GPS pilot study report
2010.01.22 Japan Chemical Industry Association

GPS pilot study report

Name: Styrene
CAS No.: 100-42-5
August 2009Showa Highpolymer Co., Ltd.

1

GPS pilot study report
2010.01.22 Japan Chemical Industry Association1.

Preface ...................................................................................................................... 7

2.

Legal Notice ............................................................................................................... 7

2.1.

Disclaimer............................................................................................................... 7

2.2.

Antitrust and Competition Compliance ................................................................... 73.

Background................................................................................................................ 7

4.

ICCA Global Product Strategy (GPS) approach......................................................... 7

5.

Prioritization of substances for GPS risk assessment ............................................... 7

6.

General guidance to tiered risk characterization ....................................................... 7

7.

GPS Risk Characterization process .......................................................................... 8

7.1.

Gathering Hazard and Exposure Information......................................................... 8

7.1.1.

Chemical Definition—Identification of Chemical/Application........................... 8

7.1.2.

Establishing Knowledge Base......................................................................... 9

7.2.

How to conduct the risk characterization ............................................................... 9

7.2.1.

Hazard Evaluation........................................................................................... 9

7.2.2.

Exposure Evaluation ....................................................................................... 9

7.2.3.

Is Information Sufficient to Complete a Risk Characterization? .................... 10

7.2.4.

Decision Point ............................................................................................... 10

7.2.5.

Documentation of the risk assessment ......................................................... 10

7.2.5.1.

Company or value chain internal use..................................................... 10

7.2.5.2.

Elements of a product stewardship summary document for the public.. 10

8.

Applying Appropriate Risk Management .................................................................. 10

9.

Annex 1.................................................................................................................... 11

9.1.

GPS “Base Set of Information”............................................................................. 11

9.1.1.

Standard Parameters to be evaluated for every substance .......................... 11

9.1.1.1.

Chemical Identity and use...................................................................... 112

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2010.01.22 Japan Chemical Industry Association
9.1.1.2.

Physical-Chemical Properties ................................................................ 11

9.1.1.3.

Environmental Fate ................................................................................ 129.1.1.4.

Environmental Toxicology ...................................................................... 129.1.1.5.

Mammalian Toxicology (significant exposure) ....................................... 129.1.2.

Tiered information requirements depending on the hazard / exposure......... 129.1.2.1.

Tiered toxicological data requirements .................................................. 129.1.3.

Alternative source of information to fulfill the Information ............................. 14

9.1.4.

Adaptations to the tiered information requirements ...................................... 14

9.2.

Sorting Criteria ..................................................................................................... 14

9.2.1.

9.3.

How to attribute a substance to a certain Tier (1-4) ...................................... 14

9.2.1.1.

Toxicological sorting criteria................................................................... 14

9.2.1.2.

Ecotoxicological sorting criteria.............................................................. 16

Hazard Identification (Human health / Environment)............................................ 17

9.3.1.

Physico-chemical properties ......................................................................... 17

9.3.1.1.

Ignition temperature (Flammability) ....................................................... 18

9.3.1.2.

Boiling point ........................................................................................... 18

9.3.1.3.

Vapor pressure....................................................................................... 18

9.3.1.4.

Water solubility....................................................................................... 18

9.3.1.5.

Partition coefficient................................................................................. 18

9.3.2.

Endpoint-specific guidance ........................................................................... 18

9.3.2.1.

Human Health Hazard Potential ............................................................ 18

9.3.2.2.

Tier 1: Minimal hazard potential ............................................................. 18

9.3.2.2.1. Acute toxicity...................................................................................... 19
9.3.2.2.2. (Eye / Skin) Irritation .......................................................................... 19
9.3.2.2.3. Corrosion ........................................................................................... 19
9.3.2.3.

Tier 2: Low hazard potential................................................................... 193

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2010.01.22 Japan Chemical Industry Association
9.3.2.3.1. Genotoxicity ....................................................................................... 19
9.3.2.3.2. Skin sensitization (in case of structural alert) .................................... 19
9.3.2.4.

