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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

The oral route is the most likely route of (repeated) exposure.

A NOAEL value is not determined by the study reliable enough to be used as starting point for the derivation of a DNEL. Thus the LOAEL value is used as a starting point.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Referenceopen allclose all

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
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents)
GLP compliance:
yes
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
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
Dose / conc.:
0.01 mg/kg bw/day (nominal)
Remarks:
Group 2
Dose / conc.:
0.05 mg/kg bw/day (nominal)
Remarks:
Group 3
Dose / conc.:
0.2 mg/kg bw/day (nominal)
Remarks:
Group 4
Dose / conc.:
1 mg/kg bw/day (nominal)
Remarks:
Group 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.
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
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
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
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

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 
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.
Endpoint:
sub-chronic toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
In water, potassium perchlorate will rapidly dissolve and completely dissociate into the perchlorate anion and the corresponding cation. Toxicity is determined only by the perchlorate moiety of the salt. as potassium is known to be non-toxic. Based on that, read-across is possible to other perchlorate salt dissociating in water without any toxic cation.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents)
GLP compliance:
yes
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
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
Dose / conc.:
0.01 mg/kg bw/day (nominal)
Remarks:
Group 2
Dose / conc.:
0.05 mg/kg bw/day (nominal)
Remarks:
Group 3
Dose / conc.:
0.2 mg/kg bw/day (nominal)
Remarks:
Group 4
Dose / conc.:
1 mg/kg bw/day (nominal)
Remarks:
Group 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.
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
Key result
Dose descriptor:
NOAEL
Effect level:
1.18 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
histopathology: non-neoplastic
Remarks on result:
other: potassium perchlorate equivalents
Key result
Dose descriptor:
LOAEL
Effect level:
11.8 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: thyroid effects
Remarks on result:
other: potassium perchlorate equivalents
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

