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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data (report dated 24 May 1977)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable published method available at the time of the study.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Protocol as described by Magnusson B and Kligman AM (Journal of Investigative Dermatology (1969), 52, 268-276)
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study conducted in 1977
Species:
guinea pig
Strain:
other: albino
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Porcellus Animal Breeding Limited
Heathfield
Surrey, UK
- Age at study initiation: no data
- Weight at study initiation: 300-350 g
- Housing: individual
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 ± 1
- Humidity (%): 50-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): “controlled”

IN-LIFE DATES: From: To:

Route:
intradermal and epicutaneous
Vehicle:
water
Route:
epicutaneous, occlusive
Vehicle:
water
No. of animals per dose:
10 males
Details on study design:
RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: one by injection; one by topical application 1 week later
- Exposure period:
- Test groups: one
- Control group: no data
- Site: shoulder region
- Frequency of applications: once
- Duration: topical application, 48 hr
- Concentrations: 5% by injection; neat for topical application

B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: 14 days after topical induction
- Exposure period: 24 hr
- Test groups: one
- Control group: no data
- Site: flank
- Concentrations: neat
- Evaluation (hr after challenge): 24 and 48 hr

OTHER:

Positive control substance(s):
not required
Reading:
other: 1st and 2nd readings
Hours after challenge:
24
Group:
test group
Dose level:
Challenge dose – neat
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No data
Remarks on result:
other: Reading:
Interpretation of results:
GHS criteria not met
Conclusions:
Tetraammine platinous chloride did not induce sensitization in a GPMT, in which a group of ten male guinea pigs were dermally challenged with the neat test compound following a two-stage induction with 5% by intradermal injection and topical application of the neat substance.
Executive summary:

The skin sensitising potential of tetraammine platinous dichloride was investigated in a guinea pig maximisation test conducted according the method of Magnusson and Kligman (as described in OECD Test Guideline 406).

 

A group of ten male animals were treated in the shoulder area by intradermal injection with 5% of the test compound, followed 7 days later by a 48-hr topical occluded application of the neat substance. A challenge dose of the neat substance was applied topically to the flank region 14 days later and examined for sensitisation reactions after 24 and 48 hr.

 

No positive reactions were evident. Hence, tetraammine platinous chloride did not induce sensitisation in this test.

 

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

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

No relevant human skin sensitisation data were identified. No in vitro skin sensitisation studies were identified, or are required, as reliable in vivo studies are already available.

 

The skin sensitising potential of tetraammine platinous dichloride was investigated in a guinea pig maximisation test conducted according the method of Magnusson and Kligman (as described in OECD Test Guideline 406). A group of ten male animals were treated in the shoulder area by intradermal injection with 5% of the test compound, followed 7 days later by a 48-hr topical occluded application of the neat substance. A challenge dose of the neat substance was applied topically to the flank region 14 days later and examined for sensitisation reactions after 24 and 48 hr. No positive reactions were evident. Hence, tetraammine platinous chloride did not induce sensitisation in this test (Jones, 1977b).

 

In an OECD Test Guideline 429 local lymph node assay, conducted to GLP, 25µl platinum(2+) tetraammine (SP-4-1) diacetate (tetraammineplatinum diacetate)in propylene glycol was applied once daily to the skin of both ears of female CBA mice (5/group), at 0, 5, 25 or 50%, for three consecutive days. Mice were monitored for mortality and overt signs of toxicity, as well as changes in body weight. Skin irritation was assessed and graded three to four hours after the final dose (on day three). Three days after this induction period (on day six), mice were given tail vein injections of radiolabelled thymidine, and were sacrificed after approximately five hours. Lymph nodes were excised and processed for radioactivity. No skin irritation was observed and lymph nodes were a normal size, with the exception of one animal given the test substance at 25% and showing eye abnormalities. The anomalous results for this animal were subsequently discounted. No mortality or substance-related toxicity was observed over the course of the experiment. SI values were 1.4, 1.3 and 2.4 for animals given respective concentrations of 5%, 25% and 50%. An SI value of over three was judged to be indicative of a substance being sensitising. Hence, under the conditions of this assay, platinum(2+) tetraammine (SP-4-1) diacetate was non-sensitising (Beerens-Heijnen, 2004).

