Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11-Nov-1997 to 11-Dec-1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
OECD guideline study to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
Study conducted in 1998

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:

- Name of test material (as cited in study report): Platinum tetramine hydrogencarbonate

- Substance type: Technical product

- Physical state: Solid (powder)

- Analytical purity: >99.9%

- 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.: 02/95

- Expiration date of the lot/batch: 31 December 1999

- Stability under test conditions: stable throughout the experimental period of the study

- Storage condition of test material: in a closed container at room temperature (< 30 degrees centigrade)

- Other:
- pH of concentrated solution ~8
- Water solubility 26g/l [presumably at or around room temperature]
- Stability in aqueous solution unknown
- Adequate stability of the test substance in the vehicle was assumed since it was prepared immediately prior to use, there were no obvious signs of decomposition during use and there were no structural moeities that would suggest instability in the vehicle.

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: HsdPOC:DH
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan-Winkelmann GmbH, D-33176 Borchen

- Age at study initiation: 8 weeks

- Weight at study initiation: males 421-496 g, females 369-465 g

- Housing: Macrolon cages type IV, 1 per cage, biological bedding (Hugro® 560)

- Diet: Ssniff® Ms-Z complete diet for guinea pigs, ad libitum

- Water: drinking water quality, with vitamin C added twice weekly, time-switched drinking water system with drinking nipples

- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5-21.7

- Humidity (relative, %): 40-64

- Air changes (per hr): no data

- Photoperiod (hrs dark / hrs light): 12 / 12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
Aqueous, 1%, trade name Tylose
Concentration / amount:
50%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
Aqueous, 1%, trade name Tylose
Concentration / amount:
50%
No. of animals per dose:
Vehicle control group 1 (designated for 1st challenge): 10 (5 males, 5 females)
Vehicle control group 2 (designated for 2nd challenge): 10 (5 males, 5 females)
Test group: 20 (10 males, 10 females)
Details on study design:
RANGE FINDING TESTS: No irritation with test substance at 50% in a preliminary test

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 (days 1, 8 and 15)

- Exposure period: 15 days

- Test groups: 10 males and 10 females

- Control group: 5 males and 5 females in each of 2 vehicle control groups (one group each designated for challenge and re-challenge). Treated with vehicle only.

- Site: Left flank, 3 x 3 cm area shaved, 2 x 2 cm patch

- Frequency of applications: once per week

- Duration: 6 hours

- Concentrations: 50% (amount 0.5 g)

B. CHALLENGE EXPOSURE
- No. of exposures: 1

- Day(s) of challenge: day 29

- Exposure period: 6 hours

- Test groups: all 20 test animals were challenged (10 males and 10 females)

- Control group: half the vehicle control animals were challenged ( 5 males and 5 females) wity test substance, like test animals.

- Site: Test substance preparation applied to right flank, vehicle applied to left flank, 3 x 3 cm areas shaved, 2 x 2 cm patches

- Concentrations: 50% (0.5 g)

- Evaluation (hr after challenge): 24 and 48

OTHER:
- Re-challenge:
- Not done due to unequivocality of the results of the 1st challenge.

- Systemic toxicity:
- Behaviour and general appearance (during the study)
- Clinical symptoms (during the study)
- Body weights (start and end of study)
Positive control substance(s):
yes
Remarks:
No concurrent positive control, but alpha-hexylcinnamaldehyde was eval. for skin sensitisation potential in same strain of guinea pig in Feb/Mar 1997 (ASTA study number 914411). 3/10 animals reacted with erythema and 1/10 with oedema after 1st challenge

Results and discussion

Positive control results:
At 1st challenge, erythema in 3/10, oedema in 1/10

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50% (0.5 g)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No adverse effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50% (0.5 g). No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No adverse effects.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50% (0.5 g)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No adverse effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50% (0.5 g). No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No adverse effects.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50% (0.5 g)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No adverse effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50% (0.5 g). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No adverse effects.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50% (0.5 g)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No adverse effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50% (0.5 g). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No adverse effects.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In a guideline study, to GLP, tetraammineplatinum(II) hydrogen carbonate did not cause skin sensitisation in a Buehler test in which guinea pigs were dermally challenged with 50% of the test compound (in 1% aqueous CMC) following a 2-week induction period involving three 6-hr epicutaneous occlusive applications of an identical concentration of the test item.
Executive summary:

The skin sensitisation potential of tetraammineplatinum(II) hydrogen carbonate was evaluated using a Buehler test in guinea pigs, conducted in accordance with OECD Test Guideline 406 and to GLP. Animals (10/sex) received three 6 -hr epictuaneous applications of the test material at 50% in 1% aqueous carboxymethyl cellulose (CMC) during a 2-week induction period .There were no skin responses to an epicutaneous occlusive challenge exposure to an identical concentration (50% in 1% aqueous CMC) 2 weeks later.

Based on the results of this study, no classification for skin sensitisation is required according to EU CLP criteria (EC 1272/2008).