cyproconazole (ISO); (2RS,3RS;2RS,3SR)-2-(4-chlorophenyl)-3-cyclopropyl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol

Endpoint summary

Description of key information

- Oral: Male LD50 = 200 mg/kg bw and female LD50 = 218 mg/kg bw, male/female, mice, according to OECD TG 401, Hamburger 1984

- Inhalation: LC50 > 5.65 mg/L, males/female, rat, according to OECD TG 403, Ullman 1985

- Dermal: LD50 > 2000 mg/L, males/females, rat, according to OECD TG 402, Durando 2005

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 Sep 1984 to 15 Oct 1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

1992

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 5 - 6 weeks
- Weight at study initiation: 18 - 24 g
- Fasting period before study: 18-20 hours prior and 4 hours after dosing
- Diet: Ad libitum (analysed for contaminants)
- Water: Ad libitum except for 2 hours prior and 3 - 4 hours after dosing
- Acclimation period: 3 - 8 days prior to dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 25 Sep 1984 to 15 Oct 1984

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Amount of vehicle: 10 mL/kg

Doses:

125, 160, 250, 320, 400, 500, 640 and 800 mg/kg

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: Animals were observed for 1 hour following treatment and at hourly intervals for the remaining of the first day and twice daily for the remaining 14 days.
- Frequency of weighing: Individual body weights on day 1, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: Macroscopic post-mortem examination. The macroscopic appearance of abnormal organs was recorded.

Statistics:

The acute oral LD50 was determined using the probit method of L.C. Miller and M.L. Tainter (Proc. Soc.exper. Biol. Med.~ (1944) p. 26).

Preliminary study:

A preliminary study was carried out to establish a dosing regime. See table 1 in ''Any other information on results''

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

200 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

218 mg/kg bw

Based on:

test mat.

Mortality:

See table 2 in ''Any other information on results incl. tables''.

Clinical signs:

other: The most common symptoms were weakness, dizziness, decreased movement, flaccidity, ataxia, laboured and decreased respiration. The first onset of symptoms occurred within 9- 10 minutes after dosing. The longest duration of symptoms lasted 72 hours in the

Gross pathology:

No particular findings were noted on any organ or tissue at necropsy, neither in animals that died nor in the mice which survived the 14 day observation period.

Table 1. Results of preliminary study

Dosage mg/kg	Mortality ratio (no. of deaths) (no. dosed)		Time of death after dosing (hours} Males                      Females
	Males	Females
125	-	0/2	-	-
250	-	0/2	-	-
500	1/2	2/2	74	29,29
1000	2/2	2/2	62,86	23,62
2000	2/2	2/2	14,38	14,38
4000	2/2	2/2	49,98	26,51

Table 2. Mortality in male and female NMR1 mice after oral administration of the test substance

Dose (mg/kg)	Males (dead/treated)	Time to death (days)	Females (dead/treated)	Time death (days)
125	1/5	1	0/5	-
160	1/5	1	1/5	2
250	4/5	1,2	4/5	2, 3
320	4/5	2,3	4/5	2, 3
400	5/5	1, 2, 3	5/5	1, 3
500	5/5	2, 3	5/5	2, 3, 4, 5
640	5/5	2, 3	5/5	2, 3
800	5/5	1, 2, 3	5/5	1, 2, 3, 4

 

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute oral LD50 was calculated to be 200 mg/kg for male and 218 mg/kg for female NMRI mice. The test substance is therefore considered toxic to mice after a single dose.

Executive summary:

In a study that was performed in accordance with OECD 401 and according to GLP, 5 male and 5 female NMRI mice were exposed to the test substance to determine the potential to produce toxicity from a single dose via the oral route (gavage). The mice were once exposed at doses of 125, 160, 250, 320, 400, 500, 640 and 800 mg/kg of the test substance dissolved in DMSO. Animals were observed for 1 hour following dosing and at hourly intervals for the remainder of day 1. For the following 14 days animals were observed for symptoms and mortality in the morning and once in the evening.

