 days. One male animal of the 1.6 mg/lg group showed 7 days after exposure a bloody nasal region with loss of hair and a slight swelling
Body weight:
1.6 mg/L: mean body weight before exposure 199 g, after 14 days 255 g
2.9 mg/L: mean body weight before exposure 208 g, after 14 days 266 g
Gross pathology:
Nothing abnormal detected.
Interpretation of results:
GHS criteria not met
Executive summary:

Sprague-Dawley rats (10 animals per sex) were exposed to the test substance at a nominal concentration of 3.67 mg/L or 7.34 mg/L in an acute inhalation study according to BASF-internal standard (BASF1978). The analytical concentrations were estimated as 1.6 or 2.9 mg/L (air). As clinical signs attempting to escape, reddish nasal secretion, and accelerated breathing were noticed in the higher dosing group.The animals were without findings within 1 - 4 days. No mortality occurred. Gross necropsy revealed no irregular findings.The LC50 (4h) was deemed as > 2.9 mg/L. In addition a LC50 (1h) was extrapolated with a value of 12.0 mg/L.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
according to BASF-internal standard
GLP compliance:
no
Test type:
other: inhalation hazard test
Species:
rat
Sex:
male/female
Route of administration:
inhalation: vapour
Remarks on duration:
1 h, 3 h and 7 h
Concentrations:
1 h: 22.64 mg/L
3 h: 25.83 mg/L
7 h: 26.25 mg/L
No. of animals per sex per dose:
1h: 12, 3 h and 7 h: each time 6
Dose descriptor:
LC50
Effect level:
> 25.8 mg/L air
Exp. duration:
3 h
Mortality:
1 h: 0/12
3 h: 1/6
7 h: 5/6
Clinical signs:
other: crusty eyes, eyelid closure, watery reddened nasal secretion, salivation, crusty fur, staggering and instabile gait, dyspnea, trembling, missing pain reflex; partly corrosion above the eyelids, nose and forelimbs; clouded cornea
Gross pathology:
sacrificed animals: nothing abnormal detected
Interpretation of results:
Category 5 based on GHS criteria
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1969
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
according to BASF-internal standard
GLP compliance:
no
Test type:
other: inhalation hazard test
Species:
rat
Sex:
male/female
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Remarks on duration:
1 h, 3 h, 8 h
Concentrations:
1 h: 13.1 mg/L
3 h: 19.83 mg/L
8 h: 22.2 mg/L
No. of animals per sex per dose:
1 h and 8 h: 6 each time; 3 h: 3
Dose descriptor:
LC50
Effect level:
19.8 mg/L air
Exp. duration:
3 h
Mortality:
1 h: 0/6
3 h: 3/6
8 h: 6/6
Clinical signs:
other: at study start: attemptions to escape, severe irritations of the mucosa, partly corrosions of the visceral cranium. After 8-h exposure violent spasms.
Gross pathology:
crusty snouts, partly slight lung emphysema
Interpretation of results:
Category 4 based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Quality of whole database:
Estimated Klimisch Rating: 2

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:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scientifically acceptable study report.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
according to BASF-internal standard
GLP compliance:
no
Limit test:
yes
Species:
rabbit
Strain:
Vienna White
Sex:
male/female
Details on test animals or test system and environmental conditions:
Mean body weights: male animals about 2.8 kg, female animals about 2.7 kg.
A standardized animal laboratory diet as well as tap water were available ad libitum.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The product was applied undiluted in a dose of 200 mg/kg to the clipped areas (about 50 cm2) of the back and flanks.
Removal of fur from the dorsal and lateral parts of the trunk with an electric hair cutter about 15 to 24 hours before application. Only animals with a healthy and undamaged skin were used in the study.
The test substance was applied uniformly to an area of about 50 cm2. The treated area of skin was then covered with aluminum foil which was fixed with an adhesive tape. The dressing was removed after 24 hours; the test substance was then washed off with warm water or with a mixture of water and Lutrol, and the area was dried with wadding.
Duration of exposure:
24 h
Doses:
200 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Investigations:
Mortality within 8 days
Signs of systemic toxicity and of local irritation
Necropsy of the animals sacrificed with carbon dioxide at the end of the observation period.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 mg/kg bw
Mortality:
none
Clinical signs:
Signs of systemic toxicity: The animals showed a slight apathy up to 2 days after application.
Signs of local irritation: 24 hours after application a necrosis was observed, which was not revesrible within 8 days after study start.
Gross pathology:
Sacrificed animals: nothing abnormal detected.
Conclusions:
The acute dermal toxicity of 2-Amino-1-diaethyl-amino-aethan in Vienna white rabbits has been determined. This entailed the product being applied undiluted in a single dose of 200 mg/kg for 24 hours on clipped areas (about 50 cm2) of the back and flanks. The determination of the LD50 was based on the DOT guidelines, but no exact LD50 was established.
Executive summary:

The study was conducted according to an internal BASF method (BASF, 1978). Vienna White rabbits (5 males and 5 females) were dermally exposed to a single dose of 200 mg/kg bw of the undiluted test substance to the clipped skin of the back and flanks and covered by semi-occlusive dressing for 24 hours. Afterwards the test substance was removed by washing. The application area comprised at least a surface area of 50 cm². The animals were observed for 14 days. The following test substance-related effects were recorded during the course of the study: No mortality occurred. The animals showed a slight apathy up to 2 days after application. Local irritation was noticed, 24 hours after application a necrosis was observed, which was not reversible within 8 days after study start. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. As a conclusion, the LD50 value for acute dermal toxicity was found to be greater than 200 mg/kg bw (based on DOT guidelines). This acute dermal study is classified as acceptable.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Species:
rabbit
Dose descriptor:
LD50
Effect level:
0.82 mL/kg bw
Dose descriptor:
LD50
Effect level:
672 mg/kg bw
Remarks on result:
other: calculated based on density of 0,82 g/ml
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
672 mg/kg bw

