[ethane-1,2-diylbis[nitrilobis(methylene)]]tetrakisphosphonic acid

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

32 days

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Objective of study:

other:

Principles of method if other than guideline:

This study investigated the effects of treatment with EDITEMPA following 10 days of treatment with compound in the feed. 15 mg and 150 mg/kg (bw) were used to enable direct comparison with the other studies. However, based on food consumption data the actual doses were determined to be 19 mg/kg (bw) and 196 mg/kg (bw) respectively. 20 Male rats were used at each dose level.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

[ethylenebis[nitrilobis(methylene)]]tetrakisphosphonic acid, sodium salt

EC Number:

244-742-5

EC Name:

[ethylenebis[nitrilobis(methylene)]]tetrakisphosphonic acid, sodium salt

Cas Number:

22036-77-7

Molecular formula:

C6H20N2O12P4.xNa

Test material form:

not specified

Radiolabelling:

yes

Test animals

Species:

other: Rat (Sprague Dawley)

Strain:

other: Sprague Dawley rats

Sex:

male

Administration / exposure

Route of administration:

other: Dietary and by oral gavage

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

This study investigated the effects of treatment with EDITEMPA following 10 days of treatment with compound in the feed. 15 mg and 150 mg/kg (bw) were used to enable direct comparison with the other studies. However based on food consumption data the actual doses were determined to be 19 mg/kg (bw) and 196 mg/kg (bw) respectively. 20 Male rats were used at each dose level.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

15 mg/kg bw/day

Remarks:

EDITEMPA was dissolved in NaOH with pH adjustement to achieve pH 7.

Doses / concentrations 2

Dose / conc.:

150 mg/kg bw/day

No. of animals per sex per dose / concentration:

Males

Control animals:

no

Results and discussion

Preliminary studies:

Little/insignificant amounts of radioactivity were detected in blood. Urinary elimination of 14C was limited, less than 1% of the last dose was recovered in urine from either group. Most radioactivity was recovered in faeces, primarily during the first 24 hours following termination of treatment. No differences in excretion patterns seen in the groups. Levels of 14C was low, no changes in tissue distribution of 14C were noted between the two groups. Recovery in bone was relatively high, ranging from 0.6 -1.1% (low dose) and 0.3-0.7% (high dose). After low dose the areas under the bone concentration time curve (AUC) were 52 and 45 micrograms/gram/day in femur and tibia respectively. After the high dose levels these were 333 and 259 micrograms/gram/day, respectively. The levels in vertebrae were slightly lower. Disappearance of 14C from vertebrae was slower (t ½ 40-43 days) than femur (20-38 days) and tibia (30-32 days).
This study demonstrates that following 10 day treatment with EDITEMPA mixed in feed accumulation and retention is limited to the bone.
Compared to multiple oral gavage dosing, less absorption of the test compound was apparent, shown by lower blood and tissue levels. Treatment at low doses in feed or by gavage resulted in similar levels of 14C in the bone. However, after high doses bone levels decreased three fold in animals fed with 14C EDITEMPA diets.

Applicant's summary and conclusion

Conclusions:

This study demonstrates that following 10 day treatment with EDITEMPA mixed in feed accumulation and retention is limited to the bone. Compared to multiple oral gavage dosing, less absorption of the test compound was apparent, shown by lower blood and tissue levels. Treatment at low doses in feed or by gavage resulted in similar levels of 14C in the bone. However, after high doses bone levels decreased three fold in animals fed with 14C EDITEMPA diets.

Executive summary:

This study investigated the effects of treatment with EDITEMPA following 10 days of treatment with compound in the feed. Doses of 15 mg and 150 mg/kg (bw) were used to enable direct comparison with the other studies. However based on food consumption data the actual doses were determined to be 19 mg/kg (bw) and 196 mg/kg (bw) respectively. 20 Male rats were used at each dose level. The results of this study demonstrates that following 10 day treatment with EDITEMPA mixed in feed accumulation and retention is limited to the bone. Compared to multiple oral gavage dosing, less absorption of the test compound was apparent, shown by lower blood and tissue levels. Treatment at low doses in feed or by gavage resulted in similar levels of 14C in the bone. However after high doses bone levels decreased three fold in animals fed with 14C EDITEMPA diets.