N-[2,5-dichloro-4-(1,1,2,3,3,3-hexafluoropropoxy)-phenyl-aminocarbonyl]-2,6-difluorobenzamide

Endpoint summary

Description of key information

- Oral: LD50 > 2000 mg/kg bw, males/females, rat, according to OECD TG 401, Hartmann, 1988.

- Inhalation: LC50 > 2350 mg/m3, males/female, rat, according to OECD TG 403, Hartmann, 1988.

- Dermal: LD50 > 2000 mg/kg bw, males/females, rat, equivalent to OECD TG 402, Hartmann, 1988.

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:

25 Jan 1988 to 08 Feb 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

Feb 1987

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Tif: RAI f (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7 - 8 weeks young adults
- Weight at study initiation: 169 - 204 g
- Fasting period before study: Prior to dosing, the animals were fasted overnight.
- Housing: housed in Macrolon cages type 4, with standardized soft wood, segregated by sex, group-housed (5 animals per cage)
- Diet: Rat chow, ad libitum
- Water: provided, ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25 Jan 1988 To: 08 Feb 1988

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

The test substance was administered at a single dose volume of 10 mL/kg bw.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations clinical signs: The animals were observed for signs of systemic toxicity twice (a.m. and p.m.) on working days, and once (a.m.) on weekend days
- The animals were weighed at the start and on day 7 and 14.
- The animals were submitted to a gross necropsy at the end of the observation period.

Statistics:

From the body weights, the group means and their standard deviations were calculated.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality observed.

Clinical signs:

other: Ruffled fur, dyspnea, hunched posture, and exophthalmos were seen, being common symptoms in acute tests. The animals recovered within 11 days.

Gross pathology:

No deviations from normal morphology were found.

Table 1 Mean body weight and standard deviation

	males			females
Dose (mg/kg)	Day 1	Day 7	Day 14	Day 1	Day 7	Day 14
2000	191/9.0	269/11.2	313/13.8	176/5.5	226/7.7	249/12.8

Table 2: Signs and symptoms

Observations

Exposure day (hours)

Days of post-exposure period

1

2

3

4

5

1

2

3

4

5

6

7

8

9

10

11

12

13

>13

2000 mg/kg males

ruffled fur

x

xx

xx

x

x

x

x

x

x

x

x

x

x

x

x

dyspnea

xx

x

x

x

x

x

x

x

x

x

x

body position curved

x

x

x

x

x

x

x

exophtalmos

x

x

x

x

x

x

x

x

x

x

2000 mg/kg females

ruffled fur

x

xx

xx

x

x

x

x

x

x

x

x

x

x

x

x

dyspnea

xx

x

x

x

x

x

x

x

x

x

x

body position curved

x

x

x

x

x

x

x

exophtalmos

x

x

x

x

x

x

x

x

x

x

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of the test substance is estimated to be > 2000 mg/kg for both male and female rats.

Executive summary:

Groups of 5 young adult male and 5 female Tif: RAI f (SPF) rats received a single oral (gavage) dose of 2000 mg/kg bw of the test substance in a study performed according to OECD TG 401 following GLP principles. Prior to dosing, the animals were fasted overnight. The animals were assessed daily for the following 14 days for any signs of systemic toxicity and their body weights were recorded at intervals throughout the study. All animals were subjected to a complete gross necropsy following their sacrifice or spontaneous death. Ruffled fur, dyspnoea, hunched posture, and exophthalmos were observed, being common symptoms in acute tests. The animals recovered within 11 days. Upon an acute oral administration and a 14 day post-treatment observation period, the following LD50 was determined for the test substance. The LD50 in both male and female rats was greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

> 2 000 mg/kg bw

Quality of whole database:

GLP compliant OECD TG 401 study.

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:

22 Mar 1988 to 12 Apr 1988

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:

May 1981

GLP compliance:

yes

Test type:

traditional method

Limit test:

yes

Species:

rat

Strain:

other: Tif: RAI f (SPF) hybrids of RII/1 x RII/2

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: age 7 - 8 weeks
- Weight at study initiation: 178 to 331 g
- Housing: Group of 5 (by sex); Macrolon cages, Type 4 with standardised soft wood bedding
- Diet: Rat diet, ad libitum.
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 22 Mar 1988 To: 12 Apr 1988

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

>= 1.9 - <= 2.8 µm

Geometric standard deviation (GSD):

>= 2.2 - <= 2.5

Remark on MMAD/GSD:

In of the vicinity of the animals, 84 to 95 % (weight) of the airborne particles had a diameter smaller than 7 μm during the exposure.

