INTEGRATED RISK ASSESSMENT case study organotin

SCHER is requested to comment and give an opinion on the health risks to consumers that result from exposure to organostannic compounds from the various nonfood consumer product sources of exposure or from other environmental sources BIOCIDES OTHERS Mostly TBT Wood preservatives Nonallergenic pillows Insoles for shoes Padding of cyclic shorts Spray for treatment of athlete’s foot Polyurethane foam Incorporation in various polymers, e.g. Carpet, flooring, textile coating, feather and downs

INTEGRATED RISK ASSESSMENT

Case study - organotin

Tuesday December 8 2011

Herman Autrup

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HISTORICAL USE - ORGANOTIN COMPOUNDS

Moth-proofing agent - 1920 Bactericides and fungicides – Dibutyl and tributyl tin

Marine antifouling paints - 1960

TBT banned from 1/1-2008 imposex mud-snail 1970

SCHER is requested to comment and give an opinion on the health risks to consumers that result from exposure

the various non-food consumer product sources of exposure or from other environmental sources

AGGEGATE EXPOSURE AND MULTIPLE PATHWAYS

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MAJOR USES OF ORGANOTIN

Glass coating

BIOCIDES - OTHERS

Mostly TBT

Wood preservatives

Non-allergenic pillows

Insoles for shoes

Padding of cyclic shorts

Spray for treatment of athlete’s foot

Polyurethane foam

Incorporation in various polymers, e.g

PVC PROCESSING

Flexible PVC – phthalates, adipates

Rigid PVC - OT >BT>MT

Food-contact material Bottles

Tamper-proof packs Credit cards

Construction material – window profiles Pipes and mouldings

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ORGANOTIN in HOUSE DUST

Kannan et al (2010) Arch Environ Contam Toxicol 58: 901- 9

RISK ASSESSMENT

 Exposure characterization

 Risk characterisation

ORGANOTIN BIOLOGICAL EFFECTS

 Bone mineralisation, TBT in utero

 Developmental neurotoxicity (MMT) – until PND21

 immunodefence – TBT lactational exposure

 Suspected endocrine function disruption

 disrupt hormone metabolism – aromatase inhibitor

 inducer of adipogenesis TBT

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HAZARD CHARACTERISATION

Human studies

Case studies - various health effcts following

acute exposure, neurotoxicity, non-allergic

irritant, acute nephropathy

 casuality could not be established

 dose-response relationship could not be characterized

TBT – incomplete uptake from GI 20-55 %

metabolism – CYP450 - dealkylation butanol, butene

TPT – incomplete uptake 40% absorption

fecal excretion – enterohepatic circulation metabolism – CYP2C6 - dearylation

DOT – absorption less than 20%

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HAZARD CHARACTHERIZATION

Carcinogenicity

TPTOH - pituitary adenoma in female rats

hepatocellular ca – female rats

and high dose

EU category 3 – IARC not evaluated TBT and DBT - no increase

DOT - thymus lymphoma

female rat high dose

HAZARD CHARACTERIZATION

IMMUNOTOXICITY

TPT decrease in blood lymphocytes and

eosinophils, thymus weight reduced

LOAEL = 0.25 ug/kg bw/day

TBT thymus weight reduced, reduced

resistence to L monocytogenes

NOAEL = 0.025 mg/kg bw/day

DBT was about 40% less active than TBT

DOT – thymus atrophy – same level as DBT

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RISK CHARACTERIZATION

COMPLEX MIXTURE

Additive, antagonistic, synergistic

Hazard index

Use of Potency factor

Group TDI – conservative approach

DERIVATION OF A GROUP – TDI

Critical effect: immunotoxicology

OTC Species NOAEL/LOAEL

Mg/kg bw/day

DOTC Rat LOAEL 2.5

TDI : 0.025 mg x UF 100 = 0.25 ug/kg bw/day

TDI expressed as Sn 0.1 ug/kg bw

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CONSUMERS - ORGANOTIN

Plastic bags – skin contact

Food contact material – folio, baking paper, baking forms Flooring material – inhalation, oral

Siliconized material – pillows (allergy friendly) - inhalation

Cloths – skin contact Napkins (plastic tape) – skin

POPULATION EXPOSURE ASSESSMENT

CONSUMER PRODUCTS

FOOD INTAKE

UPTAKE VIA THE LOCAL ENVIRONMENT

Route of exposure: dermal, oral and inhalation

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QUANTITY OF ORGANOTIN

Amount of organotin compound under

consideration – unit of exposure

The amount of tin present

Many different compounds – different MW

-potency

PADDLING POOL – DBT & TBT

CHILDREN – TOYS, PACIFIERS

Mouthing of toys – mouthing time and leach rate

DBT – dominant stabilizer in flexible PVC

“active” leach rate = 10 ng/cm2/hr Contact area = 10 cm2

Mouthing time = 10 min/day Intake (10x10/6) = 17 ng/day Exposure (17/8) = 2 ng/kg bw/day

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FOOD INTAKE - Adult kg bw/day

Food contaminants – fish high 0.071 ug Sn

median 0.007 ug Sn

Food contact material high 0.022 ug Sn

median 0.004 ug Sn Baking paper (silicone coated)

worst case 0.720 ug Sn

UPTAKE VIA ENVIRONMENT

Adult Sum ug Sn/kg bw / day

Model: EUSES2 (www.ecb.jrc.it)

Situations: Production 0.353

Stabiliser in PVC Processing 0.609 Catalyst 0.058 Wood preservation – treatment 1.273 Regional intake 0.005

INDOOR AIR AS A SOURCE

inhalation

Emission from migration/abrasion from room with PVC

flooring and wall coverings

Assume 1% emissions are airborne

Based on continuous occupancy of the room

Floor: area 10 m2, PVC (2 mm thick) 28 kg (0.48 mg/day)

Wall: area 25 m2, PVC (1 mm) 35 kg (0.58 mg/day)

Ventilation : 300 m3/day

Concentration in air: 0.48+0.58/300 = 0.035 ug Sn/m3

INTAKE DUST

Assumption: 200 mg/day

Max conc: (DBT) 3.11 mg Sn/ kg

Max intake: 0.62 ug Sn/day

Assumption: 100% release of organotin from matrix

Adult intake: 0.016 ug Sn/kg bw/day

Child intake: 0.117 ug/ Sn/kg bw/day

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OT IN FOOD CONTACT MATERIAL

Function: Stabiliser in plastics

Migration : Aqueous ( 3% acetic acid, 10% ethanol)

Fatty (iso-octane, 95% ethanol)

Food consumption:

200 g fatty food day (adult) Bakery products 23%, dairy 20%, meat 19%

EXPOSURE ESTIMATION FROM TEXTILE

Cart Concentration in the product on a weight basis

Wart Weight of the product (layer that contains tin)

n Contact frequency

t avering period

Upot = Cart x Wart x n / t

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HUMAN – INTERNAL DOSE

RISK CHARACTERISATION

Child - group TDI 0.1 ug Sn/kg bw

RISK MANAGEMENT

Cease production of biocides in wood treatment and consumer products e.g., foot spray, shoes insoles, non-allergenic pillows

Cease use of OT in baking paper

Recommendation of fish consumption – amount and type

Monte Carlo simulation of exposures for children (8 kg)

30% population % TDI 104 50% population 159 95% population 846

Risk reduction: fish, via environment, indoor air dust,

 Many different organotin compounds are in

use

 NOAEL determined on Immunotoxicity

 Not all OT er equally toxic – DOT less

 Group TDI is used for all organotin

compounds based upon weight of tin

 Several sources of exposure – fish/fishery

products being a major source