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Basic toxicokinetics

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basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
other: Klimisch scoring not applicable. Well documented study. No significant deficiencies in study design. The fact that the study has been considered by ATSDR (2003) experts indicates that the study is relevant and relevant.
Rationale for reliability incl. deficiencies:
other: Well documented study. No significant deficiencies in study design. The fact that the study has been considered by ATSDR (2003) experts indicated that the study is relevant and reliable.

Data source

Reference Type:
Comparative metabolism of radionuclides in mammals. IX. Retention of 75Se in the mouse, rat, monkey and dog.
Furchner, J.E.; London, J.E.; Wilson, J.S.
Bibliographic source:
Health Phys 29:641-648

Materials and methods

Objective of study:
Test guideline
no guideline followed
Principles of method if other than guideline:
Whole-body retention of 75Se-selenite (as selenous acid) in mice, rats, dogs and monkeys was determined with 4π liquid scintillation counters after oral and intravenous injections in all species and after intraperitoneal injection in mice and rats.

Test material

Constituent 1
Chemical structure
Reference substance name:
Selenious acid
EC Number:
EC Name:
Selenious acid
Cas Number:
Molecular formula:
selenous acid
Details on test material:
- Name of test material (as cited in study report): selenious acid

Test animals

other: mice, rats, monkeys and dogs
other: RF mice, African white-tailed rats, Macaca mulatta monkeys and Beagle dogs
Details on test animals or test system and environmental conditions:
- Age at study initiation: 3.2 - 3.6 months (mice), 10 months (rats), 39 and 46 months (monkeys), 38 and 43 months (dog)
- Weight at study initiation: 0.025 - 0.026 kg (mice), 0.130 - 0.138 kg (rats), 5.4 and 5.6 kg (monkeys), 15.6 and 15.9 kg (dog)
- Diet: commercial sources; 0.06 ppm Se in dog food, <0.1 ppm Se in rat and mouse food
- Water: ad libitum

Administration / exposure

Route of administration:
other: oral, intravenous, intraperitoneal
Details on exposure:
-Oral (i.g.) administration in rats and mice was made by gastric intubation and an additional group of mice were given 75-Se in their drinking water.
- oral administration of dogs and monkeys by food pellets which were hand-fed
- intraperitoneal injections (ip) were made in the lower left abdominal quadrant of the unanaesthetised animals
- intravenous injections (Iv) were made in the tail veins of mice, the external jugular veins of rats, the saphenous and cephalic veins of dogs and monkeys, respectively.
- the selenous acid was diluted with 0.01 N HNO3 immediately before injection
- mice and rats were injected with ca. 0.1 cm3 and dogs and monkeys with 0.5 cm3 of injection solution
- the drinking water exposed mice group received a daily dose of about 65 nCi (concn 13 nCi/cm3, consumption estimated as ca. 5 cm3/mouse*day) for up to 112 days
Duration and frequency of treatment / exposure:
drinking water exposed mice: up to 112 days
mice (iv, ip, ig): 80 days to last count
rats (iv): 115 days, (ip, ig): 144 d to last count
monkeys (iv): 130 and (ig): 136 days to last count
dogs (iv): 151 and (ig): 119 days to last count
Doses / concentrations
Doses / Concentrations:
mice (iv, ip, ig): 0.4, 0.5, 0.6 µCi, resp.
rats (iv, ip): 0.5 µCi, (ig): 0.6 µCi
monkeys (iv, ig): 2.2 µCi
dogs (iv): 2.2 µCi and (ig): 1.1 µCi
No. of animals per sex per dose / concentration:
drinking water exposed mice: 40 animals
mice (iv, ip, ig): 12 animals (all females)
rats: 6 animals each route (all males)
monkeys: 3 animals each route (all males)
dogs: 4 animals each route (all males)
Control animals:
not specified
Details on study design:
- Whole body liquid scintillation detectors were used to determine the total activity in each animal within 30 min of injection (initial body burden) and at intervals of a day or more thereafter. These detectors were also used to assay the activity in tissues and excreta.
- mice , rats and monkeys were anesthetized with Nembutal for iv injections, but dogs were not anesthetised

- drinking water exposed mice were killed in groups of four at 2, 4, 7, 15, 28, 42, 56, 70, 84 and 112 days after beginning of exposure. Whole-body activities were measured periodically before and at death when following tissues were removed, blotted dry, weighed and assayed for 75-Se activity: pelt, brain, heart, lung, gut, spleen, liver and kidney. Blood, fat, mesentries and urogenital organs were pooled and assayed as "remains". The residual carcass, containing mostly muscle and bone, was assayed as a unit, and a femur was removed, freed of soft tissue, weighed and assayed, as was a weighted portion of the muscle removed from the femur.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
- gut absorption, therefore, was considerably less in the monkeys than in the other species, where absorption appears above 90 %
Details on distribution in tissues:
- The kidney was the most important emunctory for 75Se after the first 3 days in all species and for all routes of administration
Details on excretion:
- Urinary/faecal ratios following ig administration were less during the first week than those found following other routes of administration, but these differences are not found at later times
- the results indicate that for parenteral routes during the first day after injection, excretion is predominantly urinary; at later times the U/F ratios decrease to a value somewhat less than 3.0; this ratio is low after ingestion but at later times also tends toward a value between 2.0 and 3.0

Any other information on results incl. tables

- except for monkeys the route of administration has little effect on the retention of selenium.

- the excretion data confirm the similarities in retention patterns after various routes of administration

- after the first week, there were only small differences in excretion rates and urinary/faecal (U/F) ratios; lower U/F ratios in the IG groups during the first week result from less than complete absorption

The results are presented in various figures in the original article.

Applicant's summary and conclusion

Interpretation of results (migrated information): no data Furchner et al. (1975) estimated that over 90% of an oral dose of selenious acid was absorbed in mice and dogs, although monkeys absorbed less of the administered dose (amount unspecified).
Furchner et al. (1975) estimated that over 90% of an oral dose of selenious acid was absorbed in mice and dogs, although monkeys absorbed less of the administered dose (amount unspecified).