Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Oral: Discriminating dose = 300 mg/kg bw, female rat, OECD 420, Rattray 2004

Dermal: LD50 > 2000 mg/kg bw, male/female rat, OECD 402, Rattray 2004

Inhalation: LC50 >5.16 mg/L, male/female rat, OECD 403, Durando 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:
30 July 2003 to 27 August 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
other: Alpk:APfSD (Wistar-derived)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8-12 weeks old
- Weight at study initiation: 186-245 g
- Fasting period before study: Rats were fasted overnight prior to dosing
- Housing: 5 per cage
- Diet: ad libitum
- Water: Mains water ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 15 per hour minimum
- Photoperiod (hrs dark / hrs light): 12 hours light (artificial), 12 hours dark

IN-LIFE DATES: From: 30 July 2003 To: 27 August 2003
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5 % w/v (aqueous)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Doses were prepared by adjusting the concentration of the test material in the dosing preparations
- Amount of vehicle (if gavage): Each dose volume was calculated for animals individually based on its weight at the time of dosing.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bodyweight was administered as a standard dose volume
Doses:
Sighting study: 300 or 2000 mg/kg bodyweight
Main test: 300 or 2000 mg/kg bodyweight
No. of animals per sex per dose:
Sighting study: one initially
Main test: A further four animals were tested from both dosing groups
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All rats were examined for physical and behavioural abnormalities prior to dosing. Post dosing, animals were examined for systemic toxicity twice on day 1 and daily up to day 15 thereafter. All animals were weighed prior to fasting, immediately before dosing and on days 8 and 15.
- Necropsy of survivors performed: Animals were sacrificed by halothane vapour overdose followed by exsanguination. All animals were subject to a macroscopic examination of the thoracic and abdominal viscera. All abnormalities were recorded but tissues were not submitted for histopathological examination.
Sex:
female
Dose descriptor:
discriminating dose
Effect level:
300 mg/kg bw
Based on:
test mat.
Mortality:
Following a single oral dose of 300 mg/kg, none of the animals died. Signs of slight systemic toxicity were seen in all animals, with complete recovery by day 2. Following a single oral dose of 2000 mg/kg four of the animals showed signs of toxicity including (in two animals) convulsions and were killed in extremis on day 1.
Clinical signs:
In the 300 mg/kg dose group, signs of slight systemic toxicity were seen in all animals, with complete recovery by day 2. Following a single oral dose of 2000 mg/kg four of the animals showed signs of toxicity including (in two animals) convulsions and were killed in extremis. The surviving animal in this group was fully recovered by day 2.
Body weight:
All animals initially lost weight due to the pre-dose fast but all surviving animals showed an overall bodyweight gain during the study.
Gross pathology:
One animal dosed with 300 mg/kg was found to have a speckled thymus at post mortem. This was a spontaneous finding and was not considered to be related to treatment. One of the animals killed in extremis after dosing with 2000 mg/kg had red staining around the nose and mouth. This was a non-specifiec finding related to treatment.

Table 1: Bodyweights of female rats dosed with 300 or 2000 mg/kg of test material

Dose

Animal no.

Day

Pre-dosing

(day -1)

Dosing

(day 1)

day 2

day 8

Terminal

(day 15)

300 mg/kg

49

206

184

Not performed

231

246

4

190

168

Not performed

243

264

5

192

168

Not performed

230

242

6

192

173

Not performed

225

233

7

186

170

Not performed

234

239

2000 mg/kg

63

245

218

227

282

311

72

199

181

-

-

-

73

209

191

-

-

-

74

243

194

-

-

-

75

202

188

-

-

-

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Classification derived using the criteria reported in Annex II of the OECD Guideline 420. Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the highest fixed dose of the test material administered in this study without causing any lethality (i.e. the discriminating dose-level) was 300 mg/kg to female rats. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.
Executive summary:

The acute oral toxicity of the test material was determined in accordance with the standardised guideline OECD 420 using the fixed dose procedure. Single female rats initially received one oral dose of 300 or 2000 mg/kg of the test material and were assessed daily for the following 14 days for any signs of systemic toxicity. From the results of the initial phase, fixed dose levels of 300 and 2000 mg/kg were selected for the main phase study. In the main phase, groups of four female rats were dosed and assessed for signs of toxicity for 14 days following dosing. Bodyweights were recorded at intervals during the study. Animals in extremis and those surviving to the end of the study were killed and, together with those found dead, were examined post mortem. The initial females were included in the main phase of the study, to give a total of five animals per group.