Details on inhalation exposure:

INHALATION EXPOSURE CHAMBER
All exposures were conducted in a nose-only exposure. The chamber was designed to ensure a rapid equilibration (internal active volume less than one litre) and a uniform exposure of all animals in the system. In order to avoid rebreathing of the exhaled air, "fresh" test substance (in first—pass chamber air) was supplied to each animal via individual delivery and exhaust tubes. In addition to the necessary animal and sampling ports, identical "void" outlets were opened in proportion to the total air flow through the chamber. Thus the flow in any individual aerosol delivery tube was standardized to 2 L/min (velocity 1.25 m/s).
For the inhalation period, the rats were placed in Macrolon animal holders positioned radially around the exposure chamber, so that only the snouts and nostrils of the animals were exposed to the aerosol. The chamber was maintained at an exactly balanced pressure to prevent leakage of the test atmosphere from the system, as well as dilution with outside air. The exhaust air was decontaminated by subsequent passage through an absolute filter. The aerosol concentration in the chamber was determined gravimetrically 5 times during the exposure period. Samples of the test atmosphere (1 L) were passed through a GP 92 filter. The air flow rate for the sample collection was kept constant (2 L/min) by means of a Sierra Series 110 constant flow air sampler, regardless of filter loading. The mean and standard deviation of the aerosol concentrations for the exposure was calculated. Particle size analysis was conducted with an APS-33 Aerodynamic Particle Sizer, equipped with appropriate dilution systems to avoid coincidence counts. The number distribution in the 48 size classes was converted to a mass distribution, based on the bulk density of the test substance, which was determined separately. The following environmental parameters inside the inhalation chamber were monitored at approximately the same intervals as the concentration determinations:
- Temperature
- Relative humidity
- Oxygen content

AEROSOL
The aerosol was generated from the solid test material by means of a brush-feed micronizing jet mill. The aerosol generation system consists of a dual flexible brush dust-feed mechanism, modified from a design by Milliman, and a jet mill, to be aerodynamically compatible with the brush feed and the exposure system. In this instrument, powders are transferred from a hopper brush through a slit interface to the aspiration tube of the jet mill by means of a spiral feed brush driven by a stepping motor. In the mill, the material is micronized by impaction of particle against particle in two opposing air streams. A cyclone type classifier ensures that only particles of the desired diameter leave the jet mill, while the larger ones are re-entrained into the air stream for further milling. In a preliminary experiment, the appropriate interface slit size, brush speeds, and air pressures and flows were determined for the desired concentration. The dust generator was operated at a total airflow (through the aspiration tube and the two milling jets) of 37 L/min (input pressure 210/210 kPa), and the aerosol was diluted with filtered humidified air to yield a total flow of 48 L/min. Secondary agglomerates were removed from the aerosol by means of a glass cyclone. The throughput of the solid test material was determined by weighing the dust genera tor and the cyclone before and after aerosol generation. The control animals were exposed to filtered humidified air (32 L/min) under the same conditions as described above.

ANALYSIS OF INHALATION ATMOSPHERES
The air flow through the chamber was measured with flow meters. Adjustments to maintain a total flow of 48 L/min could be made with needle valves. However, no deviations were observed in any of the exposures, once the equilibrium was reached (within the first 10 minutes after beginning of exposure).

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

2350 ± 100 mg/m³

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

OBSERVATIONS
MORBIDITY/MORTALITY
The animals were examined for clinical symptoms and mortalities during the exposure at 1, 2, and 4 hours, as well as 2 hours after the exposure and daily thereafter for 14 days.

BODY WEIGHTS
Body weights were recorded immediately prior to exposure and on days 7 and 14 of the observation period.

GROSS PATHOLOGY
Examinations were performed on all animals, which were killed after 14 days by ether anaesthesia. Particular attention was given to the respiratory tract

Statistics:

Inhalation LC50 values (including their 95 % confidence limits) for a 4 hour treatment and a subsequent 14 day observation period could not be calculated, because no mortalities were elicited by the test substance at a concentration of 2350 ± 100 mg/m3 (limit test). The body weights of the treated animals and the controls were compared by analysis of variance.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2 350 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality occurred.

