Alanine, N-(1-oxobutyl)-

Endpoint summary

Description of key information

Butanoylalanin is not irritating to skin and highly irritating to eyes.

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

Study period:

2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sex: male
- Source: LPT Laboratory of Pharmacology and Toxicology KG, 24601 Löhndorf, Germany
- Age at study initiation: 4.5 - 6 months
- Weight at study initiation: 1.9 - 2.5 kg
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 20 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 50 +/- 20
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: pulverized solids were moistened with water

Controls:

other: the surrounding untreated skin served as control

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours after patch removal

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: approx. 6 cm²
- Type of wrap if used: gauze patch, non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing: no residual test item had to be removed
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to DRAIZE

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Other effects:

No systemic intolerance reactions were observed.

Interpretation of results:

not irritating

Remarks:

Migrated information

Executive summary:

In a dermal irritation study according to OECD TG 404 Butanoylanilin was applied under semiocclusive conditions for 4 hours to the shaved skin of 3 rabbits. Skin irritation was assessed after 1, 24, 48 and 72 hours using the Draize scale. The mean irritation index for erythema and edema was determined with 0.0, thus, the test material was not irritating to the skin of rabbits. No systemic intolerance reactions were observed.

According to classification criteria Butanoylanilin is not an irritant to the skin.

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

Study period:

2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Sex: male
- Source: LPT Laboratory of Pharmacology and Toxicology KG, 24601 Löhndorf, Germany
- Age at study initiation: approx. 4.5 months
- Weight at study initiation: 1.9 - 2.5 kg
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 20 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 50 +/- 20
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:

unchanged (no vehicle)

Controls:

other: the left eye, which remained untreated, served as control

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

eye was not rinsed after instillation of the test item

Observation period (in vivo):

1, 24, 48 and 72 hours and 4 to 21 days after instillation

Number of animals or in vitro replicates:

3

Irritation parameter:

cornea opacity score

Basis:

animal: #1 and #3

Time point:

other: 24, 48, 72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: for details see section 'irritant/corrosive reponse data'

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24, 48, 72 h

Score:

>= 3 - <= 4

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: for details see section 'irritant/corrosive reponse data'

Irritation parameter:

iris score

Remarks:

redness

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: for details see section 'irritant/corrosive reponse data'

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 18 days

Remarks on result:

other: for details see section 'irritant/corrosive reponse data'

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 h

Score:

2

Max. score:

4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 48 h

Score:

1.6

Max. score:

4

Remarks on result:

other: for details see section 'irritant/corrosive reponse data'

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 18 days

Remarks on result:

other: for details see section 'irritant/corrosive reponse data'

Irritant / corrosive response data:

Under the present test conditions a single application of 1 00 mg Butanoylalanin per animal into the conjunctival sac of the right eye of three rabbits caused the following effects:

Corneal opacity
animal no. 1: 1 to 72 hours after instillation (grade 3), 4 to 16 days after Instillation (grade 2) and 17 to 21 days (grade 1);
animal no. 2: 1 and 24 hours after instillation (grade 3), 48 hours to 5 days after instillation (grade 4) and 6 to 21 days (grade 3);
animal no. 3: 1 hour to 5 days after instillation (grade 3), 6 to 14 days after instillation (grade 2) and 15 to 21 days (grade 1 ).
The fluorescein test performed after 24 hours revealed corneal staining in all 3 rabbits (whole surface). The fluorescein test performed after 7 days revealed corneal staining in animal no. 1 (3/4 of the corneal surface) and animal nos. 2 and 3 (whole surface).
The fluorescein tests performed after 14 days revealed corneal staining in animal no. 1 (3/4 of the corneal surface), in animal no. 2 (whole surface) and in animal no. 3 (3/4 of the corneal surface) . The fluorescein tests performed after 21 days revealed corneal staining in animal no. 1 ( 1/2 of the corneal surface), in animal no. 2 (whole surface) and in animal no. 3 (1 /4 of the corneal surface).
An irritation of the iris (grade 2) was observed in all animals 1 hour to 5 days after instillation, in animal no. 1 until 6 days, in animal no. 2 until 21 days after Instillation, (grade 1) in animal no. one 7 to 21 days and in animal no. three 6 to 16 days after Instillation.

Conjunctival redness (grade 1 ) was observed in all three animals 1 hour to 6 days after instillation, in animal no. 2 until 17 days and in animal no. 3 until 14 days after instillation.

Conjunctival chemosis
animal no. 1: 1 hour and 48 hours after instillation (grade 1 ), 24 hours after instillation (grade 2);
animal no. 2: 1 hour and 72 hours to 17 days after instillation (grade 1 ), 24 and 48 hours after instillation (grade. 2);
animal no. 3: 1 hour and 72 hours to 6 days after instillation (grade 1 ), 24 and 48 hours after nstillation (grade 2).
Further observations
Loss of hair at the upper and lower Iids was observed in rabbit no. one 7 to 1 6 days after instillation, in rabbit no. two 7 to 21 days and in rabbit no. three 7 to 11 days after instillation.
Whitish deposits in the conjunctival sac (probably pus) were noted in one rabbit (no. 2) 7 to 9 days after instillation.

Other effects:

No systemic intolerance reactions were observed.

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information

Executive summary:

In an eye irritation study according to OECD TG 405 the test substance was instilled into the conjunctival sac of one eye of 3 male rabbits each. Eye irritation was assessed 1, 24, 48 and 72 hours and 4 to 21 days after instillation using the Draize scale. In this study strong irritation was seen as corneal opacity (up to grade 4 of max. 4), effects on iris (up to grade 2 of max. 2), conjunctional redness (up to grade 1 of max. 3) and conjunctional chemosis (up to grade 2 of max. 4). Partly the effects (cornea and iris) appeared to be not reversible within the 21 days observation period. Loss of hair at the upper and lower eye lid and whitish deposits in the conjunctival sac became obvious. No systemic intolerance reactions were observed.

According to classification criteria Butanoylalanin causes serious damage to rabbit's eyes.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

In a dermal irritation study according to OECD TG 404 Butanoylalanin was applied under semiocclusive conditions for 4 hours to the shaved skin of 3 rabbits. Skin irritation was assessed after 1, 24, 48 and 72 hours using the Draize scale. The mean irritation index for erythema and edema was determined with 0.0, thus, the test material was not irritating to the skin of rabbits. No systemic intolerance reactions were observed.

Eye irritation:

In an eye irritation study according to OECD TG 405 the test substance was instilled into the conjunctival sac of one eye of 3 male rabbits each. Eye irritation was assessed 1, 24, 48 and 72 hours and 4 to 21 days after instillation using the Draize scale. In this study strong irritation was seen as corneal opacity (up to grade 4 of max. 4), effects on iris (up to grade 2 of max. 2), conjunctional redness (up to grade 1 of max. 3) and conjunctional chemosis (up to grade 2 of max. 4). Partly the effects (cornea and iris) appeared to be not reversible within the 21 days observation period. Loss of hair at the upper and lower eye lid and whitish deposits in the conjunctival sac became obvious. No systemic intolerance reactions were observed.

According to classification criteria Butanoylalanin is highly irritating to rabbit's eyes.

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

Justification for selection of eye irritation endpoint:
Only one study available

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Based on the study results a classification with R41 (risk of serious eye damage) according to Directive 67/548/EEC or with Eye Damage, Cat. 1 (H318: causes serious eye damage) according to Regulation (EC) No. 1272/2008 (CLP) is required.