2-[[(4-methoxyphenyl)methylhydrazono]methyl]-1,3,3-trimethyl-3H-indolium methyl sulphate

Endpoint summary

Description of key information

Two acute oral toxicity studies in rats are available, with a reported LD50 values of 841 mg/kg (Bonhard 1982) and 200-400 mg/kg (Ivens-Kohl 1989), respectively. Three acute inhalation toxicity studies in rats are available. Reported LC50 values are 0.29-0.47 mg/L (Pauluhn 1983) and 0.076 mg/L (Pauluhn 1993). The third study (Pauluhn 1994) was conducted with test item with very low dustability (below limit of detection). No mortality occurred based on a lack of exposure. Dermal toxicity was determined in rats exposed up to 2000 mg/kg bw (the study was conducted with a product containing 75% dye).

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:

1989-08-15 to 1989-11-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

; adopted 1987-02-24

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: young adults
- Weight at study initiation: males: 198 g; females: 176 g (females)
- Fasting period before study: 16 hours before and 4 hours after application
- Housing: 5 animals per macrolon cage type III
- Diet (e.g. ad libitum): pellets of Altromin R 1234, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50 +/- 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

RATIONALE FOR SELECTION OF DOSES:
The doses chosen in this experiment were based on preliminary data.

Doses:

100, 200, 300 and 400 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 clinical observations: at least twice a day (weekends once a day)
- Frequency of weighing: before application, after one week and after 14 days.
- Necropsy of survivors performed: yes, all animals

Statistics:

If a calculation of the mean (median) LD50 was possible, the calcuation was conducted after the method of "moving averages" by Spärman and Kärber.

Preliminary study:

N.A.

Sex:

male

Dose descriptor:

LD50

Effect level:

>= 300 - <= 400 mg/kg bw

Based on:

test mat.

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 200 - <= 300 mg/kg bw

Based on:

test mat.

Mortality:

All animals in the 400 mg/kg bw dose groups died within 2-4 hours after treatment. Four females and one male died in the 300 mg/kg bw dose group within 24 hours. For further details please see Table 1 in section "any other information on results incl. tables"

Clinical signs:

other: In the dose groups 200 to 400 mg/kg bw the following signs of toxicity were observed: poor general condition and prone position. Piloerection was noted in the dose groups 200 and 300 mg/kg bw for both sexes. Males of the dose group 200 mg/kg bw showed an

Gross pathology:

The intestines of animals died (dose groups 200-400 mg/kg bw) during the study were bloated. The liver of these animals were coloured black and the lungs were reddened. All animals of the dose groups 100-300 mg/kg bw examined at the end of the study were macroscopically unobtrusive.

Other findings:

N.A.

Table 1: Mortality
Dosis         (mg/kg bw)	Animals died	time of death	mortality (%)
males
100	0/5	-	0
200	0/5	-	0
300	1/5	4h	20
400	5/5	2-4h	100
females
100	0/5	-	0
200	1/5	4h	20
300	4/5	2h -1d	80
400	5/5	2h	100

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In conclusion, in an acute oral toxicity study, the LD50 was determined to be 300-400 mg/kg bw for male and 200-300 mg/kg bw for female Wistar rats.

Executive summary:

In an acute oral toxicity study (OECD 401), groups of young adult Wistar rats (5/sex) were given a single oral dose of the test item in water at doses of 100, 200, 300 and 400 mg/kg bw and were observed for14 days. The oral LD50 (males) was determined to be between 300-400 mg/kg bw and the LD50 (females) was determined to be between 200 -300 mg/kg bw. 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

200 mg/kg bw

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:

1992-06-25 to 1993-01-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: young adult rats (2-3 months)
- Weight at study initiation: 165 - 205 g
- Housing: individually in macrolon type II cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): ca. 50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose/head only

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical inhalation chamber, animals held in nose/head only restrainer
- Exposure chamber volume: 20 L
- Method of holding animals in test chamber: rat exposure restrainer
- Source and rate of air: clean dried compressed air, flow rate 15 L/min
- Method of conditioning air: by a downstream VIA-compressed air dryer
- System of generating particulates/aerosols: Wright-Dust_Feeder Type II (BGI Inc, Waltham, USA) and by an Exactomat 4200 (TSE, Bad Homburg, Germany)
- Method of particle size determination: by using a Berner-cascade-impactor
- Treatment of exhaust air: cleaning of the exhausted air by using cottonwool aerosol filter
- Temperature, humidity, pressure in air chamber: every 10 min by using a Leybold-Heraeus system; temperature: ca 23 °C, relative humidity (group 1 animals): 22% and relative humidity (group 2-6): < 5%.

