Registration Dossier

Administrative data

Description of key information

For all three routes, guideline studies are available resulting in a LD50 (oral) of 3200 mg/kg bw, a LD50 (dermal) of >2000 mg/kg bw and a 4h-LC50 of 175 mg/m3.

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:
September 9, 1981 - December 3, 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Conducted equivalent to OECD 401. The dosing volume is not according to this Guideline; no purity information provided; non-GLP.
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
; dosing volume: not constant at all dose levels and up to 25 mL/kg has been dosed (Guideline: max. 10 ml/kg)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
other: CD (Sprague-Dawley derived)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River U.K. Limited, Margate, Kent, England
- Age at study initiation: approximately 4 to 6 weeks of age
- Weight at study initiation: 95 to 130 g
- Fasting period before study: approximately 18 +/- 2 hours prior to dosing
- Housing: metal cages with wire mesh floors (randomly allocated per dose group)
- Diet (e.g. ad libitum): ad libitum (standard laboratory diet)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum period of 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.5 +/- 2.5 degrees Celsius
- Humidity (%): not controlled but remained within a range of 31-57%
- Air changes (per hr): approximately 15 per hr
- Photoperiod (hrs dark / hrs light): 12/12 hrs

IN-LIFE DATES: no data
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20% w/v
- Amount of vehicle (if gavage): varied, depending on the dose

MAXIMUM DOSE VOLUME APPLIED: 25 mL/kg bw
Doses:
Preliminary study: 0.5; 2.0; 5.0 and 8.0 g/kg bw
Main study: 0; 2.5; 3.2; 4.0; 5.0 g/kg bw
No. of animals per sex per dose:
Preliminary study: 2 males + 2 females per dose
Main study: 5 males + 5 females per dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Day 1: Animals were observed soon after dosing; then at frequent intervals for the remainder of Day 1.
Day 2-14: On subsequent days the animals were observed at least once. Clinical signs were recorded at each observation.
During the observation period the following were recorded:
-Approximate time of death
-The nature, severity, approximate time of onset and duration of each toxic sign
-Individual bodyweights on days: 1, 8 and 15
- Necropsy of survivors performed: yes
Statistics:
The acute oral median LD50 to rats was calculated using the method of Finney (1971) Probit Analysis (3rd edition) Cambridge University Press
Preliminary study:
See the table mentioned under the section "Any other information on results inc. tables" for the results of the preliminary study.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 200 mg/kg bw
Based on:
test mat.
95% CL:
2 500 - 3 900
Mortality:
See the tables in the section "Any other information on results incl. tables"
Clinical signs:
See the table in the section "Any other information on results incl. tables"
Body weight:
See the tables in the section "Any other information on results incl. tables". Depressed bodyweight gains were recorded in all surviving treated rats during the first week of observation only, compared to the control.
Gross pathology:
Autopsy of died rats revealed congestion or haemorrhage of the lungs, pallor of the liver, spleen and kidneys and in rats dying overnight, an apparent brittleness of the stomage. These findings were accompanied by congestion of the blood vessels of the stomach in one male and two females at 3.2 g/kg; one male at 4.0 g/kg and two males and one female at 5.0 g/kg. Gaseous contents of the stomach were observed in one male and one female at 3.2 g/kg, one male at 4.0 g/kg and one male and one female at 5.0 g/kg.
Survivors showed no abnormalities.

Results of the preliminary study:

Dosage (g/kg)

Mortality ratio

Time of death after dosing (hours)

Male

Female

Combined

0.5

1 / 2

0 / 2

1 / 4

<4 days

2.0

0 / 2

0 / 2

0 / 4

-

5.0

2 / 2

2 / 2

4 / 4

<22 - <70

8.0

2 / 2

2 / 2

4 / 4

<4 - <22

Results of the main study:

Sex

Dosage (g/kg)

Average bodyweight (g) at:

Mortality ratio

Time of death after dosing (hours)

