Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP OECD Guideline Study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
adopted May 12, 1981
GLP compliance:
yes
Remarks:
RCC, Research & Consulting Company AG, Itingen, Switzerland
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate)
EC Number:
248-421-0
EC Name:
Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate)
Cas Number:
27344-41-8
Molecular formula:
C28H22O6S2.2Na
IUPAC Name:
disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate)
Details on test material:
- Name of test material (as cited in study report): FAT 65029/G
- Physical state: powder, green
- Analytical purity: approx. 90%,
- Impurities (identity and concentrations): 7% NaCl, 3% H20
- Lot/batch No.: EN 372980, OP. 247/248
- Expiration date of the lot/batch: July 1992
- Storage condition of test material: in the original container, protected from light at room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Fuellinsdorf / Switzerland
- Age at study initiation: Males: 8 - 10 weeks; Females : 10 - 12 weeks
- Weight at study initiation: Males: 180.0 - 199.8 g; Females: 180.0 - 199.8 g
- Fasting period before study: no data
- Housing: groups of five
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: from 7 to 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Inhalation, according to the method of Sachsse et al. (1973, 1976). The animals are confined separately in tubes which are positioned radially around the exposure chamber. The flow-past, nose-only design of this exposure system has been developed based upon the fluid dynamic modeling of the aerosol flow from the entry to the animal's nose. The internal active volume of the chamber for exposing 40 animals by nose-only is one liter. The resulting time for the concentration at an animal port to reach 99 % of its ultimate value (T99) is 34 seconds for the 40 animal chambers. This system is constructed of anodised aluminium and readily accepts a variety of different sized Makrolon animal restraint tubes which have been designed in consideration of the anatomy and physiology of the rodent. The test article stream reaches the animal's nose through ports situated at different levels around the axis of the exposure chamber. Each level has 8 ports and can be rotated, allowing close observation of all the animals without interruption of exposure. The entire unit is modular, permitting easy cleaning and the choice of how many levels of animals will be used. The system is unique in comparison with conventional nose-only exposure systems in that it insures a uniform distribution of the test article at all chamber levels, provides a constant stream of "fresh" test article to each animal, and precludes rebreathing of the exhaled air.
The test article atmosphere was generated by using an aerosol generator (RBG-1000 Palas, Germany) connected to a Brush-feed Micronising Jet Mill and discharged through a Ni(63) charge neutralizer into the exposure chamber. This generation system was chosen in order to achieve the highest possible concentration with a mass median aerodynamic diameter of 3 µm or less.

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric determination of concentration
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: % < 3µm: group 1: 75%, group 2: 71.1% and group 3: 70.8%
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric
Duration of exposure:
4 h
Concentrations:
group 1: 1.44 mg/L air ± 0.20
group 2: 2.83 mg/L air ± 0.42
group 3: 3.94 mg/L air ± 0.51
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: up to 28 days
- Frequency of observations and weighing: Mortality: Once per hour during exposure, once after exposure on test day 1, and twice daily thereafter.
Body Weights: On test-day 1 (before exposure), 8, 15 (all groups), 22 (group 2) and 28 (group 3). Clinical Signs: Once per hour during exposure (only grossly abnormal signs, due to the animals being in restraint tubes), once after exposure and at least once daily thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The LOGIT-Model was used to evaluate the toxicity of the test material and to calculate the LC50 with its 50% confidence limits.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
3.92 mg/L air
Based on:
test mat.
95% CL:
3.61 - 4.27
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
4.32 mg/L air
Based on:
test mat.
95% CL:
3.82 - 4.89
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
3.66 mg/L air
Based on:
test mat.
95% CL:
3.44 - 3.9
Exp. duration:
4 h
Mortality:
Group 1 (1.44 mg/L) 0% died. Group 2 (2.83 mg/L) 20% died. Group 3 (3.94 mg/L) 50% died.
In group 2, one male died on test day 8 and one female on test day 9. In group 3, one male died on test day 2, two others on test day 10 and two females on test day 9.
Clinical signs:
other: No clinical signs were noted during exposure in any dose group. After exposure, hunched posture, labored respiration and rales were noted in one female of group 1 on test day 3. Sedation, hunched posture, stiff gait, labored respiration, rales and ruffled
Body weight:
No treatment-related effects were noted in animals of group 1 (1.44 mg/L). The mean body weight increase was less in group 2 (2.83 mg/L) than in
group 1 during the first week of observation. In group 3 (3.94 mg/L), one surviving male lost weight during the first three weeks of observation whereas the other male gained weight at a normal rate. The average body weight of the three surviving females of this group decreased until the end of the second week of observation and then increased again.
Gross pathology:
The lungs of all animals of group 1 were incompletely collapsed. In one male, several dark red foci were seen on the left lobe and in another male a dark red focus on the right cranial lobe. The lungs of all animals of group 2 were incompletely collapsed. A dark red or a reddish discoloration was observed in two cases. One or many dark red foci were noted in two males, and two females. The lungs of animals of group 3 were incompletely collapsed (9
cases) or not collapsed (1 case). A reddish or dark red discoloration was noted in four animals and many dark red or reddish foci in five animals.

Applicant's summary and conclusion

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