TEST ATMOSPHERE
- Brief description of analytical method used:
At least three air samples were taken from the inhalation chamber during the exposure. The flow rate of the air was 4 L/min. To analyse the test substance concentration (mg/m³ air) Sartorius teflon filter were used located in the breathing zone of the animals. The filter were gravimetrical analysed. After this analysis the filter were eluted with acetone nitrile and the elution was further analysed by using a spectral photometer.

- Samples taken from breathing zone: yes

OTHER:
- In the test atmosphere only the dye (test item) was quantitatively present without the supporting substances sodium sulphate and further additives. This was based on separation of the dye and the supporting substances due to the smaller particle size of the dye in comparison to the coarse particle size of the supporting substances.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0, 9, 51, 75, 167 and 388 mg/m³

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 clinical observations: at the day of exposition several times, afterwards twice a day
- Frequency of weighing: before exposition, on day 3 and 7, afterwards once per week
- Necropsy of survivors performed: yes
- Other examinations performed:
rectal temperataur: immediately after exposure the rectal temperature was measured

Statistics:

For the graphical presentation the standard deviation was displayed in relationship to the air control value. Statistical significant changes (versus air control) were identified with * (p<0.05) and ** (p<0.01). The clinical findings were statistically evaluated with a Pairwise Fishers Test. Body weights were statistically evaluated by variance analysis (ANOVA).

Sex:

male/female

Dose descriptor:

LC50

Effect level:

76 mg/m³ air

Based on:

test mat.

95% CL:

55.7 - 106.2

Exp. duration:

4 h

Mortality:

All males and females of the two top concentration groups died. At the concentration of 75 mg/m³ air 2 females and 2 males died. At 51 mg/m³ air one animal of each sex died. In the lowest concentration group (9 mg/m³) no mortality occurred.

Clinical signs:

other: No adverse effects were noted in the 9 mg and 51 mg/m³ air concentration groups. The animals from the remaining groups showed the following signs of toxicity: abnormal breathing (respiratory sounds, dyspnoea), serous secretion from nostrils, loss of weigh

Body weight:

No effects seen in the lowest concentration group. At 51 mg/m³ and higher the body weight was transiently reduced in the first post-treatment days in comparison to the control group.

Gross pathology:

In all surviving animals no effects were noted after the 14 days observation period. Animals, which died during the observation period showed the following gross pathology symptoms: hepatization of the lung, lung oedema, hydrothorax, reddened nasal mucosa, yellowish, foamy trachea content, cornea opacity, test substance related skin coloration, liver with lobular structure, spleen, liver and kidney pale, reddened gastrointestinal tract, partially bloated.

Other findings:

Rectal temperature:
A toxicological relevant reduction of the rectal temperature (hypothermie) was seen at 51 mg/m³ and higher concentrations. Males showed already a mild hypothermie in the lowest concentration group.

Table 1: acute inhalation toxicity: Summary of results
Group	Concentration (mg/m³ air), (gravimetrical)		Toxicological results*		Duration of signs		Time of death	Respirability (%)
males
1	air control		0 / 0 / 5		-		-	-
2	9		0 / 0 / 5		-		-	83
3	51		1 / 5 / 5		4h - 3d		0d	47
4	75		2 / 5 / 5		4h - 7d		1d - 2d	47
5	167		5 / 5 / 5		0d		0d - 1d	77
6	388		5 / 5 / 5		< 4h		< 5h	33
females
1	air control		0 / 0 / 5		-		-	-
2	9		0 / 0 / 5		-		-	83
3	51		1 / 5 / 5		4h - 7d		4d	47
4	75		2 / 5 / 5		4h - 5d		1d	47
5	167		5 / 5 / 5		4h - 1d		4h - 2d	77
6	388		5 / 5 / 5		< 4h		< 4h	33

