Potassium perchlorate

Ecotoxicological Summary

Hazard for aquatic organisms

STP

Hazard assessment conclusion:

no hazard identified

Additional information

REACH defines an intermediate as a substance that is manufactured for and consumed in or used for chemical processing in order to be transformed into another substance (Article 3(15).

Potassium perchlorate is to be registered by The London and Scandinavian Metallugical Co. Ltd. as a transported isolated intermediate <1000 tpa. Therefore according to REACH Article 18 (2), the information requirements on the substance’s intrinsic properties (physicochemical, human health, and environmental properties) are reduced to existing available data (e.g. information the registrant holds or can obtain from other sources). As there is no predicted environmental exposure no hazard data or exposure assessment is required.

 

For completeness the following literature has been reviewed to detail the potential effects of perchlorate in the environment should there be a breach of strictly controlled conditions

 

Introduction

Perclorate is a known contaminant of groundwater and drinking water (Chapter 2 The Chemistry of Perchlorate in the Environment, G.M.Brown and B.Gu, Perchlorate: Environmental Occurrence, Interactions and Treatment 2006, Eds. B.Gu and J.D.Coates). The negatively charged perchlorate ion is composed of one chlorine atom surrounded by four oxygen atoms arranged in a tetrahedral geometry. The perchlorate anion persists in groundwater, and its mobility in surface or ground water is so high that perchlorate essentially moves with the flow of water (diffusion and convection controlled movement).

 

The presence of perchlorate in groundwater and drinking water is a potential health concern because perchlorate is known to impair the functioning of the thyroid gland not only in humans but also wildlife (mammals, fish and amphibians). The tyroid gland regulates hormomes within a narrow and specific concentration range. Impairment of the thyroid can (i) effect the development of the central nervous system of the fetus and infants (ii) affect skeletal growth and development (iii) affect metabolic activity and many organ systems. Perchlorate competitely inhibits the uptake of iodide ions by the thyroid and potassium perchlorate has been used to treat hyperthyroidism. The competitive inhibition is a consequence of the hydration energies of the two ions. A report by the National Research Council (Health Implications of perchlorate ingestion. The National Academies Press, 2005) concluded that perchlorate concentrations found in groundwater are unlikely to affect the health of an adult however, the situation may be different for infants, children, pregnant women and people with pre-existing thyroid disorders.

 

Freshwater water-quality criteria for perchlorate

Dean, K.E. et al (2004) Development of freshwater water-quality criteria for perchlorate (ET&C, Vol. 23., 6, pp 1441 -1451)

The anion perchlorate (ClO2) is an oxidizing component commonly used in solid propellants for rockets and missiles; in explosives, flares, fireworks, chemical processes, and automobile air-bag inflators; and for other assorted uses. With recent advances in analytical detection capability, perchlorate has been found in a variety of ground and surface waters throughout the United States. Because perchlorate has been associated with thyroid problems in humans and may have similar effects on wildlife, it is desirable to develop a water-quality criterion to assist in identifying concentrations of perchlorate in water likely to pose an ecological health risk. In the present study, we compiled all available data regarding the effects of perchlorate to aquatic organisms, and we performed additional toxicity and bioconcentration tests as required by the U.S. Environmental Protection Agency (U.S. EPA) for the development of water-quality criteria for aquatic life. A criterion maximum concentration of 20 mg/L and a criterion continuous concentration of 9.3 mg/L were calculated based on the test results. Although these are not formal Clean Water Act

Section 304(a) criteria, which must be published by the U.S. EPA, these criteria may be useful in the determination of remedial action levels for contaminated sites, for National Pollutant Discharge Elimination System permit limits, and other water-quality management practices.