Results showed that the maximum non-lethal dose was less than 125 mg/kg in male mice and 125 mg/kg in female mice. The minimum lethal dose was 125 mg/kg in males and 160 mg/kg in females. Earliest onset of lethality occurred 14 hours after dosing in the 125 mg/kg male group and in the 800 mg/kg male and female groups. The most common symptoms were weakness, dizziness, decreased movement, flaccidity, ataxia, laboured and decreased respiration. The first onset of symptoms occurred within 9- 10 minutes after dosing. The longest duration of symptoms lasted 72 hours in the 250 mg/kg group. Recovery was complete in the survivors of all groups by 96 hours.

Based on these findings, the acute oral LD50 was calculated to be 200 mg/kg for male and 218 mg/kg for female NMR1 mice. The test substance is therefore considered toxic to mice after a single dose.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

200 mg/kg bw

Quality of whole database:

GLP compliant OECD 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:

21 Aug 1985 to 19 Sep 1985

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:

1981

GLP compliance:

yes

Test type:

traditional method

Limit test:

no

Species:

rat

Strain:

Wistar

Remarks:

KFM-HAN

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 10 weeks, same age for male and female rats
- Weight at study initiation: Males: 247- 285 g, females: 203- 227 g
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least one week under laboratory conditions after veterinary examination

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

IN-LIFE DATES: 21 Aug 1985 to 19 Sep 1985

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

not specified

Remark on MMAD/GSD:

From the particle size distribution observed it could be stated that a mean particle size of approximately 41% in the low dose and 68% in high dose was within a size range of 1 to 5 microns.

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 100 L
- Method of holding animals in test chamber: During the experiment, rats were placed around the exposure chamber in separate radial polyvinylchloride tubes with their snouts and nostrils exposed to the aerosol only.
- Rate of air (airflow): The air flow was 1000 L per hour and air pressure was 3 atmospheres.
- System of generating particulates/aerosols: The aerosol was generated by a nozzle. The test substance was supplied to the nozzle by a Grafix Exactomat Injector into a high velocity air stream. The nozzle discharged into the air of the chamber.
- Method of particle size determination: Gravimetric determination was performed using an 8-stage Andersen Ambient Particle Sizing Sampler with selectron filters, pore size 0.2 cm (micrometers) and 76 mm in diameter

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gravimetrical determinations on selectron filters, pore size 0,2 cm and 50 mm in diameter

Duration of exposure:

4 h

Concentrations:

2.61 and 5.65 mg/L air

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of weighing: At day 1 (day of exposure), 8 and 15 of the test.
- Frequency of obervations: Four times during the first day and daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: At the high dose, histopathological examination was performed on the nasal cavity, lungs with mainstream bronchi, liver, kidneys, adrenal glands and all gross lesions. Only gross lesions were examined at the low dose.

Statistics:

The LC50 was estimated without use of a statistical model.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.65 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality was observed.

Clinical signs:

other:

Remarks:

Slight sedation, dyspnoea and ruffled fur were observed in all animals 4 hours post dosing

Body weight:

Body weight development was not affected in males; however females showed a reduction in body weight gain from day 1 to 8. By study termination females had recovered and showed no treatment related effects on body weight. See table 1 in ''Any other information on results incl. tables''.

Gross pathology:

No treatment-related findings were observed.

Table 1. Body weight gain in male and female rat following inhalation of the test substance

Animal No.	Body weight males
	Conc. Test Substance 2606 mg/m3			Conc. Test Substance 5645 mg/m3
	Day 1	Day 8	Day 15	Day 1	Day 8	Day 15
1/ 11	261	289	309	260	272	300
2/ 12	254	287	310	248	252	283
3/ 13	284	320	340	282	300	328
4/ 14	272	302	319	272	272	310
5/ 15	247	269	285	260	280	330
	Body weight females
	Day 1	Day 8	Day 15	Day 1	Day 8	Day 15
6/ 16	217	217	227	227	233	248
7/ 17	225	222	231	217	220	234
8/ 18	217	220	230	227	223	241
9/ 19	223	220	221	203	207	232
10/ 20	219	224	231	213	216	235

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study, the acute inhalation LC50 of the test substance suspended in air for male and female rats was determined to be higher than 5.65mg/ L air. No classification is required.

