Registration Dossier

Administrative data

Description of key information

Oral: LD50 > 2000 mg/kg bw female rat, OECD TG 420, 2016

Inhalation: LC50 > 5.14 mg/L bw, male/female rat, OECD TG 403, 2018

Dermal: LD50 > 2000 mg/kg bw male/female rat, OECD TG 402, 2016

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:
2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP. All relevant validity criteria were met.
Justification for type of information:
Information as to the availability of the in vivo study is provided in 'attached justification'.
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
inspected: June 2015; signature: September 2015
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Recognised supplier
- Age at study initiation: 8 - 12 weeks.
- Weight at study initiation: 166 g (300 mg/kg bw sighting test; sentinel); 171 - 181 g (2000 mg/kg bw sighting test and main study); The weight variation did not exceed ±20% of the mean weight at the start of treatment.
- Fasting period before study: Overnight before dosing and three to four hours after dosing.
- Housing: Group housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): Certified diet from recognised supplier, provided ad libitum (except for fasting period).
- Water (e.g. ad libitum): ad libitum (except for fasting period)
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70%
- Air changes (per hr): > 15 air changes per hour
- Photoperiod: 12 h light / 12 h dark

IN-LIFE DATES: From: To: 2015-12-16 to 2016-01-06
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
For the purpose of the 2000 mg/kg dose level the test item was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level. For the purpose of the 300 mg/kg dose level the test item was freshly prepared, as required, as a solution in arachis oil BP. Arachis oil BP was used because the test item did not dissolve/suspend in distilled water. The test item was formulated within 2 hours of being applied to the test system. In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose.
Doses:
300 mg/kg bw in Arachis oil BP vehicle (starting dose and initial sighting test); 2000 mg/kg bw (initial sighting test and main study)
No. of animals per sex per dose:
1 (sighting study) and 4 (main study); total 5 per dose according to sequential guideline testing strategy.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 0.5, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
300 mg/kg bw (sighting test): No mortality
2000 mg/kg bw (definitive test): No mortality.
Clinical signs:
300 mg/kg bw (sighting test): No signs of systemic toxicity were noted.
2000 mg/kg bw (definitive test): No signs of systemic toxicity were noted.
Body weight:
300 mg/kg bw (sighting test): Expected bodyweight gains were seen over the study period.
2000 mg/kg bw (definitive test): All animals showed expected bodyweight gains over the study period.
Gross pathology:
300 mg/kg bw (sighting test): No abnormalities were noted at necropsy.
2000 mg/kg bw (definitive test): No abnormalities were noted at necropsy.
Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the oral LD50 was established to exceed 2000 mg/kg bw in female Wistar rats. Under the conditions of this study, and according to the OECD TG 420 criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.
Executive summary:

The study was performed according to OECD TG 420 and EU Method B.1 bis Acute Toxicity (Oral) and in accordance with GLP to assess the acute oral toxicity of the test material following a single oral administration in the female Wistar strain rat by the fixed dose method. The test substance was administered by oral gavage in an initial sighting study at 300 mg/kg. In the absence of significant toxicity the test substance was then administered by oral gavage in a further initial sighting at 2000 mg/kg. Subsequently a further group of four fasted females was given a single oral dose of test item, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study and gross necropsy performed. There was no mortality during the course of the study. No signs of systemic toxicity were noted in the remaining animals. Animals showed expected gains in bodyweight over the study period and there were no abnormalities noted at necropsy. Under the conditions of this study the oral LD50 was established to exceed 2000 mg/kg bw in the female Wistar rat. Under the conditions of this study, and according to the OECD TG 420 criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The available information as a whole meets the tonnage driven information requirements of REACH.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP. All relevant validity criteria were met. Minor deviation: relative humidity not considered to affect the study reliability.
Justification for type of information:
Information as to the availability of the in vivo study is provided in 'attached justification'.
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
relative humidity was lower than targetted (actual 20-30 %). This was considered to be unavoidable and is considered not to have affected the purpose or validity of the study.
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
yes
Remarks:
See above
GLP compliance:
yes (incl. certificate)
Remarks:
inspected: July 2017; signature: November 2017
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Remarks:
RccHan : WIST
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Recognised supplier
- Age at study initiation: 8 - 12 weeks; females were nulliparous and non pregnant.
- Weight at study initiation: 200 - 350 g
- Fasting period before study: None.
- Housing: Housed in groups of up to five by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes provided with environmental enrichment items.
- Diet (e.g. ad libitum): Certified diet from recognised supplier, provided ad libitum (except for exposure period period)
- Water (e.g. ad libitum): ad libitum (except for exposure period period)
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70% targeted (20-30 % achieved - not considered to impact study integrity).
- Air changes (per hr): > 15 air changes per hour
- Photoperiod: 12 h light / 12 h dark
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Remarks:
Oxygen concentration (%) was monitored during the study by an electronic oxygen analyzer. The test atmospheres were generated to contain at least 19% oxygen.
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The test item was aerosolized using a metal concentric jet nebulizer located at the top of the exposure chamber. The nebulizer was connected to a glass syringe attached to an infusion pump, which provided a continuous supply of test item under pressure, and to a metered compressed air supply.
- Exposure chamber volume: approximately 30 litres (dimensions: 28 cm diameter x 50 cm high)
- Method of holding animals in test chamber: Prior to the day of exposure each rat was acclimatized (for approximately 2 hours) to a tapered polycarbonate restraining tube. During the exposure period, each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber ‘O’ ring. Only the nose of each animal was exposed to the test atmosphere.
- Source and rate of air: filtered air; chamber flow rate was maintained at 40 L/min providing 80 air changes per hour.
- Method of conditioning air: Compressed air was supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters before it was introduced to the nebulizer.
- System of generating particulates/aerosols: metal concentric jet nebulizer; the concentration within the exposure chamber was controlled by adjusting the rate of the infusion pump and air flow settings into the chamber. The chamber flow rate was maintained 40 L/min providing 80 air changes per hour.
- Method of particle size determination: Particle size was determined using a cascade impactor. The device consisted of six impactors stages. The mean amount for each stage was used to determine the cumulative amount below each cut-off point size to calculate the proportional (%) aerosol of defined size ranges. The resulting values were converted to probits and plotted against Log10 cut-point size. From this plot, the Mass Median Aerodynamic Diameter (MMAD) was determined (as the 50% point) and the geometric standard deviation was calculated. In addition, the proportion (%) of aerosol less than 4 μm (considered to be the inhalable fraction) was determined.

- Treatment of exhaust air: The extract from the exposure chamber passed through a ‘scrubber’ trap and was connected with a high efficiency filter to a metered exhaust system. The chamber was maintained under negative pressure. A schematic of the dynamic (continuous flow) system is presented in the full study report.
- Temperature, humidity, in air chamber: The temperature and relative humidity inside the exposure chamber were measured by an electronic thermometer/humidity meter: 19 to 20 °C and 30 to 70% humidity. (Chamber temperature actual was: 19 to 20 °C ; Chamber relative humidity actual was: 20 – 30% during exposure).

TEST ATMOSPHERE
- Brief description of analytical method used: The test atmosphere was sampled nine times during the exposure period. The sampling procedure involved a known volume of test atmosphere being drawn through a glass fibre filter. Each filter was then submitted for chemical analysis by gas chromatography (GC).