 

Perchlorate effects in wildlife

Amphibians

W.L., Goleman et.al 2002 Environmentally relevant concentrations of ammoniul perchlorate inhibit development and metamorphosis in xenopus laevis(ET&C, Vol. 21., 2, pp 424 -430)

Perchlorate salts (sodium and potassium) have been used experimentally for years to inhibit amphibian metamorphosis, the concentrations used to block metamorphosis are generally greater (250 to 1000 mg/L) than concentrations of perchlorate reported in contaminated surface and groundwater. In a recent study of surface waters and sediments at Longhorn Army Ammunition Plant (LHAAP) in Texas perchlorate levels as high as 31.2 mg perchlorate/L were reported and whole-tissue samples of american bullfrog (Rana catesbeiana) tadpoles collected from a contaminated pond at LHAAP yielded perchlorate concentrations of 1130 to 2567 µg perchlorate/L. Goleman et. al (2002) exposed eggs and larvae of Xenopus laevis to varying environmentally relevant concentrations of perchlorate for 70 days. The 5- and 70-d median lethal concentrations (LC50s) were 510 ± 36 mg ammonium perchlorate/L and 223 ± 13 mg ammonium perchlorate/L, respectively. Ammonium perchlorate did not cause any concentration-related developmental abnormalities at concentrations below the 70-d LC50. Ammonium perchlorate inhibited metamorphosis in a concentration-dependent manner as evident from effects on forelimb emergence, tail resorption, and hindlimb growth. These effects were observed after exposure to ammonium perchlorate concentrations in the parts-per-billion range, at or below concentrations reported in surface waters contaminated with ammonium perchlorate. Ammonium perchlorate significantly inhibited tail resorption after a 14-d exposure in the U.S. Environmental Protection Agency (U.S. EPA) Endocrine Disruptor Screening and Testing Committee (EDSTAC) Tier I frog metamorphosis assay for thyroid disruption in amphibians.

 

 

W.L., Goleman et.al 2002 Environmentally relevant concentration of annomium perchlorate inhibit thyroid function and alter sex rations in developing xenopus laevis. (ET&C, Vol. 21., 3, pp 590 - 597)

Embryos and larvae of the South African frog Xenopus laevis were exposed to ammonium perchlorate (AP) or control medium for 70 d. The dosage levels (59 ppb, 14,140 ppb) bracketed a range of perchlorate concentrations measured in surface waters at the Longhorn Army Ammunition Plant (LHAAP) in Karnack, Texas, USA. The experiment also included a 28-d nontreatment recovery period to assess the reversibility of AP effects. There were no significant effects of AP on mortality or hatching success.

There were no effects of AP on developmental abnormalities such as bent/asymmetric tails or edema. Ammonium perchlorate inhibited forelimb emergence, the percentage of animals completing tail resorption, and hindlimb development during the 70-d exposure period. Only the upper AP concentration reduced whole-body thyroxine content, whereas both concentrations caused significant hypertrophy of the thyroid follicular epithelium. Both concentrations of AP caused a skewed sex ratio, significantly reducing the percentage of males at metamorphosis. The effects of AP on metamorphosis and thyroid function were reversed during

the 28-d nontreatment recovery period. The authors concluded that AP inhibits thyroid activity and alters gonadal differentiation in developing X. laevis. These effects were observed at concentrations at or below concentrations reported in surface waters contaminated with ammonium perchlorate, suggesting that this contaminant may pose a threat to normal development and growth in natural amphibian populations. Based on the hypertrophy of the thyroid follicular epithelium and the skewed sex ratio towards females a NOEC <59 µg/L can be concluded.

 

Tietge, J.E., (2005) Metamorphic inhibition of xenopus laevis by sodium perchlorate: Effects on development and thyroid histology (ET&C, Vol. 24., 4, pp 926 - 933)

Xenopus laevis larvae were exposed to sodium perchlorate during metamorphosis, a period of TH-dependent development, in two experiments. In the first experiment, stage 51 and 54 larvae were exposed for 14 d to 16, 63, 250, 1,000, and 4,000 µg perchlorate/ L. In the second experiment, stage 51 larvae were exposed throughout metamorphosis to 8, 16, 32, 63, and 125 µg perchlorate/L. Metamorphic development and thyroid histology were the primary endpoints examined.