Executive summary:

In this acute inhalation toxicity study performed in accordance with OECD TG 403 and in accordance with GLP principles, 5 male and 5 female Wistar rats per group were exposed to the test substance to determine the potential to produce toxicity from a single exposure. The rats were exposed to concentrations of 2.61 and 5.65 mg/L air of the test substance via the inhalation (nose-only exposure) route for 4 hours. The airflow was 1000 mL/ hour and air pressure was 3 atmospheres. The nozzle discharged into the air of the exposure chamber. The parameters of inhalation exposure including; oxygen content, relative humidity, temperature, particle size and airflow velocity were all monitored. The actual concentration of the test substance in the chamber was determined gravimetrically. The measurements were conducted at regular intervals throughout the exposure period. The study was terminated 15 days post dosing. The animals were observed for clinical signs of toxicity four times a day during the first day and daily thereafter. Individual bodyweights were recorded at day 1 (pre-test), day 8 and day 15 of the test. Necropsy was performed on all animals. At the high dose, histopathological examination was performed on the nasal cavity, lungs with mainstream bronchi, liver, kidneys, adrenal glands and all gross lesions. Only gross lesions were examined at the low dose.

Results showed that no animals died during the study. Slight sedation, dyspnoea and ruffled fur were observed in all animals 4 hours post dosing. All rats had recovered completely by 24 hours after initiation of exposure. Body weight development was not affected in males; however females showed a reduction in body weight gain from day 1 to 8. By study termination females had recovered and showed no treatment related effects on body weight.

Based on the results of this study, the acute inhalation LC50 of the test substance suspended in air for male and female rats was determined to be higher than 5.65 mg/ L air.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

> 5.65 mg/L air

Physical form:

inhalation: aerosol

Quality of whole database:

GLP compliant simliar to OECD 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:

26 Jul 2005 to 16 Aug 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Qualifier:

according to guideline

Guideline:

other: JMAFF 59 NohSan No. 4200, January 28

Version / remarks:

1985

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: Young adult (9-10 weeks)
- Weight at study initiation: Males 282-330 g and females 194-217 g at experimental start.
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NIH). Litter paper was placed beneath the cage and was changed at least three times per week
- Water: ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 26 Jul 2005 to 16 Aug 2005

Type of coverage:

occlusive

Vehicle:

other: Distilled water

Details on dermal exposure:

TEST SITE
- Area of exposure: 2 inch x 3 inch, 4-ply gauze pad was placed on a dose area of approximately 2 inches x 3 inches
- % coverage: 10% of the body surface
- Type of wrap if used: The gauze pad and entire trunk of each animal were wrapped with 3-inch Durapore tape to avoid dislocation of the pad and to minimize loss of the test substance.

REMOVAL OF TEST SUBSTANCE
- Washing: After 24 hours of exposure to the test substance, the pads were removed and the test sites were gently cleansed of any residual test substance.

TEST MATERIAL
- Constant volume or concentration used: yes
- For solids, paste formed: yes

Duration of exposure:

24 hours

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 weighing: Individual body weights of the animals were recorded prior to test substance application (initial) and again on Days 7 and 14 (termination).
- Frequency of observations: The first several hours after application and at least once daily thereafter for 14 days
- Necropsy of survivors performed: yes, gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.
- Clinical signs: Gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea and coma.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: No signs of gross toxicity, dermal irritation, adverse pharmacologic effects or abnormal behaviour.

Gross pathology:

There were no signs of gross abnormalities.

Table 1. Individual body weights/weight gains and doses

Animal No.	Sex	Body Weight (g)					Dose^1
		Day 0 Weight	Day 7 Weight	Gain*	Day 14 Weight	Gain*	g
4106	M	330	356	26	407	77	0.94
4107	M	282	316	34	390	108	0.81
4108	M	290	329	39	389	99	0.83
4109	M	316	347	31	403	87	0.90
4110	M	307	340	33	388	81	0.88
4111	F	194	212	18	236	42	0.55
4112	F	200	219	19	241	41	0.57
4113	F	212	224	12	241	29	0.61
4114	F	206	221	15	253	47	0.59
4115	F	217	230	13	254	47	0.62

* - Body weight gain from Day 0.

