Registration Dossier

Administrative data

Description of key information

Acute Toxicity:
- oral: LD50: 100 mg/kg bw (rat)
- dermal: LD50: 582 mg/kg bw (rabbit)
- inhalation: LC50: 17.3 mg/L air (rat)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

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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)
Principles of method if other than guideline:
The substance was administered by stomach intubation to Wistar-derived male rats, 90-120 grams in weight and 3 to 4 weeks of age .
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 3-4 weeks
- Weight at study initiation: 90-120 g
- Fasting period before study: No
- Diet (e.g. ad libitum): Wayne diets ad libitum
- Water (e.g. ad libitum): ad libitum







Route of administration:
oral: gavage
Vehicle:
water
Remarks:
undiluted and 10% dilution in distilled water
Details on oral exposure:
- Lower concentrations of the undiluted substance could not be investigated due to the small volumes of sample required
VEHICLE (experiments with dilution)
- Concentration in vehicle: 10%
Doses:
undiluted: 0.25, 0.5 and 1ml/kg bw = 178, 355 and 710 mg/kg bw (conversion is based on the density d: 0.71 g/cm3)
diluted: 0.5, 1 and 2 ml/kg bw = 35.5, 71 and 142 mg/kg bw (conversion is based on the dilution factor 1:10 and the substance density d: 0.71 g/cm3)
No. of animals per sex per dose:
5 (males only)
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: At least once daily; weighing on the day of dosing and after 14 days
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight, gross pathology
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1.41 mL/kg bw
Based on:
test mat.
Remarks:
10% solution
Remarks on result:
other:
Remarks:
equals 100 mg/kg bw
Sex:
male
Dose descriptor:
LD50
Effect level:
< 178 mg/kg bw
Remarks on result:
other: conversion in mg/kg is based on the density d: 0.71 g/cm3
Sex:
male
Dose descriptor:
LD50
Effect level:
> 71 - < 142 mg/kg bw
Remarks on result:
other: 10% dilution of the test substance; conversion in mg/kg is based on the density d:0.71 g/cm3
Mortality:
Undiluted:
710 mg/kg bw: 5/5, days to death: 2, 3, 3, 3, 3
355 mg/kg bw: 5/5, days to death: 2, 3, 3, 5, 5
178 mg/kg bw: 4/5, days to death: 2, 3, 3, 3

Diluted sample:
142 mg/kg bw: 5/5, days to death: 0, 0, 1, 1, 1
71 mg/kg bw: 0/5,
35.5 mg/kg bw: 0/5
Clinical signs:
Sluggish and gasping
Body weight:
The surviving animals gained weight
Gross pathology:
Animals that died:
Lungs with petichiae;
Stomachs distended, liquid filled, red, walls thickened, ulcerated and adhered to surrounding tissue;
Intestines yellow or red, gas filled;
Kidneys slightly enlarged;
Adrenale enlarged;
Livers, spleens and kidneys mottled

In survivors: Livers mottled, stomach walls thickened.
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The reported LD50 is 1.41 mL/kg.
Whereas 1 mL = 0.10 mL sample diluted in distilled water; and density = 0.71 g/cm³.
This results in a LD50 value of 100 mg/kg bw.
Executive summary:

A single dose of the test substance (diluted and undiluted) was given peroral to non-fasted male Wistar rats at 3 different concentrations. The undiluted sample testing provoked death for all tested concentration groups. Exposure to the lowest applied concentration of 178 mg/kg bw killed 4/5 rats. Higher concentrations killed all animals. A second test with a 10% solution of the test substance revealed 100% mortality for the highest tested concentration (142 mg/kg bw), whereas no detahs occured in the lower concentration groups. Clinical signs observed after treatment were sluggishness and gasping. Dead animals showed effects of the lungs, stomachs, intestines, kidneys, adrenal gland and livers. Surviving rats had mottled livers and thickened stomach walls.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
GLP compliance:
no
Species:
mouse
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Doses:
no data
No. of animals per sex per dose:
no data
Control animals:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
649 mg/kg bw
95% CL:
> 554 - < 759
Mortality:
no data
Clinical signs:
increased excitablity replaced by inhibition, disturbances in the coordination of movements, clonic spasms.
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
study cannot be used for classification
Conclusions:
An LD50 of 649 mg/kg bw was estimated.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
100 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
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 403 (Acute Inhalation Toxicity)
Version / remarks:
2009
Deviations:
yes
Remarks:
Only females and two exposure concentrations tested
Principles of method if other than guideline:
- Principle of test:
A constant exposure time of 4 h was used and the concentration of test material in the chamber air was varied. The test material pumped into the top of a vertical glass evaporator tube, which was heated sufficiently to cause vapourization. Dried air was introduced through the bottom of the tube (countercurrent to the sample flow) and the resultant vapour-containing atmosphere passed to a 9-L exposure chamber. Chamber concentrations were determined by adjustment of sample and/or air flow rates.
GLP compliance:
no
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Charge No.of test material: 01067
- Identification: TK 2527
- Source: Chemicals and Plastics, South Charleston

FORM AS APPLIED IN THE TEST (if different from that of starting material): Vapour
Species:
rat
Strain:
Wistar
Sex:
female
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 9L
- The sample was metered into heated vaporizer through which a metered flow of N2 gas was maintained. The resultant vapor was then diluted with air and oxygen to produce a oxygen concentration of 20.9%
- Temperature in air chamber: 25°C
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
4000 and 8000 ppm
No. of animals per sex per dose:
6 (females only)
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: several times on the day of exposure and daily thereafter.
- Frequency of weighing: just before exposure and at sacrifice
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight
Sex:
female
Dose descriptor:
LC50
Effect level:
5 700 ppm
95% CL:
4 600 - 7 000
Exp. duration:
4 h
Remarks on result:
other: equivalent to 17.3 mg/l air
Mortality:
8000 ppm: 6/6 (3 animals within exposure, 1 animal after 2.5 h, 2 animals after 24 h).
4000 ppm: 0/6
Clinical signs:
other: 8000 ppm: gasping, nasal irritation, poor coordination, bloody nasal discharge, tonic convulsions. 4000 ppm: wet noses, eyes partly closed within 10 min, slight loss of coordination within 25 min.
Body weight:
The surviving animals gained weight.
Gross pathology:
Dead animals: lungs red, intestines yellow, gas and liquid filled
Survivors: no remarkable findings
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the available study results, the test item provokes inhalative toxic effects after a 4 hour vapour exposure period in rats. The mean lethal concentration was calculated to be 17 mg/L (5700 ppm).
Executive summary:

Acute inhalation toxicity was analyzed in a study performed with female Wistar rats. The animals were dosed with 4000 and 8000 ppm of vapourized test substance. After a 4 h exposure to 8000 ppm of the vapour all animals were dead within 24 h. No deaths occurred for the low level exposure scenario. Based on these observations a LC50 of 17.3 mg/L (5700 ppm) was calculated.

Main clinical signs observed after 8000 ppm vapour inhalation were gasping, nasal irritation, poor coordination, bloody nasal discharge and tonic convulsions.