Metamorphosis was retarded significantly in the first study at concentrations >250 µg perchlorate/L but histological effects were observed at 16 µg perchlorate/L. In the second study, metamorphosis was delayed by 125 µg perchlorate/L and thyroid size was increased significantly at 63 µg perchlorate/L. These studies demonstrate that inhibition of metamorphosis readily can be detected using an abbreviated protocol. However, thyroid gland effects occur at concentrations below those required to elicit developmental delay, demonstrating the sensitivity of this endpoint and suggesting that thyroidal compensation is sufficient to promote normal development until perchlorate reaches critical concentrations.

Fish

Schmidt, F. et al. (2012) Effects of the anti-thyroidal compound potassium-perchlorate on the thyroid system of the zebrafish (Aquatic Toxicology, 109, pp 47 - 58)

Modified fish early life stage tests were conducted with zebrafish exposed to concentration of potassium perchlorate (0, 62.5, 125, 250, 500 and 5000 µg perchlorate/L to identify adverse effects on the hypothalamic-pituitary-thyroid axis. Higher perchlorate concentrations led to conspicuous alterations in thyroidal tissue architecture and to effects in the pituitary. In the thyroid, severe hyperplasia at concentrations ≥ 500 μg/L together with an increase in follicle number could be detected. The most sensitive endpoint was the colloid, which showed alterations at ≥250 μg/L. The tinctorial properties and the texture of the colloid changed dramatically. Interestingly, effects on epithelial cell height were minor. The pituitary revealed significant proliferations of TSH-producing cells resulting in alterations in the ratio of adeno- to neurohypophysis. The liver as the main site of T4 deiodination showed severe glycogen depletion at concentrations ≥ 250 μg/L. In summary, the thyroid system in zebrafish showed effects by perchlorate from concentrations ≥ 250 μg/L, thus documenting a high sensitivity of the zebrafish thyroid gland for goitrogens. In the future, such distinct alterations could lead to a better understanding and identification of potential thyroid-disrupting chemicals.

 

Patino, R., (2003) Effects of ammonium perchlorate on the reproductive performance and thyroid follicle histology of zebrafish (ET&C, Vol. 22., 5, pp 1115 - 1121)

Adult zebrafish were reared up to eight weeks in control water or in water containing ammonium perchlorate (AP) at measured perchlorate concentrations of 18 (environmentally relevant, high) and 677 mg/L. Groups of eight females were paired with four males on a weekly basis to assess AP effects on spawned egg volume, an index of reproductive performance. All treatments were applied to four to five spawning replicates. At 677 mg/L, spawn volume was reduced within one week and became negligible after four weeks. At 18 mg/L, spawn volume was unaffected even after eight weeks. Also, perchlorate at 18 mg/L did not affect percentage egg fertilization. Fish were collected at the end of the exposures (677 mg/L, four weeks; control and 18 mg/L, eight weeks) for whole-body perchlorate content and thyroid histopathological analysis. Fish perchlorate levels were about one-hundredth of those of treatment water levels, indicating that waterborne perchlorate does not accumulate in whole fish. At 677 mg/L for four weeks, perchlorate caused thyroid follicle cell (nuclear) hypertrophy and angiogenesis, whereas at 18 mg/L for eight weeks, its effects were more pronounced and included hypertrophy, angiogenesis, hyperplasia, and colloid depletion. In conclusion, an eightweek exposure of adult zebrafish to 18 mg/L perchlorate (high environmentally relevant concentrations) affected the histological condition of their thyroid follicles but not their reproductive performance. The effect of 677 mg/L perchlorate on reproduction may be due to extrathyroidal toxicity. Further research is needed to determine if AP at lower environmentally relevant concentrations also affects the thyroid follicles of zebrafish.

