2-{2-chloro-4-mesyl-3-[(tetrahydrofuran-2-ylmethoxy)methyl]benzoyl}cyclohexane-1,3-dione

Endpoint summary

Description of key information

Oral (OECD 423), rat: LD50 cut-off value = 5000 mg/kg bw

Oral (equivalent or similar to OECD 423), mouse: LD50 >2000 mg/kg bw

Inhalation (similar to OECD 403), rat: LC50 > 1.34 mg/L air

Dermal (OECD 402), rat: LD50 > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 July - 17 Aug 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted 17 Dec 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

THE DEPARTMENT OF HEALTH, UK

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: CD (Crl: CD (SD) IGS BR)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, UK
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 184 - 232 g
- Fasting period before study: overnight fast immediately before dosing and for approximately 3 to 4 h after dosing
- Housing: in groups of three in suspended solid-floor polypropylene cages on woodflakes, environmental enrichment items were provided
- Diet: certified Rat and Mouse Diet, Code 5LF2 (BCM IPS Limited, London, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: the test material did not dissolve/suspend in distilled water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: all available information on the toxicity of the test substance was used

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females in total

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 0.5, 1, 2 and 4 h after dosing and subsequently once daily for 14 days. Individual body weights were recorded prior to dosing and 7 and 14 days after treatment.
- Necropsy of survivors performed: yes

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 cut-off according to OECD 423

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: Hunched posture was noted in one animal 2 and 4 h after dosing. Five animals appeared normal throughout the study and the remaining animal appeared normal one day after dosing.

Gross pathology:

No abnormalities were noted at necropsy.

Table 1. Results for the acute oral toxicity study (mortality and clinical signs)

Dose [mg/kg bw]	Toxicological results*	Duration of clinical signs	Time of death	Mortality (%)
Females
2000	0/1/5	24h	-	0
LD50 ≥5000 mg/kg bw

* number of dead animals / number of animals with clinical signs / number of animals used

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Conclusions:

The study was performed in accordance to OECD TG 423 under GLP conditions and is considered reliable. The acute oral LD50 cut-off of the test material (as defined in the OECD TG 423) was ≥5000 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 Sep - 17 Oct 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

according to guideline

Guideline:

other: Guideline for Preparation of Study Results Submitted When Applying for Registration of Agricultural Chemicals, Toxicity studies (Notification No. 12-Nousan-8147, November 24, 2000, 14-Seisan-7269 and 7270, December 10, 2002).

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted 17 Dec 2001

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

mouse

Strain:

other: CrljBgi:CD1 (ICR), SPF

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rationale for alternative/additional species to rat: ICR mice have enough historical background data and are used widely in toxicity studies.
- Source: ORIENTBIO INC, Gyonggi-do, Korea
- Females nulliparous and non-pregnant: Not stated
- Age at study initiation: 8 weeks
- Weight at study initiation: 24.4 - 25.2 g
- Fasting period before study: Approximately 4 hours
- Housing: 3 animals per cage, polycarbonate cages
- Diet: (TEKLAD CERTIFIED GLOBAL 18% PROTEIN RODENT DIET 2918C), ad libitum
- Water: Filtered and purified tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.2 - 23.8
- Humidity (%): 42.0 - 55.9
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: Group 1 animals, 29 Sep to 13 Oct 2006. Group 2 animals, 2 Oct to 17 Oct to 2006

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20%
- Amount of vehicle: 10 mL/kg bw
- Justification for choice of vehicle: Water for injection was chosen based on information provided by the sponsor, and based on results of a preliminary test (preliminary test not reported)
- Lot/batch no.: AAW6AN

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: The test substance was weighed and then added to the vehicle

CLASS METHOD
- Rationale for the selection of the starting dose: Based on information provided by the study sponsor, a dose level of 2000 mg/kg bw was selected as the starting dose, which was expected to show low toxicity

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: For 30 minutes after dosing and at 1, 2, 4 and 6 hours after dosing on Day 0 and once daily thereafter for 14 days (Days 1 to 14)
- Determination of body weights: Body weights were recorded prior to dosing (Day 0), on Days 3 and 7 and on the day of necropsy, Day 14
- Necropsy of survivors performed: Yes, a complete gross postmortem examination was performed on all animals
- Clinical signs including body weight: All animals were observed for mortality, general condition and clinical signs (time, onset, severity and recovery)

Statistics:

Statistical analysis was not performed. Mean values and standard deviations of body weights are presented.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No clinical signs of toxicity were observed up to the end of the 14-day observation period.

