Registration Dossier

Skin irritation:

The acute dermal irritation/corrosion of N-(3(5)-Methyl-1H-pyrazol-l-yl-methyl)- acetamid (P 70/05) was tested in three albino rabbits according to OECD Guideline 404 (Acute Dermal Irritation / Corrosion). The test item was applied as the original substance after grinding in a mortar at a dose of 0.5 g to a shaved dorsal area of trunk and covered with a gauze patch and aluminium foil which was held in contact with the skin with an occlusive dressing.

The administration of 0.5 g of N-(3(5)-Methyl-lH-pyrazoM-yl-methyl)-acetamid (P 70/05)

to shaved dorsal area of the trunk of albino rabbits did not cause any skin irritation at any observation time.

Eye irritation:

The acute eye irritation/corrosion of N-(3(5)-Methyl-1H-pyrazoI-l-yl-methyl)-acetamid (P 70/05) was tested in three albino rabbits according to OECD Guideline 405 (Acute Eye Irritation / Corrosion). The test item was instilled as the original substance at a single dose of 0.1 ml to one of the eyes in each animal. The untreated eye was used as control.

The animals were examined for clinical signs and the eyes were examined for lesions of the conjunctivae, cornea and iris 60 minutes, 24, 48 and 72 hours and from day 4 till day 14 after instillation of the test item. The grades for ocular lesions were recorded in accordance with the guideline.

A single instillation of N-(3(5)-Methyl-lH-pyrazol-l-yl-methyN-(3(5)-Methyl-lH-pyrazol-l-yl-methyl)-acetamid (P 70/05) into the conjunctival sac of three albino rabbits caused a damage of the epithelia of the cornea, slight effects to the iris, slight to moderate redness and swelling of the conjunctivae and a purulent secretion from the eye. All effects were reversible within anan observation period of 13 days. The alterations of the eyes after instillation of N-(3 (5)-Methyl-1 H-pyrazol-1 -yl-methyl)- acetamid (P 70/05) meet the criteria for classification as an eye irritant.

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-05-10 - 2007-06-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

The study room and cages were cleaned and disinfected before the animals arrived. During the study, the room and cages were cleaned at regular intervals.
Cages of stainless steel with bottom grid of oval steel and with tub for
faeces, dimensions of the cages: 50 x 55 x 40 cm.
The animals were housed individually.
Air conditioned: temperature: 19.5 - 23.0 °C relative humidity: 30 - 50 % artificial light was set to give a cycle of 12 hours light and 12 hours dark; the light phase was from 6.30 a.m. - 6.30 p.m.

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

other: Tylose MH 1000 in deionised water

Controls:

not required

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Ani	Expo	Observed grades of skin alterations at each observation time
mal	sure	Erythema					Oedema
No.	period	hours after administration				X	hours after administration				X
		1	24	48	72	Test item	1	24	48	72	Test item
1	3 min	0	0	0	0		0	0	0	0
	lh	0	0	0	0		0	0	0	0
	4 h	0	0	0	0	0	0	0	0	0	0
	Control	0	0	0	0		0	0	0	0
2	4 h	0	0	0	0	0	0	0	0	0	0
	Control	0	0	0	0		0	0	0	0
3	4 h	0	0	0	0	0	0	0	0	0	0
	Control	0	0	0	0		0	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal irritation/corrosion of N-(3(5)-Methyl-1H-pyrazol-l-yl-methyl)- acetamid (P 70/05) was tested in three albino rabbits according to OECD Guideline 404 (Acute Dermal Irritation / Corrosion). The test item was applied as the original substance after grinding in a mortar at a dose of 0.5 g to a shaved dorsal area of trunk and covered with a gauze patch and aluminium foil which was held in contact with the skin with an occlusive dressing. The test was started with one rabbit with exposure periods of three minutes, one hour and four hours. Because no serious skin reaction was observed in this animal the result was confirmed using two further animals with a four-hour exposure. After each exposure the administration area was cleaned with deionised water.
Animals were examined for mortality, clinical signs and signs of irritation response 60 minutes, 24, 48, 72 hours after patch removal. The grading of skin reaction given in the guideline was used for the evaluation of the dermal irritation.
The administration of 0.5 g of N-(3(5)-Methyl-lH-pyrazoM-yl-methyl)-acetamid (P 70/05) to shaved dorsal area of the trunk of albino rabbits did not cause any skin irritation at any observation time. No systemic toxic effects were observed.

Executive summary:

The acute dermal irritation/corrosion of N-(3(5)-Methyl-1H-pyrazol-l-yl-methyl)- acetamid (P 70/05) was tested in three albino rabbits according to OECD Guideline 404 (Acute Dermal Irritation / Corrosion). The test item was applied as the original substance after grinding in a mortar at a dose of 0.5 g to a shaved dorsal area of trunk and covered with a gauze patch and aluminium foil which was held in contact with the skin with an occlusive dressing. The test was started with one rabbit with exposure periods of three minutes, one hour and four hours. Because no serious skin reaction was observed in this animal the result was confirmed using two further animals with a four-hour exposure. After each exposure the administration area was cleaned with deionised water.

Animals were examined for mortality, clinical signs and signs of irritation response 60 minutes, 24, 48, 72 hours after patch removal. The grading of skin reaction given in the guideline was used for the evaluation of the dermal irritation.