¹ The test substance was applied as a 70% w/w mixture in distilled water.

Interpretation of results:

GHS criteria not met

Conclusions:

The single dose acute dermal LD50 of the test substance is greater than 2000 mg/kg of body weight in male and female rats.

Executive summary:

An acute dermal toxicity study was performed in accordance with OECD TG 402 and according to GLP prinicples. The test was conducted with 5 male and 5 female Sprague-Dawley rats to determine the potential for the test substance to produce toxicity from a single topical application. 2000 mg/kg bw of the test substance was applied to the skin for 24 hours by using an occlusive dressing. The animals were observed for mortality, signs of gross toxicity, and behavioural changes at least once daily for 14 days. Body weights were recorded prior to application and again on days 7 and 14 (termination). Necropsies were performed on all animals at terminal sacrifice.

Results showed that all animals survived, gained body weight and appeared active and healthy during the study. There were no signs of gross toxicity, dermal irritation, adverse pharmacologic effects or abnormal behaviour. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Under the conditions of this study, the single dose acute dermal LD50 of the test substance is greater than 2000 mg/kg bw in male and female rats.

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 402 study

Additional information

All available data was assessed and the studies representing the worst-case effects was included as key studies. Other studies are included as supporting information. The key study is considered to be worst-case and was selected for the CSA. For acute oral toxicity, the test substance was considered to be toxic towards mice and rats. For acute inhalation toxicity, no effects were observed in both studies, therefore, the highest concentration can be used as discriminating concentration. For acute dermal toxicity, the test substance did not show toxic effects in rats and rabbits. 

 

Acute toxicity: oral

In the key study (Hamburger 1984) that was performed in accordance with OECD TG 401 and according to GLP, 5 male and 5 female NMRI mice were exposed to the test substance to determine the potential to produce toxicity from a single dose via the oral route (gavage). The mice were once exposed at doses of 125, 160, 250, 320, 400, 500, 640 and 800 mg/kg bw of the test substance dissolved in DMSO. Animals were observed for 1 hour following dosing and at hourly intervals for the remainder of day 1. For the following 14 days animals were observed for symptoms and mortality in the morning and once in the evening.

Results showed that the maximum non-lethal dose was less than 125 mg/kg bw in male mice and 125 mg/ kg bw in female mice. The minimum lethal dose was 125 mg/kg bw in males and 160 mg/kg bw in females. Earliest onset of lethality occurred 14 hours after dosing in the 125 mg/kg bw male group and in the 800 mg/kg bw male and female groups. The most common symptoms were weakness, dizziness, decreased movement, flaccidity, ataxia, laboured and decreased respiration. The first onset of symptoms occurred within 9- 10 minutes after dosing. The longest duration of symptoms lasted 72 hours in the 250 mg/kg bw group. Recovery was complete in the survivors of all groups by 96 hours.

Based on these findings, the acute oral LD50 was calculated to be 200 mg/kg bw for male and 218 mg/kg bw for female NMR1 mice. The test substance is therefore considered toxic to mice after a single dose.

 

Three supporting studies are available for this endpoint which support the findings of the key studies. The first supporting study (Durando 2005) was performed in accordance with OECD TG 425 following GLP principles, an acute oral toxicity test was conducted in 6 female Sprague-Dawley rats. The animals were once exposed at doses of 110, 350 or 1100 mg/kg bw of the test substance dissolved in CMC. In this study, the acute oral LD50 of the test substance is estimated to be 350 mg/kg bw in female rats with a 95% confidence interval of 58.05 to 1430 mg/kg bw. In the second supporting study (Hamburger 1984) was performed equivalent to OECD TG 401 and in accordance with GLP, 5 male and 5 female Han Wister rats were exposed to the test substance. The rats were once exposed at doses of 200-8000 mg/kg bw of the test substance dissolved in DMSO. In this study, the test substance is calculated to have an oral LD50 in the male rat of 1115 mg/kg bw (583 -2575), in the female of 1342 mg/kg bw (663 -2804). The third supporting study (Hamburger 1987) was conducted according to OECD TG 401 and followed GLP. The acute oral LD50 of the test substance in CD-1 male mice was 270 ± 24.5 mg/kg bw. Histopathological observation of the liver from dead and surviving animals did not reveal clear signs of hepatic toxicity, except cytoplasmic vacuolisation.