Gross pathology:

Necropsy revealed no substance-related findings.

Table 1. Acute oral toxicity (mortality and clinical signs)

Dose [mg/kg bw]	Mortality	Clinical signs
	N*	N*
Females
2000	0/6	0/6

*N= Number of animals / total number of animals used

Table 2: Body weight and body weight gain (g)

Step / Dose (mg/kg bw)	Animal No.	Day after treatment				Gain (Day 0 to 14)
		0	3	7	14
Step 1 / 2000	2101	25.02	26.00	26.61	27.92	2.90
	2102	25.22	25.95	26.54	28.75	3.53
	2103	24.78	25.91	27.73	27.83	3.05
	Mean	25.01	25.95	26.96	28.17	3.16
	SD	0.22	0.05	0.67	0.51	0.33
	N	3	3	3	3	3
Step 2 / 2000	2201	24.77	25.54	24.89	25.69	0.92
	2202	24.42	25.24	25.36	26.33	1.91
	2203	24.47	25.73	26.43	28.10	3.63
	Mean	24.55	25.50	25.56	26.71	2.15
	SD	0.19	0.25	0.79	1.25	1.37
	N	3	3	3	3	3

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Conclusions:

The study was performed under GLP conditions and is considered to be equivalent to OECD TG 423. No mortality (0/6 mice) occurred after a single gavage dose of 2000 mg/kg bw of the test substance. The LD50 was concluded to be >2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

>= 5 000 mg/kg bw

Quality of whole database:

The available information comprises adequate and reliable studies (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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:

23 July - 15 Oct 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted 12 May 1981

Deviations:

not applicable

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (MAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147 (2-1-3)

Version / remarks:

partially revised on 26 July 2001

GLP compliance:

yes (incl. QA statement)

Remarks:

THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM, UK

Test type:

traditional method

Limit test:

yes

Species:

rat

Strain:

other: Crl:CD (SD) IGS BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately 8 - 12 weeks
- Weight at study initiation: 200 - 350g
- Housing: in groups of five per sex in solid-floor polypropylene cages with stainless steel lids on softwood flakes, environmental enrichment items (wooden chew blocks and cardboard “fun tunnels”) were provided
- Diet: EU Rodent Diet 5LF2 (BCM IPS Limited, London, UK), ad libitum (with the exception of the exposure period)
- Water: mains drinking water, ad libitum (with the exception of the exposure period)
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

4.84 µm

Geometric standard deviation (GSD):

2.77

Remark on MMAD/GSD:

The MMAD of 4.84 was larger than would generally be acceptable. During characterisation, attempts were made to reduce the particle size in order to increase the inhalable portion of the test material. This resulted in a reduction in the achievable atmosphere concentration but an increase in the percentage of particles <4um. It was therefore concluded to be preferable to expose the animals to the maximum attainable concentration of the test material even though this resulted in an MMAD >4um, as this maximised the exposure of the animals to particles <4µm.

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical exposure chamber (28 cm diameter x 50 cm high)
- Exposure chamber volume: 30 L
- Method of holding animals in test chamber: Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber ‘O’ ring. Only the nose of each animal was exposed to the test atmosphere.
- Source and rate of air: Compressed air was supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters before it was introduced to the dust feeder.
- System of generating particulates/aerosols: A dust atmosphere was produced from the test material using a Wrights Dust Feeder (BGI Inc., Waltham, USA) located at the top of the exposure chamber and driven by a variable speed motor. The dust feed was connected to a metered compressed air supply. A particle separator was introduced before the aerosol entered the exposure chamber in order to remove large particles and thereby increase the inhalable por ion of the generated aerosol.
- Method of particle size determination: The particle size of the generated atmosphere inside the exposure chamber was determined 3 times during the exposure period using a Marple Personal Cascade Impactor (Schaefer Instruments Ltd, Oxon, UK).
- Treatment of exhaust air: The extract from the exposure chamber passed through a scrubber trap and was connected with a high efficiency filter to a metered exhaust system.
- Temperature, humidity, pressure in air chamber: The temperature and relative humidity inside the exposure chamber were measured by an electronic thermometer/humidity meter (Hanna Instruments Ltd, Beds, UK) located in a vacant port in the animals' breathing zone of the chamber and recorded every 15 min throughout the 4-h exposure period. Temperature was 19 °C and relative humidity 38 - 59%. The chamber was maintained under negative pressure.


