2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[N-(4-chloro-2,5-dimethoxyphenyl)-3-oxobutyramide]

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 4 DEC 1989 to 18 DEC 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Reference 2

Reference Type:

publication

Title:

Investigation of possible metabolism of Pigment Yellow 17, a 3,3'-dichlorobenzidine-based pigment, after inhalation exposure in rats

Author:

Hofmann T, Schmidt D

Year:

1993

Bibliographic source:

Arch. Toxicol. 67: 141-144

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[N-(2-methoxyphenyl)-3-oxobutyramide]

EC Number:

224-867-1

EC Name:

2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[N-(2-methoxyphenyl)-3-oxobutyramide]

Cas Number:

4531-49-1

Molecular formula:

C34H30Cl2N6O6

IUPAC Name:

2,2'-[(3,3'-dichlorobiphenyl-4,4'-diyl)didiazene-2,1-diyl]bis[N-(2-methoxyphenyl)-3-oxobutanamide]

Test material form:

solid: nanoform

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Kastengrund, SPF breeding colony
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: males mean: 227 g; females mean: 195 g
- Housing: macrolon cages (type 4) groups of 5 respectively 2 (= control animal and animal killed 1 day post application)
- Diet: rat diet Altromin 1324 ( Altromin-GmbH, Lage/Lippe, Germany); ad libitum
- Water: Tap water; ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 2
- Humidity (%): 50 +/- 20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical plastic cage
- Exposure chamber volume: 60 L
- Method of holding animals in test chamber: each animal was in a plastic tube
- Source and rate of air: laminar air stream of 1000 L/hour at 4 bar from above
- System of generating particulates/aerosols: dustgenerator "Wright Dust Feed" of L. Adams Ltd., London, UK
- Method of particle size determination: "Anderson-Kaskadenimpaktor Mark III" of Anderson Samples Inc, Atlanta, USA
- Treatment of exhaust air: exhaust device at the basement of the exposure chamber in line with a diverse system of filters

TEST ATMOSPHERE ANALYSIS
- Brief description of analytical method used: gravimetric measurement: The test atmosphere was sucked through filters ("Experimentiertrommelgasfilter", Elster AG, Mainz-Kastel, Germany; as well as a fibre glass and a membrane filter (diameter of pores 0.65 µm) Satorius Membranfilter GmbH, Göttingen, Germany) by means of vacuum. The exhaust quantity was 3 L/min, which resulted in an air flow of 1.25 m/sec. The filters were positioned in an exsiccator 24 h before use. The filters were weighed before and after each measurement by means of electrical scales.

TEST ATMOSPHERE
- Particle size distribution: < 0.6 µm to > 10.3 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.0 - 1.1/ 2.3 - 2.8

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric measurement

Duration of exposure:

4 h

Concentrations:

230 mg/m³ air

No. of animals per sex per dose:

6/sex/treatment group
1/sex/control group

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: twice a day
- Frequency of weighing: weekly
- Necropsy of survivors performed: yes

- Control urine and blood samples were collected from control animals.
- On day 1, 2 and 7 one male and one female were sacrificed to obtain blood samples. Final sacrifice of the remaining 3 animals/sex was on day 14 of the observation period.
- Urin samples were collected starting on the day of exposure till day 7 of the observation period and the last night before sacrifice.
- To collect urine the rats were placed in metabolism cages overnight without witdrawal of food and water. For technical reasons urine was collected continously on day 6 and 7.
- Blood was collected via puncture of the retro-orbital plexus.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 230 mg/m³ air

Exp. duration:

4 h

Remarks on result:

other: no animals died within the 14 day observation period

Mortality:

- no deaths occurred

Clinical signs:

other: - during the exposition: irregular breathing, narrowed palpebral fissures and female animals showed additional stilted gate - no more clinical signs were observed in males 330 minutes p.a. and in females 450 minutes p.a.

Body weight:

- Body weight development was impaired in the first week, probably due to the frequent placement in metabolism cages.
- But all animals except for one female did excess their initial body weight at the end of the test period.

Gross pathology:

- no macroscopically visible changes were found

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Exposure of male and female Wistar rats to 230 mg/m³ test item for 4 hours did not result in the death of the animals during a 14 day observation period, resulting in a LC50 value of > 230 mg/m³.

Executive summary:

Acute inhalation toxicity of the test item has been investigated in male and female Wistar rats. They were exposed to 230 mg test substance per cubic meter for 4 h (maximal applicable dose). All animals survived the 14 day observation period. No macroscopic visible changes were observed at necropsy at the end of the observation period, resulting in a LC50 value of > 230 mg/m³ for the inhalation of dust.

Classification for acute inhalation toxicity is not necessary according to Regulation (EC) No 1272/2008 .