Clinical signs:

other: The symptoms, piloerection, hunched posture, dyspnea, were seen and in similar extent in both sexes. These findings disappeared within 2 days.

Body weight:

The males exposed to the test article exhibited a significantly higher body weight increase during the second week after exposure

Gross pathology:

No treatment-related deviations from normal morphology were detected at necropsy.

Table 1 Exposure atmospheres

Parameter	1 - Control Group (air)	2 – Exposure Group (test substance)
Exposure day	22 Mar 1988	12 April 1988
Nominal concentration (mg/m^3)	Control *	3003
Mean exposure concentration ** (mg/m^3) ± SD		2350 ± 100
Mass median aerodynamic diameter (MMAD) (mm)		1.9 – 2.8
Geometric standard deviation (GSD)		2.2 – 2.5
Particles < 7 mm (% w/w)		84 – 95
Particles < 3 mm (% w/w)		52 – 73
Air flow (L/min) through generator through chamber	32	37 48
Mean chamber temperature (ºC) *** ± SD	22.3 ± 0.1	23.0 ± 0.1
Mean relative humidity (%) *** ± SD	47 ± 1	38 ± 1
Mean oxygen content (%) *** ± SD	21.0 ± 0	21.0 ± 0

* exposed to filtered humidified air

** determined gravimetrically 5 times during exposure period

*** determined 5 times during the exposure period

Table 2 Observation of symptoms

Observations

Exp. day

Day of post exposure period

de

ae

1

2

3

4

5

6

7

8

9

>9

Control males

no effect observed in all animals

Test article exposed males

piloerection

++

+

hunched post.

+

dyspnoea

++

+

Control females

no effect observed in all animals

Test article exposed females

piloerection

++

+

hunched post.

+

dyspnoea

++

+

 Exp.day = exposure day (de = during, ae = after exposure)

+ = slight ++ moderate = +++ = severe

hunched post. = hunched posture

Interpretation of results:

GHS criteria not met

Conclusions:

The acute inhalation LC50 of the test substance in rats was found to be greater than 2350 mg/m3 for both males and females.

Executive summary:

The acute inhalation toxicity of the test substance was evaluated in groups of 5 male and 5 female young adult albino rats (Tif: RAI f (SPF)), rats in accordance with OECD TG 403 following GLP principles. The animals were exposed to 0 (control – purified air) or 2350 mg/m³ test article in a nose-only exposure system and were examined for clinical symptoms and mortalities during the exposure at 1, 2, and 4 hours, as well as 2 hours after the exposure and daily thereafter for 14 days. Body weights were recorded immediately prior to exposure and on days 7 and 14 of the observation period. Gross pathological examinations were performed on all animals, which were killed after 14 days by ether anaesthesia. Particular attention was given to the respiratory tract.

Upon a 4hour aerosol inhalation exposure and a 14 day post-treatment observation period, no mortalities were elicited by the test substance at a concentration of 2350 ± 100 mg/m3. Due to the properties of the test material, it was not possible to generate higher aerosol concentrations of the test substance. The mass median aerodynamic diameter (MMAD) of the particles was between 1.9 and 2.8 µm, with a geometric standard deviation (GSD) of 2.2 to 2.5. In the vicinity of the animals, 84 to 95 % of the airborne particle mass had a diameter smaller than 7 µm. The animals of both sexes exposed to the test substance experienced the symptoms piloerection, hunched posture and dyspnoea to a similar extent. They recovered within 2 days. From the absence of mortalities it can be assumed that the LC50 to male and female rats is greater than 2350 mg/m3 air.

In conclusion, the acute inhalation LC50 of the test substance in rats was found to be greater than 2350 mg/m3 for both males and females.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

>= 2 350 mg/m³ air

Physical form:

inhalation: aerosol

Quality of whole database:

GLP compliant OECD TG 403 study

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:

16 Feb 1988 to 01 Mar 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

Feb 1987

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Tif: RAI f (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adult of 7 to 8 weeks
- Weight at study initiation: 224 to 250 g
- Housing: Group of 5 (by sex); Macrolon cages, Type 3 with standardised soft wood bedding
- Diet: Rat diet, ad libitum.
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 16 Feb 1988 To: 01 Mar 1988

Type of coverage:

occlusive

Vehicle:

arachis oil

Details on dermal exposure:

TEST SITE
- Area of exposure: an area on the back of the rat
- Pre-treatment: Approximately 24 hours before treatment an area on the back of the rat of at least 10% of the body surface was shaved with an electric clipper.
- % coverage: 10 % of the total body surface
- Type of wrap if used: The treated area was covered with a gauze-lined semi occlusive dressing fastened around the trunk with an adhesive elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing: After 24 hours, the dressings were removed and treated area was the skin was cleaned with lukewarm water. Thereafter, the skin reaction was appraised repeatedly.