 

Acute toxicity: inhalation

In the key acute inhalation toxicity study (Ullman 1985) performed in accordance with OECD TG 403 and in accordance with GLP principles, 5 male and 5 female Wistar rats per group were exposed to the test substance to determine the potential to produce toxicity from a single exposure. The rats were exposed to concentrations of 2.61 and 5.65 mg/L air of the test substance via the inhalation (nose-only exposure) route for 4 hours. The airflow was 1000 mL/ hour and air pressure was 3 atmospheres. The nozzle discharged into the air of the exposure chamber. The parameters of inhalation exposure including; oxygen content, relative humidity, temperature, particle size and airflow velocity were all monitored. The actual concentration of the test substance in the chamber was determined gravimetrically. The measurements were conducted at regular intervals throughout the exposure period. The study was terminated 15 days post dosing. The animals were observed for clinical signs of toxicity four times a day during the first day and daily thereafter. Individual bodyweights were recorded at day 1 (pre-test), day 8 and day 15 of the test. Necropsy was performed on all animals. At the high dose, histopathological examination was performed on the nasal cavity, lungs with mainstream bronchi, liver, kidneys, adrenal glands and all gross lesions. Only gross lesions were examined at the low dose.

Results showed that no animals died during the study. Slight sedation, dyspnoea and ruffled fur were observed in all animals 4 hours post dosing. All rats had recovered completely by 24 hours after initiation of exposure. Body weight development was not affected in males; however females showed a reduction in body weight gain from day 1 to 8. By study termination females had recovered and showed no treatment related effects on body weight.

Based on the results of this study, the acute inhalation LC50 of the test substance suspended in air for male and female rats was determined to be higher than 5.65mg/ L air.

 

One supporting study is available for this endpoint which supports the findings of the key study. This acute inhalation toxicity study (Durando 2005) was conducted according to OECD TG 403 and GLP principles. Rats were exposed to the test atmosphere of 2.05 mg/L for 4 hours. Based on these findings, the single exposure acute inhalation LC50 of the test substance is greater than 2.03 mg/L in male and female rats under the conditions of this study.

 

Acute toxicity: dermal

The key acute dermal toxicity study (Durando 2005) was performed in accordance with OECD TG 402 and according to GLP principles. The test was conducted with 5 male and 5 female Sprague-Dawley rats to determine the potential for the test substance to produce toxicity from a single topical application. 2000 mg/kg bw of the test substance was applied to the skin for 24 hours by using an occlusive dressing. The animals were observed for mortality, signs of gross toxicity, and behavioural changes at least once daily for 14 days. Body weights were recorded prior to application and again on days 7 and 14 (termination). Necropsies were performed on all animals at terminal sacrifice. Results showed that all animals survived, gained body weight and appeared active and healthy during the study.

There were no signs of gross toxicity, dermal irritation, adverse pharmacologic effects or abnormal behaviour. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Under the conditions of this study, the single dose acute dermal LD50 of the test substance is greater than 2000 mg/kg bw in male and female rats.

 

Two supporting studies are available for this endpoint which supports the findings of the key study. The first study (Hamburger 1984) is equivalent to OECD TG 402 and according to GLP, the test substance was applied as a single dose of 2000 mg/kg bw to shorn skin of 5 male and 5 female rats. The acute dermal LD50 was higher than 2000 mg/kg bw in both male and female rats. The second supporting study (Hamburger 1985) was conducted according to OECD TG 402 and following GLP, the test substance was applied as a single dose of 2000 mg/kg bw to shorn skin of 5 male and 5 female New Zealand White Rabbits. The acute dermal LD50 was higher than 2000 mg/kg bw in both male and female rabbits.

Justification for classification or non-classification

Based on the result of the acute oral toxicity study, the test substance is classified as Acute Tox Oral Cat. 3; H301 toxic if swallowed, in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. (EC) 1272/2008. Classification for the dermal and respiratory route is not warranted.