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 
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.
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Reason / purpose for cross-reference:
read-across source
Specific details on test material used for the study:
Review on several perchlorate salts. Due to the dissociating behaviour of soluble perchlorates the toxicity is only caused by the perchlorat moiety as potassium is known not to be toxic.
Dose descriptor:
LOEL
Effect level:
>= 35 other: mg/d
Based on:
other: perchlorate anion
Sex:
not specified
Conclusions:
The review summarizes existing studies on human oral uptake of perchlorate salts. It is summarized that in most publicated studies an effect on humans can be observed at an uptake of 35 mg potassium per day or more.
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Version / remarks:
The methodes described are similar to OECD 408. Some minor deviations have no impact on the reliability of the study.
Deviations:
yes
Remarks:
The methodes described are similar to OECD 408. Some minor deviations have no impact on the reliability of the study.
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents)
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
The test animals were obtained from Charles River Laboratories (Raleigh, NC) and acclimated for 11 days. Animals were 6 - 7 weeks old at the date of study inition, weighed 195 - 197 g (males) and 151 - 153 g (females), respectively. The animals were housed in induvidual cages. Diet: PMI Certified Rodent Chow, ad libitum was given. Water: reverse osmosis water, ad libitum was given. The 90-day treatment period was followed by a 30 day recovery period.
Environmental conditions: 18 - 26 °C, 30 - 70 % humidity, 10 - 15 air changes per hour, 12 h light / 12 h dark photo period
Route of administration:
oral: drinking water
Vehicle:
water
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
The perchlorate concentrations were determined by ion chromatography.
Duration of treatment / exposure:
satellite groups: 14 days
main study group: 90 days
Frequency of treatment:
continous during application period
Dose / conc.:
0 mg/kg bw/day (nominal)
Remarks:
control group
Dose / conc.:
0.01 mg/kg bw/day (nominal)
Dose / conc.:
0.05 mg/kg bw/day (nominal)
Dose / conc.:
0.2 mg/kg bw/day (nominal)
Dose / conc.:
1 mg/kg bw/day (nominal)
Dose / conc.:
10 mg/kg bw/day (nominal)
No. of animals per sex per dose:
10 male + 10 female
Control animals:
yes, concurrent vehicle
Positive control:
for micronucleus interpretation (additional animals treated with cyclophosphamide)
Observations and examinations performed and frequency:
daily: mortality; weekly: body weight, food consumption, water consumption
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Neuropathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
no effects observed
Other effects:
effects observed, treatment-related
Description (incidence and severity):
Hormonal effects were observed due to changes in T3 and T4 (decrease) and TSH (increase). All observed hormonal effects were reversible.
Key result
Dose descriptor:
LOEL
Effect level:
10 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
organ weights and organ / body weight ratios
other: changes in T3, T4 and TSH levels
Key result
Dose descriptor:
NOAEL
Effect level:
1 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no exposure-related effect observed at this concentration
Key result
Critical effects observed:
yes
Lowest effective dose / conc.:
10 mg/kg bw/day (nominal)
System:
endocrine system
Organ:
thyroid gland
Treatment related:
yes
Dose response relationship:
not specified
Relevant for humans:
yes
Conclusions:
No toxicologically meaningful differences were observed between the control and perchlorate-treated groups with respect to survival, clinical observations, body weights, food consumption, water consumption, ophthalmology, hematology, clinical chemistry, estrous cycling, sperm parameters, or bone marrow micronucleus formation. A target organ effect was produced by AP in the thyroids of male and female rats at the 10 mg/kg/day level after 14 and 90 days of exposure. The effect was characterized by significantly increased thyroid weights and thyroid histopathology consisting primarily of follicular cell hypertrophy with microfollicle formation and colloid depletion. These changes were reversible after a nontreatment recovery period of 30 days. Statistically significant changes in TSH and thyroid hormones were observed at all ammonium perchlorate dosage levels tested; however, no thyroid organ weight or histopathological effects were observed at AP dosage levels < or = 1.0 mg/kg/day.
Endpoint:
sub-chronic toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Justification for type of information:
In water, potassium perchlorate will rapidly dissolve and completely dissociate into the perchlorate anion and the corresponding cation. Toxicity is determined only by the perchlorate moiety of the salt. as potassium is known to be non-toxic. Based on that, read-across is possible to other perchlorate salt dissociating in water without any toxic cation.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Version / remarks:
The methodes described are similar to OECD 408. Some minor deviations have no impact on the reliability of the study.
Deviations:
yes
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents)
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
The test animals were obtained from Charles River Laboratories (Raleigh, NC) and acclimated for 11 days. Animals were 6 - 7 weeks old at the date of study inition, weighed 195 - 197 g (males) and 151 - 153 g (females), respectively. The animals were housed in induvidual cages. Diet: PMI Certified Rodent Chow, ad libitum was given. Water: reverse osmosis water, ad libitum was given. The 90-day treatment period was followed by a 30 day recovery period.
Environmental conditions: 18 - 26 °C, 30 - 70 % humidity, 10 - 15 air changes per hour, 12 h light / 12 h dark photo period
Route of administration:
oral: drinking water
Vehicle:
water
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
The perchlorate concentrations were determined by ion chromatography.
Duration of treatment / exposure:
satellite groups: 14 days
main study group: 90 days
Frequency of treatment:
continous during application period
Dose / conc.:
0 mg/kg bw/day (nominal)
Remarks:
control group
Dose / conc.:
0.01 mg/kg bw/day (nominal)
Dose / conc.:
0.05 mg/kg bw/day (nominal)
Dose / conc.:
0.2 mg/kg bw/day (nominal)
Dose / conc.:
1 mg/kg bw/day (nominal)
Dose / conc.:
10 mg/kg bw/day (nominal)
No. of animals per sex per dose:
10 male + 10 female
Control animals:
yes, concurrent vehicle
Positive control:
for micronucleus interpretation (additional animals treated with cyclophosphamide)
Observations and examinations performed and frequency:
daily: mortality; weekly: body weight, food consumption, water consumption
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Neuropathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
no effects observed
Other effects:
effects observed, treatment-related
Description (incidence and severity):
Hormonal effects were observed due to changes in T3 and T4 (decrease) and TSH (increase). All observed hormonal effects were reversible.
Key result
Dose descriptor:
LOEL
Effect level:
11.8 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
organ weights and organ / body weight ratios
other: changes in T3, T4 and TSH levels
Remarks on result:
other: potassium perchlorate equivalents
Key result
Dose descriptor:
NOAEL
Effect level:
1.18 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no exposure-related effect observed at this concentration
Remarks on result:
other: potassium perchlorate equivalents
Key result
Critical effects observed:
yes
Lowest effective dose / conc.:
10 mg/kg bw/day (nominal)
System:
endocrine system
Organ:
thyroid gland
Treatment related:
yes
Dose response relationship:
not specified
Relevant for humans:
yes
Conclusions:
No toxicologically meaningful differences were observed between the control and perchlorate-treated groups with respect to survival, clinical observations, body weights, food consumption, water consumption, ophthalmology, hematology, clinical chemistry, estrous cycling, sperm parameters, or bone marrow micronucleus formation. A target organ effect was produced by AP in the thyroids of male and female rats at the 10 mg/kg/day level after 14 and 90 days of exposure. The effect was characterized by significantly increased thyroid weights and thyroid histopathology consisting primarily of follicular cell hypertrophy with microfollicle formation and colloid depletion. These changes were reversible after a nontreatment recovery period of 30 days. Statistically significant changes in TSH and thyroid hormones were observed at all ammonium perchlorate dosage levels tested; however, no thyroid organ weight or histopathological effects were observed at AP dosage levels < or = 1.0 mg/kg/day.

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.
The LOEL for ammonium perchlorate was determined to be 10.0 mg /kg bw/d.
The LOEL for potassium perchlorate is 11.8 mg /kg bw/d.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LOAEL
11.8 mg/kg bw/day
Study duration:
subchronic
Species:
rat
System:
endocrine system
Organ:
thyroid gland

Additional information

Justification for classification or non-classification