Dosing

1 week

2 weeks

Male

0

112

193

255

0 / 5

-

2.5

117

181

247

2 / 5

<70

3.2

122

181

248

2 / 5

<22 - <46

4.0

122

157

215

3 / 5

<22 - <46

5.0

125

171

235

4 / 5

<22 - <70

Female

0

104

166

194

0 / 5

-

2.5

107

154

186

1 / 5

<46

3.2

103

146

184

2 / 5

<22 - <27

4.0

106

138

175

4 / 5

<22 - <70

5.0

105

-

-

5 / 5

<22 - <46

Recovery of the survivors, as judged by external appearance and behaviour, was apparently complete by Day 10. Clinical signs:

Signs

Signs of reaction ratio

Dosage (g/kg)

0

2.5

3.2

4.0

5.0

Pilo-erection

10 / 10

10 / 10

10 / 10

10 / 10

10 / 10

Abnormal body carriage (hunched posture)

0 / 10

10 / 10

10 / 10

10 / 10

10 / 10

Abnormal gait (waddling)

0 / 10

10 / 10

10 / 10

10 / 10

10 / 10

Lethargy

0 / 10

10 / 10

10 / 10

10 / 10

10 / 10

Decreased respiratory rate

0 / 10

10 / 10

10 / 10

10 / 10

10 / 10

Diarrhoea

7 / 10

10 / 10

10 / 10

10 / 10

10 / 10

Pallor of extremities

0 / 10

10 / 10

10 / 10

10 / 10

10 / 10

Ptosis

0 / 10

6 / 10

9 / 10

10 / 10

10 / 10

Diuresis

0 / 10

2 / 10

2 / 10

2 / 10

0 / 10

Increased salivation

0 / 10

5 / 10

6 / 10

10 / 10

10 / 10

Gasping respiration

0 / 10

2 / 10

1 / 10

1 / 10

2 / 10

Râles

0 / 10

5 / 10

2 / 10

6 / 10

5 / 10

Abnormal gait (walking on toes)

0 / 10

0 / 10

0 / 10

2 / 10

1 / 10

Increased lacrimation

0 / 10

3 / 10

6 / 10

7 / 10

5 / 10

Bloodstained muzzle

0 / 10

2 / 10

2 / 10

4 / 10

3 / 10

Body tremors

0 / 10

0 / 10

4 / 10

2 / 10

4 / 10

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a study conducted similar to OECD 401, the LD50 oral in rats was shown to be 3200 mg/kg (95% confidence limits: 2500 to 3900 mg/kg).
Executive summary:

The acute oral toxicity in rats has been studied similar to OECD 401. The only deviation from the OECD Guideline were the used dosing volumes, which were not constant at all dose levels and up to 25 mL/kg (Guideline: max. 10 ml/kg). The substance was dosed in corn oil at 0, 2.5, 3.2, 4.0 and 5.0 g/kg bw in 5 male and 5 female rats (doses based on the results from the preliminary study). Signs of reaction to treatment observed shortly after dosing in all treated rats included pilo-erection, an abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, decreased respiratory rate, pallor of the extremities and diarrhoea. Mortalities occurred amongst rats treated at 2.5 g/kg and above from within 22 hours to 70 hours of dosing. Autopsy of died rats revealed congestion or haemorrhage of the lungs, pallor of the liver, spleen and kidneys and in rats dying overnight, an apparent brittleness of the stomage.

Terminal autopsy findings were within normal limits. Depressed bodyweight gains were recorded in all surviving treated rats during the first week of observation only, compared to the control. The acute oral toxicity was determined to be 3200 mg/kg (95% confidence limits: 2500 to 3900 mg/kg). Based on this result, the substance does not need to be classified for acute toxicity by the oral route.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
3 200 mg/kg bw
Quality of whole database:
The study has Klimisch score 2