TEST MATERIAL
- Amount applied: 4 mL/kg
- Concentration: 2000 mg/kg bw test substance suspended in Oleum arachidis
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes, concurrent no treatment

Remarks:

A control gauze patch was applied to the contralateral flank.

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of weighing: Individual body weights of the animals were recorded on Days 1, 7 and 14.
- Frequency of observations: Animals were observed daily; a.m. and p.m. on working days, a.m. on weekend days
- Necropsy of survivors performed: yes, on Day 15 and were subjected to gross necropsy at the end of the observation period.
- Clinical signs: Clinical signs were recorded daily. Ruffled fur, dyspnoea, abnormal body positions, and spontaneous activity were monitored.

Statistics:

From the body weights, the group means and their standard deviations were calculated.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Not treatment-related observations: ruffled fur, dyspnea, abnormal body positions, and reduced spontaneous activity were seen, being common symptoms in acute tests. The animals recovered within 5 days.

Gross pathology:

No deviations from normal morphology were found at autopsy.

Table 1 Rate of deaths

Dose mg/kg	Totals			Hours aft. Treatment				Day of post exposure period
	in grp	Deaths		1	2	3	5	1	2	3	4	5	6	7	8	9	10	11	12	13	>13
		no	%
2000 mg/kg, males	5	0	0
2000 mg/kg, females	5	0	0

 

Table 2 Mean body weight and standard deviation

	Males			Females
dose mg/kg	day 1	day 7	day 14	day 1	day 7	day 14
2000	244/ 6.3	281/23.6	328/21.4	233/ 6.6	243/ 6.5	259/10.9

Table 3 Signs and symptons

Observations

Exposure day: hours

Day of post-exposure period

1

2

3

5

1

2

3

4

5

6

7

8

9

10

11

12

13

>13

2000 mg/kg, males

ruffled fur

x

x

x

x

x

x

x

x

dyspnoea

x

x

x

x

x

x

x

hunched post.

x

x

ventr.recumb

x

x

x

x

x

red.spont.act

x

x

x

x

2000 mg/kg, females

ruffled fur

x

x

x

x

x

x

x

x

dyspnoea

x

x

x

x

x

x

x

hunched post.

x

x

ventr.recumb

x

x

x

x

x

red.spont.act

x

x

x

x

x = slight xx = moderate XXX = marked

hunched post. = hunched posture ventr.recumb. = ventral recumbency

red.spont.act = reduced spontaneous activity

Interpretation of results:

GHS criteria not met

Conclusions:

The acute median lethal percutaneous dose (LD50) to rats of test substance was found to be greater than 2000 mg/kg bw.

Executive summary:

An acute dermal study was performed in accordance with OECD TG 402 following GLP principles. The test was conducted with Tif: RAI f (SPF) rats to determine the potential for the test substance to produce toxicity from a single topical application. Approximately 24 hours before treatment, an area of at least 10 % of the body surface of the back of one group of 10 rats (5/sex) was shaved with an electric clipper. Test article was evenly dispersed on the skin at a dosage of 2000 mg/kg bw in Oleum arachidis in a dose volume of 4 mL/kg bw and covered with a semi-occlusive dressing. After an exposure period of 24 hours, the dressing was removed and the skin was cleaned with lukewarm water. Thereafter, the skin reaction was appraised repeatedly. Mortality, signs and symptoms were recorded daily, body weight at start and on days 7 and 14 of the study, and the animals were subjected to gross necropsy at the end of the 14-day observation period.

No mortality occurred; ruffled fur, dyspnoea, abnormal body positions, and reduced spontaneous activity were seen, being common symptoms in acute tests. The animals recovered within 5 days. Body weight growth was observed and no deviations from normal morphology were found at autopsy. Upon an acute dermal application and a 14-day post-treatment observation period, the LD50 for the test substance in rats was greater than 2000 mg/kg bw in both sexes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

> 2 000 mg/kg bw

Quality of whole database:

GLP compliant OECD TG 402 like study

Additional information

All available data was assessed and the studies representing the worst-case effects were included as key or weight-of-evidence studies. Other studies are included as supporting information. Dosing with the test substance in rat and mouse results in low acute toxicity by the oral, dermal and inhalation routes of exposure. The key studies are considered to be worst-case and were selected for the CSA. Two acute toxicity studies with metabolites of the test substance are available with a combined male/female LD50 of 1273 and 2065 mg/kg bw.