Additional information

Acute toxicity: oral

In an acute oral toxicity study according to an internal BASF method (BASF, 1980), Sprague Dawley rats were given a single oral dose of the test substance diluted in water at 681, 1000, 1470 or 2150 mg/kg bw. Animals were then observed for mortality and for clinical symptoms of toxicity for 14 days. All animals were subjected to necropsy. As clinical signs dyspnea, gasping, apathy, anomalous position, staggering, spastic gait, piloerection, cyanosis, ecsiccosis, and poor general state were noticed at the highest dose level. The oral LD50 was estimated as 984 mg/kg bw. This acute oral study is classified as acceptable (key study). It satisfies the guideline requirement for an acute oral study according to OECD 401 in principle.
Furthermore, in a supporting study according to an internal BASF method (BASF, 1969), Gassner rats were given a single oral dose of the test substance diluted in water at 200, 1600, 1800, 2000, 2500, 3200, 6400 mm3/kg; concentrations of 2, 20 or 30% (v/v) were applied. Animals were then observed for mortality and for clinical symptoms of toxicity for 14 days. All animals were subjected to necropsy. As clinical signs dyspnea, apathy, crusty eyes and rhinarium were noticed. The oral LD50 was deemed as appr. 1508 mg/kg bw (original value: appr. 1850 mm3/kg). This acute oral study is classified as acceptable. It satisfies the guideline requirement for an acute oral study accordingto OECD 401 in principle.


Acute toxicity: dermal

The study was conducted according to an internal BASF method (BASF, 1978) following the principles of OECD TG 402. Vienna White rabbits (5 males and 5 females) were dermally exposed to a single dose of 200 mg/kg bw of the undiluted test substance to the clipped skin of the back and flanks and covered by semi-occlusive dressing for 24 hours. Afterwards the test substance was removed by washing. The application area comprised at least a surface area of 50 cm². The animals were observed for 14 days. The following test substance-related effects were recorded during the course of the study: No mortality occurred. The animals showed a slight apathy up to 2 days after application. Local irritation was noticed, 24 hours after application a necrosis was observed, which was not reversible within 8 days after study start. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. As a conclusion, the LD50 value for acute dermal toxicity was found to be greater than 200 mg/kg bw (based on DOT guidelines). This acute dermal study is classified as acceptable (key study).
The test substance is regarded as skin corrosive agent, causing local effects.

This result is supported by the value given by Patty et al. (Industrial Hygiene and Toxicology, 1962), who list a dermal LD50 in the rabbit of 672 mg/kg.


Acute toxicity: inhalation
The acute inhalation toxicity is assessed using a weight of evidence approach.

In an inhalation risk test (BASF 1980, 78/850), 6 rat per group were exposed to the saturated vapour of the test substance for 1, 3, and 7h. The concentration was determined by weighing the amount of substance lost from the reservoir during the experiment. It was estimated between 22 and 25mg/L in the different groups. Corrosive effects were observed. No animals died after 1h, 1/6 died after 3h, and none of the rats survived a 7 hour exposure.

A second inhalation risk test (BASF 1969, XIX 235) described similar results: No deaths after 1 hour, 3/6 died after 3 h (vapour concentration estimated as 20 mg/L), and no rat survived exposure for 8h.

In an acute inhalation study according to BASF-internal standard (BASF, 1980), 20 rats (10 animals per sex) were exposed to the vapour of the test substance. The analytical concentrations were 2.35 and 2.5 mg/L. As clinical signs irregular breathing, eyelid closure, clotty fur, long-legged and staggering gait, and ruffled fur were observed up to max. 5 days after study beginning. One animal died after 1 day (2.5 mg/L), necropsy revealed no irregular findings. In sacrificed animals, observations were: heart: dilatation of the atrium, acute congestive hyperemia; liver: slightly pale-grey. The LC50 (4h) was deemed as > 2.5 mg/L (> 530 ppm).

In an aerosol study, Sprague-Dawley rats (10 animals per sex) were exposed to the test substance at a nominal concentration of 3.67 mg/L or 7.34 mg/L (BASF, 1978). The analytical concentrations were estimated as 1.6 or 2.9 mg/L (air). As clinical signs attempting to escape, reddish nasal secretion, and accelerated breathing were noticed in the higher dosing group.The animals were without findings within 1 - 4 days. No mortality occurred. Gross necropsy revealed no irregular findings. The LC50 (4h) was deemed as > 2.9 mg/L.

In summary, two studies led to results just above or below the classification criteria according to GHS, UN for acute inhalation cat. 4 (i.e., LC 50 vapour = 20mg/L), while the aerosol study would not warrant classification. Also taking into account the not very exact method to determine the vapour concentration, classification as acute inhalation category 4 seems unjustified and instead the test substance is classified for acute inhalation category 5 (GHS, UN).


Further studies (i.p. route)
The test substance was applied i.p. in mice (BASF, 1980) and a LD50 range value of 50 – 200 mg/kg bw was named. In another study (BASF, 1969), a LD50 value of 123 mg/kg bw was estimated, corresponding to 152 µL test substance/kg. Intraabdominal adherence was observed in gross pathology.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008 (CLP).As a result the substance is considered to be classified for acute oral and dermal toxicity under Regulation (EC) No 1272/2008, as amended for the sixth time in Regulation (EC) No 605/2014 as follows: acute toxicity: cat. 4, H302, harmful if swallowed; category 3, H311, toxic in contact with skin, and for acute inhalation toxicity category 5.