4,4'-[1,3-phenylenebis(azo)]bisbenzene-1,3-diamine

Endpoint summary

Description of key information

Skin

In vivo

Rabbit (three animals) (OECD 404): not irritating (Kemira, 1990)

in vitro

no data available

Eye

In vivo

Rabbit (three animals) (OECD 405): not irritating (Kemira, 1990)

Respiratory system

no data available

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: Study following official guideline in GLP

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

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: Interfauna UK Ltd, Wyton, Huntingdon, England
- Weight at study initiation: the animals were weighed immediately before application of the test substance
- Housing: the rabbits were individually housed in stainless steel cages with flat rod bases or polyethyelene cages with perforated bases. Excrement trays beneath the cages contained low-dust (wood) bedding . Bedding was regularly spotted for contaminants and changed at least twice weekly.All the animals were kept in one room
- Diet (e.g. ad libitum): standard diet "Saniff K4" approx. 100-120 g per animal/day, once per day in the morning
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: the animals were kept for at least 14 days in the quarantine station and monitored for diseases. During this period pooled faeces specimens were examined for coccidia oocysts

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 50%
- Air changes (per hr): apporx. 10 times per hour
- Photoperiod (hrs dark / hrs light): 12 hours, artificial illumination from 6 to 18 hrs CET time

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: the contralateral skin area not treated with test substance served as control

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4h

Observation period:

1, 24, 48 and 72h, 7d, 14d

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6 cm square

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the exposed skin areas were carefully washed with wtaer without altering the existing responses

SCORING SYSTEM: draize score at 24, 48 and 72h and the total of these three values was divided by 3 to give the irritation index. This index was separately calculated for erythema/eschar formation and for oedema formation.

Irritation parameter:

erythema score

Remarks:

(draize score)

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

edema score

Remarks:

(draize score)

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

erythema score

Remarks:

(draize score)

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

edema score

Remarks:

(draize score)

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

erythema score

Remarks:

(draize score)

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

edema score

Remarks:

(draize score)

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Interpretation of results:

other: not classified under Regulation 1272/2008

Conclusions:

The substance was tested for skin irritation following OECD 404. Under the test conditions the substance did not show irritating properties.

Executive summary:

The substance was tested for skin irritation following OECD 404. Three New Zealand White rabbits were exposed to the test item in a semi-occlusive patch for 4 hours after clipping the lateral area of the dorso. Skin effects like oedema and erythema were checked and the mean values at 24,48 and 72h were calculated and resulted equal to zero for the three animals. Under the experimental conditions the substance is not considered as skin irritant.

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: Study following official guideline in GLP

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Interfauna UK Ltd, Wyton, Huntingdon, England
- Weight at study initiation: the animals were weighed immediately before application of the test substance
- Housing: the rabbits were individually housed in stainless steel cages with flat rod bases or polyethyelene cages with perforated bases. Excrement trays beneath the cages contained low-dust (wood) bedding . Bedding was regularly spotted for contaminants and changed at least twice weekly.All the animals were kept in one room
- Diet (e.g. ad libitum): standard diet "Saniff K4" approx. 100-120 g per animal/day, once per day in the morning
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: the animals were kept for at least 14 days in the quarantine station and monitored for diseases. During this period pooled faeces specimens were examined for coccidia oocysts

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 50%
- Air changes (per hr): apporx. 10 times per hour
- Photoperiod (hrs dark / hrs light): 12 hours, artificial illumination from 6 to 18 hrs CET time

Controls:

other: the other eye remained untreated and served as control

Amount / concentration applied:

100ul equivaletn to 90 mg

Duration of treatment / exposure:

24h

Observation period (in vivo):

after rinsing with water the irritant effect was scored after 1,24,48,72h and 7,14,21d

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the eye was rinsed with saline
- Time after start of exposure: immediately after termination of 24h

SCORING SYSTEM: draize scoring system. The irritation indices/mean irritation indices were calculated for cornea, iris, erythema and swelling . Only effects persisting after 24h were included in the evaluation

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein

Irritation parameter:

conjunctivae score

Remarks:

(draize score)

Basis:

other: mean of three animals

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

cornea opacity score

Remarks:

(draize score)

Basis:

other: mean of three animals

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

iris score

Remarks:

(driaze score)

Basis:

other: mean of three animals

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

other: discharge

Basis:

other: mean of three animals

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

chemosis score

Basis:

animal:

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Other effects:

any serious lesions or toxic effects were recorded: no effect

Interpretation of results:

other: not classified under Regulation 1272/2008

Conclusions:

The substance was tested for eye irritation following OECD 405. Under the test conditions the substance did not show irritating properties.

Executive summary:

The substance was tested for eye irritation following OECD 405. The eyes of three New Zealand White rabbits were instilled with test item for 24h and then rinsed with saline solution. Irritating/corrosive effects in the cornea, iris and conjuncitvae (erythema,swelling and discherage) were checked and the mean calculated values at 24,48 and 72h for each animal resulted equal to zero. Under the experimental conditions the substance is not considered as eye irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There are valid in vivo data available for the assessment of the skin and eye irritation potential of the test substance.

Skin

The potential of the test substance to cause acute dermal irritation or corrosion was assessed in vivo in rabbits according to OECD guideline 404. In this study the test article did not show any irritative/corrosive potential by a single topical application of 0.5 g of the test substance to the intact skin of 3 White New Zeland rabbits for 4 hours under semiocclusive conditions. The average score (24, 48 and 72 hours) for irritation was calculated to be 0.0 for erythema and 0.0 for edema.

 

Eye

The potential of the test substance to cause eye irritation or corrosion was assessed in 3 rabbits according to OECD guideline 405. The test substance did not show any irritative/corrosive potential after 24h after exposure. Irritation score was calculate for cornea (0.0), iris (0.0) conjunctivae (0.0) and discharge (0.0).

 

Respiratory system

no information available.

 

Justification for classification or non-classification

Under Regulation 1272/2008 a substance is classified as skin irritant Cat. 2 if:

1) Mean value of ≥ 2,3 - ≤ 4,0 for erythema/ eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions; or

2)Inflammation that persists to the end of the observation period normally 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; or

3) In some cases where there is pronounced variability of response among animals, with very definite positive effects related to chemical exposure in a single animal but less than the criteria above.

Mean values at 24, 48 and 72h for oedema or erythema are zero for all animals, therefore the test substance is not classified as skin irritant.

Under Regulation 1272/2008 a substance is classified as eye irritant Cat. 2 if it is presentat least in 2 of 3 tested animals, a positive response of

1)    corneal opacity ≥ 1 and/or

2)   iritis ≥ 1, and/or

3)  conjunctival redness ≥ 2 and/or

4)  conjunctival oedema (chemosis) ≥ 2

calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days.

All the scores calculated as mean value at 24, 48 and 72h for the test substances for all tested animals are zero therefore the substance is not classified as eye irritant.