 

The skin sensitisation potential of tetramineplatinum hydrogen carbonate was evaluated using a Buehler test in guinea pigs, in accordance with OECD Test Guideline 406. Animals (10/sex) received three 6 -hr epicutaneous 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 occlusivechallenge exposure to an identical concentration (50% in 1% aqueous CMC) 2 weeks later (Berthold, 1998).

 

The skin sensitisation potential of tetraammineplatinum hydrogen carbonate was assessed in an OECD Test Guideline 406 guinea pig maximisation test,using groups of 20 test and 10 control animals.Guinea pigs were induced with a suspension of 25% test material in arachis oil by intradermal injection (in combination with a preparation of Freund’s complete adjuvant), followed one week later by a second induction by topical application of 75% of the test substance in arachis oil under a 48-hr occlusive patch. Control animals were similarly treated but without the test substance. Two weeks after the topical inductions, a challenge dose of 75% was applied under a 24-hr occlusive patch to both test and control animals. These doses were selected after a preliminary range-finding study. No positive reactions were observed in the test or control animals on examination at 24 and 48 hr after removal of the challenge patches. Tetraammineplatinum hydrogen carbonate was not a contact sensitiser in this GPMT (Jones, 1989).

Tetraammineplatinum diacetate and hydrogen carbonate are considered to fall within the scope of the read-across category "tetraammineplatinum(II) salts". See section 13 in IUCLID for full read-across justification report.


Migrated from Short description of key information:
Tetraammine platinous chloride did not induce sensitisation in a GPMT, in which a group of ten male guinea pigs were dermally challenged with the neat test compound following a two-stage induction with 5% by intradermal injection and topical application of the neat substance (Jones, 1977b).

In a guideline LLNA, to GLP, tetraammineplatinum diacetate was non-sensitising at concentrations of up to 50% (Beerens-Heijnen, 2004).

In a guideline study, to GLP, tetraammineplatinum 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 (Berthold, 1998).

In a guideline study, to GLP, tetraammineplatinum hydrogen carbonate did not induce sensitisation in a GPMT, in which a group of 20 guinea pigs were dermally challenged with a 75% concentration of the test compound following a two-stage induction with 25% by intradermal injection and 75% by topical application (Jones, 1989).

Justification for selection of skin sensitisation endpoint:
Well-conducted study in line with OECD guidelines, andf the only substance-specific skin sensitisation study available.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Tetraammineplatinum dichloride showed a lack of allergenic potential in an occupational study involving 547 workers exposed to airborne TPC, chloroplatinates or a combination thereof (341 of whom were exposed to soluble platinum for at least 50% of their work) (Linnett and Hughes, 1999).

 

In a study of 26 workers employed for an average of nearly 4 years, occupational exposure to relatively high levels of atmospheric tetraammine platinum dichloride (10-20 μg/m3) did not cause respiratory sensitisation to this substance, and there was no indication of sensitisation to platinum salts in skin prick tests (Steinfort et al., 2008).

 

[The use of such data, for an understanding of the respiratory sensitising potential of tetraammineplatinum dichloride, is limited, particularly for the purpose of classification and labelling.]


Migrated from Short description of key information:
Tetraammineplatinum dichloride displayed no evidence of respiratory sensitisation potential in two occupational studies (Linnett and Hughes, 1999; Steinfort et al., 2008).

Justification for classification or non-classification

Based on the results of the available and reliable GPMT with tetraammineplatinum dichloride, and the lack of skin sensitisation apparent in studies with tetraammineplatinum hydrogen carbonate and tetraammineplatinum diacetate, tetraammineplatinum dichloride does not require classification for skin sensitisation according to EU CLP criteria (EC 1272/2008).

 

Based on the results of the two available occupational studies, there is insufficient evidence to classify tetraammineplatinum dichloride for respiratory sensitisation.