Diammonium hexachloroplatinate

Respiratory sensitisation

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: Non-guideline experimental study published in peer-reviewed literature. No details on GLP status. Limited reporting detail in published paper (for example, purity/impurity profile of the test substance).

Data source

Reference

Reference Type:

publication

Title:

Lung function changes in mice sensitized to ammonium hexachloroplatinate

Author:

Williams WC, Lehmann JR, Boykin E, Selgrade MK and Lehmann DM

Year:

2015

Bibliographic source:

Inhalation Toxicology 27(10), 468-480

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Female BALB/c mice were administered the test substance (ammonium hexachloroplatinate (AHCP), 1% in DMSO) on the shaved back on test days 0, 5 and 15, and on the ears on test days 10, 11 and 12. Control animals received the vehicle only. The mice were challenged with AHCP (10, 31 or 100 ug in saline) by oropharyngeal aspiration on test days 24 and 29. Immediate responses to the test substance challenge were measured using whole-body plethysmography (WBP). Additionally, WBP was used to measure responses to the non-specific bronchoconstrictor acetyl-beta-methylcholine chloride (Mch) on test days 26 and 31. Lymph node cell counts, eosinophil content in bronchoalveolar lavage fluid (BALF), and total serum immunoglobulin E (IgE) were also assessed.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Diammonium hexachloroplatinate

EC Number:

240-973-0

EC Name:

Diammonium hexachloroplatinate

Cas Number:

16919-58-7

Molecular formula:

Cl6Pt.2H4N

IUPAC Name:

diammonium hexachloroplatinate

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): Ammonium hexachloroplatinate (AHCP)
- Substance type: no data.
- Physical state: no data.
- Analytical purity: no data.
- Impurities (identity and concentrations): no data.
- Composition of test material, percentage of components: no data.
- Isomers composition: no data.
- Purity test date: no data.
- Lot/batch No.: no data.
- Expiration date of the lot/batch: no data.
- Stability under test conditions: no data.
- Storage condition of test material: no data.

Test animals

Species:

mouse

Strain:

Balb/c

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Wilmington, MA, USA
- Age at study initiation: 8-9 weeks old.
- Weight at study initiation: no data.
- Housing: group housing based on treatment groups in polycarbonate cages with hardwood chip bedding.
- Diet (e.g. ad libitum): "balanced diet mouse chow" (5POO Prolab RHM3000, PMI Nutrition International, Richmond, IN, USA).
- Water (e.g. ad libitum): ad libitum.
- Acclimation period: no data.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5°C +/- 1.5°C.
- Humidity (%): 55% +/- 5%.
- Air changes (per hr): no data.
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle.
- Note: all animals were housed in an Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC)-approved facility.

IN-LIFE DATES: no data.

Test system

Route of induction exposure:

dermal

Remarks:

3 doses of 100 uL on the shaved back; 3 doses of 25 uL/ear.

Route of challenge exposure:

other: oropharyngeal aspiration

Vehicle:

DMSO

Remarks:

for induction (topical)/saline for challenge (inhalation).

Concentration:

Dermal induction was 1% AHCP in DMSO.
Inhalation challenge provided 10, 31 or 100 ug of AHCP in saline.

No. of animals per dose:

No data.

Details on study design:

RANGE FINDING TESTS: No data.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 6.
- Exposure period: test days 0-15 (to back); test days 10-12 (to ears).
- Test groups: no data.
- Control group: vehicle only.
- Site: shaved back (3 applications); ears (3 applications/ear).
- Frequency of applications: 3 applications to back (test days 0, 5 and 15); 3 applications/ear (test days 10, 11 and 12).
- Duration: no data.
- Concentrations: 1% AHCP in DMSO.

B. CHALLENGE EXPOSURE
- No. of exposures: 2.
- Day(s) of challenge: test days 24 and 29.
- Exposure period: test days 24-29.
- Test groups: 10, 31 or 100 ug AHCP in saline.
- Control group: vehicle only.
- Site: inhalation (oropharyngeal aspiration).
- Concentrations: 10, 31 or 100 ug AHCP in saline.
- Evaluation (hr after challenge): immediate (by whole-body plethysmography).

Challenge controls:

acetyl-beta-methylcholine chloride (Mch)

Results and discussion

Results:

Respiratory challenge with the mid- and high-doses of AHCP (31 and 100 ug) resulted in a dose-dependent increase in the number of lymph node cells present in the auricular lymph nodes. This number increased significantly with a second challenge with 10, 31 or 100 ug AHCP. "An antigen-specific immediate response was evident in AHCP-sensitised mice following the first OPA challenge on day 24 with 31 and 100 ug AHCP [...] Immediate responses were similar in mice receiving a second OPA challenge with AHCP on day 29." The lungs were also responsive to non-specific stimuli (Mch) on challenge. The proportion of eosinophils in the BALF, a marker of allergic inflammation, increased from <0.5% in non-sensitised mice to about 5% in dermally pre-sensitised mice, challenged with AHCP. Total serum IgE levels were significantly elevated in in platinum pre-sensitised mice, compared to non-sensitised mice, when measured on day 19 and 26.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Conclusions:

In this non-guideline study, it has been demonstrated that a single targeted airway delivery of ACHP is sufficient to trigger an allergic lung response in dermally sensitised mice.

Executive summary:

In a non-guideline study, ammonium hexachloroplatinate (AHCP), at a concentration of 1% in DMSO, was applied to the shaved backs of female BALB/c mice on test days 0, 5 and 15, and on to the dorsum of both ears on test days 10, 11 and 12, to induce dermal sensitisation. Control animals received the vehicle only. The mice were challenged with AHCP (10, 31 or 100 ug in saline) by oropharyngeal aspiration (OPA; which delivers test material directly to the lungs) on test days 24 and 29, to assess the role of inhalation exposure on dermally sensitised animals. Immediate lung responses to the test substance challenge were measured using whole-body plethysmography (WBP). Additionally, WBP was used to measure responses to the non-specific bronchoconstrictor acetyl-beta-methylcholine chloride (Mch) on test days 26 and 31. Lymph node cell counts, eosinophil content in bronchoalveolar lavage fluid (BALF), and total serum immunoglobulin E (IgE) were also assessed.

 

"An antigen-specific immediate response was evident in AHCP-sensitised mice following the first OPA challenge on day 24 with 31 and 100 ug AHCP [...] Immediate responses were similar in mice receiving a second OPA challenge with AHCP on day 29." The lungs were also responsive to non-specific stimuli (Mch) on challenge.The proportion of eosinophils in the BALF, a marker of allergic inflammation, increased from <0.5% in non-sensitised mice to about 5% in dermally pre-sensitised mice, challenged with AHCP. Total serum IgE levels were significantly elevated in in platinum pre-sensitised mice, compared to non-sensitised mice, when measured on day 19 and 26.

 

Overall, in this non-guideline study, it has been demonstrated that a single targeted airway delivery of AHCP is sufficient to trigger an allergic lung response in dermally sensitised mice.