TEST ATMOSPHERE
- Brief description of analytical method used: The actual chamber concentration was measured at regular intervals during the exposure period. The gravimetric method used glass fibre filters (Gelman type A/E 25 mm) placed in a filter holder. The holder was temporarily sealed in a vacant port in the exposure chamber in the animals' breathing zone and a suitable, known volume of exposure chamber air was drawn through the filter using a vacuum pump.
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

1.34 ± 0.64 mg/L (maximum attainable concentration)
25.2 mg/L (nominal concentration)

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: All animals were observed for clinical signs at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, 1 hour after termination of exposure and subsequently once daily for 14 days. Individual body weights were recorded prior to treatment on the day of exposure and on Days 7 and 14.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1.34 mg/L air (analytical)

Based on:

test mat.

Remarks:

maximum attainable concentration

Exp. duration:

4 h

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: See field "any other information on results, incl. tables"

Body weight:

All animals gained the expected body weight over the study period.

Gross pathology:

No abnormalities were noted at necropsy.

Clinical Signs

Signs of hunched posture and pilo-erection are commonly seen in animals for short periods on removal from the chamber following 4-hour inhalation studies. Wet fur is commonly recorded both during and for a short period after exposure. These observations are considered to be associated with the restraint procedure and, in isolation, are not indicative of toxicity.

In addition to the observations considered to be due to the restraint procedure, clinical signs were limited to increased respiratory rate. This observation was recorded in all animals during exposure, on removal from the chamber and one-hour post exposure. In addition, there was an isolated instance of fur staining by the test material, this observation only persisted for the first hour post-exposure.

One day after exposure, two animals appeared normal and observations amongst the other animals were limited to increased respiratory rate and/or hunched posture. These clinical signs gradually receded to leave the animals appearing normal from Days 2 to 5 post-exposure.

Table 1. Results for the acute inhalation toxicity study (mortality and clinical signs)

Target concentration [mg/L air]	Toxicological results*	Duration of clinical signs	Time of death	Mortality (%)
Males
1.34	0/3/5	Days 0 to 4	---	0
Females
1.34	0/5/5	Days 0 to 4	---	0
LC50 > 1.34 mg/L air

* number of dead animals / number of animals with clinical signs / number of animals used

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Conclusions:

The study was performed under GLP conditions and in accordance to Japanese Ministry of Agriculture, Forestry and Fisheries (MAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147 (2-1-3). The study is considered to be equivalent to OECD TG 403. The LC50 was >1.34 mg/L air, this was the maximum attainable concentration.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

> 1.34 mg/L air

Physical form:

inhalation: dust / mist

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

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:

4 - 18 Aug 2004

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:

adopted 24 February 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)

Version / remarks:

adopted 9 Oct 2017

Deviations:

no

Remarks:

The study was correctly conducted in accordance with an old version of the guideline as a standard acute method. The current requirements of the Fixed Dose Procedure in the current guideline version do not apply.

GLP compliance:

yes (incl. QA statement)

Remarks:

THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM, UK

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Crl: CD (SD) IGS BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, UK
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 200 - 300 g
- Housing: individually during the 24-h exposure period and in groups of five per sex in suspended solid-floor polypropylene cages on woodflakes, environmental enrichment items were provided
- Diet: certified Rat and Mouse Diet, Code 5LF2 (BCM IPS Limited, London, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Remarks:

moistened with distilled water

Details on dermal exposure:

TEST SITE
- Area of exposure: clipped skin of the back and flanks
- % coverage: 10%
- Type of wrap if used: The treated skin was covered with a surgical gauze which was held in place with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: Treated skin and surrounding hair was wiped with cotton wool moistened with distilled water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2000 mg/kg bw

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
Frequency of observations and weighing: Animals were observed 0.5, 1, 2 and 4 h after dosing and subsequently once daily for 14 days. Individual body weights were recorded prior to application of the test substance on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: Evidence of overt toxicity was recorded at each observation. After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to Draize.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No clinical signs of toxicity were noted during the 14-day observation period.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

- Other observations: There were no signs of dermal irritation.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Conclusions:

The study was performed in accordance to OECD TG 402 under GLP conditions and is considered reliable. The LD50 was determined to be > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Reliable studies on the potential for the test substance to cause acute oral, inhalation and dermal toxicity are available.