The administration of 0.5 g of N-(3(5)-Methyl-lH-pyrazoM-yl-methyl)-acetamid (P 70/05)

to shaved dorsal area of the trunk of albino rabbits did not cause any skin irritation at any observation time.

No systemic toxic effects were observed.

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-05-10 - 2007-06-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

The study room and cages were cleaned and disinfected before the animals arrived. During the study, the room and cages were cleaned at regular intervals.
The animals were housed individually.
Air conditioned: temperature: 18.5 - 22.5 °C, with a shortly rising on 24.5 °C,
relative humidity: 33 - 70 % artificial light was set to give a cycle of 12 hours light and 12 hours dark; the light phase was from 6.30 a.m. - 6.30 p.m.

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 ml of the test item (approx. 51 mg)

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

3 male rabbits

Details on study design:

The test was carried out with three male rabbits.
Both eyes of each animal were examined before testing. Two to three drops of a fluorescein sodium solution (0.5 % in deionised water) were instilled into the conjunctival sac and rinsed out again after 30 sec with deionised water. No ocular defects were observed in any of the animals.
A volume of 0.1 ml of the test item (approx. 51 mg) was instilled into the conjunctival sac of one eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then held together gently for approximately 1 second in order to prevent loss of the material. The other eye of the same animal, which remained untreated, served as control.
The treated eyes were carefully rinsed out with deionised water one hour after instillation because partly a lot of test item could be observed in the conjunctival sac.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.8

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Conclusions:

The acute eye irritation/corrosion of N-(3(5)-Methyl-1H-pyrazoI-l-yl-methyl)-acetamid (P 70/05) was tested in three albino rabbits according to OECD Guideline 405 (Acute Eye Irritation / Corrosion). The test item was instilled as the original substance at a single dose of 0.1 ml to one of the eyes in each animal. The untreated eye was used as control.
The animals were examined for clinical signs and the eyes were examined for lesions of the conjunctivae, cornea and iris 60 minutes, 24, 48 and 72 hours and from day 4 till day 14 after instillation of the test item. The grades for ocular lesions were recorded in accordance with the guideline.
A single instillation of N-(3(5)-Methyl-lH-pyrazol-l-yl-methyl)-acetamid (P 70/05) into the conjunctival sac of three albino rabbits caused a damage of the epithelia of the cornea, slight effects to the iris, slight to moderate redness and swelling of the conjunctivae and a purulent secretion from the eye.
All effects were reversible within an observation period of 13 days. None of the animals died or showed clinical signs during the course of testing.
The alterations of the eyes after instillation of N-(3 (5)-Methyl-1 H-pyrazol-1 -yl-methyl)- acetamid (P 70/05) meet the criteria for classification as an eye irritant.

Executive summary:

The acute eye irritation/corrosion of N-(3(5)-Methyl-1H-pyrazoI-l-yl-methyl)-acetamid (P 70/05) was tested in three albino rabbits according to OECD Guideline 405 (Acute Eye Irritation / Corrosion). The test item was instilled as the original substance at a single dose of 0.1 ml to one of the eyes in each animal. The untreated eye was used as control.

The animals were examined for clinical signs and the eyes were examined for lesions of the conjunctivae, cornea and iris 60 minutes, 24, 48 and 72 hours and from day 4 till day 14 after instillation of the test item. The grades for ocular lesions were recorded in accordance with the guideline.

A single instillation of N-(3(5)-Methyl-lH-pyrazol-l-yl-methyl)-acetamid (P 70/05) into the conjunctival sac of three albino rabbits caused a damage of the epithelia of the cornea, slight effects to the iris, slight to moderate redness and swelling of the conjunctivae and a purulent secretion from the eye. All effects were reversible within an observation period of 13 days. None of the animals died or showed clinical signs during the course of testing. The alterations of the eyes after instillation of N-(3 (5)-Methyl-1 H-pyrazol-1 -yl-methyl)- acetamid (P 70/05) meet the criteria for classification as an eye irritant.

Endpoint conclusion:

adverse effect observed (irritating)

Endpoint conclusion:

no study available

No data gaps were identified. The available data are adequate for risk assessment and classification and labelling purposes.

Justification for selection of skin irritation / corrosion endpoint:

Only one study available. The key study is GLP-compliant and has Klimisch score 1.

Justification for selection of eye irritation endpoint:

Only one study available.The key study is GLP-compliant and has Klimisch score 1.

Effects on eye irritation: irritating

Skin irritation:

According to the CLP Regulation (EU GHS Regulation (EC) No 1272/2008) classification and labelling is not required for skin irritation of N-(3(5)-Methyl-1 H-pyrazol-1 -yl-methyl)-acetamid, based on reliable data from an in-vivo study according to OECD 404.

Eye irritation:

According to the CLP Regulation (EU GHS Regulation (EC) No 1272/2008) classification and labelling is required for eye irritation of N-(3(5)-Methyl-1 H-pyrazol-1 -yl-methyl)-acetamid, based on reliable data from an in-vivo study according to OECD 405. Since the substances has the potential to induce reversible eye irritation a classification in Category 2 (irritating to eyes) is required.