Potassium perchlorate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

No data are available

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

30 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

A high quality, modern GLP- and guideline-compliant 2-generation study performed with the read-across substance ammonium perchlorate is available.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

A two-generation reproductive toxicity study (York et al, 2001) 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 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, 0.3 mg/kg bw/d is identified by the authors as the NOAEL for this study.

Short description of key information:
A high quality, modern GLP- and guideline-compliant oral (drinking water) 2-generation study performed in the rat with the read-across substance ammonium perchlorate is available.

Justification for selection of Effect on fertility via oral route:
High quality, modern GLP- and guideline-compliant study performed with a read-across substance

Effects on developmental toxicity

Description of key information

High quality, modern GLP- and guideline-compliant developmental toxicity studies performed in the rat and rabbit with the read-across substance ammonium perchlorate using oral (drinking water) are available; studies are supported by other non-standard investigations.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 mg/kg bw/day

Study duration:

subacute

Species:

rabbit

Quality of whole database:

High quality, modern GLP- and guideline-compliant developmental toxicity studies performed in the rat and rabbit with the read-across substance ammonium perchlorate are available; studies are supported by other non-standard investigations.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

A developmental toxicity study with ammonium perchlorate in Sprague-Dawley rats (York et al, 2003) identified delays in foetal skeletal ossification only at the highest dose level of 30 mg/kg bw/d. Foetal findings were associated with maternal toxicity (increased thyroid weights). Reduced foeatl thyroid colloid was observed at 1 and 30 mg/kg bw/d; maternal TSH was increased and T4 was decreased in all treated groups; T3 was reduced only at 30.0 mg/kg bw/d.  Foetal TSH was increased at 1.0 and 30.0 mg/kg bw/d, T4 was reduced at 30.0 mg/kg bw/d and T3 was decreased in all treated groups. The maternal NOAEL was 1.0 mg/kg bw/d based on increased absolute and relative maternal thyroid weights and histopathology findings. The developmental NOAEL was 1.0 mg/kg bw/d, based on delayed ossification occurred at 30 mg/kg bw/d.  The colloid depletion in the thyroids and increased TSH and decreased T3 and T4 levels at lower exposures were considered by the authors to be adaptive and not adverse. No adverse effects on development were observed at dose levels that did not cause maternal toxicity.

A developmental toxicity study with ammoniun perchlorate in the rabbit (York et al, 2001) did not identifiy any effects on uterine or litter parameters. 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.

Lampe et al (1697) identified effects of potassium perchlorate on the maternal and foetal thyroid in rabbits administered potassium perchlorate in the diet at a single dose level of 100 mg/kg bw/d. Brown-Grant & Sherwood (1971) demonstrated that the oral (drinking water) administration of 1% potassium perchlorate had no significant effect on the blastocyst survival or the ability to implant following the removal of the litter; Brown-Grant (1966) also showed a lack of effect on gestation in the rat.

Justification for selection of Effect on developmental toxicity: via oral route:
High quality, modern GLP- and guideline-compliant study performed with a read-across substance; study reports the lowest NOAEL

Justification for classification or non-classification

The available data do not indicate any specific reproductive of developmental toxicity of potassium perchlorate or the read-across substance ammonium perchlorate. No classification for reproductive toxicity is therefore proposed according to CLP.