N,N-bis(2-hydroxypropyl)benzamide

Endpoint summary

Description of key information

In vivo OECD TG 404 study on rabbits: not irritating to skin

In vivo OECD TG 405 study on rabbits: not 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:

From June 05th to July 24th, 2001

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

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: 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:

TEST ANIMALS
- Source: elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne/France
- Age at study initiation: 12-13 weeks for males, 10-11 weeks for females
- Weight at study initiation: 2.3-2.4 Kg
- Housing: Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with autoclave wood and haysticks for gnawing
- Diet (e.g. ad libitum): Pelleted standard Kliba 3418, batch no. 90/01 rabbit maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst) available ad libitum.
- Water (e.g. ad libitum): Community tap water available ad libitum.
- Acclimation: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

bi-distilled

Controls:

no

Amount / concentration applied:

0,5 g of substance per animal, diluted in bi-distilled water

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3 per test (both sexes)

Details on study design:

TEST SITE
- Area of exposure: approximately 6 cm2
- Type of wrap if used: surgical gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): lukewarm tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM: individual mean score for erythema/eschar and oedema

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1 h after removal

Score:

0

Max. score:

0

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 h after removal

Score:

0

Max. score:

0

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 48 h after removal

Score:

0

Max. score:

0

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 72 h after removal

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1 h after removal

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 h after removal

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 48 h after removal

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 72 h after removal

Score:

0

Max. score:

0

Irritant / corrosive response data:

The test item did not elicit any skin reactions at the application site of any animal at any of the observation times. The individual mean score for erythema/escar and oedema for each of the three animals was therefore 0.
No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin

Other effects:

No clinical signs of systemic toxicity and no mortality occured. No staining by the test item of the treated skin was observed. The body weights of alla rabbits were considered to be within the noraml range of variability.

Interpretation of results:

GHS criteria not met

Conclusions:

Substance did not induce any reaction in rabbit skin. All erythema and oedema scores were 0. Therefore the substance can be considered as not irritating to skin

Executive summary:

The primary skin irritation potential of the substacne was investigated by topical semi-occlusive application of 0,5 g to 6 cm2 intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment ws four hours. The scoring of skin reactions was performed 1,24,48 and 72 hours after removal of the dressing. The test item did not elicit any skin reactions at the application site of any animal at any of the observation times. The individual mean score for erythema/escar and oedema for each of the three animals was therefore 0. The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any measuring interval. Therefore the substance can be considered as not irritating to 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:

From July 3th to July 19th, 2001

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

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: 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:

TEST ANIMALS
- Source: elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne/France
- Age at study initiation: 10-11 weeks (both sexes)
- Housing: Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with autoclave wood and haysticks for gnawing
- Diet (e.g. ad libitum): Pelleted standard Kliba 3418, batch no. 90/01 rabbit maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst) available ad libitum.
- Water (e.g. ad libitum): Community tap water available ad libitum.
- Acclimation: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0,1 g/animal

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

10 days

Number of animals or in vitro replicates:

3 per test (1 male, 2 females)

Details on study design:

REMOVAL OF TEST SUBSTANCE
Substance was not removed.
SCORING SYSTEM: Cumulative Scores for the Eye Irritation Scores, including corneal opacity, iridic effects, conjunctival reddening and/or chemosis.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 7 d

Remarks on result:

probability of weak irritation

Remarks:

One rabbit showed reversible irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible within: 10 days

Remarks on result:

probability of mild irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.56

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

2.89

Max. score:

6

Reversibility:

fully reversible within: 10 days

Irritant / corrosive response data:

Eye reactions (mean values from 24 to 72 hours) consisted of grade 0.33 corneal opacity, grade 0.00 iris lesions, grade 2.00 redness of the conjunctivae and grade 0.56 chemosis of the conjunctivae. A slight corneal opacity was observed in one fenale from 24 to 72 hours after treatment.
Slight to moderate reddening of the conjunctivae was observed in the male from 1 hour to 7 days after treatment. Slight to marked reddening was also noted in both females from 1 to 72 hours after treatment.
Slight swelling of the conjunctivae was evident in male at the 1 and 24 hours readings. Slight to obvious swelling (with partial eversion of lids) was observed in both females from either 1 to 24 hours after treatment.
A slight to moderate mucus discharge was observed in both females at the 1, 24 and 48 hours readings.
Moderate reddening of the sclera was noted in the male from 1 to 24 hours after treatment. Slight to moderate reddening was observed in both females during the observation period but cleared by day 7.
No corrosion of the cornea was observed at any of the reading times.

Other effects:

No abnormal findings were noted in the treated eye of any animal on test day 10 at termination. No staining of the treated eyes by the test itme was observed. The body weights were considered to be within the normal range of variability.

Interpretation of results:

GHS criteria not met

Conclusions:

Although the substance showed some effects on eyes of rabbits, except for the conjunctivae redness grade which anyhow resulted at the lower level for classification, all the other parameters measured in the study are well below the limit of classification not showing any effect of the chemical on the eye.
As the substance is a powder and was applied as such (undiluted) to the eyes, the redness effect on conjunctivae is probably due to the physical effect of the powder and not to the chemical nature of the substance and as a consequence the substance is not considered as irritant to eyes.

Executive summary:

An in vivo study on rabbits was performed according to OECD TG 405. A dose of 0.1 g of the substance was instillated into one eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48, 72 hours, 7 and 10 days after application. The scores at reading times 24, 48 and 72 hours were used in calculating the respective mean values for each type of lesion.

No effects on iris were noted in any animal at any reading time.

The substance induced corneal opacity in one female, with mean score of 1 (mean of three animals 0.33), and conjunctival chemosis in all three rabbits, with total mean scores of 0.56 (0.33 and 1 for the two females, 0.33 for the male).

The most relevant effect was conjunctival redness, with mean score of 2 and 2.33 in females, and 1.67 on male.

The overall irritation score, calculated as the mean cumulative scores of all effects at 24, 48 and 72 hours, was determined to be 2.89.

All effects were reversible within 10 days.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

No effects on rabbit's skin were induced by the substance in a valid and reliable in vivo study on rabbits (OECD 404). All erythema and oedema scores were 0. Therefore, the substance is not classified for skin irritation according to CLP criteria.

Although the substance showed some effects on eyes of rabbits in a valid in vivo study according to OECD TG 405,

except for the conjunctivae redness grade which anyhow resulted at the lower level for classification, all the other parameters measured in the study are well below the limit of classification not showing any effect of the chemical on the eye.

As the substance is a powder and was applied as such (undiluted) to the eyes, the redness effect on conjunctivae is probably due to the physical effect of the powder and not to the chemical nature of the substance and as a consequence the substance is not considered as irritant to eyes.

No study is available regarding respiratory irritation, therefore no conclusion on classification can be done.