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Diss Factsheets

Administrative data

Description of key information

Acute oral LD50 of the test item was determined to be 1056 mg/kg bw for female Sprague Dawley rats in an OECD 401 and GLP compliant study.

The test item is considered non-toxic in rabbits, at a dose of 2000 mg/kg bw by dermal application, based upon the absence of mortality and criteria set forth by FIFRA.

Acute inhalation LC50 of the test item was considered to be greater than 6.89 mg/L air for not respirable dust. However, clinical signs during exposure and post exposure were noted as well as a declined body weight in the treated group between day 2 and day 4 post exposure.

Another study revealed LC50 of 0.67 mg/L for respirable dust and 0.763 mg/L for respirable liquid aerosol.

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:
1984-04-27 to 1984-07-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: stored at room temperature
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, Inc., Kingston, New York
- Weight at study initiation: initial body weights did not exceed 20 % of mean body weights
- Fasting period before study: overnight
- Housing: individually in suspended wire-mesh cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: approx. one week
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: as appropriate
- Lot/batch no.: 52500

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
250; 500; 1000; 1500; 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation at one, two, and four hours post treatment, and once daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology
Statistics:
The mortality data were analyzed separately for males by a modified Behrens-Reed-Muench Cumulant Method (Thakur and Fezio, 1981). For the females and for the sexes combined. LD50´s and their 95 % confidence intervals were computed using a maximum likelihood Logit Method (Bliss, 1952).
Preliminary study:
The Group 2 (1000 mg/kg bw) animal was found dead on Day 2 postdose; the Group 3 (1500 mg/kg bw) animal at 4 hours; the Group 4 (2000 mg/kg bw) animal on Day 3; and the Group 5 (2500 mg/kg bw) animal was found dead on Day 2. Clinical observations included rough coat in all groups; soft feces and urine stains in all treatment groups, except Group 3; slight depression and/or depression in Groups 2, 3, 4 and 5; and red stains on the nose and/or eyes and hunched appearance in Group 4. Animals in Groups 3, 4, and 5 lost weight between initiation and death. The Group 2 animal gained weight.
All surviving animals had no observable gross pathology findings at necropsy. In the animals which were found dead, gross pathology findings were noted for the lung, stomach, intestines, and liver.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 795 mg/kg bw
Based on:
test mat.
95% CL:
> 1 437 - < 2 243
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 056 mg/kg bw
Based on:
test mat.
95% CL:
> 783 - < 1 329
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 470 mg/kg bw
Based on:
test mat.
95% CL:
> 1 226 - < 1 713
Clinical signs:
other: Clinical observations included soft feces, rough haircoat, urine stains, and slight depression and/or depression in all groups; ataxia, hunched appearance and prostration in Groups 3, 4 and 5; labored respiration in Group 3 and 4; and tremors in Group 5.
Gross pathology:
All surviving animals had no observable gross pathology findings at necropsy. In the animals which were found dead, gross pathology findings were noted for the stomach, intestine, kidneys, and liver.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
LD50 of the test item for acute oral toxicity is determined to be 1056 mg/kg bw for female Sprague Dawley rats.
Executive summary:

The test item was evaluated for acute oral toxicity in male and female rats. Based upon the findings of this study, the acute oral LD50 in males was calculated to be 1795 mg/kg bw, with 95 % confidence limits of 1437 and 2243 mg/kg bw; the oral LD50 in females was calculated to be 1056 mg/kg bw, with 95 % confidence limits of 783 and 1329 mg/kg bw; and the combined LD50 in males and females was calculated to be 1470 mg/kg bw, with 95 % confidence limits of 1226 and 1713 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 056 mg/kg bw
Quality of whole database:
GLP and guideline compliant study.

