Institute of Occupational, Social-,
and Environmental Medicine

Uptake and elimination of permethrin related to
the use of...
Institute of Occupational, Social-,
and Environmental Medicine

Background Information
 Clothing with long-lasting permet...
Institute of Occupational, Social-,
and Environmental Medicine

Properties of Permethrin


Neurotoxin in target organisms...
Institute of Occupational, Social-,
and Environmental Medicine

Main Issues of our Study
 What is the internal permethrin...
Institute of Occupational, Social-,
and Environmental Medicine

Study Design
 N= 30 male volunteers (age 20-34 years, med...
Institute of Occupational, Social-,
and Environmental Medicine

Study Design
 Collection of 12 urine samples in total; co...
Institute of Occupational, Social-,
and Environmental Medicine

Determination of Internal Exposure
Metabolism scheme of pe...
Institute of Occupational, Social-,
and Environmental Medicine

Time Curve of DCCA-Excretion
Pooled analysis of “wearing c...
Institute of Occupational, Social-,
and Environmental Medicine

Time Curve of DCCA-Excretion

DCCA in urine (mean conc.) [...
Institute of Occupational, Social-,
and Environmental Medicine

Elimination Half-lifes

DCCA in urine (mean conc.) [µg/l]
...
Institute of Occupational, Social-,
and Environmental Medicine

Comparison of Excreted Amounts
Comparison of Area Under th...
Institute of Occupational, Social-,
and Environmental Medicine

Summary and Conclusions I
 Uptake of permethrin from clot...
Institute of Occupational, Social-,
and Environmental Medicine

Summary and Conclusions II
 According to long half-life, ...
Institute of Occupational, Social-,
and Environmental Medicine

Thank you very much for your attention!
14
Institute of Occupational, Social-,
and Environmental Medicine

Ratio trans-DCCA / cis-DCCA

Initial ratio trans-/ cisPerm...
Institute of Occupational, Social-,
and Environmental Medicine

Producer of Clothing and Metabolite Excretion

DCCA in uri...
Upcoming SlideShare
Loading in …5
×

10.4 Rossbach

283 views

Published on

Published in: Health & Medicine, Technology
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
283
On SlideShare
0
From Embeds
0
Number of Embeds
7
Actions
Shares
0
Downloads
4
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