None of the animals in the 300 mg/kg group died. Signs of slight systemic toxicity were seen in all animals, all of which had fully recovered by day 2. All animals showed an overall bodyweight gain during the study. There were no treatment related abnormalities post mortem. Following a single oral dose of 2000 mg/kg, four of the animals showed signs of severe toxicity including (in two animals) convulsions and were killed in extremis on day 1. The surviving animal showed signs of toxicity following dosing but had recovered by day 2 and showed an overall body weight gain during the study. At examination post mortem one of the animals killed in extremis had red staining around the nose and mouth.

The highest fixed dose of the test material administered in the study without causing any lethality (i.e. the discriminating dose-level) was 300 mg/kg to female rats.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
300 mg/kg bw
Quality of whole database:
The study presented to assess the acute toxicity of the test substance was performed in line with GLP and accepted standardised guidelines with a high standard of reporting. The study was assigned a reliability score of 1 in accordance with the criteria for assessing data quality as outlined in Klimisch (1997) and considered suitable for assessment as an accurate reflection of the test substance.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Remarks:
The acute inhalation toxicity study was conducted solely to comply with a non-EU national registration requirement, and has been provided here in accordance with REACH, Article 22(1)e.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 December 2015 to 30 December 2015
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:
1997
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Version / remarks:
1989
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF 12-Nousan-8147
Version / remarks:
1999
Deviations:
no
GLP compliance:
yes
Test type:
traditional method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: SAGE® Labs
- Age at study initiation: 10-11 weeks old
- Weight at study initiation: 333-386 g (males), 218-250 g (females)
- Fasting period before study: No
- Housing: Singly housed in suspended stainless steel caging which conforms to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals.
- Diet (e.g. ad libitum): Envigo Teklad Global 16% Protein Rodent Diet® #2016 ad libitum
- Water (e.g. ad libitum): Municipal water ad libitum
- Acclimation period: 22 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 43-58
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 h cycle

IN-LIFE DATES: From: 08 December 2015 To: 30 December 2015
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
2.15 µm
Geometric standard deviation (GSD):
2.22
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose-only inhalation chamber, the base unit terminates the chamber with a 0.5-inch diameter tube for discharged air.
- Exposure chamber volume: 6.7 L
- Method of holding animals in test chamber: Animals were individually housed in polycarbonate holding tubes which seal to the chamber with an "O" ring during exposure.
- Source and rate of air: Air compressor, 36.0 Lpm
- Method of conditioning air: Filtered generator air was supplied to the spray atomization nozzle by an air compressor, and measured with a Mass Flow Controller. Additional filtered mixing air from the same air compressor, measured with a Mass Flow Controller, was introduced into the chamber to help uniformly distribute the test atmosphere by creating a vortex at the chamber inlet. Chamber airflow was monitored throughout the exposure period and recorded periodically. The exposure was conducted under slight negative pressure.
- System of generating particulates/aerosols: The test substance was aerosolized using a modified Wright Dust Generator. The test substance was packed into the dust container and compressed 1000 lbs/in^2 using a lab press. The container was then fitted with a cutting head. Compressed generator and mixing air were supplied to the dust generator. The aerosolized dust was then fed directly into the chamber through the dust outlet assembly.
- Method of particle size determination: An eight-stage 1 ACFM Andersen Ambient Particle Sizing Sampler. Samples were withdrawn from the breathing zone of the animals at two intervals. The filter paper collection stages were weighed before and after sampling to determine the mass collected upon each stage. The mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) were determined graphically using two-cycle logarithmic probit axes.
- Temperature, humidity, pressure in air chamber: 20-21°C, 35-39%
- Compressed generator / mixing air: 30/30 psi
- T90/T99: 0.43 min / 0.86 min


TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric samples were withdrawn at 6 intervals from the breathing zone of the animals. Samples were collected using 37 mm glass fiber filters (Whatman™ GF/B) in a filter holder attached by ¼ inch Tygon® tubing to a vacuum pump. Filter papers were weighed before and after collection to determine the mass collected. This value was divided by the total volume of air sampled to determine the chamber concentration. Sample airflows were measured using a Mass Flow Controller.
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
>= 4 h
Concentrations:
5.16 mg/L
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:Observed for mortality during the exposure period. Examined for signs of gross toxicity, and behavioral changes upon removal from the exposure tube and at least once daily thereafter for 14 days. Individual body weights of the animals were recorded prior to test substance exposure (initial) and again on Days 1, 3, 7, and 14 (terminal).
- Necropsy of survivors performed: yes
Statistics:
Not applicable (limit test, no mortalities).
Preliminary study:
Prior to initiation of the full inhalation study, pre-test trials were conducted to establish generation procedures to achieve, to the extent possible, the desired chamber concentration (5.0 mg/L) and desired particle size distribution (mass median aerodynamic diameter between 1 and 4 μm). The procedures and aerosolization equipment used in the full test were based on the results of pre-test trial number 3 which provided a gravimetric chamber concentration of 5.20 mg/L and a mass median aerodynamic diameter of 2.25 μm.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.16 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
All animals survived.
Clinical signs:
other: Following exposure all rats exhibited irregular respiration. In addition, one male was hypoactive. All animals recovered by Day 1 and appeared active and healthy for the remainder of the 14-day observation period.
Body weight:
All animals gained body weight during the study.
Gross pathology:
No gross abnormalities were noted.

Table 1: Summary of acute study test atmosphere characteristics of CA3250

Test atmosphere characteristics

Parameter

Target concentration (mg/L)

 

5.0

Gravimetric concentration

5.16±0.11 mg/L (n=6)

Nominal concentration

9.49 mg/L

Particle size MMAD; GSD

 2.12, 2.17 µm; 2.19, 2.25

 

(at 1.5 and 3 hours into exposure respectively)

Particle size distribution

% total particles captured (by weight)

Size range (µm)

Run 1 (1.5 hours into exposure)

Run 2 (3 hours into exposure)

Particles<9.0 µm (% w/w)

2.4

3.2

Particles < 5.8 µm (% w/w)

5.4

5.6

Particles< 4.7µm (% w/w)

6.5

7.2

Particles<3.3 µm (% w/w)

19.0

18.9

Particles < 2.1 µm (% w/w)

26.6

27.5

Particles< 1.1µm (% w/w)

25.1

21.1

Particles<0.7 µm (% w/w)

8.4

7.8

Particles < 0.4 µm (% w/w)

3.5

5.0

Particles < 0 µm (% w/w)

3.2

3.6

Average total air flow

36.0 L/min

Air changes / hour

322

Temperature (exposure chamber)

20-21°C

Humidity (exposure chamber)

35-39%

T99

0.86 m

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the single exposure acute inhalation LC50 of the test substance is greater than 5.16 mg/L in male and female rats.
Executive summary:

An acute inhalation toxicity test was conducted with rats to determine the potential of the test substance to produce toxicity from a single exposure via the inhalation (nose-only exposure) route.

After establishing the desired generation procedures during the pre-test trials, ten healthy rats (5/sex) were exposed to the test atmosphere for 4 hours. Chamber concentration and particle size distributions of the test atmosphere were determined periodically during the exposure period. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for up to 14 days following exposure. Body weights were recorded prior to exposure (initial) and again on Days 1, 3, 7, and 14 (terminal). Necropsies were performed on all animals at terminal sacrifice.

The gravimetric chamber concentration was 5.16 mg/L. The average mass median aerodynamic diameter was estimated to be 2.15 µm based on graphic analysis of the particle size distribution as measured with a 1 ACFM Andersen Ambient Particle Sizing Sampler with an average geometric standard deviation of 2.22.

All animals survived exposure to the test atmosphere and gained body weight during the study. Following exposure, all rats exhibited irregular respiration. In addition, one male was hypoactive. However, all animals recovered by Day 1 and appeared active and healthy for the remainder of the 14-day observation period. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Therefore, under the conditions of this study, the single exposure acute inhalation LC50 of the test substance is greater than 5.16 mg/L in male and female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The study presented to assess the acute toxicity of the test substance was performed in line with GLP and accepted standardised guidelines with a high standard of reporting. The study was assigned a reliability score of 1 in accordance with the criteria for assessing data quality as outlined in Klimisch (1997) and considered suitable for assessment as an accurate reflection of the test substance.

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:
10 September 2003 to 07 October 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed to GLP and in line with the standardised guideline OECD 402, EU Method B.3 and EPA OPPTS 870.1200 with no deviations thought to impact the reliability of the presented results.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Alpk:APfSD (Wistar-derived)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8-12 weeks old
- Weight at study initiation: 255-276 g males, 190-207 g females
- Housing: Individually
- Diet: ad libitum
- Water: ad libitum, mains water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 15 changes minimum
- Photoperiod (hrs dark / hrs light): 12 hours light (artificial), 12 hours dark

IN-LIFE DATES: From: 10 September 2003 To: 7 October 2003
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorso-lumbar region of each animal (7 cm x 7 cm area was clipped free of hair with veterinary clippers to allow administration of the test material).
- Type of wrap if used: The test substance was applied to the shorn back of each animal and was kept in contact with the skin for approximately 24 hours using an occlusive dressing wrapped around the trunk. Each dressing consisted of a foil backed gauze patch to cover the treated area and was held in place by a cohesive bandage secured with two pieces of surgical tape.