The test filter samples received were extracted with methanol to achieve the working concentration. Blank filters were accurately fortified with known amounts of test item and either analysed without further procedure or purged with nitrogen prior to analysis. A range of standard solutions were prepared in methanol from a stock solution of 1.024 mg/mL by serial dilution covering the concentration range 0.0517 to 0.1551 mg/mL. Full details of the analytical method are provided in the full study report. The linearity of the analytical system used for sample analyses was demonstrated with a good relationship between peak areas measured and working standard concentrations. The regression coefficients calculated were found to be 0.994. The fortified samples of filters were found to have a recovery value of ± 10% of the fortification. The results indicate the accurate use of the test item and filters during this study. Working solutions of the test item were shown to be sufficiently stable to complete the analysis without deterioration of the analyte. Full details of the analytical method are provided in the full study report.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- Particle size distribution: The particle size of the generated atmosphere inside the exposure chamber was determined three times during each exposure period using a cascade impactor. The particle size distribution for each group is reported in table 1.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The Mass Median Aerodynamic Diameter (MMAD) was determined and is reported for each group in table 1.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Following an appropriate equilibration period a single group of ten rats (five males and five females), was subjected to a single exposure to the test item for a period of four hours. Based on the results of the sighting test (no mortality and/or observations at mean achieved atmosphere 2.05 mg/L), a target concentration of 5.0 mg/L was used for the definitive test exposure. As the mean achieved concentration was 103% of target and no mortalities occurred, no further exposure levels were required. Full details are provided in table 2.
No. of animals per sex per dose:
5 per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, one hour after termination of exposure and subsequently once daily for up to fourteen days. Any evidence of mortality or overt toxicity was recorded at each observation. Individual body weights were recorded on arrival, prior to treatment on the day of exposure and on Days 1, 3, 7 and 14 or after mortality.
- Necropsy of survivors performed: yes (and in the event of any mortalities)
- Other examinations performed: clinical signs, body weight,organ weights, and any other relevant toxicological effects were reported.
Statistics:
Using the mortality data obtained, where applicable: an estimate of the acute inhalation median lethal concentration (LC50) would be calculated using validated data analysis software which utilized Log-Normal (Probit) regression models in order to calculate the LC50 values and associated 95% confidence limits for males and females separately.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.14 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Effect levels based on analytically confirmed: mean achieved concentrations for each exposure/sex.
Mortality:
No mortalities during the study.
Clinical signs:
other: In group 1: 5.14 mg/L: During exposure, all exhibited decreased respiratory rate. On removal from the chamber all animals exhibited decreased respiratory rate and ataxia, one hour post-exposure no change was noted. At Day 1 post-exposure, all exhibited l
Body weight:
In group 1: 5.14 mg/L: All exhibited body weight losses on the first day post-exposure. Except for three males and one female which exhibited body weight losses from Days 1 to 3 post-exposure, body weight gains were noted for all during the remainder of the recovery period.
Gross pathology:
In group 1: 5.14 mg/L: Dark and/or pale patches on the lungs and/or pale lungs were noted amongst eight of ten at necropsy. No macroscopic abnormalities were detected in two males.
Other findings:
- Other observations: The respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity during necropsy.

Table 1. Characteristics of the achieved atmosphere:

Group Number

Mean Achieved Atmosphere Concentration (mg/L)

Mean Mass Median Aerodynamic Diameter (µm)

Inhalable Fraction

(% <4 µm)

Geometric Standard Deviation

1

5.14

1.69

83.6

2.43

 

Table 2. Mean achieved atmosphere concentrations:

Group Number

Atmosphere Concentration

Mean Achieved (mg/L)

Standard Deviation

Nominal (mg/L)

1

5.14

0.22

15.25

 

Table 3. Mortality data summary:

Group Number

Mean Achieved Atmosphere Concentration

(mg/L)

Deaths

Male

Female

Total

1

5.14

0/5

0/5

0/10

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the inhalation LC50 (male/female) was: greater than 5.14 mg/L within the RCCHan WIST rat.
Executive summary:

The study was performed according to OECD TG 403 and EU Method B.2 in accordance with GLP to assess the acute inhalation toxicity of the test item. Following a sighting test, one group of ten RccHanTM : WIST strain rats (five males and five females) were exposed to an aerosol atmosphere of the test item. The groups were exposed for four hours using a nose only exposure system, followed by a fourteen day observation period. The mean achieved atmosphere concentrations was Group 1: 5.14 mg/L. The characteristics of the achieved atmosphere where Mean Mass Median Diameter (particle size) and Inhalable Fraction <4 μm: Group 1: 3.48 μm and 83.6%. The Geometric Standard Deviation was 2.43. There was no mortalities in Group 1. Common abnormalities noted during the study included decreased respiratory rate, ataxia, lethargy, noisy respiration, hunched posture, pilo-erection, sneezing, wet fur and fur stained by clear sticky test item. All animals recovered to appear normal from Days 8 to 11 post-exposure. All animals exhibited body weight losses on the first day post-exposure. Except for three males and one female which exhibited body weight losses from Days 1 to 3 post-exposure, body weight gains were noted for all animals during the remainder of the recovery period. Dark and/or pale patches on the lungs and/or pale lungs were noted amongst eight animals at necropsy. No macroscopic abnormalities were detected in two males. Under the conditions of this study, the 4-hour inhalation LC50 (male/female) was greater than 5.14 mg/L within the RCCHan WIST rat.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating conc.
Value:
5 140 mg/m³
Quality of whole database:
The available information as a whole meets the tonnage driven information requirements of REACH.

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:
2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP. All relevant validity criteria were met.
Justification for type of information:
Information as to the availability of the in vivo study is provided in 'attached justification'.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
inspected: June 2015; signature: September 2015
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Recognised supplier
- Age at study initiation: 8 - 12 weeks.
- Weight at study initiation: 211 - 292 g; the single deviation from ±20% mean weight was not considered to significantly impact the conduct of the study; was within the guideline recommended range.
- Fasting period before study: Not applicable
- Housing: suspended solid floor polypropylene cages furnished with woodflakes; the initial two animals were housed individually throughout the study. The further group of eight animals (four male and four female) were housed individually during the 24 Hour exposure period and in groups of four, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): Certified diet from recognised supplier, provided ad libitum.
- Water (e.g. ad libitum): ad libitum.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70%
- Air changes (per hr): > 15 air changes per hour
- Photoperiod: 12 h light / 12 h dark

IN-LIFE DATES: From: To: 2016-05-25 to 2016-06-16
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: the day before treatment the back and flanks were clipped free of hair. Dorsal area application.
- % coverage: Approximately 10% of total body surface
- Type of wrap if used: The area of application was covered piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test item
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Concentration (if solution): Not applicable.
- Constant volume or concentration used: Not applicable.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 per sex per dose (5 male/5 female); treated sequentially following application to 1 sentinel per sex per dose .
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations and mortality checks were conducted at approximately 0.5, 1, 2, and 4 hours and subsequently once daily for 14 days. Local effects were examined once daily for 14 days after the completion of the 24-hour exposure period. Full details on the scoring and criteria (consistent with Draize) are given in the full study report. Individual bodyweights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
Statistics:
No statistical analyses were performed.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
- Clinical observations: No signs of systemic toxicity were noted during the observation period.
- Dermal reactions: An isolated incident of very slight erythema was noted at the test site of one female (maximum score = 1; in 1 female at day 1 only). No other signs of dermal irritation were noted.
Body weight:
All animals showed expected gains in body weight during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the dermal LD50 was established to exceed 2000 mg/kg bw in male/female Wistar rat. Under the conditions of this study and under the Globally Harmonized Classification System of Classification and Labelling of Chemicals (GHS), the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.
Executive summary:

The study was performed according to OECD TG 402 and EU Method B.3 Acute Toxicity (Dermal) and in accordance with GLP to assess the acute dermal toxicity of the test substance in the Wistar strain rat. A group of ten animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the undiluted test item to intact skin at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. There were no signs of system toxicity or abnormalities on necropsy. There was no mortality during the study. An isolated incident of very slight erythema was noted at the test site of one female. No other signs of dermal irritation were noted. Animals showed expected gains in bodyweight over the study period. Under the conditions of this study, the dermal LD50 was established to exceed 2000 mg/kg bw in male/female Wistar rat. Under the conditions of this study, and according to the GHS criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The available information as a whole meets the tonnage driven information requirements of REACH.