Wet noses, partly closed eyes and a slight loss of coordination were observed for animals exposed to 4000 ppm of the vapour. At necropsy, dead rats showed gas and liquid filled red lungs and yellow intestines. Surviving rats were without remarkable finding at necropsy. Based on the estimated LC50, the test substance can be categorized for inhalative toxicity cat. 4 based on GHS criteria.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
02 May 1955
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Inhalation Risk Test
Principles of method if other than guideline:
- Principle of test:
The test demonstrates the toxicity of an atmosphere saturated with vapours of the volatile components of a test substance at the temperature chosen for vapour generation (20 °C). 6 rats per exposure-time were exposed sequentially to the vapour, generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glassdisc in a glass cylinder for 1 min, 2 min and 4 min.
GLP compliance:
no
Remarks:
predating GLP
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
air
Details on inhalation exposure:
- Temperature in air chamber: 23°C
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
1 min
Remarks on duration:
additional expsoure times: 2 min and 4 min
Concentrations:
120 mg/L air (40000 ppm); nominal concentration based on the substance loss
No. of animals per sex per dose:
6 (no gender stated)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 8 days
- Frequency of observations: several times on the day of exposure and once on the days thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
not specified
Remarks on result:
not determinable
Mortality:
4 min exposure: all dead; all 6 animals died within 10 min after the exposure
2 min exposure: all dead; 5/6 animals died within 2 min after the exposure. One animal died 3 h post exposure
1 min exposure: all dead; 2/6 animals died within 9 min after exposure, 3/6 animals died after 2-3h; all animals died within 48 h post exposure
Clinical signs:
other: Blue-red paws (4 min exposure), convulsions, lateral position, twitching, dyspnoea
Body weight:
no data
Gross pathology:
Pulmonary hyperemia
Interpretation of results:
study cannot be used for classification
Conclusions:
The inhalation of a highly saturated vapour-air-mixture (120 mg/L) caused 100% mortality of rats within 1 min of exposure.
Executive summary:

In this study 6 rats were exposed to 120 mg/L of vapourized test substance for 1min, 2 min and 4 min. All exposure durations provoked a 100% mortality within 48h.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
- Principle of test:
Concentrated vapour inhalation consists of subjecting groups of six rats to a flowing stream of vapor-ladened air. The vapour-air mixture is generated by passing 2.5 mL/minute of dried air at room temperature through a fritted glass disc immersed to a depth of at least one inch in approximately 50 ml of the test chemical contained in a gas-washing bottle.
GLP compliance:
no
Remarks:
predating GLP
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
air
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
saturated vapour, 8000, 4000, 2000, or 1000 ppm (nominal concentrations)
No. of animals per sex per dose:
6
Control animals:
not specified
Sex:
not specified
Dose descriptor:
LC50
Effect level:
4 000 ppm
Exp. duration:
4 h
Mortality:
saturated vapour: 4/6 rats during 3.75 min exposure and the other 2 died within 24 h
8000 ppm (24 mg/l): 6/6 animals within 3 h.
4000 ppm (12 mg/l)/4h: 3/6.
2000 ppm (6 mg/l)/4h: 1/6.
1000 ppm (3 mg/l)/4h: 0/6.
Clinical signs:
other: saturated vapour: convuslions, loud rales, corneal opacity. 8000 ppm: convulsions, bloddy discharge of the nostrils, irritation of the ears and feet to the point of rawness. 4000 ppm: eye and nostril irritation, tremor, poor coordination.
Body weight:
no data
Gross pathology:
Congestion of the lungs, liver, kidneys and spleen after saturated vapour exposure
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the available study results, the test item provokes inhalative toxic effects after vapour exposure in rats. This study gives only limited information of the applied methods and results, however, 3/6 animals died within 4 h at 4000 ppm ( approx. 12 mg/L) and 100% died within 3 h at 8000 ppm (24 mg/L).
Executive summary:

This report provides inhalation toxicity data based on experiments performed with rats and the test item as a saturated vapour and a vapour of varying concentrations (1000, 2000, 4000, 8000 ppm). 100% mortality was observed within 24 h and 3 h of exposure with the saturated vapour and a vapour of 8000 ppm. Inhalation of 4000 ppm and 2000 ppm caused mortality in 3/6 and 1/6 animals after 4 h, respectively. No deaths were detected for the lowest exposure concentration of 1000 ppm. Rats showed convulsions, loud rales, corneal opacity (saturated vapour) or convulsions, bloddy discharge of the nostrils, irritation of the ears and feet to the point of rawness (8000 ppm) as well as irritation of the eye and nostril, tremor and poor coordination (4000 ppm). Gross necropsy revealed congestion of the lungs, liver, kidneys and spleen in rats expsosed to the saturated vapour. This study gives only limited information of the applied methods and results.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Principles of method if other than guideline:
no data
GLP compliance:
not specified
Species:
other: mammal
Strain:
not specified
Sex:
not specified
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
other: no data
Analytical verification of test atmosphere concentrations:
not specified
Remarks on duration:
Exposure unspecified
Concentrations:
no data
No. of animals per sex per dose:
no data
Control animals:
not specified
Sex:
not specified
Dose descriptor:
LC50
Effect level:
5 mg/L air
Remarks on result:
other: Exposure unspecified
Mortality:
no data
Clinical signs:
other: no data
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
study cannot be used for classification
Conclusions:
A LC50 of 5000 mg/m3 (5 mg/L) was derived by inhalation toxicity testing with mammals (no further specification).
Executive summary:

This secondary source information reports a LC50 of 5000 mg/m3 (5 mg/L) after inhalation exposure of mammals with the test item.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
17 300 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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
other: Draize (one day cuff method)
Principles of method if other than guideline:
- Principle of test:
Penetration of rabbit skin was estimated by a technique closely to the one-day cuff method of Draize and associates, using groups of 5 male albino rabbits weighing 2 to 3 kg. The fur was removed from the entire trunk by clipping, and the dose was retained beneath an impervious plastic film. The animals are immobilized during the 24 hour contact period, after which the film was removed and the rabbits are caged for the subsequent 14 day observation period.
GLP compliance:
no
Remarks:
predating GLP
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 3-5 month
- Weight at study initiation: 2- 3 kg
- Diet (e.g. ad libitum): Rockland rabbit diet
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
0.252, 0.5, 1.0, 2.0 mL/kg bw = 179, 355, 710 and 1420 mg/kg bw (conversion in mg/kg bw is based on the density d: 0.71 g/cm3)
No. of animals per sex per dose:
5 (males only)
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: day 0, 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Sex:
male
Dose descriptor:
LD50
Effect level:
582 mg/kg bw
95% CL:
376 - 895
Remarks on result:
other: original value 0.82 mL/kg
Mortality:
1420 mg/kg bw: 5/5, days to death: 1, 1, 1, 1, 1
710 mg/kg bw: 3/5, days to death: 6, 1, 1
355 mg/kg bw: 1/5, days to death: 1
179 mg/kg bw: 0/5
Clinical signs:
Local effects: the substance caused hemorrhage and necrosis of the skin and underlaying muscular layers
Body weight:
The survivors of the 355 and 710 mg/kg bw dose group lost weight
Gross pathology:
Animals that died: pale or mottled livers, pale, mottled or roughened surfaces of the kidneys, and congested or hemorrhagic intestines. Spleens were darkened to the point of being called black, pancreas congested and testes hemorrhagic.
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The mean lethal dose of the test substance after single dermal application for 24 hours was found to be 582 mg/kg bw in rabbits.
Executive summary:

Penetration of rabbit skin was estimated by a technique closely to the one-day cuff method of Draize and associates, using groups of 5 male albino rabbits weighing 2 to 3 kg. The fur was removed from the entire trunk by clipping. The different substance concentrations (0.252, 0.5, 1.0, 2.0 mL/kg bw) were retained beneath an impervious plastic film. The animals were immobilized during the 24 hour contact period, after which the film was removed and the rabbits were caged for the subsequent 14-day observation period. Based on the available mortality data a LD50 of 0.82 mg/L (equivalent to 582 mg/kg bw) was derived. The substance provoked local effects (hemorrhage and necrosis of the skin and underlaying muscular layers). Moreover, gross pathology analysis revealed effects on the liver, kidneys, intestines, spleens, pancreas and testes.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
other: Draize (one day cuff method)
Principles of method if other than guideline:
- Principle of test:
Four male New Zealand White rabbits, 3 to 5 months of age, were immobilized during the 24-hour contact period with the compound retained under impervious plastic sheeting around the clipped intact skin of the trunk. Thereafter, excess fluid was removed to prevent ingestion. After 24 h the wrapping and remaning fluid was removed with cleansing tissue and the animal was returned to its cage for further observation.
GLP compliance:
no
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Charge No.of test material: 01067
- Identification: TK 2527
- Source: Chemicals and Plastics, South Charleston
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 3-5 month
- Weight at study initiation:2-3 kg
- Diet (e.g. ad libitum): Rockland rabbit diet
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
0.5, 1 and 2 mL/kg bw = 355, 710 and 1420 mg/kg bw (conversion based on density d: 0.71 g/cm3)
No. of animals per sex per dose:
4
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Frequently observation during expsoure; daily observation during the post-exposure period; bodyweights measured before dosing and at day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 632 mg/kg bw
95% CL:
295 - 1 342
Remarks on result:
other: original value 0.891 mL/kg conversion in mg/kg bw is based on the density d: 0.71 g/cm3
Mortality:
1420 mg/kg bw: 4/4, days to death: 1, 1, 1, 1.
710 mg/kg bw: 2/4, days to death: 1, 4.
355 mg/kg bw: 1/4, days to death was not recorded.
Clinical signs:
Systemic toxicity:
Coordination loss after 24 h (1 mL/kg)

