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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian germ cell study: gene mutation
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 March 1980 to 9 May 1980
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Method used was similar to guideline, though this type of study is no longer recommended for regulatory testing. Nevertheless, the data from this study is useful in the overall weight of evidence.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 477 (Genetic Toxicology: Sex-linked Recessive Lethal Test in Drosophila melanogaster)
Deviations:
no
Principles of method if other than guideline:
Spencer and Stern (1948) Genetics 33, 43-74
GLP compliance:
not specified
Type of assay:
Drosophila SLRL assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Pt(NH3)4Cl2H2O
- Substance type: cream powder
- Physical state: solid
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Purity test date: no data
- Lot/batch No.: 31099A
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: stored in glass bottle at 0-4oC, protected from light
- Other:

Test animals

Species:
Drosophila melanogaster
Strain:
other: Males: Oregon; K Females: Muller-5
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: in-house; derived from cultures obtained from the Genetics Department, University of Edinburgh
- Age at study initiation:  1 week
- Assigned to test groups randomly: [no/yes, under following basis: ] yes
- Fasting period before study: 2-3 hr
- Housing: glass jars
- Diet (e.g. ad libitum): Drosophila medium with powdered yeast sprinkled on top


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: feed
Vehicle:
- Vehicle(s)/solvent(s) used: 1% sucrose
- Justification for choice of solvent/vehicle:
- Concentration of test material in vehicle: 64 or 320 µg/ml
- Type and concentration of dispersant aid (if powder): placed on filter paper
:

Details on exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency): Daily on each day of treatment
Flies remove to clean jars without normal feeding solution for 2-3 hours then given the treated filter papers for 17 hr before being removed to jars containing normal nutrient medium

Duration of treatment / exposure:
17 hr/day for 3 days
Frequency of treatment:
17 hr/day for 3 days
Post exposure period:
24 hr before beginning mating
Doses / concentrations
Remarks:
Doses / Concentrations:
64 or 320 µg
Basis:
nominal in diet
No. of animals per sex per dose:
50 males selected for mating
Control animals:
yes, concurrent vehicle
Positive control(s):
ethylmethanesulphonate
- Justification for choice of positive control(s): recommended substance
- Route of administration: oral
- Doses / concentrations: 50 μg/ml in 1% sucrose solution

Examinations

Tissues and cell types examined:
Presence or absence of red-eyed males
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: as the result of a range-finding study to find a top dose in which survival was at least 50% without markedly impaired fertility

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): Treated males mated with s sets of virgin females for 3 days each, before being placed with new females for a further 6 days. The offspring (F1 generation) were then mated together to produce the F2 generation. Cultures considered to carry X-lethals or suspect lethals/semi-lethals were retested using red-eyed females from the F2 generation.

METHOD OF ANALYSIS: examination by eye for the absence or presence of red-eyed flies in F2 and F3 generations.

Evaluation criteria:
Vials containing 3 or more red-eyed (wild-type) males were scored as non-lethal. F2 cultures having at least 11 phenotypically M-5 males and no wild-type males were considered to show the X-lethal mutation. Cultures having less than 11 M-5 males or containing 1-2 wild-type males were regarded as suspect semi-lethals or lethals
Statistics:
Fisher’s exact probability test

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
RESULTS OF RANGE-FINDING STUDY 1
- Dose range: 0.32, 1.6, 8.0, 40 and 200 mg/ml
- Solubility: suspension
- Clinical signs of toxicity in test animals: 83-90% on the three top doses died, 40-60% died on the two lower doses
- Evidence of cytotoxicity in tissue analyzed: not applicable
- Rationale for exposure: to determine dose level giving at least 50% survival


RESULTS OF DEFINITIVE STUDY
The test substance did not induce sex-linked recessive lethal mutations (see below)
- Appropriateness of dose levels and route: appropriate
- Statistical evaluation: see below


Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative

Tetraammineplatinum (II) chloride did not induce sex-linked recessive lethal mutations in the progeny of Drosophila melanogaster following oral administration at concentrations of 64 or 320 µg/kg bw/day.
Executive summary:

Tetraammine platinum (II) chloride was assessed for mutagenic potential in an assay for sex-linked recessive lethal mutations in Drosophila melanogaster.

 

Males were treated with treated either 64 or 320 µg/kg bw/day given orally for 17 hr daily on three consecutive days in a 1% sucrose “feed”. Twenty four hr after treatment they were mated with groups of untreated virgin females so that each stage of the spermatogenic cycle was sampled. Cultures having at least 11 phenotypically M-5 males and no wild-type males were considered to show the X-lethal mutation and were collected and mated within the treatment group and the resulting progeny were scored for the presence or absence of red-eyed (wild-type) males. All cultures having X-lethal mutations or suspected lethal/semi-lethal mutations were subjected to a further round of mating to confirm the mutations.

 

The test compound did not increase the mutation frequency when compared to vehicle treated controls.

 

Tetraammineplatinum (II) chloride showed no mutagenic potential in this assay for sex-linked recessive lethal mutations in Drosophila melanogaster.