*= 1st number: number of dead animals, 2nd number: number of animals with clinical symptoms,

3rd number: number of animals

Table 2: Analysis of particle distributions, target concentration 8.5 mg/m³ air
N	Impactor stage (µm)		Cut-off diameter (µm)		Mass/stage (µm)	rel. Mass (%)	Cumul. Mass (%)
1	0.016 - 0.031		0.016		0.00	0.00	0.00
2	0.031-0.063		0.031		0.00	0.00	0.00
3	0.063-0.125		0.063		0.00	0.00	0.00
4	0.125-0.250		0.125		0.00	0.00	0.00
5	0.250-0.500		0.250		0.10	4.35	0.00
6	0.500-1.00		0.500		0.20	8.70	4.35
7	1.00-2.00		1.00		0.80	34.78	13.04
8	2.00-4.00		2.00		1.10	47.83	47.83
9	4.00-8.00		4.00		0.10	4.35	95.65
10	8.00-16.0		8.00		0.00	0.00	100
11	16.0-30.0		16.00		0.00	0.00	100

Mass Median Aerodynamic Diameter (MMAD): 1.69 µm

Geometric standard deviation: 1.83

Respirability (% < 3 µm):

a) mass related: 83 % (measured)

b) number related: 100 % (extrapolated)

Table 3: Analysis of particle distributions, target concentration 51.1 mg/m³ air
N	Impactor stage (µm)		Cut-off diameter (µm)		Mass/stage (µm)	rel. Mass (%)	Cumul. Mass (%)
1	0.016 - 0.031		0.016		0.00	0.00	0.00
2	0.031-0.063		0.031		0.00	0.00	0.00
3	0.063-0.125		0.063		0.00	0.00	0.00
4	0.125-0.250		0.125		0.00	0.00	0.00
5	0.250-0.500		0.250		0.00	0.00	0.00
6	0.500-1.00		0.500		0.30	6.67	0.00
7	1.00-2.00		1.00		0.70	15.56	6.67
8	2.00-4.00		2.00		2.20	48.89	22.22
9	4.00-8.00		4.00		0.90	20.00	71.11
10	8.00-16.0		8.00		0.20	4.44	91.11
11	16.0-30.0		16.00		0.20	4.44	95.56

Mass Median Aerodynamic Diameter (MMAD): 3.21 µm

Geometric standard deviation: 2.24

Respirability (% < 3 µm):

a) mass related: 47 % (measured)

b) number related: 100 % (extrapolated)

Table 4: Analysis of particle distributions, target concentration 75 mg/m³ air
N	Impactor stage (µm)		Cut-off diameter (µm)		Mass/stage (µm)	rel. Mass (%)	Cumul. Mass (%)
1	0.016 - 0.031		0.016		0.00	0.00	0.00
2	0.031-0.063		0.031		0.00	0.00	0.00
3	0.063-0.125		0.063		0.00	0.00	0.00
4	0.125-0.250		0.125		0.00	0.00	0.00
5	0.250-0.500		0.250		0.00	0.00	0.00
6	0.500-1.00		0.500		0.20	4.17	0.00
7	1.00-2.00		1.00		1.00	20.83	4.17
8	2.00-4.00		2.00		2.30	47.92	25.00
9	4.00-8.00		4.00		1.00	20.83	72.92
10	8.00-16.0		8.00		0.10	2.08	93.75
11	16.0-30.0		16.00		0.20	4.17	95.83

Mass Median Aerodynamic Diameter (MMAD): 3.20 µm

Geometric standard deviation: 2.12

Respirability (% < 3 µm):

a) mass related: 47 % (measured)

b) number related: 99 % (extrapolated)

Table 5: Analysis of particle distributions, target concentration 167 mg/m³ air
N	Impactor stage (µm)		Cut-off diameter (µm)		Mass/stage (µm)	rel. Mass (%)	Cumul. Mass (%)
1	0.016 - 0.031		0.016		0.00	0.00	0.00
2	0.031-0.063		0.031		0.00	0.00	0.00
3	0.063-0.125		0.063		0.00	0.00	0.00
4	0.125-0.250		0.125		0.00	0.00	0.00
5	0.250-0.500		0.250		0.10	2.63	0.00
6	0.500-1.00		0.500		0.20	5.26	2.63
7	1.00-2.00		1.00		0.90	23.68	7.89
8	2.00-4.00		2.00		2.40	63.16	31.58
9	4.00-8.00		4.00		0.20	5.26	94.74
10	8.00-16.0		8.00		0.00	0.00	100
11	16.0-30.0		16.00		0.00	0.00	100