REMOVAL OF TEST SUBSTANCE
- Washing: The dressings were carefully cut using blunt tipped scissors, removed and discarded. The skin at the site of application was cleansed of any residual test material using clean swabs of absorbent cotton wool soaked in clean warm water and then dried gently with clean tissue paper.
- Time after start of exposure: At the end of the 24 hour contact period.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The amount of test material applied was calculated for each animal according to its weight at the time of dosing.
- For solids, paste formed: The test material was moistened to a dry paste with a small amount (1 mL) of water.
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 males and 5 females per group
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Prior to the start of the study, all rats were examined for any physical or behavioural abnormalities. The animals were observed twice following application on day 1 (only gross abnormalities were noted at this time as the presence of the dressings may have affected the behaviour and movement of the rats). Subsequent observations for signs of systemic toxicity and skin irritation were made once daily up to day 15. The animals were weighed immediately before dosing (day 1) and on days 8 and 15 (termination).
- Necropsy of survivors performed: All animals were killed by an overdose of halothane vapour followed by exsanguination. All animals were examined post mortem. An external observation was performed and a detailed examination of all thoracic and abdominal viscera. All abnormalities were recorded but tissues were not submitted for histopathological examination.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None of the animals died during the course of the study. None of the animals exhibited signs of systemic toxicity.
Clinical signs:
All the animals were stained yellow by the test substance for up to 5 days. Signs of slight skin irritation were seen in all animals but had completely resolved by day 14.
Body weight:
All animals gained weight during the study.
Gross pathology:
There were no macroscopic abnormalities at examination post mortem.

Table 1: Body weights

Sex

Animal no.

Day

Day of dosing (Day 1)

Day 8

Terminal (Day 15)

Male

1

276

313

357

2

263

309

379

3

255

304

366

4

274

324

392

5

261

307

371

Mean

265.8

311.4

373

S.D.

8.9

7.8

13.3

Female

6

203

227

264

7

190

195

218

8

197

215

242

9

207

222

227

10

195

206

222

Mean

198.4

213.0

234.6

S.D.

6.7

12.8

18.8

Table 2: Irritation observations

Sex

Animal no.

Observation

Day

2

3

4

5

6

7

8

9

10

11

12

13

Male

1

Desquamation

S

S

S

S

S

S

S

Erythema

S

S

S

Oedema

S

Scabs: small scattered

P

P

P

P

P

P

P

2

Desquamation

S

S

S

S

S

S

S

Erythema

S

Scabs: small scattered

P

P

P

P

P

P

P

3

Desquamation

S

S

S

S

S

Oedema

S

Scabs: small scattered

P

Scab: edge of application area

P

P

P

4

Desquamation

S

S

S

S

S

S

S

S

S

S

S

Oedema

S

Scabs: small scattered

P

P

P

P

P

P

P

P

P

P

5

Desquamation

S

S

Oedema

S

Scabs: small scattered

P

Scab: edge of application area

P

P

Female

6

Desquamation

S

S

S

S

S

S

S

S

Erythema

S

S

Oedema

S

Scabs: small scattered

P

P

P

P

P

P

P

P

7

Desquamation

S

S

Scab: edge of application area

P

P

P

P

P

P

8

Desquamation

S

S

S

S

S

S

S

Oedema

S

Scabs: small scattered

P

P

P

P

P

P

P

Scab: edge of application area

P

P

P

9

Desquamation

S

S

10

Oedema

S

Scab: edge of application area

P

P

P

P

P

P

P = Present

S = Slight

Interpretation of results:
not classified
Remarks:
Migrated information The test material failed to elicit any toxicological response in any animal during the course of the study. Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the acute dermal median lethal dose of the test material was estimated to be in excess of 2000 mg/kg to male and female rats. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.
Executive summary:

The acute dermal toxicity of the test material was determined in accordance with the standardised guidelines OECD 402, EU Method B.3 and EPA OPPTS 870.1200. Five male and female rats received a single dermal application of 2000 mg/kg of the test material and were assessed daily for the following 14 days for any signs of systemic toxicity. None of the animals died and there were no signs of systemic toxicity. Signs of slight irritation were seen in all animals but had completely resolved by day 14. All animals gained weight during the study. There were no macroscopic abnormalities at examination post mortem. The acute dermal median lethal dose of the test material was estimated to be in excess of 2000 mg/kg to both male and female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The study presented to assess the acute toxicity of the test substance was performed in line with GLP and accepted standardised guidelines with a high standard of reporting. The study was assigned a reliability score of 1 in accordance with the criteria for assessing data quality as outlined in Klimisch (1997) and considered suitable for assessment as an accurate reflection of the test substance.

