1H-Pyrazole, 1,4-dimethyl-

Endpoint summary

Description of key information

Skin: OECD 404: Not irritating (BASF, 1995)
Eye: OECD 405: Corrosive (BASF, 1995)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, FRG
- Age at study initiation: young adults
- Weight at study initiation: males 3.15 and 3.74 kg, and female 3.86 kg
- Housing: single housing, in stainless steel wire mesh cages with grating; floor area: 3000 cm2; no bedding in the cages; sawdust in the waste trays
- Diet: about 130 g per animal per day, Kliba-Labordiaet 341, Klingentalmuehle AG, Kaiseraugst, Switzerland
- Water: about 250 mL tap water per animal per day
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air: fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin sites of the same animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): the test patch (2.5 cm x 2.5 cm) was moistened with a dose of 0.5 mL unchanged liquid test substance

Duration of treatment / exposure:

4 hours

Observation period:

8 days

Number of animals:

2 males, 1 female

Details on study design:

TEST SITE
- Area of exposure: upper third of the back or flanks
- Type of wrap if used: the test substance has been covered with a test patch (idealbinde, pfaelzische verbandstoff-fabrik, Kaiserslautern) and Fixomull® stretch (adhesive sleeve), Beiderdorf AG

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test substance was removed with lutrol® (Polyethylenenglycol DAB, BASF Aktiengesellschaft) and lutrol®/water (1:1)
- Time after start of exposure: 4 hours

SCORING SYSTEM: readings were performed 1 h, 24 h, 48 h, 72 h and 8 d after removal of the patch

GENERAL OBSERVATIONS: A check was made twice each workday and once on Saturdays, Sundays and on public holidays for general observations and for any dead or moribund animals.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: mean 24 - 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean 24 - 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean 24 - 72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

animal: #1, #2, #3

Time point:

other: mean 24 - 72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

In animal #3 scaling was observed at the 72 h reading.

Interpretation of results:

not irritating

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, FRG
- Age at study initiation: young adults
- Weight at study initiation: male 3.52 kg, and females 3.98 and 3.96 kg
- Housing: single housing, in stainless steel wire mesh cages with grating; floor area: 3000 cm2; no bedding in the cages; sawdust in the waste trays
- Diet: about 130 g per animal per day, Kliba-Labordiaet 341, Klingentalmuehle AG, Kaiseraugst, Switzerland
- Water: about 250 mL tap water per animal per day
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air: fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the same animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL to the conjunctival sac of the right eyelid

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

1 male, 2 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the substance was washed out with tap water
- Time after start of exposure: 24 hours after application

SCORING SYSTEM: readings were performed 1 h, 24 h , 48 h, 72 h, 8 d, 15 d and 21 d after application

GENERAL OBSERVATIONS: A check was made twice each workday and once on Saturdays, Sundays and on public holidays for general observations and for any dead or moribund animals.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: mean 24 - 72 h

Score:

2.3

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: mean 24 - 72 h

Score:

1.3

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: mean 24 - 72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: mean 24 - 72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 15 days

Irritation parameter:

iris score

Basis:

animal: #2, #3

Time point:

other: mean 24 - 72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean 24 - 72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: mean 24 - 72 h

Score:

2.3

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: mean 24 - 72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean 24 - 72 h

Score:

2.3

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: mean 24 - 72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: mean 24 - 72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 15 days

Irritant / corrosive response data:

Discharge of blood, suppuration, pupil contracted, loss of corneal tissue, and marginal vascularization of the cornea were observed in all animals exposed. In 2 out of 3 animals small retractions of the eyelid were additionally observed.

Interpretation of results:

corrosive

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin

An OECD 404 dermal irritation study was performed in compliance with GLP. Three New Zeeland White rabbits were exposed for 4 hours to the undiluted test substance under semiocclusive conditions. After the 4 hours exposure period the test substance was removed with lutrol and lutrol/water (1:1). The animals were observed the following 8 days and the skin was scored after 1, 24, 48, 72 hours and 8 days. Erythema was observed in all animals. Two animals had an mean erythema score over the 24, 48, and 72 -hour time point of 0.3. This effect was fully reversible within 48 hours. One animal had a mean erythema score of 1.3 and this was fully reversible within 8 days. No edema was observed in all three animals. Under the conditions of the test the test substance was not irritating to skin.

Eye

An OECD 405 eye irritation/corrosion study was performed in compliance with GLP. Three New Zeeland White rabbits were exposed for 24 hours to 0.1 mL undiluted test substance. After 24 hours the test substance was washed out with water. The animals were observed for the following 21 days and readings were performed 1, 24, 48, 72 hours, 8, 15, and 21 days after application. Discharge of blood, suppuration, pupil contracted, loss of corneal tissue, and marginal vascularization of the cornea were observed in all animals exposed. In 2 out of 3 animals small retractions of the eyelid were additionally observed. Under the conditions of the test the test substance was corrosive to eyes.

Justification for selection of skin irritation / corrosion endpoint:
only study available

Justification for selection of eye irritation endpoint:
only study available

Effects on eye irritation: corrosive

Justification for classification or non-classification

Based on the available information for skin and eye corrosion/irritation the substance is classified as Eye Damage 1 (H318) in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.