Local toxicity:
Erythema or edema, necrosis (0.5 mL/kg)
Edema, necrosis (1 mL/kg)
Necrosis (2 mL/kg)
Body weight:
No evaluable data
Gross pathology:
Animals that died: mottled livers, kidney medullae dark.
Survivors: no abnormalities
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The mean lethal dose of the test substance after single dermal application for 24 hours was found to be 632 mg/kg bw in rabbits.
Executive summary:

Four male New Zealand White rabbits, 3 to 5 months of age and with a weight of 2-3 kg, were immobilized during the 24-hour contact period with the compound (0.5, 1, 2 mL/kg) retained under impervious plastic sheeting around the clipped intact skin of the trunk. Thereafter, excess fluid was removed to prevent ingestion. After 24 h the wrapping and remaining fluid was removed with cleansing tissue and the animals were returned to their cages. After 24 h of treatment with the highest dose of 2 mL/kg all animals died and showed necrotic skin reactions. Dosage of 1 mL/kg caused 50% mortality and skin irritation (edema, necrosis). Deaths occurred after 24 h and 4 days. Moreover, animals showed coordination loss at 24 h. The lowest applied concentration of 0.5 mL/kg caused death for 1/4 animals and skin irritation (erythema or edema, necrosis). Gross pathological findings in dead animals included mottled livers and darkened kidney medulla.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
582 mg/kg bw

Additional information

Oral:

In an acute oral toxicity study (1979, reliability 2) five non-fasted male Wistar rats were exposed to a single dose of the test substance at 3 different concentration. The undiluted test substance was applied at concentrations of 178, 355, 710 mg/kg bw. Moreover, a second test with a 10% dilution of the test substance at concentrations of 35.5, 71 and 142 mg/kg bw was conducted. The undiluted sample testing provoked death for all tested concentration groups. Exposure to the lowest applied concentration of 178 mg/kg bw killed 4/5 rats. Higher concentrations killed all animals. The second test with the 10% solution of the test substance revealed 100% mortality for the highest tested concentration (142 mg/kg bw), whereas no deaths occured in the lower concentration groups. Clinical signs observed after treatment were sluggishness and gasping. Dead animals showed effects of the lungs, stomachs, intestines, kidneys, adrenal gland and livers. Surviving rats had mottled livers and thickened stomach walls.

Another single oral dose toxicity test (1950, reliability 2) was performed with five non-fasted, male Sherman strain rats exposed to 4 concentrations (252, 500, 1000, 2000 mg/kg bw) of the test substance. The chemical was administered as a 20% dilution in water by stomach tube. A concentration dependent toxicity after a single ingestion was observed. All animals died within 1 day after treatment with 2000 mg/kg bw of the test substance. No deaths occurred in the low dose group of 252 mg/kg bw. Based on the study results a mean lethal dose of 540 mg/kg bw was calculated. Rats exposed to a dosage above the oral LD50 were sluggish and showed a reduced body temperature. One rat was narcotic. At autopsy, dead animals had congested lungs livers and kidneys, hemorrage or necrosis of the stomach, and hemorrhage or opacity, congestion of the intestine.

