Registration Dossier

Administrative data

Endpoint:
respiratory sensitisation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990-05-07 to 1990-07-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

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

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The method is based on Karol et al. 1985, Karol et al. 1978, DeCeaurriz et al. 1987, Barrow et al. 1977, Botham et al. 1988, Botham et al. 1989.
The exposure criteria are according to OECD 403. The corresponding EC directive is fulfilled as far as it is relevant for this type of study. General recommendations on the measurement technique (ASTM E 981-84, ALARIE, 1973) were taken into account.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: granular
Details on test material:
Reactive Yellow 27

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Remarks:
Prirbright-White
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Versuchstierzucht Winkelmann, Borchen
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 1-2 months
- Weight at study initiation: 310 ± 20 g
- Housing: Makrolon-cages type IV (4 animals per cage); cages were cleaned once a week and disinfected with Zephirol (10%), Litter: wooden granular (Typ S 8/15; Ssniff - Spezialdiaten GmbH, D 4770 Soest)
- Diet (e.g. ad libitum): ad libitum; fixed formula standard diet “Altromin 3022 – Haltungsdiät für Meerschweinchen“ from Altromin GmbH, Lage
- Water (e.g. ad libitum): ad libitum; tap water
- Acclimation period: at least 1 week
- Indication of any skin lesions: Only health and symptom free animals were used for the study.

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

Test system

Route of induction exposure:
intradermal
Route of challenge exposure:
inhalation
Vehicle:
water
Remarks:
for intradermal injection
Concentration:
intradermal induction: 5% test item in water
challenge: 45 mg/m³
No. of animals per dose:
8
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 times intradermal application: two applications, each of 100 µL
- Test groups: two applications of 100 µL
- Control group: two applications of 100 µL water
- Site: on the flank; Day 0: cranial, Day 2: thoracal, Day 4: caudal
- Frequency of applications: every second days
- Duration: 4 days
- Concentrations: 5% suspension of the test item in water

B. CHALLENGE EXPOSURE
- No. of exposures: 2 à 30 min
- Day(s) of challenge: 2
- Exposure period: day 21 to 24
- Site: head-nose exposition
- Concentrations: 45 mg/m³ air
- Evaluation (hr after challenge): respiratory rate, respiratory volume, respiratory minute volume, inspiration and expiration time was evaluated during and 20 h after challenge exposure; animals were killed 1 day after the last challenge exposure

OTHER:
Body weights:
Body weights were taken befor the 1st application, on day 3 and 7 afterwards once per week

Clinical Signs:
Animals were observed at least once per day

Necropsy:
On day 25 the animals were sacrificed and analysed by gross pathology. The weight of the lung were taken.
Challenge controls:
yes
Positive control substance(s):
none
Negative control substance(s):
none

Results and discussion

Results:
Induction: No test item-related effects.

Challenge: Some animals showed difficult breathing during and/or after the challenge phase. This partial marginal effects are not given any patho-diagnostic relevance, since corresponding reactions have also been identified in the control animals. See also table 2 in "Any other information on results incl. tables".

Lung function tests: The test item showed no sensitising potential in lungs.

Body weight: There were no changes in body weights observed.

Gross pathology: No test item-related effects.

Lung weights: No changes in lung weights were observed in any animals.
Positive control results:
n.a.
Negative control results:
No effects were observed in vehicle control animals.

Any other information on results incl. tables

Table 2: Number of Animals with positive reaction during challenge phase

Induction Anaphylaxis Immediate Delayed
Vehicle 0/8 (1)/8 (4)/8
Test item 0/8 (1)/8 (2)/8

1st number: animals tested positive

2nd number: number of exposed animals

Some animals showed laboured respiration during and/or after the challenge phase. These partial marginal effects are not given any patho-diagnostic relevance, since corresponding reactions have also been identified in the control animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In this study, the test item showed no sensitising potential in lungs of guinea pigs.
Executive summary:

In a respiratory sensitization study with the test item, young adult Pirbright-White-Dunkin-Hartley guinea pigs (8 females/group) were tested for respiratory sensitisation. The test was carried out according to published methods of KAROL et al. 1985 and 1978; DeCEAURRIZ et al. 1987; BARROW et al, 1977, BOTHAM et al., 1988 and BOTHAM et al., 1989. The animals were treated intradermally with the test item 5% in water. After three weeks the control and test item group animals were challenged with a 30-min inhalation exposure with the test item.

No effects in body and lung weights were observed compared to the control. No gross pathological findings were observed.

During and after the challenge phase some animals showed difficult breathing. Since corresponding reactions have also been identified in the control animals, the partial marginal effects are not given any pathodiagnostic relevance.

According to this study, the test item is not a respiratory sensitizer, which might be attributable to the barely respirable particles.