Environmental Perchlorate Exposure and Human Health: from Newborn to Cancer.

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Presentation transcript:

Environmental Perchlorate Exposure and Human Health: from Newborn to Cancer

ClO 4 - Structure of Perchlorate

T 4 (Thyroxine) Synthesis NIS

History of Perchlorate’s Clinical Use  Treatment of Grave’s Disease 200 mg TID to 600 mg TID  Case reports of agranulocytosis and of aplastic anemia at 1,000 mg/day (+)  1980-currentTreatment for amiodarone toxicity 900 mg/day initiation 100 mg/day maintenance

Industrial Use

US Map Showing Perchlorate Sites in Southwest

Environmental Contamination by Perchlorate  CDHS 1985 study at a Sacramento aerospace site was rejected by CDC as the assay was only sensitive to 0.4 ppm ClO 4 -.  CDHS in April 1997 reported a more sensitive assay at ppm (or 4 ppb) ClO 4 -.  Sacramento contamination level was found to be 0.3 ppm or 300 ppb.  Southern California waters found to be at 5 – 8 ppb ClO 4 - or mg/day. Why the contamination? Is it important?

Map of Southern California Water Distribution

Known Human Health Effects of Perchlorate Known Toxicity: –Bone marrow effects occur at 1000 (+) mg/day. –Transient neonatal goiter seen at 600 mg/day. Treatment Dosages: –Initiation dose at 900 mg/day – Predominant dose of 600 mg/day –Maintenance dose at 100 mg/day Note: Animal studies essentially show no non-thyroidal perchlorate effect.

Pathologic and Therapeutic Exposure Ranges (mg/day)

Unknown Health Effects of Perchlorate  Effect on workers at occupational levels? What are the occupational levels?  Effect on neonate, children, and adults at Environmental levels?  Increased risk of thyroid cancer at Environmental levels?

Occupational Study

Occupational Study Results Hormone Level vs Exposure

Occupational Study Results Hormone (T 4 ) Level vs Exposure

Pathologic, Therapeutic, and Occupational Exposure Ranges (mg/day)

Environmental Exposures

Counties in California and Nevada with Perchlorate in Drinking Water

Congenital Hypothyroidism in California and Nevada

Transient Neonatal (T 4 ) Hypothyroidism in Nevada

Transient Neonatal (TSH) Hypothyroidism in Nevada

Transient Neonatal (T 4 ) Hypothyroidism by Dosage

Transient Neonatal (T 4 ) Hypothyroidism by Age (days)

Transient Neonatal (TSH) Hypothyroidism in Chile

Pediatric Hypothyroidism in Chile (School-aged 6-8 year/olds)

Adult Thyroid Disease Medical data from demographically similar areas

Adult Hypothyroid Disease Medical data from demographically similar areas

Thyroid Cancer

The Thyroid and Environmental Perchlorate Exposure

Pathologic, Therapeutic, Occupational and Environmental Exposure Ranges (mg/day) Why do we find “safe” levels?

Pharmacology of Perchlorate

Laboratory Exposure Study of Perchlorate in Water

Summary

Human Health and Perchlorate Exposure Ranges

Acknowledgements Martha Doemland, PhD Zili Li, MD, MPH Feng Xiao Li, MD, PhD Dan Byrd, PhD Gloria Deyhle, RN David Sesser, BA Michael Skeels, PhD, MPH Arnold Engel, MD Lisa Mims, MPA James Howgate, MPH Leslie Butler, MPH