Acute oral toxicity study in rats, Hartmann 1988

Groups of 5 young adult male and 5 female Tif: RAI f (SPF) rats received a single oral (gavage) dose of 2000 mg/kg bw of the test substance in a study performed according to OECD TG 401 following GLP principles. Prior to dosing, the animals were fasted overnight. The animals were assessed daily for the following 14 days for any signs of systemic toxicity and their body weights were recorded at intervals throughout the study. All animals were subjected to a complete gross necropsy following their sacrifice or spontaneous death. Ruffled fur, dyspnoea, hunched posture, and exophthalmos were observed, being common symptoms in acute tests. The animals recovered within 11 days. Upon an acute oral administration and a 14 day post-treatment observation period, the following LD50 was determined for the test substance. The LD50 in both male and female rats was greater than 2000 mg/kg bw.

  

Acute inhalation toxicity study in rats, Hartmann 1988

The acute inhalation toxicity of the test substance was evaluated in groups of 5 male and 5 female young adult albino rats (Tif: RAI f (SPF)), rats in accordance with OECD TG 403 following GLP principles. The animals were exposed to 0 (control – purified air) or 2350 mg/m³ test article in a nose-only exposure system and were examined for clinical symptoms and mortalities during the exposure at 1, 2, and 4 hours, as well as 2 hours after the exposure and daily thereafter for 14 days. Body weights were recorded immediately prior to exposure and on days 7 and 14 of the observation period. Gross pathological examinations were performed on all animals, which were killed after 14 days by ether anaesthesia. Particular attention was given to the respiratory tract.

Upon a 4 hour aerosol inhalation exposure and a 14 day post-treatment observation period, no mortalities were elicited by the test substance at a concentration of 2350 ± 100 mg/m3. Due to the properties of the test material, it was not possible to generate higher aerosol concentrations of the test substance. The mass median aerodynamic diameter (MMAD) of the particles was between 1.9 and 2.8 µm, with a geometric standard deviation (GSD) of 2.2 to 2.5. In the vicinity of the animals, 84 to 95 % of the airborne particle mass had a diameter smaller than 7 µm. The animals of both sexes exposed to the test substance experienced the symptoms piloerection, hunched posture and dyspnoea to a similar extent. They recovered within 2 days. From the absence of mortalities it can be assumed that the LC50 to male and female rats is greater than 2350 mg/m3 air.

In conclusion, the acute inhalation LC50 of the test substance in rats was found to be greater than 2350 mg/m3 for both males and females.

 

Acute dermal toxicity in rats, Hartmann 1988

An acute dermal study was performed in accordance with OECD TG 402 following GLP principles. The test was conducted with Tif: RAI f (SPF) rats to determine the potential for the test substance to produce toxicity from a single topical application. Approximately 24 hours before treatment, an area of at least 10 % of the body surface of the back of one group of 10 rats (5/sex) was shaved with an electric clipper. Test article was evenly dispersed on the skin at a dosage of 2000 mg/kg bw in Oleum arachidis in a dose volume of 4 mL/kg bw and covered with a semi-occlusive dressing. After an exposure period of 24 hours, the dressing was removed and the skin was cleaned with lukewarm water. Thereafter, the skin reaction was appraised repeatedly. Mortality, signs and symptoms were recorded daily, body weight at start and on days 7 and 14 of the study, and the animals were subjected to gross necropsy at the end of the 14-day observation period.

No mortality occurred; ruffled fur, dyspnoea, abnormal body positions, and reduced spontaneous activity were seen, being common symptoms in acute tests. The animals recovered within 5 days. Body weight growth was observed and no deviations from normal morphology were found at autopsy. Upon an acute dermal application and a 14-day post-treatment observation period, the LD50 for the test substance in rats was greater than 2000 mg/kg bw in both sexes.

Justification for classification or non-classification

Based on the result of the acute oral, acute dermal and acute Inhalation toxicity study classification for acute toxicity is not warranted in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. (EC) 1272/2008.