Inhalation:

Acute inhalation toxicity was analyzed in a study performed with female Wistar rats (1979, reliability 2). The animals were dosed with 4000 and 8000 ppm of vapourized test substance. After a 4 h exposure to 8000 ppm of the vapour all animals were dead within 24 h. No deaths occured for the low level exposure scenario. Based on this observations a LC50 of 17.3 mg/L (5700 ppm) was calculated.

Main clinical signs observed after 8000 ppm vapour inhalation were gasping, nasal irritation, poor coordination, bloody nasal discharge and tonic convulsions. Wet noses, partly closed eyes and a slight loss of coordination were observed for animals expsoed to 4000 ppm of the vapour. At necropsy, dead rats showed gas and liquid filled red lungs and yellow intestines. Surviving rats were without remarkable finding at necropsy.

In another study (1950; reliability 2) rats inhaled the test item as a saturated vapour and a vapour of varying concentrations (1000, 2000, 4000, 8000 ppm). 100% mortality was observed within 24 h and 3 h of exposure with the saturated vapour and a vapour of 8000 ppm. Inhalation of 4000 ppm and 2000 ppm caused mortality in 3/6 and 1/6 animals after 4h, respectively. No detahs were detected for the lowest exposure concentration of 1000 ppm. Rats showed convulsions, loud rales, corneal opacity (saturated vapour) or convulsions, bloddy discharge of the nostrils, irritation of the ears and feet to the point of rawness (8000 ppm) as well as irritation of the eye and nostril, tremor and poor coordination (4000 ppm). Gross necropsy revealed congestion of the lungs, liver, kidneys and spleen in rats expsosed to the saturated vapour. This study gives only limited information of the applied methods and results.

Additional data were available from an inhalation risk test (1955; reliability score 2). In this study 6 rats were exposed to 120 mg/L of vapourized test substance for 1min, 2 min and 4 min. All exposure durations provoked a 100% mortality within 48h. Clinical signs were convulsions, lateral position, twitching, dyspnoea. At necropsy, pulmonary hyperemia was observed.

Dermal:

Penetration of rabbit skin was estimated by a technique closely to the one-day cuff method of Draize and associates, using groups of 5 male albino rabbits weighing 2 to 3 kg (1950, reliability 2). The fur was removed from the entire trunk by clipping. The different substance concentrations (0.252, 0.5, 1.0, 2.0 mL/kg bw) were retained beneath an impervious plastic film. The animals were immobilized during the 24 hour contact period, after which the film was removed and the rabbits were caged for the subsequent 14-day observation period. Based on the available mortality data a LD50 of 0.82 mg/L (equivalent to 582 mg/kg bw) was derived. The substance provoked local effects (hemorrhage and necrosis of the skin and underlaying muscular layers). Moreover, gross pathology analysis revealed effects on the liver, kidneys, intestines, spleens, pancreas and testes.

A similar study (1979, reliability 2) with four male New Zealand White rabbits, 3 to 5 months of age and with a weight of 2-3 kg, were immobilized during the 24-hour contact period with the compound (0.5, 1, 2 mL/kg) retained under impervious plastic sheeting around the clipped intact skin of the trunk. Thereafter, excess fluid was removed to prevent ingestion. After 24 h the wrapping and remaning fluid was removed with cleansing tissue and the animals were returned to their cages. After 24 h of treatment with the highest dose of 2 mL/kg all animals died and showed necrotic skin reactions. Dosage of 1 mL/kg caused 50% mortality and skin irritation (edeme, necrosis). Deaths occured after 24 h and 4 days. Moreover, animals showed coordination loss at 24 h. The lowest applied concentration of 0.5 mL/kg caused death for 1/4 animals and skin irritation (erythema or edema, necrosis). Gross pathological findings in dead animals included mottled livers and darkened kidney medulla. Based on the study findings, the LD50 was found to be 632 mg/kg bw.

Justification for classification or non-classification

According to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 the substance is classified as acute toxic via the oral route Cat. 3 (toxic if swallowed); acute toxic via the inhalation route Cat. 4 (harmful if inhaled), and acute toxic via the dermal route Cat. 3 (toxic in contac with skin).