Registration Dossier

Administrative data

Endpoint:
respiratory sensitisation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: OECD 403
Deviations:
no
Qualifier:
according to
Guideline:
other: EEG 84/449
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
None
Specific details on test material used for the study:
FAT 40061/C
yellow powder
test substance was stored at room temperature protected from light

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Versuchstierzucht Winkelmann, Borchen; BOR:DHPW (Pirbright - White - Dunkln - Hartley)
- Age at study initiation: 1-2 months
- Weight at study initiation: 250g ± 10 %
- Housing: groups of 4 animals in Makrolon Typ IV cages, bedding wood granula Typ S 8/15 (Ssniff - Spezialdiäten GmbH, D 4770 Soest)
- Diet (e.g. ad libitum): Altromin 3022 ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): ca. 50 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Route of induction exposure:
intradermal
Route of challenge exposure:
other: respiration
Vehicle:
water
Concentration:
Induction phase:
3 intradermal injections 5 % solution in water on day 0, 2 and 4 with 2 times 100 µl of the test solution; the stability of Lanasol Yellow 4G was analytically verified

Challenge phase: (2 weeks after the intradrmal induction pahse)
129 ± 11.1 mg Lanasol Gelb 4G/m³ air for 30 min; The generated dust had a particle size with an MMAD of 2 bis 4 µm, a GSD of ca. 2.4 and the fraction below 3 µm was 67 to 42 %.
No. of animals per dose:
8 females
Details on study design:
RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 3-fold intradermal application of 2 times 100 µl of a 5 % (g/v) solution of FAT 40016/C in Levatitwater in the flank on day 0 (Monday) cranial, day 2 (Wednesday) thoracal, day 4 (Friday) caudal.
- Test groups: test substance 5 % in water
- Control group: vehicle only
- Site: flank
- Frequency of applications: Monday/Wednesday/Friday


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge:
day 21 contr./1-4 / ca.139 mg Hapten/m³ (group 1a);
day 22 contr./5-8 / ca.137 mg Hapten/m³ (group 1b)
day 22 Hapten/9-12/ ca.122 mg Hapten/m³ (group 2a)
day 23 Hapten/13-17/ ca.117 mg Hapten/m³ (group 2b)

- Exposure period: 30 min
- Test groups: dust inhalation
- Control group: dusat inhalation
- Site: head-nose only

During the challenge phase reactions of the acute type have been determined (respiratory frequence, respiratory volume per minute, inspiratory volume, as well as the inspiration and expiration time and the peak expiratory flow. Subsequently the respiratory rate was followed over a period of 20 hours to record also delayed type reactions. At the end of the experiment, the guinea pigs have been killed and the lung weight was determined.
Challenge controls:
yes
Positive control substance(s):
trimellitic anhydride (TMA)
other: ovalbumine
Negative control substance(s):
none

Results and discussion

Results:
Mass medain aerodynamic diameter (MMAD): 3.60 µm; geometric standard deviation 2.42
Number medain aerodynamic diameter (NMAD):0.339 µm;
Surface medain aerodynamic diameter (SMAD): 1.64 µm

Respirability:
Mass related: 42 % (measured)
Number related: 100 % (extrapolated)

Any other information on results incl. tables

Lung functionality: FAT 40061 challenge

Vehicle control:

Anaphylactic shock syndrom (animals died): 0/8 delayed type sensitivity: 0/4; spontaneous response type 2/8

Test substance group:

Anaphylactic shock syndrom (animals died): 0/8 delayed type sensitivity: 0/4; spontaneous response type 3/8

The mean gravimetric challenge concentration was determined to 137 mg test substance/m³ air. The dust rate was considered to be stable, no hints on segregation have been available.

Clinical symptoms:

Induction

Controls: no local skin irritation effects have been noted

test group: individual animals showed local reactions consisting of dark skin coloring combined with incrustration. Transient erythema on naked skin areals visible

Challenge:

During and after the 30 min exposure period no clinical symptoms have been noted.

Lung functionality:

During challenge exposure no significant alterations of lung parameters have been noted. Individual animals showed a slightly enhanced inspiration volume. No hints on delayed-type reactions were noted.

Body weight:

No differneces between test and control groups have been noted.

Pathology:

No abnormalities have been noted, neither in the test nor in the control groups.

Lung weight:

No significant differences have been noted in the test group neither on absolute nor on relative lung weight.

Overall results and discussion:

The results of the study do not show any differences in the respiration behaviour of the acute or delayed type. Positive controls with ovalbumne or TMA clearly demonstrated such effects.

As a conclution it can be stated that FAT 40061 was not able to induce lung effects comparable with ovalbumine or TMA. Therefore the test material is judged to be none sensitizing in this model.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Conclusions:
FAT 40061/C was determined to be not sensitising in this experiment.
Executive summary:

The experiment was performed according to the OECD 403, to determine the acute inhalation toxicity on 4 female guinea pigs.

FAT 40061/C was atomized under dynamic conditions in a cylindrical inhalation chamber. The pressure was adjusted to about 200 kPa, the inlet air was about 28 liters/min the outlet air about 20 liters/min. To optimize respirability of the particles, a particle separator was used separationg big particles from the air stream (all particles <= 5 µm can pass to 100 %; particles >10 µm cannot pass). Temperature in the incubation chamber was about 22 °C, humidity about 36 %.

Under these test conditions, FAT 40061/C was not found to be a sensitizer.