N,N'-naphthalene-1,5-diylbis[4-[(2,3-dichlorophenyl)azo]-3-hydroxynaphthalene-2-carboxamide]

Endpoint summary

Description of key information

The structural analogue Pigment Red 242 (nano form) was found to be non toxic upon acute oral toxicity in rats treated with 2000 mg/kg bw. In addition, the structural analogue Pigment Red 144 showed no acute dermal toxicity in rabbits up to 2000 mg/kg bw. This observation is supported by the physico-chemical properties which indicate absent or very low skin permeability. Regarding inhalation toxicity the structural analogue Pigment Red 220 was found to be non toxic in rat exposed with whole body 4 h with up to 2200 mg/m³ air.  

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and OECD testing guideline compliant study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: HanIbm: WIST

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., CH-4414 Füllinsdorf
- Age at study initiation: 8 weeks (males) and 10 weeks (females)
- Weight at study initiation: males: 193 - 210 g, females: 167 - 184 g
- Fasting period before study: overnight
- Housing: Groups of five
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: October 30 to November 13, 1991

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 ml


MAXIMUM DOSE VOLUME APPLIED: 10 ml

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weight on test days 1 (pre-administration), 8 and 15. Clinical signs: Each animal was examined for changes in appearance and behaviour four times during day 1, and daily during days 2-15.
- Necropsy of survivors performed: yes
:

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality occurred.

Mortality:

None

Clinical signs:

other: None

Gross pathology:

No findings

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Please refer to attached read across justification document (Chapter 13).

Reason / purpose for cross-reference:

read-across source

Limit test:

yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality occurred.

Mortality:

None

Clinical signs:

other: None

Gross pathology:

No findings

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Reliable and valid.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Unreliable testing facility: study protocol equivalent or similar to OECD Guideline 403 (TS concentration in testing atmosphere <5 mg/l, no MMAD / GSD, whole body exposure, no details on analytical verification of test atmosphere concentration, body weight determined only twice [start and end]; TS purity not specified; no GLP)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

Dust

Deviations:

yes

Remarks:

TS concentration in testing atmosphere <5 mg/l, no MMAD / GSD, whole body exposure, no details on analytical verification of test atmosphere concentration, body weight determined only twice [start and end]; TS purity not specified

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ARS/Sprague-Dawley, Madison, Wisconsin
- Age at study initiation: no data (young albino rats)
- Weight at study initiation: 205
- Housing: housed in stock cages
- Diet (e.g. ad libitum): standard laboratory diet (Purina Rat Chow, Ralston Purina Company, St. Louis, Missouri); ad libitum, except during inhalation exposure
- Water (e.g. ad libitum): drinking water; ad libitum , except during inhalation exposure
- Acclimation period: at leat 5 days

ENVIRONMENTAL CONDITIONS
No data

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: test animals were exposed in a specially constructed Plexiglas inhalation chamber. The chamber was designed so that the animals could be introduced to the test atmosphere after the maximum dust concentration was established.
- Exposure chamber volume: 70 liters
- Method of holding animals in test chamber: not further specified; each animal was caged separately during exposure to minimize filtration of inspired air by animal fur.
- Source and rate of air: air flow rate through the system was 4.1 L/min at 29.92 inches Hg and 25°C (measured with a rotameter connected upstream of the dust feeder). The rotameter was calibrated with a wet-test meter after the exposure was completed.
- System of generating particulates/aerosols: dust was suspended with a specially designed dust feeder capable of producing high concentrations over a long period of time. The test material powder was passed through a high-velocity stream of clean dry air (-40°C dewpoint). The resulting air and dust mixture was then introduced into the exposure chamber at the top center, dispersed by a baffle plate and exhausted at the bottom of the chamber.
- Method of particle size determination: a sample of airborne dust was collected from the test atmosphere for the purpose of conducting a microscopic determination of particle size distribution. Particles were counted with respect to three size ranges, viz. 5 µm or smaller (considered to be respirable), 6-25 µm and >25 µm. The smallest particle which can be detected by the light-field technique employed is approximately µm. The largest particle observed was also recorded.
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: the temperature of the test atmosphere was 22.5°C and the pressure was 30.50 inches Hg.

TEST ATMOSPHERE
- Brief description of analytical method used: the concentration of test material dust present in the exposure chamber was determined by sampling the test atmosphere in the breathing zone of the animals being exposed. The total weight of dust collected on a glass fiber filter was divided by the total volume of air drawn through the filter during the sampling period. Air flow rate for sampling was regulated by a calibrated limiting orifice. The average concentration of airborne dust, obtained by repeated air sampling, was 2200 mg/m3 air at 25°C and 29.92 inches Hg.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Table 1

Analytical verification of test atmosphere concentrations:

not specified

Remarks:

not specified

Duration of exposure:

4 h

Concentrations:

2200 mg/m3

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: initial and final body weights and reactions were recorded; the exposure was designed to run for a 4-hour period, during which time observations were made with respect to incidence of mortality and reactions displayed. At the end of the exposure period, the rats were returned to their stock cages and observed for the following 14 days.
- Necropsy of survivors performed: yes, gross pathologic examinations were scheduled to be conducted upon all animals which might succumb during the test period and upon those sacrificed at the end of the 14-day observation period.

