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EC number: 259-627-5 | CAS number: 55406-53-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
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
- 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.
Reference
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
- 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.
Referenceopen allclose all
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
- 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.
Reference
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.
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