Potassium perchlorate

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium perchlorate

EC Number:

232-235-1

EC Name:

Ammonium perchlorate

Cas Number:

7790-98-9

Molecular formula:

ClHO4.H3N

IUPAC Name:

ammonium perchlorate

Test material form:

solid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on species / strain selection:

The test animals were obtained from Charles River Laboratories, Inc., Kingston, NY, USA

Sex:

male/female

Details on test animals or test system and environmental conditions:

12 h light/ 12 h darc cycle; 22 +- 2 °C, 50 +- 15% relative humidity, 12 - 15 air changes/h; 2 weeks of acclimation time

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

validated ion chromatography method

Duration of treatment / exposure:

14 and 90 days, respectively

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.01 mg/kg bw/day (nominal)

Remarks:

Group 2

Doses / concentrations 2

Dose / conc.:

0.05 mg/kg bw/day (nominal)

Remarks:

Group 3

Doses / concentrations 3

Dose / conc.:

0.2 mg/kg bw/day (nominal)

Remarks:

Group 4

Doses / concentrations 4

Dose / conc.:

1 mg/kg bw/day (nominal)

Remarks:

Group 5

Doses / concentrations 5

Dose / conc.:

10 mg/kg bw/day (nominal)

Remarks:

Group 6

No. of animals per sex per dose:

20 or 30, respectively

Control animals:

yes

Details on study design:

For each dose group and the control group at least 20 male and 20 female animals were used. At day 14 and day 90, respectively, 10 male and 10 female animals of each group were euthanized and necropsied. In the groups 1, 3, 5 and 6 10 additional animals of each sex were euthanized after a 90-day period of treatment followed by a 30-day period of recovery.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

On all test animals the following examinations and analysis were conducted:
- ophthalmology prior to study initiation
- body weights, weight gain, food and water consumption
- clinical pathology and TSH, T3 and T4 analyses
- estrous cycling or sperm analysis, respectively
- gross necropsy and histopathology
- micronucleus formation

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, non-treatment-related

Food consumption and compound intake (if feeding study):

effects observed, non-treatment-related

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

effects observed, non-treatment-related

Ophthalmological findings:

no effects observed

Haematological findings:

effects observed, non-treatment-related

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

The absolute thyroid weights increased in the group 6 (dose of 10.0 mg/kg/day).

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

The non-neoplastic thyroid histopathological effects are summarizes in the table.

Histopathological findings: neoplastic:

no effects observed

Effect levels

1

Key result

Dose descriptor:

NOAEL

Effect level:

1 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

histopathology: non-neoplastic

2

Key result

Dose descriptor:

LOAEL

Effect level:

10 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: thyroid effects

Target system / organ toxicity

Critical effects observed:

yes

Lowest effective dose / conc.:

10 mg/kg bw/day (actual dose received)

System:

endocrine system

Organ:

thyroid gland

Treatment related:

yes

Dose response relationship:

not specified

Relevant for humans:

yes

Any other information on results incl. tables

The non-neoplastic thyroid histopathological effects are summarizes in the table.

total incidences	Group 1 (0 mg/kg/day)	Group 2 (0.01 mg/kg/day)	Group 3 (0.05 mg/kg/day)	Group 4 (0.2 mg/kg/day)	Group 5 (1.0 mg/kg/day)	Group 6 (10.0 mg/kg/day)
14-day interval, males	1/8	0/10	1/10	0/10	0/10	10/10
14 -day interval, females	0/10	0/10	0/10	0/10	0/10	7/10
90-day interval, males	2/10	0/10	0/10	0/10	1/10	8/10
90-day interval, females	0/10	0/10	0/10	0/10	0/10	9/10

Applicant's summary and conclusion

Conclusions:

The NOAEL for ammonium perchlorate was determined to be 1.00 mg /kg bw/d.
The NOAEL for potassium perchlorate is 1.18 mg /kg bw/d.