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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Endpoint:
two-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published summary of a guideline- and GLP-compliant study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2001

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Reference substance name:
Ammonium perchlorate
EC Number:
232-235-1
EC Name:
Ammonium perchlorate
Cas Number:
7790-98-9
IUPAC Name:
ammonium perchlorate
Test material form:
not specified
Details on test material:
Potassium perchlorate lot 03907LF obtained from Aldrich (99.8% purity)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, MI
- Age at study initiation: 38-39 days
- Weight at study initiation: not reported
- Fasting period before study: not relevant
- Housing: individual (not during mating or lactation)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS: no data

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Details on exposure:
Rats were continuously exposed to levels of ammonium perchlorate in the drinking water
Details on mating procedure:
No details reported
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Continuous; pre-mating, during mating, gestation and lactation
Frequency of treatment:
Daily / continuous
Details on study schedule:
No further details
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 0.3, 3.0, 30 mg/kg bw/d
Basis:
other: target exposure levels
No. of animals per sex per dose:
30
Control animals:
yes, concurrent vehicle
Details on study design:
No further details
Positive control:
Not required

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: daily

FOOD CONSUMPTION: Yes
- Time schedule for examinations: daily

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: daily
Oestrous cyclicity (parental animals):
Yes (P generation females from 21 days pre-mating)
Sperm parameters (parental animals):
Parameters examined in [all/P/F1 male parental generations
Litter observations:
Litters were observed twice daily for viability; dead pups were necropsied. Offspring were observed daily for clinical signs. Bodyweights were recorded at Day 1, 4, 7, 14 and 21. Sexual maturation was assessed.
Postmortem examinations (parental animals):
Gross necropsy, sperm analysis, deatiled histopathology (control and high dose); thyroid (all groups)
Postmortem examinations (offspring):
At least 3 pups/sex/litter (F2) were necropsied; histopathology was perfomred on the adrenals, brain, thyroids, liver, spleen, kidneys and thymus. Pooled blood samples were assesed fo T3, T4 and TSH levels.
Statistics:
Various tests were employed
Reproductive indices:
Mating and lactation indices reported
Offspring viability indices:
Viability and survival indices reported

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
thyroid pathology at 3 and 30 mg/kg bw/d
Other effects:
no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
not examined

Details on results (P0)

Effects in parental animals were limited to increased thyroid weight and associated histopathology (hyperplasia, hypertrophy) at dose levels of 3 and 30 mg/kg bw/d. Increased TSH levels (males and female F1) and decreased T4 levels (male F1) were seen at 30 mg/kg bw/d.

Effect levels (P0)

open allclose all
Dose descriptor:
NOAEL
Effect level:
30 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effects on fertility or reproducitve parameters seen at the highest dose level
Remarks on result:
other: Generation: reproductive toxicity (migrated information)
Dose descriptor:
NOAEL
Effect level:
0.3 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Increased thyroid weights and thyroid hyperplasia at 3.0 mg/kg bw//d and above
Remarks on result:
other: Generation: parental toxicity (migrated information)
Dose descriptor:
NOAEL
Effect level:
0.3 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Increased thyroid weight at 3.0 mg/kg bw/d and above
Remarks on result:
other: Generation: offspring (migrated information)

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Increased thyroid weight at 3 and 30 mg/kg bw/d
Gross pathological findings:
no effects observed
Histopathological findings:
effects observed, treatment-related
Description (incidence and severity):
thyroid histopathology at 3 and 30 mg/kg bw/d

Details on results (F1)

Effects in offspring were limited to incraesed thyroid weight and associated histopathology (hyperplasia, hypertrophy) at 3 and 30 mg/kg bw/d.

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

No effects of treatment were seen on reproductive parameters in this study.

Applicant's summary and conclusion

Conclusions:
No effects of treatment were seen on reproductive parameters in this study.
Executive summary:

This two-generation reproductive toxicity study was performed to examine the effects of ammonium perchlorate on the male and female reproductive systems in rats, and on the growth and development of offspring. Adult Sprague-Dawley rats (30/sex/group) were given continuous access to ammonium perchlorate in their drinking water at doses of 0, 0.3, 3.0, and 30.0 mg/kg bw/d. F1 generation rats were given the same ammonium perchlorate doses as the P1 generation beginning at weaning and continuing through to the day of sacrifice. Standard reproductive parameters were evaluated; additionally blood was collected for determination of serum thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) levels. Histopathological examinations were conducted on major tissues, including the thyroid. No significant changes in developmental parameters were observed. In the F1 generation adult rats, relative thyroid weights were significantly increased in all dose groups for female rats and in the 3.0 and 30.0 mg/kg bw/d dose groups for male rats. Histopathological changes in the thyroid consisted of hypertrophy and hyperplasia that increased in incidence and severity in a dose-related manner. Dose-related, statistically significant changes in TSH and T4 or T3 occurred at doses higher than those that resulted in changes in thyroid weight and thyroid histopathology, 30 mg/kg bw/d. It is therefore concluded that perchlorate is not a reproductive toxicant in rats when administered in the drinking water at doses up to 30 mg/kg bw/d, but it can affect the thyroid at dose levels of ≥3 mg/kg bw/d. Based on these findings, the authors identify 0.3 mg/kg bw/d as a NOAEL for this study.