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:
January 30 - February 28, 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD guideline and according to GLP principles. Purity not given.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
other: CD albino (A Caesarean derived strain of Sprague-Dawley)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK, Manston Road, Margate, Kent
- Age at study initiation: no data
- Weight at study initiation: 194-274 g
- Fasting period before study: no data
- Housing: 5 rats per cage, cages were made of polypropylene and had detachable wire mesh tops and floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-25
- Humidity (%): 39
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: none
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The whole body exposure chambers were of square section and were fitted with pyramidal tops. The chambers were made of Perspex. Each chamber was divided by wire mesh partitions to provide 10 separate animal compartments.
- Exposure chamber volume: approximately 0.13 m3
- Method of holding animals in test chamber: the rats were placed into separate animal compartments of the exposure chamber
- Airflow: 30 litres per minute
- System of generating particulates/aerosols: The aerosol generator was designed to produce and maintain an atmosphere containing a high proportion (>85%) of respirable droplets. All parts of the generator were made of stainless steel. The test substance was supplied to the generatot from a syringe driven at a constant rate by a syringe pump.
- Method of particle size determination: May multistage liquid impinger with 0.04M dibenzylamine solution as the trapping agent. The air sample was taken at a flow rate of 10 litres per minute and the collection characteristics of the May impinger at this flow rate were as follows:
Stage 1 - particles greater than 5.5 µm mean aerodynamic diameter (a.d.)
Stage 2 - particles between 5.5 and 2.0 µm mean a.d.
Stage 3 - particles less than 2.0 µm mean a.d.
- Temperature, humidity, pressure in air chamber: The temperature was recorded at 30 minute intervals during the exposure.

TEST ATMOSPHERE
- Sampling: 5 samples/exposure into a gas absorption trap.
- Analysis of samples: HPLC-UV (216 nm)
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:
yes
Remarks:
(see section "details on inhalation exposure")
Duration of exposure:
4 h
Remarks on duration:
continuous whole body exposure
Concentrations:
Atmosphere concentrations of TAKENATE 500: 58.3, 198.8, 224.7 and 358.0 mg/m^3 of chamber air.
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 rats were observed continuously during exposure and at least twice daily during the observation period. All rats were weighed daily.
- Necropsy of survivors performed: yes
- Other examinations performed: food and water consumption, lung weight.
Statistics:
The LC50 was calculated by the log probit method of Miller and Tainter.
Sex:
male
Dose descriptor:
LC50
Effect level:
175 mg/m³ air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: whole body exposure
Sex:
female
Dose descriptor:
LC50
Effect level:
187 mg/m³ air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Finney, 1971, Probit method; whole body exposure
Mortality:
control: 0/10
58.3 mg/m^3: 0/10
198.8 mg/m^3: 2/10
224.7 mg/m^3: 9/10 (includes 2 rats killed for humane reasons. Deaths due to exposure taken as 8/10 instead of 7/10, because an animal had the same symptoms as spontaneously dying animals)
358.0 mg/m^3: 10/10
Clinical signs:
Signs that the aerosol of TAKENATE 500 was irritant to the mucous membranes and respiratory system were evident in all groups during exposure. The severity of the reactions and the rapidity of onset were related to the exposure level.
During the observation period rales, (sounds of varied character heard on ausculation of the chest), laboured breathing and sneezing were observed for up to 14 days following exposure. Brown staining and red-brown to black encrustation around the eyes and on the snout were observed for up to 11 days.
The appearance and behaviour of rats in the control was normal during the exposure and during the observation period.
Body weight:
A moderate or marked decrease in bodyweight was observed at 58.3 and 198.8 mg/m^3, respectively, over a period of 3-6 days after exposure.
224.7 and 358.0 mg/m^3: Progressive decrease in bodyweight prior to death with the exception of the surviving rat in 224.7 mg/m^3. This rat gained weight from day 9 of the observation period.
Gross pathology:
No macroscopic abnormalities at control and 58.3 mg/m^3.
Abnormalities seen in rats that died as a result of exposure were oedema, congestion and hepatisation of the lungs and distended gas filled stomachs and intestines. Abnormalities in surviving rats were limited to small areas of consolidation sub-pleural and dark red foci in the lung.
The adrenals of one rat at 224.7 mg/m^3 were pale and enlarged and those of two other rats at this dose level were enlarged.
Other findings:
- Food and water consumption: Food and water consumption was reduced to approximately 40-50% of normal at 58.3 mg/m^3 for 3-4 days following exposure and, subsequently, food and water consumption was normal. Little or no food was consumed at 198.8 mg/m^3 for 5 days following exposure and water consumption was reduced to approximately 30% of normal. Normal food and water consumption was resumed over the next 4-5 days.
The rats that died as a result of exposure to higher concentrations of TAKENATE 500 consumed little or no food and water prior to death. Normal food and water consumption was observed for the surviving rat at 224.7 mg/m^3 from day 12 of the observation period. Food and water consumption was normal for the control.