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:
1985-05-14
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
1981
Deviations:
no
GLP compliance:
not specified
Test type:
traditional method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 21.274A

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
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, Kingston, N. Y.
- Age at study initiation: approx. 7 weeks
- Housing: individually in stainless-steel- wire-mesh cages
- Diet: ad libitum during non exposure periods
- Water: ad libitum throughout non exposure periods, via automatic water supply
- Acclimation period: three weeks quarantine

ENVIRONMENTAL CONDITIONS
- Temperature: 22 - 25.5 °C
- Humidity: 31 - 46 %
- Photoperiod: 12 / 12 hrs dark / hrs light
Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 100 L
- Total chamber airflow: 16.7 L/min
- System of generating particulates/aerosols: Dust by use of a Wright Dust Feeder
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
6.89 mg/L
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 and weighing: The appearance and behavior of all animals were observed every 30 minutes during exposure, Immediately following the exposure, and twice dally during the 14-day postexposure period. Body weights of all animals were recorded immediately prior to exposure and on Days 2, 3, 4, 7, and 14 postexposure.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
not applicable
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 6.89 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
One female in the treatment group was found dead on Day 5 post exposue.
Clinical signs:
other: At one hour of exposure, all animals exhibited dyspnea, salivation and rhinorrhea; these persisted throughout the exposure period. All animals showed lacrimation as well during the last one and one-half hours of exposure. During the 14-day postexposure pe
Body weight:
The mean body weights of all groups had increased by Day 14. However, the mean body weights of both sexes in the treated group declined from Day 2 postexposure through Day 4 postexposure.
Gross pathology:
Gross observations of animals necropsied at terminal sacrifice included dilatation of renal pelvis(es), pelvis fluid filled, dark red pinpoint foci 1n kidneys, and enlarged cervical lymph nodes. Incidences of these were more frequent in females than males.
Observations at necropsy of the Group 2 female found dead (Day 5 postexposure) showed findings in the spleen, intestines, stomach, lung, and nares.
Interpretation of results:
GHS criteria not met
Conclusions:
Acute inhalation LD50 of the test item was considered to be greater than 6.89 mg/L air. However, clinical signs during exposure and post exposure were noted as well as a declined body weight in the treated group between day 2 and day 4 postexposure.
Executive summary:

In this study, the test item was applied to male and female rats for a 4 h exposure period by inhalation. Only one female rat was found dead on day 5 post exposure. Observations at necropsy showed findings in the spleen, intestines, stomach, lung, and nares. At one hour of exposure, all animals exhibited clinical signs as dyspnea, salivation and rhinorrhea; these persisted throughout the exposure period. All animals showed lacrimation as well during the last one and one-half hours of exposure. During the 14-day postexposure period, some of the predominant clinical signs were bloody crusts (nose/eyes/mouth/chest/ears), rough haircoat, thin, languid, wheezing, and urine stains. Generally, onset of a majority of these observations was at Day 4 except for bloody crust about the nose which were first noted after removal from the exposure chamber. Four of the five males were normal in appearance by Day 13 postexposure; all surviving females were normal in appearance on Day 11. The mean body weights of all groups had increased by Day 14. However, the mean body weights of both sexes in the treated group declined from Day 2 postexposure through Day 4 postexposure.

Gross observations of animals necropsied at terminal sacrifice included dilatation of renal pelvis(es), pelvis fluid filled, dark red pinpoint foci in kidneys, and enlarged cervical lymph nodes. Incidences of these were more frequent in females than males.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1990-11-08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Version / remarks:
1984
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
traditional method
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 90045420 (powder formulation)
- Source and lot/batch No.of test material: 90045420 (liquid formulation: 40.1 %)
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, Kingston, New York, USA
- Age at study initiation: 7 to 10 weeks
- Weight at study initiation: 225 to 331 g (males); 193 to 246 g (females)
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: > 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 40-70 %
- Photoperiod: 12 / 12 hrs dark / hrs light
Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Mass median aerodynamic diameter (MMAD):
4.3 µm
Geometric standard deviation (GSD):
2.9
Remark on MMAD/GSD:
An average of 8.1 % of the particles were less than or equal to 1 µm. An average of 82 % of the particles were 10 µm or less in size.
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Wright Dust Feeder
- Exposure chamber volume: 100 litres
- Source and rate of air: 20 litres per minute

TEST ATMOSPHERE
- Brief description of analytical method used:
Samples for gravimetric determination of the test item dust exposure levels were drawn from the breathing zone in the exposure chamber using Whatman® glass microfibre filter paper (Type GF/F, 3.7 cm) mounted open-faced in a Gelman filter holder. Samples were withdrawn once per hour from the normal sampling portal and once during exposure from the distribution sampling portal. The filter papers were weighed before and after sample collection and the gravimetric concentration in mg per L was calculated by dividing the weight difference in milligrams by the volume of air sampled in liters.

