Strontium hydrogen phosphate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study is not performed according to a validated guideline or GLP principles. Although basic information is limited, sufficient data are provided to derive an endpoint conclusion. The test substance is not strontium hydrogen phosphate, but strontium phosphate. The pH of phosphate is known to be higher than for the hydrogenphosphate, but as these anions are in equilibrium with each other they are expected to behave similar in aqueous solutions (HPO42- + H2O↔PO43- + H3O+ (pKa = 12.32)). A report with further details on the hypothesis for the analogue approach is attached in section 13.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1975

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Feeding study

GLP compliance:

no

Remarks:

Study performed before GLP guidelines were in place

Test type:

other: feeding study

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

strontium phosphate

IUPAC Name:

strontium phosphate

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): strontium phosphate
- Supplier: Thomas Tyrer & Co., London

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: animal colony of test lab
- Age at study initiation: 21 days
- Diet: Stock diet, ad libitum (composition: wheat 70%, Bengal Gram (Cicer arietinum) 20%, fish meal 5%, yeast powder 4% and oil 1%)
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- No data

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

- Concentration in feed: 0%, 0.5%, 1% and 2% Sr

Doses:

0, 500, 1000 and 2000 mg/kg bw (estimated by calculation)

No. of animals per sex per dose:

5-6

Control animals:

yes

Details on study design:

- Duration of administration: 2, 4 or 6 weeks (control and 2000 mg/kg bw/day groups) or 6 weeks (500 and 1000 mg/kg bw/day groups).
- Duration of observation period following administration: 14 days (recovery groups)
- Frequency of observations and weighing: observations not reported, weight gain was recorded at day 1 and end of treatment (day 14, 28 or 42 resp.)
- Necropsy of survivors performed: yes
- Other examinations performed: Alkaline and acid phosphatase activity in liver, small intestine, kidney and bone was recorded; radiography of tibia and femurs, determination of Sr-concentration in liver, small intestine and kidney tissue.

Statistics:

The statistical significance of the results was estimated by using Student's t test (where possible).

Results and discussion

Preliminary study:

Preliminary experiments did not reveal any appreciable changs at 500 or 1000 mg/kg bw/day when dosed for 4 weeks.

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Based on 30% mortality at 2000 mg/kg bw

Mortality:

Mortality up to 30% was recorded in rats of the 2000 mg/kg bw/ day group (exposed for 4-6 weeks). Time point of mortality was not reported. No mortality reported in other groups.

Clinical signs:

other: Paralysis was seen in rats exposed to 2000 mg/kg bw/d for 4 to 6 weeks. No adverse effects were noticed in rats in the 500 and 1000 mg/kg bw/d groups.

Gross pathology:

Hemorrhages and widening of the epiphyseal cartilage plate were seen in rats exposed to 2000 mg/kg bw/d for 4 to 6 weeks. Considerable calcification was induced in the recovery group, but no gross skeletal damage or external signs were noted. No adverse effects were noticed in rats in the 500 and 1000 mg/kg bw/d groups.

Other findings:

Effects on alkaline phosphatase activity in the tissues are further summarized in 7.5.1, since they are not relevant for the acute endpoints.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results of a feeding study in which rats were exposed repeatedly to a maximum concentration of 2000 mg/kg bw/ day, it can be concluded that the LD50 for acute oral toxicity for strontium phosphate is > 2000mg/kg bw.

Executive summary:

A feeding study was performed in which young male rats were exposed to approximately 0, 500, 1000 or 2000 mg/kg bw/day for 2, 4 or 6 weeks (control and 2000 mg/kg bw/day groups) or 6 weeks (500 and 1000 mg/kg bw/day groups). Mortality up to 30% was recorded in rats of the 2000 mg/kg bw/ day group (exposed for 4-6 weeks). No mortality was reported in other groups. Paralysis and reduction in body weight gain were seen in rats exposed to 2000 mg/kg bw/d. No clinical signs or pathological findings were noticed in rats in the 500 and 1000 mg/kg bw/d groups. Hemorrhages and widening of the epiphyseal cartilage plate were seen in rats exposed to 2000 mg/kg bw/d for 4 to 6 weeks. Based on these results, it can be concluded that the LD50 for acute oral toxicity for strontium phosphate is > 2000mg/kg bw/day. Based on the rationale attached in section 13, these data can be read-across to Strontium hydrogenphosphate. Strontium hydrogenphosphate does not need to be classified for acute toxicity by the oral route.