- Lung weight to bodyweight ratio: The lung weight to bodyweight ratio was within normal limts for surviving rats and for the rats killed during the observation period. High values (>1) were found for rats dying during or within 2-3 days of exposure. The high value for one rat at 224.7 mg/m^3 is due to decreased bodyweight rather than increased lung weight.

The mean percentage by weight of respirable particles (aerodynamic diameter <5.5 µm) was 88.5% (S.D. 0.95%)

Interpretation of results:
other: Acute toxicity Category 2 (Fatal if inhaled)
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
In an acute inhalation study in rats, conducted in accordance with OECD 403 and GLP, a 4h-LC50 of 0.17 mg/L (males) and 0.19 mg/L (females) was determined.
Executive summary:

In an acute inhalation study in rats, conducted in accordance with OECD 403 and GLP, a 4h-LC50 of 0.17 mg/L was determined. The rats (5 males and 5 females per dose) were exposed by whole body. The mean achieved doses were 58.3, 198.8, 224.7 and 358.0 mg/m^3 of chamber air. Two of the 10 animals in the 198.8 mg/m^3 group, nine of the 10 animals in the 224.7 mg/m^3 group (includes 2 rats killed for humane reasons) and all animals of the highest dose group died during exposure. The rats in the other dose group survived. Exposure to TAKENATE 500 in an aerosol form produced irritant effects to the mucous membranes, the skin and the respiratory system of the rat.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
175 mg/m³
Quality of whole database:
The study has Klimisch score 2

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:
June 25, 1992 - July 9, 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in accordance with OECD 402 and GLP. There is 1 deviation: during the 14 days observation period, the animals were not caged individually but by sex. But it is assumed that this deviation does not significantly influence the reliability of the study. Batch number and purity not given.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
; during the 14 days observation period, the animals were not caged individually but by sex
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Manston, Kent, UK
- Age at study initiation: approximately 10 to 14 weeks old
- Weight at study initiation:
Males: 244 - 265 g
Females: 202 - 243 g
- Fasting period before study: not applicable
- Housing:
The animals were housed in suspended polypropylene cages furnished with softwood sawdust. The animals were housed individually during the 24-hour exposure period and in groups of 5, by sex, for the remainder of the study
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum period of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23 °C
- Humidity (%): 47 - 75% (on 2 occasions >70%)
- Air changes (per hr): 15 per hr
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: an area equivalent to 10% of the total body surface ( 5 cm x 4 cm)
- Type of wrap if used: surgical gauze semi-occluded with a piece of self-adhesive bandage (HYPERTIE), the bandage was further secured with a piece of BLENDERM wrapped around each end

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual material was removed by wiping with cotton wool moistened with arachis oil
- Time after start of exposure: 24 hr

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw = 1.69 mL/kg bw
- Concentration (if solution): undiluted

VEHICLE
Not applicable
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Deaths and overt signs of toxicity were recorded 0.5; 1; 2 and 4 hours after dosing and subsequently once daily for 14 days
Individual bodyweights were recorded prior to treatment on day 0 and on days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: dermal reactions were also recorded
Statistics:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths
Clinical signs:
- No signs of systemic toxicity were noted
- Adverse skin reactions were noted at the treatment site of all animals from day 5 onwards
These reactions included:
*well-defined erythema and oedema
*light brown discolouration
*small superficial scattered scabs
*keratolysis (glossy skin)
*dried blood
*crust formation
*scabbing lifting to reveal glossy skin hardened dark brown scab and desquamation
Body weight:
One female showed a slight loss in bodyweight during the 1st week. All other animals showed gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal toxicity study conducted in accordance with OECD 402 and GLP (limit test), a LD50 of >2000 mg/kg bw was found. No deaths occurred.
Executive summary:

In an acute dermal toxicity study, conducted in accordance with OECD 402 and GLP (limit test), 5 female and 5 male rats were semi-occlusively exposed for 24 hours to the undiluted test substance at a dose of 2000 mg/kg bw. No apparent systemic toxicity was seen and no deaths occurred. Dermal reactions were noted, starting from day 5 onwards. The conducted gross pathology did not detect any abnormalities.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
The study has Klimisch score 2

Additional information

In the acute oral toxicity performed according to OECD 401, rats were given a single dose of 0, 2.5, 3.2, 4.0 or 5.0 g/kg bw test substance by gavage. Signs of reaction to treatment observed shortly after dosing in all treated rats included pilo-erection, hunched posture, abnormal gait, lethargy, decreased respiratory rate, pallor of extremities and diarrhoea. Mortalities occurred among rats treated at 2.5 g/kg bw and above resulting in an LD50 of 3200 mg/kg bw. Autopsy of died rats revealed congestion or haemorrhage of the lungs, pallor of the liver, spleen and kidneys and in rats dying overnight, an apparent brittleness of the stomach. Terminal autopsy findings were within normal limits.

Two guideline acute dermal studies in rats were available. One study resulted in an LD50 of >5000 mg/kg bw. In the other study, rats exposed to 2000 mg/kg bw of undiluted test substance for 24 hours semi-occlusive showed no clinical signs and no deaths occurred. No gross abnormalities were noted. The LD50 was established to exceed 2000 mg/kg bw.

Two guideline acute inhalation studies in rats were available (one nose-only and one whole body). The nose-only study resulted in an LC50 of 350 mg/m3.

The whole-body study resulted in the lowest LC50 of 175 mg/m3 after dosing of 58.3, 198.8, 224.7 and 358.0 mg/m3 of test substance. Mortality occurred at 198.8 mg/m3 and higher. Effects observed were irritant effects to mucous membranes, the skin and the respiratory tract in all dose groups (from 58.3 mg/m3 onwards), the severity of the reactions and the rapidity of onset were related to the exposure level. During the observation period rales, laboured breathing and sneezing were observed for up to 14 days following exposure. Decrease in bodyweight was observed at all dose levels accompanied by a reduction in food and water consumption. No macroscopic abnormalities at control and 58.3 mg/m3. Abnormalities seen in rats that died as a result of exposure were oedema, congestion and hepatisation of the lungs and distended gas filled stomachs and intestines. Abnormalities in surviving rats were limited to small areas of consolidation sub-pleural and dark red foci in the lung. Lung weight to bodyweight ratio: The lung weight to bodyweight ratio was within normal limts for surviving rats and for the rats killed during the observation period. High values (>1) were found for rats dying during or within 2-3 days of exposure.


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

Justification for selection of acute toxicity – inhalation endpoint
The study with the lowest dose descriptor

Justification for selection of acute toxicity – dermal endpoint
The study with the lowest dose descriptor

Justification for classification or non-classification

Acute toxicity

Based on the results described above, the substance does not have to be classified for acute oral and dermal toxicity. However, the substance has to be classified with category 2, H330 "Fatal if inhaled", for acute inhalation according to Regulation EC 1272/2008.

Specific target organ toxicity - single exposure (STOT-SE)

In the acute inhalation study (whole body) next to respiratory irritation also acute inflammation (congestion and hepatisation at 198.8 mg/m3 and higher) of the lungs was seen. These effects are morphological changes that are potentially reversible but provide clear evidence of marked organ dysfunction as confirmed by rales and laboured breathing.  A similar effect cannot be excluded to occur in humans, and therefore, a STOT single exposure classification is appropriate. The effect level of 25.9 ppm (= 198.8 mg/m3) is below the concentration limit set for STOT SE Cat.1 (1.0 mg/L for aerosols, see Table 3.8.2) and thus classification with STOT SE Category 1 is warranted. This classification is not based on a possible effect on the nervous system, as there does not seem to be any indication that the substance has an effect on the nervous system.