Mass Median Aerodynamic Diameter (MMAD): 1.96 µm

Geometric standard deviation: 1.81

Respirability (% < 3 µm):

a) mass related: 77% (measured)

b) number related: 100 % (extrapolated)

Table 6: Analysis of particle distributions, target concentration 388 mg/m³ air
N	Impactor stage (µm)		Cut-off diameter (µm)		Mass/stage (µm)	rel. Mass (%)	Cumul. Mass (%)
1	0.016 - 0.031		0.016		0.00	0.00	0.00
2	0.031-0.063		0.031		0.00	0.00	0.00
3	0.063-0.125		0.063		0.00	0.00	0.00
4	0.125-0.250		0.125		0.00	0.00	0.00
5	0.250-0.500		0.250		0.00	0.00	0.00
6	0.500-1.00		0.500		0.10	2.13	0.00
7	1.00-2.00		1.00		0.50	10.64	2.13
8	2.00-4.00		2.00		2.20	46.81	12.77
9	4.00-8.00		4.00		1.40	29.79	59.57
10	8.00-16.0		8.00		0.10	2.13	89.36
11	16.0-30.0		16.00		0.40	8.51	91.49

Mass Median Aerodynamic Diameter (MMAD): 4.18 µm

Geometric standard deviation: 2.11

Respirability (% < 3 µm):

a) mass related: 33% (measured)

b) number related: 97 % (extrapolated)

Interpretation of results:

Toxicity Category II

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In conclusion, the LC50 of the test item can be estimated to be 76 mg/m³ air.

Executive summary:

In an acute inhalation toxicity study equivalent to OECD 403, groups of young adult male and female Wistar rats (5 per sex/concentration) were exposed by the inhalation route (nose/head only) to the test item for 4 hours at mean concentrations of 0, 9, 51, 75, 167 and 388 mg/m³ air. Animals then were observed for 14 days. Mortality and distinct clinical signs were observed after exposure to the test substance at 51 mg/m³ air and higher. No mortality and no signs of toxicity occured after inhalation to 9 mg/m³. Based on the results obtained, the LC50 for both sexes is 76 mg/m³ air.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

76 mg/m³ air

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:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards and is described in sufficient detail. Comparable to guideline study.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

: 3 instead of 5 animals per dose

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: WIGA, Sulzfeld, Germany
- Age at study initiation: no data
- Weight at study initiation: 233 g (males), 184 g (females)
- Housing: no data
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS: no data

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: 50 cm²
- Cover: inert plastic film

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with tempered water
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (50% concentration), 1000 mg/kg (50% concentration, 400 mg/kg (50% concentration), 200 mg/kg (25% concentration) and 100 mg/kg (25% concentration)

Duration of exposure:

24 hours

Doses:

2000, 1000 and 400 mg/kg bw (test item concentration: 50% in water); 200 and 100 mg/kg bw (test item concentration: 25% in water)

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Investigations: Mortality, clinical signs, local effects
- Necropsy performed: yes

Statistics:

N.A.

Preliminary study:

N.A.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 2 000 mg/kg bw

Based on:

test mat.

Mortality:

see table 1 in section "any other information on results incl. tables"

Clinical signs:

other: Systemic clinical signs: dyspnea, apathia, excitation, ataxia, spastic gait and poor general condition

Gross pathology:

Dead animals: heart: acute hyperemia; stomach organs, fat tissue/musculature: substance-related discoloration

Surviving animals: no effects

Other findings:

N.A.