1. A drop of the test substance was placed on a weighed filter. The filter was weighed immediately and again after desiccating overnight. This was done in triplicate. The resultant data was used to determine the fraction of solids (or non-volatiles) in the test mixture.

2. For each exposure, the filter was weighed (out of holders) before and immediately after sampling (wet weight). Filters were weighed a third time, after overnight desiccating (dry weight). The exposure level was calculated on both a "wet" and "dry" basis by dividing the appropriate net weight on the filter by the volume of air sampled to give the gravimetric concentration (mL/L).

3. The exposure level was calculated on a formulation basis by dividing the exposure concentration on a "dry" basis (mg/L) Step 2, by the fraction of solids, Step 1.

- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Nominal concentrations: 24, 7.0, 1.6, and 4.6 mg/L
Gravimetric concentrations: 3.4, 1.8, 0.45, and 0.75 mg formulation/L
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, body weight, gross necropsy including nasal passages and trachea
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
0.68 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: dust formulation
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
0.67 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: dust formulation
Key result
Sex:
female
Dose descriptor:
LC50
Effect level:
0.67 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: dust formulation
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
0.78 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: liquid formulation
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
0.63 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: liquid formulation
Key result
Sex:
female
Dose descriptor:
LC50
Effect level:
0.99 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: liquid formulation
Mortality:
Dust formulation:
High Dose: 5/5 animals died between day 1 to 8 in both sexes, respectively.
Mid Dose: 3/5 animals died between day 2 to 7 in both sexes, respectively.
Low Dose: 0/5 animals died.

Liquid formulation:
High: 5/5 animals died between day 1 to 4 in both sexes, respectively.
Mid: 4/5 males and 1/5 females died between day 1-2
Low: 0/5 animals died.
Clinical signs:
other: 1. Exposure Period: During the dust exposures, the most commonly noted signs of toxicity were decreased activity, eye closure and excessive lacrimation. During the high level exposure (Group I), gasping and mortality were also noted. During the liquid aer
Body weight:
Substantial weight losses were observed during the first week following the dust and liquid aerosol exposures. Recovery of weight occurred over time and most surviving animals were in excess of their pre-exposure body weight by termination of the study.
Gross pathology:
Edema, emphysema and reddened lungs were observed in those animals found dead. These are common findings in animals which die and are necropsied without exsanguination. Red facial and yellow/red ano-genital staining occurred in many of the animals found dead. The facial stains, from Harderian gland secretion, and the yellow urinary ano-genital stains are common findings in animals found dead. Pale lungs and black/red/tan/brown foci in lungs were seen in some of the animals killed at the terminal sacrifice. The toxicologic significance of these findings, if any, remains equivocal on the basis of a postmortem examination.
Other findings:
- Organ weights: not applicable
- Histopathology: not applicable
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Acute inhalation LC50 values for combined sexes were determined to be 0.68 mg/L dust and 0.78 mg/L liquid aerosol.
Executive summary:

A series of four-hour, whole-body inhalation exposures was performed with seven groups, each consisting of five male and five female Sprague-Dawley CD® rats, to determine the median lethal concentration of the test item using a powder and liquid formulation. The animals were exposed to the test item as a dust at concentrations of 1.7, 0.72 and 0.38 mg/L resulting in mortalities within 7 days after exposure of 100, 60 and 0 %, respectively. The animals were exposed to the test item as a liquid aerosol at concentrations of 3.4, 1.8, 0.75 and 0.45 mg/L resulting in mortalities within 3 days after exposure of 100, 100, 50 and 0 %, respectively. The LC50 for the dust was calculated to be 0.68 mg/L for the combined sexes, 0.67 mg/L for the males and 0.67 mg/L for the females. The LC50 for the liquid aerosol was calculated to be 0.78 mg/L for the combined sexes, 0.63 mg/L for the males and 0.99 mg/L for the females. Although the powder (98.2 % Active Ingredient) had over twice the active ingredient content of the liquid formulation (40.1 % Active Ingredient), the powders' LC50 was only slightly lower than the liquid formulation.The reason for this difference was unclear but may have been attributable to particle size/lung deposition differences, the liquid formulation may be more easily absorbed than the dust or toxicity of other ingredients in the liquid formulation.Signs of irritation such as excessive lacrimation or eye closure or gasping were commonly noted during exposure and up to two hours post-exposure.During the 14-day post-exposure observation period, similar signs of toxicity persisted during the first week after exposure and then generally abated among surviving animals.