10.4 Rossbach

  1. 1. Institute of Occupational, Social-, and Environmental Medicine Uptake and elimination of permethrin related to the use of permethrin treated clothing for forestry workers B. Rossbach, A. Niemietz, P. Kegel, S. Letzel Institute of Occupational-, Social-, and Environmental Medicine University Medical Center of the Johannes Gutenberg University, Mainz, Germany The 9th International Symposium on Biological Monitoring in Occupational and Environmental Health 9th – 11th September 2013, Lowry Centre, Manchester, UK
  2. 2. Institute of Occupational, Social-, and Environmental Medicine Background Information  Clothing with long-lasting permethrin treatment is sold to improve protection against tick related diseases  Use of respective clothing entails uptake of permethrin into the body  Uptake by the dermal route likely  Dermal uptake of permethrin slow in general, typical rate of uptake: 2% of the applied dose[1]  After uptake: metabolic cleavage, conjugation and excretion of metabolites in urine  Excretion half-lifes after dermal uptake from permethrin containing ointments: about 30h[2] [1] Appel et al., Int. J. Hyg. Environ. Health, 211: 88 (2008); [2] Tomalik-Scharte et al., Eur J Clin Pharmacol, 61: 399 (2005) 2
  3. 3. Institute of Occupational, Social-, and Environmental Medicine Properties of Permethrin  Neurotoxin in target organisms (insects, mites) after contact or uptake  Effects in humans: • Local effects: reversible unpleasant sensations (prickling, numbness, itching), dermal and mucosal irritations, respiratory tract irritation • Systemic effects: headache, dizziness, fatigue, intestinal disorders, nausea, vomiting • Inconsistent classification with respect to carcinogenicity (IARC Cat. 3: not classifiable, USEPA: “likely to be carcinogenic to humans after oral uptake”)  No biomonitoring limit value such as BAT or BEI available  Environmental background exposure in the general population, reference values available for Germany  WHO acceptable daily intake (ADI): 0,05 mg/kg body weight[3] [3] World Health Organisation (WHO)/Food and Agriculture Organization (FAO) Pesticide residues in food 1999 Evaluations Part II - Toxicology: Permethrin, 1999 3
  4. 4. Institute of Occupational, Social-, and Environmental Medicine Main Issues of our Study  What is the internal permethrin exposure of persons, who wore permethrin treated clothing for just one day?  What are the kinetics of uptake and excretion like? Is there a favorable time range for monitoring internal exposure?  Is there an influence of climate and/or physical workload on internal exposure when wearing permethrin treated clothes 4
  5. 5. Institute of Occupational, Social-, and Environmental Medicine Study Design  N= 30 male volunteers (age 20-34 years, median 25)  Wearing of permethrin treated clothing for forestry workers (long sleeved jacket and long pants), three times for 8h each  Undergarments standardized  Varying external conditions (“wearing conditions”) I. Comfort conditions without any further restrictions regarding the subjects´ whereabouts over the whole 8h period II. At the minimum 4h stay under condition of increased temperature (≤ 25°C and ≤ 65% rel. hum.) III. Like II., additional simulation of physical workload using a bicycle ergometer (six 10-min-intervals with HR 140-150 min-1) 5
  6. 6. Institute of Occupational, Social-, and Environmental Medicine Study Design  Collection of 12 urine samples in total; collection before, during and after wearing permethrin treated clothes  Time of sampling and particular type of sample in detail: spot urine sample “wearing period” 0 0 0 8 16 2420 32 20 40 40 40 48 6072 80 96 8h urine sample 0 40 100 120 120 20144 140 504 500 Zeit ab beginning of wearing [h] time fromTragebeginn [h]120 60 80 100 140 500 60 Zeit ab T Zeit ab Tragebeginn [h]  Timespan between repeated wearing of clothing under differing conditions: at least 3 weeks 6
  7. 7. Institute of Occupational, Social-, and Environmental Medicine Determination of Internal Exposure Metabolism scheme of permethrin Analytical method[4] (simplified) Urine sample (10 ml) Cl O Cl O O Acidic hydrolysis cis/trans permethrin (mixture of isomers) R Cl OH Cl HO pH-controlled liquid/liquid extraction O O trans-DCCA Derivatization + R Cl OH Cl O cis-DCCA [4] HO O O Analysis by gas chromatography/ tandem mass spectrometry (GC/MS-MS) 3-PBA according to Schettgen et al., J. Chrom. B, 778: 121 (2002) 7
  8. 8. Institute of Occupational, Social-, and Environmental Medicine Time Curve of DCCA-Excretion Pooled analysis of “wearing conditions” I to III DCCA in urine [µg/l] 100 maximum average excretion: 12,1 µg/l 10 maximum 1 mean minimum 0.1 period of wearing „reference value“ general population[4] 0.01 0 8 20 40 60 80 100 120 140 500 510 Time [h] 8 [4] German Federal Environmental Agency, Bundesgesundheitsbl. Gesundheitsforsch. Gesundheitsschutz, 48: 1187 (2005)
  9. 9. Institute of Occupational, Social-, and Environmental Medicine Time Curve of DCCA-Excretion DCCA in urine (mean conc.) [µg/l] Separate analysis of “wearing condition” I to III wearing condition I II III 10 1 Maximum values (percentage of samples > “reference value“): condition I: 8.6 µg/l (53%) condition II: 12.9 µg/l (61%) condition III: 15.0 µg/l (79%) period of wearing „reference value“ general population[4] 0.1 0 8 20 40 60 80 100 120 140 500 510 Time [h] 9 [4] German Federal Environmental Agency, Bundesgesundheitsbl. Gesundheitsforsch. Gesundheitsschutz, 48: 1187 (2005)
  10. 10. Institute of Occupational, Social-, and Environmental Medicine Elimination Half-lifes DCCA in urine (mean conc.) [µg/l] Calculation by linear regression, regarding samples from 20 to 144 h from beginning of wearing wearing condition I II III 10 1 t1/2cond I : 36,2 h t1/2cond II : 30,9 h t1/2cond III : 30,0 h 0.1 0 8 20 40 60 80 100 120 140 500 510 Time [h] 10
  11. 11. Institute of Occupational, Social-, and Environmental Medicine Comparison of Excreted Amounts Comparison of Area Under the Curves (AUC) resulting for different wearing conditions DCCA in urine (mean conc.) [µg/l] 16 wearing condition I II III 14 12 10 𝑐𝐼𝐼𝐼 𝐴𝑈𝐶0−144 = 𝟖𝟑𝟏 µ𝑔 ∙ ℎ (= 0.96 ∙ 𝐴𝑈𝐶0−∞ ) 𝑙 8 +72% 𝑐𝐼𝐼 𝐴𝑈𝐶0−144 𝑐𝐼 𝐴𝑈𝐶0−144 6 4 µ𝑔 ∙ ℎ = 𝟔𝟑𝟒 (= 0.94 ∙ 𝐴𝑈𝐶0−∞ ) 𝑙 µ𝑔 ∙ ℎ = 𝟒𝟖𝟐 (= 0.91 ∙ 𝐴𝑈𝐶0−∞ ) 𝑙 +32% 2 0 0 20 40 60 80 100 Time [h] 120 140 500 510 11
  12. 12. Institute of Occupational, Social-, and Environmental Medicine Summary and Conclusions I  Uptake of permethrin from clothing and its elimination from the body can be tracked well by biomonitoring  Maximum of excretion 8 to 16h after termination of wearing  First void urine of the day following wearing best reflects internal exposure  Exceedance of reference value in 50% of the study subjects even after one-time exposure  Half-lifes of about 30h and elimination of ≥ 90% within 144h in line with dermal uptake of permethrin[2] [2] Tomalik-Scharte et al., Eur J Clin Pharmacol, 61: 399 (2005) 12
  13. 13. Institute of Occupational, Social-, and Environmental Medicine Summary and Conclusions II  According to long half-life, accumulation of permethrin can be expected in case of daily use of respective clothing at work  Internal exposure clearly dependent on wearing conditions with increase of exposure by hot and humid climate and/or physical workload  Possible explanation(s):  Increased release of permethrin from garment due to higher temperature and/or sweat  Enhanced dermal uptake due to increased dermal perfusion and maceration of stratum corneum 13
  14. 14. Institute of Occupational, Social-, and Environmental Medicine Thank you very much for your attention! 14
  15. 15. Institute of Occupational, Social-, and Environmental Medicine Ratio trans-DCCA / cis-DCCA Initial ratio trans-/ cisPermethrin in garments: 3:1 15
  16. 16. Institute of Occupational, Social-, and Environmental Medicine Producer of Clothing and Metabolite Excretion DCCA in urine (mean conc.) Mittlere Konzentation DCCA im Urin [µg/l] 25 Hersteller A Producer A Producer B Hersteller B 21.5 µg/l 20 Producer A AUC: 203 µg/l*h t1/2: 41,4 h 15 Producer B AUC: 1098 µg/l*h t1/2: 29,9 h 10 5 3.5 µg/l 0 8 20 40 60 80 100 120 140 500 510 Zeitpunkt der Probenahme [h] Time [h] 16

×