Table 1: Mortality
Dose (mg/kg bw)	Concentration (%)	Animal number	found dead within
			1 hour	24 hours	48 hours	7 days	14 days
2000	50	3m	0/3	0/3	1/3	1/3	1/3
		3f	0/3	2/3	2/3	2/3	2/3
1000	50	3m	0/3	0/3	1/3	0/3	0/3
		3f	0/3	1/3	1/3	1/3	1/3
400	50	3m	0/3	0/3	0/3	0/3	0/3
		3f	0/3	0/3	0/3	0/3	0/3
200	25	3m	0/3	0/3	0/3	0/3	0/3
		3f	0/3	1/3	1/3	1/3	1/3
100	25	3m	0/3	0/3	0/3	0/3	0/3
		3f	0/3	1/3	1/3	1/3	1/3

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The dermal LD50 in male and female rats is approx. 2000 mg/kg bw based on a product containing 75% of the test item. The corrected LD50 is approx. 1500 mg/kg.

Executive summary:

In an acute dermal toxicity study Sprague Dawley rats (3 males and 3 females per dose group) were dermally exposed to a product containing 75% of the test item in water for 24 hours to 50 cm² of body surface area at 2000, 1000, 400, 200 and 100 mg/kg bw. Animals were observed for a total of 14 days. The animals showed the following systemic clinical signs: dyspnea, apathia, excitation, ataxia, spastic gait and poor general condition. Two females and one male animal of the high dose group died during the observation period. Furthermore, one female animal of the dose groups 100, 200 and 1000 mg/kg bw was found dead within the 14 days. Gross pathology of animals found dead showed an acute hyperemia of the heart and a substance-related discoloration of the stomach, fat tissue and of the musculature. Animals survived the entire observation period showed no treatment related effects at gross pathology observations. Based on the results obtained, the dermal LD50 value of the product in rats was established to be approx. 2000 mg/kg body weight for both sexes. Based on the test item (75%), the corrected LD50 is approx. 1500 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 500 mg/kg bw

Additional information

Information related to the acute toxicity of the test item is available.

In an acute oral toxicity study (equivalent to OECD 401), groups of young Wistar rats (5/sex/dose) were given a single oral dose of the test item in water at doses of 0, 310, 630, 1000, 1250 and 1600 mg/kg bw. The LD50 value was determined to be 841 mg/kg bw (Bomhard 1982). In a second acute oral toxicity study (OECD 401, Ivens-Kohl 1989), groups of young adult Wistar rats (5/sex) were given a single oral dose of the test item in water at doses of 100, 200, 300 and 400 mg/kg bw. The oral LD50 was determined to be between 300-400 mg/kg bw (males) and between 200-300 mg/kg bw (females). According to CLP, LD50 values <= 300 mg/kg warrant classification as Acute Tox 3.

Three acute inhalation toxicity studies (equivalent or according to OECD 403) are available. In one study the LC50 was determined to be 290 mg/m³ for females and 474 mg/m³ for males (Pauluhn 1983). In a second acute inhalation toxicity study the LC50 value for both sexes was 76 mg/m³ (Pauluhn 1993). The author concluded, that the increased acute toxicity in the second study is based on the decreased aerodynamic diameter of the inhalable particles. In the first study the mass median aerodynamic diameter was 6.94 µm and in the second study at the highest concentration 4.18 µm. In the third acute inhalation toxicity study the test item showed very low dustability (gravimetric determination of the test item concentration was not possible, below limit of detection). No effects were reported in any animal. It can be concluded, that the test item is toxic upon inhalation (Acute Tox 2) but exposure is not expected for low dustability products.

In an acute dermal toxicity study, the dermal LD50 value in rats was established to be greater than 2000 mg/kg body weight for males and between 100 and 200 mg/kg bw for female rats. This pronounced gender difference is not in line with results from repeat dose toxicity studies and together with the missing dose-response-relationship in females questions the validity of the study. The study was repeated in the same year by the same author, and a dermal LD50 in male and female rats was reported to be approx. 2000 mg/kg bw (Jäckh 1981). The study was conducted with a product containing 75% dye. Therefore, the LD50 for the dye is approx. 1500 mg/kg (= Acute Tox 4).

Justification for selection of acute toxicity – oral endpoint
GLP guideline study

Justification for selection of acute toxicity – inhalation endpoint
GLP guideline study

Justification for selection of acute toxicity – dermal endpoint
Study conducted to generally accepted scientific standards

Justification for classification or non-classification

Based on the available data, the test item does warrant classification for acute oral toxicity (Cat. III, H301), acute dermal toxicity (Cat. IV, H312) and acute inhalation toxicity (Cat. II, H330).