Additional information

ORAL:

Key study: OECD TG 420, 2016 : The study was performed according to OECD TG 420 and EU Method B.1 bis Acute Toxicity (Oral) and in accordance with GLP to assess the acute oral toxicity of the test material following a single oral administration in the female Wistar strain rat by the fixed dose method. The test substance was administered by oral gavage in an initial sighting study at 300 mg/kg. In the absence of significant toxicity the test substance was then administered by oral gavage in a further initial sighting at 2000 mg/kg. Subsequently a further group of four fasted females was given a single oral dose of test item, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study and gross necropsy performed. There was no mortality during the course of the study. No signs of systemic toxicity were noted in the remaining animals. Animals showed expected gains in bodyweight over the study period and there were no abnormalities noted at necropsy. Under the conditions of this study the oral LD50 was established to exceed 2000 mg/kg bw in the female Wistar rat. Under the conditions of this study, and according to the OECD TG 420 criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.

INHALATION:

Key study: OECD TG 403, 2018 : The study was performed according to OECD TG 403 and EU Method B.2 in accordance with GLP to assess the acute inhalation toxicity of the test item. Following a sighting test, one group of ten RccHanTM : WIST strain rats (five males and five females) were exposed to an aerosol atmosphere of the test item. The groups were exposed for four hours using a nose only exposure system, followed by a fourteen day observation period. The mean achieved atmosphere concentrations was Group 1: 5.14 mg/L. The characteristics of the achieved atmosphere where Mean Mass Median Diameter (particle size) and Inhalable Fraction <4 μm: Group 1: 3.48 μm and 83.6%. The Geometric Standard Deviation was 2.43. There was no mortalities in Group 1. Common abnormalities noted during the study included decreased respiratory rate, ataxia, lethargy, noisy respiration, hunched posture, pilo-erection, sneezing, wet fur and fur stained by clear sticky test item. All animals recovered to appear normal from Days 8 to 11 post-exposure. All animals exhibited body weight losses on the first day post-exposure. Except for three males and one female which exhibited body weight losses from Days 1 to 3 post-exposure, body weight gains were noted for all animals during the remainder of the recovery period. Dark and/or pale patches on the lungs and/or pale lungs were noted amongst eight animals at necropsy. No macroscopic abnormalities were detected in two males. Under the conditions of this study, the 4-hour inhalation LC50 (male/female) was greater than 5.14 mg/L within the RCCHan WIST rat.

DERMAL:

Key study: OECD TG 402, 2016 : The study was performed according to OECD TG 402 and EU Method B.3 Acute Toxicity (Dermal) and in accordance with GLP to assess the acute dermal toxicity of the test substance in the Wistar strain rat. A group of ten animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the undiluted test item to intact skin at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. There were no signs of system toxicity or abnormalities on necropsy. There was no mortality during the study. An isolated incident of very slight erythema was noted at the test site of one female. No other signs of dermal irritation were noted. Animals showed expected gains in bodyweight over the study period. Under the conditions of this study, the dermal LD50 was established to exceed 2000 mg/kg bw in male/female Wistar rat. Under the conditions of this study, and according to the GHS criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.

Justification for classification or non-classification

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for acute toxicity: oral.

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for acute toxicity: inhalation

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for acute toxicity: dermal

The substance meets classification criteria under Regulation (EC) No 1272/2008 for Specific Target Organ Toxicity: Single Exposure – Category 3 (narcotic effects): H336

Ataxia, and lethargy was observed in studies at Acute Inhalation: GHS Category 4 dose levels. All effects were transient in nature.