Potassium perchlorate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study design not based on internationally adopted test guidelines but conducted in accordance with sound scientific principles

Data source

Reference

Reference Type:

publication

Title:

Effectsof methylmercaptoimidazole (MMI), propylthiouracil (PTU), potassium perchlorate (KClO4) and potassium iodide (KI) on the serumconcentrations of thyrotrophin (TSH) and thyroid hormones in the rat

Author:

Mannisto PT, Ranta T & Leppaluoto J.

Year:

1979

Bibliographic source:

Acta Endocrinologica 91: 271-281

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Groups of male rats were administered the test substance potassium perchlorate in drinking water for at least four days at graded dose levels. The rats were terminated in the early afternoon and serum concentrations of T3, T4 and TSH were measured by radioimmunossay techniques. Increases in serum TSH and decreases in serum T3 and/or T4 were monitored.

GLP compliance:

no

Test type:

other: Toxicokinetics study

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Potassium perchlorate

EC Number:

231-912-9

EC Name:

Potassium perchlorate

Cas Number:

7778-74-7

Molecular formula:

ClHO4.K

IUPAC Name:

potassium perchlorate

Test material form:

not specified

Details on test material:

Potassium perchlorate administered in tap water at doses of 0, 10, 50, 100 and 500 mg/L.
The KClO4 and other test materials and the hormones used in the assays were obtained from Sigma (St Louis) USA.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: male outbred Sprague Dawley rats obtained but no details of the supplier are given in the publication
- Age at study initiation: no details
- Weight at study initiation: 180-220g
- Fasting period before study: no details
- Housing: group housed in cages of 2-5 animals
- Individual metabolism cages: no
- Diet (e.g. ad libitum): ad libitum access to diet containing 0.1-0.5 mg iodine/kg
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22°C
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12 h

IN-LIFE DATES: From: no data To: no data

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on oral exposure:

VEHICLE
- Justification for use and choice of vehicle (if other than water): water used
- Concentration in vehicle:0, 10, 50, 100 and 500 mg/L for potassium perchlorate

Doses:

0, 10, 50, 100 and 500 mg/L

No. of animals per sex per dose:

5-6 rats per group in first experiment and 5-7 in second experiment.

Control animals:

yes

Details on study design:

In the first series of experiments graded doses of several test materials, including potassium perchlorate, were given to groups of 5-6 rats for 4 days.Dosing was at circa 1 pm each day.
In the second series of experiments a single dose of several test materials, including potassium perchlorate, was given to groups of 5-7 rats for up to 4 days. Rats were terminated by decapitation on days 2, 4, 6, 9 and 14.
Whole trunk blood was obtained from each rat at scheduled termination. Rats were terminated at approximately the same time as daily dosing occurred - 1 pm - to avoid circadian disruption of TSH production.
Radioimmunoassays for serum T3, T4 and TSH were completed using 100µL serum incubated overnight with antiserum and tracer at 4°C in buffer. The immunocomplex was precipitated with polyethyleneglycol and TSH measured using a standard rat TSH kit.

Statistics:

No data

Results and discussion

Preliminary study:

No data

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

> 500 other: mg/l

Based on:

test mat.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

> 50 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Estimated value; assumes water consumption of 10 mL/kg bw/d

Mortality:

None reported

Clinical signs:

other: None reported

Gross pathology:

No data

Other findings:

No data

Any other information on results incl. tables

Effects of graded doses of antithyroid drugs on serum T3, T4 and TSH following administration for 4 days:

Potassium perchlorate at a dose of 10 mg/L resulted in no change in serum hormone levels but at 50 mg/L there were significant reductions in T3 and T4, which remained low at the higher dose levels of 100 and 500 mg/L. Serum TSH increased at both 100 and 500 mg/L.

When the serum thyroid hormone levels were monitored as a function of time, following administration of a single dose level (100 mg/L), T3 and T4 levels fell from day 0 to day 6 and TSH increased from day 0 or 2 , on days 4 and 6 and continued to rise up to day 14.

Each of the antithyroid drugs induced a different pattern of serum immunoassayable hormone levels at the beginning of treatment. In potassium perchlorate treated rats T3 and T4 decreased similarly while TSH increased. Generally the T3 and T4 levels did not fall before TSH serum levels increase although according to classical feedback theory the antithyroid drugs should primarily decrease T3 or T4 which then results in increased TSH . In all of the assays evaluated serum thyroid hormone levels were not observed to fall before TSH levels began to increase. The authors postulate the inability of the radioimunoassay to detect low (but physiologically significant) serum level changes in T3 or T4.

Applicant's summary and conclusion

Interpretation of results:

other: data not adequate for classifcation

Conclusions:

No deaths occured in rats following the administration of potassium perchlorate in drinking water for 4 days at concentrations of up to 500 mg/L.

Executive summary:

Male Sprague-Dawley rats were administered graded doses of antithyroid drugs in drinking water for 4 days. Potassium perchlorate was dosed at 0, 10, 50, 100 or 500 mg/L. The rats were terminated and serum T3, T4 and TSH concentrations determined. Potassium perchlorate caused a rise in serum TSH and a reduction in thyroid hormones. The highest concentration tested is estimated to be equivalent to a dose level of 50 mg/kg bw.