Statistics:

In the event of significant mortality following the initial exposure, arrangements were made to conduct additional experiments at lower dust concentrations in order to acquire data sufficient to calculate the acute dust inhalation median lethal concentration (LC50) of the test material employing the method of Litchfield and Wilcoxon.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2 200 mg/m³ air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: No deaths were noted during the four-hour exposure period or 14-day observation period which followed

Mortality:

No deaths were noted during the four-hour exposure period or 14-day observation period which followed.

Clinical signs:

other: No abnormal behavioral reactions were noted during the four-hour exposure period or 14-day observation period which followed.

Body weight:

Some animals lost weight and the average body weight gain was slightly lower than historical control data (Table 1).

Gross pathology:

Necropsy, performed on all animals at the end of the two-week observation period, revealed slight to moderate diffuse focal red discoloration of the lungs in six rats. There were no other gross pathologic alterations in any of the other tissues and organs examined.

Table 2: Body weight data

Animal number and sex	Individual and mean body weights and body weight gain (g)
	Body weights (g) after		14-day body weight gain
	0 day	14 days
1-Male	241	234	-7
2-Male	221	249	28
3-Male	236	262	26
4-Male	228	223	-5
5-Male	223	231	8
Mean	230	240	10
1-Female	187	210	23
2-Female	185	174	-11
3-Female	175	170	-5
4-Female	179	174	-5
5-Female	175	195	20
Mean	180	185	4
Historical control data: the average 14-day body weight gain for a group of rats equally sexed and weighing 175 to 225 grams is approximately 25 to 35 grams.

 

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Justification for type of information:

Please refer to attached read across justification document (Chapter 13).

Reason / purpose for cross-reference:

read-across source

Duration of exposure:

h

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2 200 mg/m³ air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: No deaths were noted during the four-hour exposure period or 14-day observation period which followed

Mortality:

No deaths were noted during the four-hour exposure period or 14-day observation period which followed.

Clinical signs:

other: No abnormal behavioral reactions were noted during the four-hour exposure period or 14-day observation period which followed.

Body weight:

Some animals lost weight and the average body weight gain was slightly lower than historical control data (Table 1).

Gross pathology:

Necropsy, performed on all animals at the end of the two-week observation period, revealed slight to moderate diffuse focal red discoloration of the lungs in six rats. There were no other gross pathologic alterations in any of the other tissues and organs examined.

Reference 3

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

> 2.2 mg/L air

Physical form:

inhalation: aerosol

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (TS purity not specified; size of application area not reported; 4 animals used (without justification); abraded skin was treated in 2 animals)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

4 animals used (without justification); abraded skin was treated in 2 animals; size of application area not reported

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: local supplier
- Age at study initiation: 8-11 weeks
- Weight at study initiation: 2.5-2.7 kg
- Housing: individually in elevated wire mesh cages
- Diet (e.g. ad libitum): Purina Rabbit Chow ad lib.
- Water (e.g. ad libitum): water from bottles ad lib.
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
Housing in temperature controlled rooms (no further details)

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: back, intact or abraded skin (each 2 animals; abraded with a 21 gauge bent tip needle. The abrasions, made every 2 to 3 cm longitudinally, scratched the stratum corneum, but did not disturb the derma or produce bleeding)
- % coverage: not reported (regarding the body weight of ca. 2500 mg and the formula BSA = 9.5 * (body weight in g)exp(2/3), the test site should be > 180 cm2 for guideline conformity)
- Type of wrap if used: impervious material

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm tap water

TEST MATERIAL
- Concentration (if solution): 50% w/v suspension in distilled water
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations: once daily; weighing once weekly
- Necropsy of survivors performed: yes
- Other examinations performed: evaluation of local effects according to OECD Draize scheme after 25 hours, 7 and 14 days

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Abrasion (2/4 animals) had no effect on local or systemic effects

Mortality:

no mortality

Clinical signs:

other: in 1 animal (intact skin): Diarrhea, days 3 & 4 and 7 to 10; Abdomen bloated, days 4 to 7; Anorexia, days 5 and 6; Adipsia, days 5 and 6; no fecal matter in pan day 5.

Gross pathology:

One animal had yellow exudate from nose/mouth and another had bloated intestines. No abnormal findings in the other two animals (with abraded skin).

Other findings:

Neither erythema nor edema were observed.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Please refer to attached read across justification document (Chapter 13).

Reason / purpose for cross-reference:

read-across source

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Abrasion (2/4 animals) had no effect on local or systemic effects

Mortality:

no mortality

Clinical signs:

other: in 1 animal (intact skin): Diarrhea, days 3 & 4 and 7 to 10; Abdomen bloated, days 4 to 7; Anorexia, days 5 and 6; Adipsia, days 5 and 6; no fecal matter in pan day 5.

Gross pathology:

One animal had yellow exudate from nose/mouth and another had bloated intestines. No abnormal findings in the other two animals (with abraded skin).

Other findings:

Neither erythema nor edema were observed.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

reliable and valid

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result, the substance is not considered to be classified for acute oral, dermal or inhalation toxicity under Regulation (EC) No. 1272/2008.