 

Bernhardt, R.R. et al (2006) Perchlorate induces hermaphroditism in threespine sticklebacks (ET&C, Vol. 25., 8, pp 2087 - 2096)

Describes morphological and developmental characteristics for threespine stickleback (Gasterosteus aculeatus) that were spawned and raised to sexual maturity in perchlorate-treated water (30, 60 and 100 mg/L) (G1,2003) and for their offspring (G2,2004) that were not directly treated with perchlorate. The G1,2003 displayed a variety of abnormalities, including impaired formation of calcified traits, slower growth rates, aberrant sexual development, poor survivorship, and reduced pigmentation that allowed internal organs to be visible. Yet these conditions were absent when the offspring of contaminated fish (G2,2004) were raised in untreated water, suggesting a lack of transgenerational effects and that surviving populations may be able to recover following remediation of perchlorate-contaminated sites.

 

Mukhi, S., et al (2005) Novel biomarkers or perchlorate exposure in zebrafish (ET&C, Vol. 24., 5, pp 1107 - 1115)

The present study examined time-course and concentration-dependent effects of perchlorate on thyroid follicle hypertrophy, colloid depletion, and angiogenesis; alterations in whole-body thyroxine (T4) levels; and somatic growth and condition factor of subadult and adult zebrafish. Changes in the intensity of the colloidal T4 ring previously observed in zebrafish also were examined immunohistochemically. Three-month-old zebrafish were exposed to ammonium perchlorate at measured perchlorate concentrations of 0, 11, 90, 1,131, and 11,480 ppb for 12 weeks and allowed to recover in clean water for 12 weeks. At two weeks of exposure, the lowest-observed-effective concentrations (LOECs) of perchlorate that induced angiogenesis and depressed the intensity of colloidal T4 ring were 90 and 1,131 ppb, respectively; other parameters were not affected (whole-body T4 was not determined at this time). At 12 weeks of exposure, LOECs for colloid depletion, hypertrophy, angiogenesis, and colloidal T4 ring were 11,480, 1,131, 90, and 11 ppb, respectively. All changes were reversible, but residual effects on angiogenesis and colloidal T4 ring intensity were still present after 12 weeks of recovery (LOEC, 11,480 ppb). Whole-body T4 concentration, body growth (length and weight), and condition factor were not affected by perchlorate. The sensitivity and longevity of changes in colloidal T4 ring intensity and angiogenesis suggest their usefulness as novel markers of perchlorate exposure. The 12-week LOEC for colloidal T4 ring is the lowest reported for any perchlorate biomarker in aquatic vertebrates.

Conclusion on classification

Amphibian NOEC 16 µg perchlorate/L based on Tietge et al. (2005) and histological effect

Daphnia magna 48h - LC50 = 60.73 mg ClO₄^-/L

Daphnia EC10reproduction 101.79 mg ClO₄ ^-/L

Daphnia EC10feeding 238.63 mgClO₄^-/L

Fish chronic/sublethal NOEC ≥250 μg/L which showed alteration in the colloid based on Schmidt et al. (2012)

Fish sublethal biomarker response 11 μg/L based on Mukhi (2005) Colloidal T4 ring intensity

 

Fish acute LC50 values (see Bernhardt, R.R. et al (2006)

Gambusia holbrooki (mosquitofish) 404 mg/L

Oncorhynchus mykiss (rainbow trout) 2100 mg/L

Pimephales promelas (fathead minnow) 1655 mg/L

Lepomis macrochirus (bluegill sunfish) 1470 mg/L

 

The publication by Dean et al. 2004 recommends water-quality criterion of maximum concentrations of 20 mg/L and continuous concentration of 9.3 mg/L however, when compared to other summaries detailed above the concentrations recommended by Dean et al would induce sub-lethal effects during chronic exposure, it is recommended based on the reviewed documentation that environmental concentrations of perchlorate should be <11 μg/L to ensure that sub-lethal effects are not occuring in aquatic species.