Phosphinic acid, aluminum salt (3:1)

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From January 16 to April 12, 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Guidelines for Testing of Toxic Chemicals, Ministry of Health, People’s Republic of China, 272.

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Guidelines for the testing of chemicals Section 4: Health Effects, Ministry of environmental protection of People’s Republic of China, 474, 2003.

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5395 (In Vivo Mammalian Cytogenetics Tests: Erythrocyte Micronucleus Assay)

Deviations:

no

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

479-150-8

EC Name:

-

Cas Number:

7784-22-7

Molecular formula:

AlH6O6P3

IUPAC Name:

Phosphinic acid, aluminum salt (3:1)

Test material form:

solid: particulate/powder

Test animals

Species:

mouse

Strain:

ICR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Shanghai SLAC Laboratory Animals Co., Ltd
- Age at study initiation: 6-8 weeks old
- Weight at study initiation: 26.7 - 29.6 g
- Quarantined: for 5 days after receipt and were observed each day for signs of illness.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.8 - 22.5 °C
- Humidity (%): 42 - 50 %
- Photoperiod: 12 hour light/dark cycle.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: corn oil
- Concentration of test material in vehicle: 10 mL/kg body weight

Duration of treatment / exposure:

Two oral gavages (two treatments at 24 hour intervals).

Frequency of treatment:

Single application.

Post exposure period:

All mice were euthanized at approximately 24 hours following the final treatment.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Remarks:

main study

Doses / concentrations 2

Dose / conc.:

250 mg/kg bw/day (nominal)

Remarks:

main study

Doses / concentrations 3

Dose / conc.:

500 mg/kg bw/day (nominal)

Remarks:

main study

Doses / concentrations 4

Dose / conc.:

1 000 mg/kg bw/day (nominal)

Remarks:

main study

No. of animals per sex per dose:

5 animals per each sex per dose

Control animals:

yes

Positive control(s):

Cyclophosphamide.

Examinations

Tissues and cell types examined:

Polychromatic erythrocytes (PCEs) and normochromatic erythrocytes (NCEs) were analyzed.

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: range finding study.

Evaluation criteria:

Criteria for a valid test:
The mean incidence of micronucleated PCEs must not exceed 5/1000 PCEs (0.5 %) in the negative (vehicle) control. The incidence of micronucleated PCEs in the positive control group must be significantly increased relative to the vehicle control group (p <0.01).

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not examined

Vehicle controls validity:

not examined

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

A statistically significant increase in the number of micronucleated PCEs per 10,000 PCEs (total PCEs per group) was not observed at any dosage at harvest relative to the respective vehicle control.
In the range finding study sag, fluffy fur, salivation and death were observed at 2000 mg/kg bw.
No death was observed during the course of the main study. Sag, fluffy fur and salivating were observed in animals at 1000 mg/kg bw.

Any other information on results incl. tables

In this study, all criteria for a valid test were met. Cyclophosphamide (CP) induced a significant increase in micronucleated PCEs (p<0.01) and a reduction in the PCEs/ECs ratio of 14.1 % and 13.4 % in female and male mice, respectively. In addition, the negative and positive control data were consistent with historical control data, indicating that the study was validly conducted.

Applicant's summary and conclusion

Conclusions:

Aluminium hypophosphite did not induce a statistically significant increase in the incidence of micronucleated PCEs in the bone marrow of male and female ICR mice. Therefore, Aluminium hypophosphite was concluded to be negative in the in vivo mouse micronucleus assay.

Executive summary:

The purpose of this study was to evaluate the clastogenic potential of Aluminium hypophosphite, as measured by its ability to induce micronuclei in the polychromatic erythrocytes (PCEs) in the bone marrow of ICR mice.

According to the result of Aluminium hypophosphite to mice in the range finding study, a two oral administration at 24 hours interval of Aluminium hypophosphite was conducted by oral gavages to 5 male mice and 5 female mice per group at 0 (vehicle control, corn oil), 250, 500, 1000 mg/kg bw. Five male mice and five female mice received a two abdominal injection dosage of 40 mg/kg of CP as positive control. The dose volume for all groups was 10 mL/kg. All mice were euthanized at approximately 24 hours following the final treatment. After euthanasia, bone marrow was collected from sternum, and smears were prepared and stained with Giemsa stain. 2000 PCEs per animal were examined microscopically for the presence of micronucleated PCEs. The proportion of PCEs to total erythrocytes (PCEs/ECs ratio) was also determined to evaluate the test article bone marrow toxicity.

Under the conditions of the assay described in this report, a two oral administration of Aluminium hypophosphite at all dose level, did not induce a significant increase in the incidence of micronucleated PCEs in the bone marrow of male and female ICR mice. Therefore, Aluminium hypophosphite was concluded to be negative in the in vivo mouse micronucleus assay.