Substantial decreases in body weight were observed during the first week following exposures, however, recovery occurred over time and most surviving animals were in excess of their pre-exposure body weight by termination of the study.Postmortem findings included discolored respiratory tissues in both spontaneously dying and sacrificed animals.These and other observations were generally not considered clearly related to treatment.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating conc.
Value:
670 mg/m³ air
Quality of whole database:
GLP and Guideline study.

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:
1991-11-14
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
Version / remarks:
1984
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- lot/batch No.of test material: 9106-6269
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Eastern Rabbit Breeding Laboratory, Taunton, MA)
- Age at study initiation: 10-12 weeks old
- Weight at study initiation: 2000 - 3000 g
- Housing: individually in suspended stainless steel cages. Hardwood chips were used as non-contact bedding under the cages.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 4 days of quarantine

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 1.5 °C
- Humidity: 30 - 70 %
- Air changes: min. 10 - 13 per hr
- Photoperiod: 12 / 12 hrs dark / hrs light
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: trunk
- % coverage: approx. 10 % of body surface
- Type of wrap if used: Vetrap impervious bandaging

REMOVAL OF TEST SUBSTANCE
- Washing: skin was gently wiped and rinsed with USP water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2000 mg/kg bw
- For solids, paste formed: no; gauze patches were moistened with physiological saline
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 and weighing: daily observation for clinical signs; weighing at the beginning and end of the study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No animal died during the 14 day observation period following treatment.
Clinical signs:
other: There were no overt signs of toxicity noted in any test animal during the observation period.
Gross pathology:
No findings
Other findings:
Skin reactions:
Erythrema (scores 1 and 2) was noted on 10/10 animals, on Day 1. Erythrema was reversed in all animals by Day 2. No signs of Edema was noted on any animal during the observation period.
Interpretation of results:
GHS criteria not met
Conclusions:
The test item is considered non-toxic in rabbits, at a dose of 2000 mg/kg bw by dermal application, based upon the absence of mortality and criteria set forth by FIFRA.
Executive summary:

The test item was evaluated for its potential to produce systemic toxicity or death following topical application at a dose of 2000 mg/kg bw in male and female New Zealand White albino rabbits. Based on the absence of moratlity and the criteria of the study protocol, the test substance is defined as non-toxic via the dermal route. It should be noted that erythrema (score 1 and 2) were observed in 10/10 animaly at Day 1, which were fully reversible at Day 2.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
GLP and guideline study.

Additional information

Acute oral toxicity

The test item was evaluated for acute oral toxicity in male and female rats. Based upon the findings of this study, the acute oral LD50 in males was calculated to be 1795 mg/kg bw, with 95 % confidence limits of 1437 and 2243 mg/kg bw; the oral LD50 in females was calculated to be 1056 mg/kg bw, with 95 % confidence limits of 783 and 1329 mg/kg bw; and the combined LD50 in males and females was calculated to be 1470 mg/kg bw, with 95 % confidence limits of 1226 and 1713 mg/kg bw.

Acute inhalation toxicity

In an inhalation study, the test item was applied to male and female rats for a 4 h exposure period. Only one female rat was found dead on day 5 post exposure. Observations at necropsy showed findings in the spleen, intestines, stomach, lung, and nares. At one hour of exposure, all animals exhibited clinical signs as dyspnea, salivation and rhinorrhea; these persisted throughout the exposure period. All animals showed lacrimation as well during the last one and one-half hours of exposure. During the 14-day postexposure period, some of the predominant clinical signs were bloody crusts (nose/eyes/mouth/chest/ears), rough haircoat, thin, languid, wheezing, and urine stains. Generally, onset of a majority of these observations was at Day 4 except for bloody crust about the nose which were first noted after removal from the exposure chamber. Four of the five males were normal in appearance by Day 13 postexposure; all surviving females were normal in appearance on Day 11. The mean body weights of all groups had increased by Day 14. However, the mean body weights of both sexes in the treated group declined from Day 2 postexposure through Day 4 postexposure.

