Registration Dossier

Administrative data

Endpoint:
respiratory sensitisation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Publication is well documented, only the part related to exposure to the test substance is taken into account, non GLP

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Four-week-old male Hartley guinea pigs were intraperitoneally injected with 1 mL of an NaCl solution containing 100 μg ovalbumin (OA). These animals and not-pre-treated control animals were then exposed to the test substance (500 ppb) for 4 wk (6 h/d, 5 d/wk) . At the end of exposure, GPs were challenged with an OA aerosol ( 0.1% in NaCl) and pulmonary functions were measured. The day after, guinea pigs were anesthetized and several endpoints related to inflammatory and allergic responses were assessed in blood, whole-lung histology, and bronchoalveolar lavage (BAL) .
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
No data given

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River France
- Age at study initiation: Four-week-old
- Weight at study initiation: 414.4 ± 24.6 g
- Housing: Between exposures, four animals were housed per cage in suspended Plexiglas cages fitted with dust-free bedding.
- Diet (e.g. ad libitum): Animals were not fed during exposure but had access to food and water ad libitum between each exposure period.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 7 d

No additional data available

Test system

Route of induction exposure:
other: not applicable
Route of challenge exposure:
inhalation
Vehicle:
other: NaCl solution
Concentration:
500 ppb, 2.2 mg/m3
No. of animals per dose:
8 males
Details on study design:
Four groups of eight guinea pigs were used:
Group 1. Air-exposed control.
Group 2. Air-exposed ovalbumin-sensitized.
Group 3. Test substance-exposed.
Group 4. Test substance-exposed ovalbumin-sensitized.
Animals were acclimated for at least 7 d before the experiment started. At d 0 and d 1, intraperitoneal injections of OA (groups 2, 4) or NaCl (groups 1, 3) were performed. At d 21, sensitization was determined (intradermal reaction) after OA provocation. Aldehyde exposure lasted from d 0 to d 26. Assessment of respiratory function parameters took place both before and after OA provocation, 3 d after the end of exposure (d 29). On the day after (d 30), animals were sacrificed by intraperitoneal injection of pentobarbital sodium in order to evaluate the inflammatory and atopic responses.
Positive control substance(s):
not specified
Negative control substance(s):
other: Air-exposed

Results and discussion

Results:
No allergic reactions were noted in nonsensitized GPs challenged with OA. Therefore, all results from control GPs have been pooled.

Characteristics of sensitized guinea pigs:
Increased Penh reflecting enhanced bronchoconstrict ion.
Changes in pulmonary histology reflecting an irritation of the respiratory tract.
Increased number of eosinophils in blood.
Increased number of inflammatory cells (macrophages, neutrophils, and eosinophils) in BAL.
Increased levels of proteins in BALF reflecting an alteration of vascular and epithelial permeability of the respiratory tract.
Increased levels of the bronchoconstrictor lipid mediator LTC4/D4/E4.
Positive control results:
No information provided
Negative control results:
In guinea pigs treated with the test substance, ovalbumin (OA) provocation induced no modifications in respiratory functions.

Any other information on results incl. tables

Mortality, Clinical Signs, and Body Weights: Exposure to the test substance did not induce any mortality.

Respiratory Functions: In control GPs, ovalbumin (OA) provocation induced no modifications in respiratory functions.

Histopathology: For test substance-exposed GPs, histological examination of nasal cavities revealed a slight irritation (metaplasia/hyperplasia) of the respiratory epithelium for nonsensitized GPs.Histological examination of the trachea and lungs showed a slight irritation of respiratory epithelium for nonsensitized GPs.

Blood Parameters: No effects on eosinophils, monocytes, lymphocytes, neutrophils, and basophils in test substance treated non-sensitized guinea pigs. In nonsensitized GPs, the test substance induced significant reduction of triglycerides.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Conclusions:
After exposure to the test substance a challenge with OA did not induce reactions related to respiratory sensitization.
In pre-sensitized animals a decrease both in OA-induced bronchoconstriction and in eosinophil and neutrophil numbers in BAL, an increase in the bronchodilatator mediator prostaglandin E2 (PGE2), and a decrease in the bronchoconstrictor mediators LTC4/D4/E4 was reportedafter exposure to the ets substace.
Executive summary:

Four-week-old male Hartley guinea pigs were exposed to the test substance (500 ppb) for 4 wk (6 h/d, 5 d/wk) . At the end of exposure, GPs were challenged with an OA aerosol ( 0.1% in NaCl) and pulmonary functions were measured. The day after, guinea pigs were anesthetized and several endpoints related to inflammatory and allergic responses were assessed in blood, whole-lung histology, and bronchoalveolar lavage (BAL) .

Exposure to the test substance did not lead to a allegic reaction after the challenge with OA on any of the parameters investigated.

In the nasal cavities slight irritation (metaplasia/hyperplasia) of the respiratory epithelium was observed. Histological examination of the trachea and lungs showed a slight irritation of respiratory epithelium for nonsensitized GPs.