Oral:

The acute oral toxicity of the test substance was assessed in a study performed according to OECD Guideline 423 and in compliance with GLP (M-398610-01-1, 2004). A group of three fasted female Sprague-Dawley CD rats was treated with the test material at a dose level of 2000 mg/kg bw. This was followed by a further group of three fasted females treated with the same dose level. The test material was administered by gavage as a suspension in arachis oil BP. The animals were observed for 14 days. There were no deaths and all the animals showed the expected gains in bodyweight over the study period. Hunched posture was noted in one animal during the day of dosing. Five animals appeared normal throughout the study and the remaining animal appeared normal one day after dosing. No abnormalities were detected at necropsy.

The acute oral LD50 cut-off of the test material (as defined in the OECD 423) was ≥ 5000 mg/kg bw.

The acute oral toxicity of the test substance was assessed in a study equivalent or similar to OECD Guideline 423 and in compliance with GLP (M-398576-01-2, 2007). A group of three fasted female CrljBgi:CD1 (ICR) mice was treated with the test material at a dose level of 2000 mg/kg bw. This was followed by a further group of three fasted females treated with the same dose level. The test material was administered by gavage as a suspension in water. The animals were observed for 14 days. There were no deaths. No clinical signs of toxicity were observed. A decrease in body weight gain was evident in one female in Step 2 on Day 7 after dosing. Body weight gain of this female then increased normally to Day 14. This was not considered to be a test substance related change, since the effect was temporary. The body weights of all other animals increased normally during the observation period. No abnormalities were detected at necropsy.

The acute oral LD50 of the test material was concluded to be greater than 2000 mg/kg bw.

Inhalation:

The acute inhalation toxicity of the test substance was assessed in a study similar to OECD Guideline 403 and performed in compliance with GLP (M-398619-01-1, 2004). A group of 10 Sprague-Dawley rats (5/sex) was exposed to the test substance as a dust. The animals were exposed for four hours using a nose-only exposure system, followed by a 14-day observation period. The mean achieved atmosphere concentration was 1.34 mg/mL which was the mean maximum attainable concentration. The mean mass median aerodynamic diameter (MMAD) was 4.84 µm with a geometric standard deviation of 2.77. The MMAD of 4.84 was larger than would generally be acceptable. Attempts were made to reduce the particle size, but this led to a reduction in the maximum achievable concentration. It was decided to expose the animals to the maximum attainable concentration of the test material even though this resulted in an MMAD >4um, as this maximised the exposure of the animals to particles <4µm. No animal died during this study and all the animals showed normal bodyweight development. Common abnormalities noted in all the animals until 1 h after exposure ended, included increased respiratory rate, hunched posture, pilo-erection and wet fur and there was an isolated instance of fur staining by the test material. Two of ten animals recovered quickly to appear normal by Day 1, while an increased respiratory rate and/or hunched posture persisted in 8/10 animals and gradually became less severe until Day 5 post-exposure. No abnormalities were detected at necropsy.

The acute inhalation LC50 was considered to be greater than 1.34 mg/L air (analytical).

Dermal:

The acute dermal toxicity of the test substance was assessed in a study performed according to OECD Guideline 402 and in compliance with GLP (M-398615-01-1, 2004). A group of ten animals (five male and five female Sprague Dawley rats) was given a single, 24-hour, semi-occluded dermal application of the test material to intact skin at a dose level of 2000 mg/kg bw. The animals were observed for 14 days. There were no deaths and all the animals showed the expected gains in bodyweight over the study period. No signs of systemic toxicity and no signs of dermal irritation were observed. No abnormalities were noted at necropsy.

The acute dermal LD50 of the test material was found to be greater than 2000 mg/kg bw.

This finding is further supported by a supporting study conducted similar to OECD Guideline 402 but not in compliance with GLP (M-217827-01-1, 2002). There was no mortality, and no clinical signs of toxicity were observed. No skin irritation was noted at the test site and not treatment-related changes were observed at necropsy. In this study a LD50 of greater than 2000 mg/kg bw was observed.

Justification for classification or non-classification

The available data on acute oral, inhalation and dermal toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.