Gross observations of animals necropsied at terminal sacrifice included dilatation of renal pelvis(es), pelvis fluid filled, dark red pinpoint foci in kidneys, and enlarged cervical lymph nodes. Incidences of these were more frequent in females than males.

Another acute inhalation study was conducted, designed to assess the toxic effects and determine the median lethal concentration of the test item, when administered by inhalation using a powder and a liquid formulation to Sprague-Dawley CD® rats (5/sex/group) for four hours. Exposures commenced on 11 July 1990 and observations were completed on 20 August 1990. Exposure levels were determined gravimetrically. Particle size distribution determinations were determined using a Delron DCI-6 cascade impactor. Physical observations for abnormal signs were conducted on all animals as a group, at fifteen minute intervals during the first hour of exposure and hourly for the remainder of the exposure. All animals received detailed physical observations just prior to exposure, hourly for two hours post-exposure, and once daily thereafter. Body weight measurements were obtained just prior to exposure on Day 1 and on Days 2, 3, 5, 8 and just prior to sacrifice on Day 15. After a 14-day post-exposure observation period, all survivors were sacrificed. Complete gross postmortem examinations were performed on all animals.

The mean exposure concentrations for the dust, as determined gravi-metrically, were 1.7, 0.72 and 0.38 mg/L, resulting in mortalities within 7 days after exposure of 100, 60 and 0%, respectively. The LC50 was calculated to be 0.68 mg/L for the combined sexes, 0.67 mg/L for the males and 0.67 mg/L for the females. Particle size distribution determinations showed an average mass median aerodynamic diameter of 4.3 microns and an average geometric standard deviation of 2.9. An average of 8.1% of the particles were less than or equal to 1 micron in size.An average of 82 % of the particles were 10 microns or less in size.

The mean exposure concentrations for the liquid aerosol, as determined gravimetrically, were 3.4, 1.8, 0.75 and 0.45 mg/L, resulting in mortalities within 3 days after exposure of 100, 100, 50 and 0 %, respectively. The LC50 was calculated to be 0.78 mg/L for the combined sexes, 0.63 mg/L for the males and 0.99 mg/L for the females. Particle size distribution determinations showed an average mass median aerodynamic diameter of 2.4 microns and an average geometric standard deviation of 2.7. An average of 19% of the particles were less than or equal to 1 micron in size. An average of 94% of the particles were 10 microns or less in size.

Signs of irritation such as excessive lacrimation or eye closure or gasping were commonly noted during exposures and up to two hours post-exposure. During the 14-day post-exposure observation period, similar signs of toxicity persisted during the first week after exposure and then generally abated among surviving animals. Substantial decreases in body weight were observed during the first week following exposures, however, recovery occurred over time and most surviving animals were in excess of their pre-exposure body weight by termination of the study.

Postmortem findings included discolored respiratory tissues in both spontaneously dying and sacrificed animals. These and other observations were generally not considered clearly related to treatment.

Acute dermal toxicity

The test item was evaluated for its potential to produce systemic toxicity or death following topical application at a dose of 2000 mg/kg bw in male and female New Zealand White albino rabbits. Based on the absence of moratlity and the criteria of the study protocol, the test substance is defined as non-toxic via the dermal route up to a dose of 2000 mg/kg bw.

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 (EC) No 1272/2008. Based on available data on acute oral and inhalation toxicity, the test item is classified and labelled as acute toxic Cat. 4 for the oral route (H302: "Harmful if swallowed") and acute toxic Cat. 3 for inhalation route (H331: "Toxic if inhaled") according to Regulation (EC) No 1272/2008 (CLP), as amended for the eighth time in Regulation (EU) No 2016/918.

No classification for acute dermal toxicity is warranted.