Potassium perchlorate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

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 414 (Prenatal Developmental Toxicity Study)

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

IUPAC Name:

ammonium perchlorate

Test material form:

not specified

Details on test material:

Obtained from Aldrich Chemical Company; 99.8% purity

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Covance, PA
- Age at study initiation: not stated
- Weight at study initiation: not stated

- Housing: no details
- Diet: 180 g/d
- Water: ad libitum
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
No details

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on exposure:

Rabbits were exposed on Days 6-28 of gestation

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

Dams were supplied assumed pregnant (naturallly mated)

Duration of treatment / exposure:

Rabbits were exposed on Days 6-28 of gestation

Frequency of treatment:

Daily / continuous

Duration of test:

Rabbits were exposed on Days 6-18 of gestation and terminated on Day 29

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 0.1, 1, 10, 30, 100 mg/kg bwd
Basis:
other: target dose levels

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0, 0.1, 0.9, 10.4, 30.3, 102.3 mg/kg bw/d
Basis:
actual ingested

No. of animals per sex per dose:

25

Control animals:

yes, concurrent vehicle

Examinations

Maternal 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: yes
- Time schedule for examinations: daily

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation Day #29
- Organs examined: thyroids/parathyroids

OTHER: blood was collected from does for determination of serum thyroid stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) levels and the thyroid was subjected to histopathologic examination

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes / No / No data
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: all per litter
- Head examinations: Yes: half per litter

Statistics:

Various tests were utilised

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
Maternal toxicity was limited to thyroid histopathology at dose levels of 10 mg/kg bw/d and higher, reduced T4 levels were also seen at 30 and 100 mg/kg bw/d

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Effect level:

1 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

No maternal deaths were attributed to perchlorate exposure. Ammonium perchlorate at dose levels up to 100.0 mg/kg bw/d did not affect uterine or litter parameters studied, and all values were found to be within the historical ranges of the laboratory. The litter averages forcorpora lutea, implantations, litter sizes, live and dead foetuses, percent dead or resorbed conceptuses, and fetal body weights were comparable and also did not differ significantly in the six dose groups. All placentae appeared normal and no dam had a litter consisting of only resorbed conceptuses. The maternal thyroid was identified as the target organ for ammonium perchlorate; increased incidences of thyroid follicular hypertrophy were observed in does treated with ≥10 mg/kg bw/d and significantly decreased T4 was observed in does treated with 30 mg/kg bw/d.

Applicant's summary and conclusion

Conclusions:

No evidence of developmental toxicity was seen under the conditions of this study. The thyroid was confirmed as the target of perchlorate toxicity.

Executive summary:

A developmental toxicity study was conducted to evaluate the embryofoetal toxicity and teratogenic potential of ammonium perchlorate in New Zealand White [Hra:(NZW)SPF] rabbits. Pregnant rabbits were given continual access to ammonium perchlorate in drinking water at target doses of 0, 0.1, 1.0, 10.0, 30.0, and 100.0 mg/kg bw/d on gestation Days 6 -28 and were sacrificed on gestation Day 29. Blood was collected from does for determination of serum thyroid stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) levels and the thyroid was subjected to histopathologic examination. No maternal deaths were attributed to perchlorate exposure. Ammonium perchlorate at dose levels up to 100.0 mg/kg bw/d did not affect uterine or litter parameters studied, and all values were found to be within the historical ranges of the laboratory. The litter averages for corpora lutea, implantations, litter sizes, live and dead foetuses, percent dead or resorbed conceptuses, and fetal body weights were comparable and also did not differ significantly in the six dose groups. All placentae appeared normal and no dam had a litter consisting of only resorbed conceptuses. The maternal thyroid was identified as the target organ for ammonium perchlorate; increased incidences of thyroid follicular hypertrophy were observed in does treated with ≥10 mg/kg bw/d and significantly decreased T4 was observed in does treated with ≥30 mg/kg bw/d. A maternal NOAEL of 1.0 mg/kg bw/d was derived; in the absence of any effects, the developmental NOAEL was found to be 100 mg/kg bw/d.