Additional information

Oral

The acute oral toxicity of the test material was determined in accordance with the standardised guideline OECD 420 using the fixed dose procedure. Single female rats initially received one oral dose of 300 or 2000 mg/kg of the test material and were assessed daily for the following 14 days for any signs of systemic toxicity. From the results of the initial phase, fixed dose levels of 300 and 2000 mg/kg were selected for the main phase study. In the main phase, groups of four female rats were dosed and assessed for signs of toxicity for 14 days following dosing. Bodyweights were recorded at intervals during the study. Animals in extremis and those surviving to the end of the study were killed and, together with those found dead, were examined post mortem. The initial females were included in the main phase of the study, to give a total of five animals per group.

None of the animals in the 300 mg/kg group died. Signs of slight systemic toxicity were seen in all animals, all of which had fully recovered by day 2. All animals showed an overall bodyweight gain during the study. There were no treatment related abnormalities post mortem. Following a single oral dose of 2000 mg/kg, four of the animals showed signs of severe toxicity including (in two animals) convulsions and were killed in extremis on day 1. The surviving animal showed signs of toxicity following dosing but had recovered by day 2 and showed an overall body weight gain during the study. At examination post mortem one of the animals killed in extremis had red staining around the nose and mouth.

The highest fixed dose of the test material administered in the study without causing any lethality (i.e. the discriminating dose-level) was 300 mg/kg to female rats.

Dermal

The acute dermal toxicity of the test material was determined in accordance with the standardised guidelines OECD 402, EU Method B.3 and EPA OPPTS 870.1200. Five male and female rats received a single dermal application of 2000 mg/kg of the test material and were assessed daily for the following 14 days for any signs of systemic toxicity. None of the animals died and there were no signs of systemic toxicity. Signs of slight irritation were seen in all animals but had completely resolved by day 14. All animals gained weight during the study. There were no macroscopic abnormalities at examination post mortem. The acute dermal median lethal dose of the test material was estimated to be in excess of 2000 mg/kg to both male and female rats.

The available data is considered to be complete and the results determined, oral discriminating dose of 300 mg/kg and the dermal LD50 ≥ 2000 mg/kg, were taken forward for risk assessment.

Inhalation

An acute inhalation toxicity test was conducted with rats to determine the potential of the test substance to produce toxicity from a single exposure via the inhalation (nose-only exposure) route in accordance with OECD TG 403 and following GLP. Ten healthy rats (5/sex) were exposed to the test atmosphere for 4 hours. The gravimetric chamber concentration was 5.16 mg/L. The average mass median aerodynamic diameter was estimated to be 2.15 µm based on graphic analysis of the particle size distribution as measured with a 1 ACFM Andersen Ambient Particle Sizing Sampler with an average geometric standard deviation of 2.22. All animals survived exposure to the test atmosphere and gained body weight during the study. Following exposure, all rats exhibited irregular respiration. In addition, one male was hypoactive. However, all animals recovered by Day 1 and appeared active and healthy for the remainder of the 14-day observation period. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period. Therefore, under the conditions of this study, the single exposure acute inhalation LC50 of the test substance is greater than 5.16 mg/L in male and female rats.


Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for selection of acute toxicity - inhalation endpoint

Only one study available.

Justification for classification or non-classification

Oral

In accordance with the criteria for classification as defined in Annex III of the OECD Guideline 420, the test material meets the criteria for classification as Acute toxicity oral category 4: Harmful if swallowed (H302) of Regulation (EC) No. 1272/2008, Annex I, Part 3, 3.1.2.

Dermal

In accordance with criteria for classification as defined in Regulation (EC) No. 1272/2008, Annex I, Part 3, 3.1.2, the test material does not require classification for acute dermal toxicity as no signs of toxicity were noted during the course of the study.

Inhalation

In accordance with criteria for classification as defined in Regulation (EC) No. 1272/2008, Annex I, Part 3, 3.1.2, the test material does not require classification for acute inhalation toxicity as no signs of toxicity were noted during the course of the study.