Tier 3: Medium hazard potential............................................................. 20

9.3.2.4.1. Repeated dose toxicity (e.g. a 28-days study)................................... 20
9.3.2.5.

Tier 4: High hazard potential .................................................................. 20

9.3.2.5.1. Reproductive and developmental toxicity .......................................... 20
9.3.3.

Environmental Hazard Potential.................................................................... 20

9.3.3.1.

Tier 1: Minimal hazard potential ............................................................. 20

9.3.3.1.1. Degradation/biodegradation .............................................................. 20
9.3.3.2.

Tier 2-3: Low to medium hazard potential.............................................. 20

9.3.3.2.1. Aquatic toxicity (algae, daphnia, fish) ................................................ 21
9.3.3.3.

Tier 4: High hazard potential .................................................................. 21

9.3.3.3.1. Chronic toxicity (daphnia, fish)........................................................... 21
9.4.

Dose-Response Assessment ............................................................................... 21

9.4.1.

Metabolism and Pharmacokinetics ............................................................... 21

9.4.2.

Potency ......................................................................................................... 21

9.4.3.

NOAEL / LOAEL approach............................................................................ 21

9.4.4.

MOS approach .............................................................................................. 21

9.5.

Exposure assessment .......................................................................................... 22

9.5.1.

General Use Pattern ..................................................................................... 22

9.5.1.1.

Use categories ....................................................................................... 22

9.5.1.1.1. Isolated intermediate used/stored off site .......................................... 22
9.5.1.1.2. Substance that is included into or onto a matrix ................................ 22
9.5.1.1.3. Non-dispersive use – Professional (industry point-sources).............. 22
9.5.1.1.4. Wide dispersive use........................................................................... 22
9.5.2.

Considerations and uncertainties.................................................................. 224

GPS pilot study report
2010.01.22 Japan Chemical Industry Association
9.5.3.

General exposure assessment guidance...................................................... 22

9.5.4.

Occupational exposure estimation assessment ............................................ 22

9.5.4.1.

Measurements ....................................................................................... 22

9.5.4.2.

Modeling approaches............................................................................. 22

9.5.4.3.

Inhalation ............................................................................................... 22

9.5.4.4.

Dermal ................................................................................................... 22

9.5.4.5.

Oral ........................................................................................................ 22

9.5.5.

Consumer exposure estimation .................................................................... 22

9.5.5.1.

Inhalation ............................................................................................... 22

9.5.5.2.

Dermal, two options: .............................................................................. 23

9.5.5.3.

Oral, two options: ................................................................................... 23

9.5.6.

Environmental exposure assessment ........................................................... 23

9.5.7.

Generic Supply Chain Exposure Assessment............................................... 23

9.5.7.1.
9.5.8.

Information on the safe use of substances in the supply chain ............. 23

Exposure Assessment................................................................................... 23

9.5.8.1.

Tools....................................................................................................... 23

9.5.8.2.

Functioning of the Tier-One Tools preferred by industry: stop ............... 23

9.5.9.

Industry Input to exposure assessment ........................................................ 23

9.5.10.

Downstream User Activities....................................................................... 23

9.5.11. Industry Strategy ........................................................................................... 23
9.5.12.

Generic Environmental Exposure Assessment ......................................... 23

9.5.13.

Exposure assessment as input to risk characterization............................. 23

9.5.14.

Exposure assessment in defining conditions of safe use .......................... 24

9.5.15.

Environmental risk assessment with base set information: ....................... 24

9.5.16.

Environmental modeling tools ................................................................... 24

9.6.

Risk characterization ............................................................................................ 24

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GPS pilot study report
2010.01.22 Japan Chemical Industry Association
9.6.1.

Conclusion in situations where no LOAEL has been identified ..................... 24

9.7.

Triggers for additional data requirements............................................................. 24

9.8.

Examples of Possible Risk Management Actions to Consider ............................. 28

9.9.

Process of Setting Priorities for CSA ................................................................... 30

9.10.

Frequently Asked Questions on ICCA Implementation of the Global ProductStrategy (GPS)................................................................................................................ 31
9.10.1.

GPS Background....................................................................................... 31

9.10.2.

GPS & Responsible Care® ....................................................................... 31

9.10.3.

GPS & Other Programs (REACH, HPV).................................................... 31

9.10.4.

Product Stewardship Summaries .............................................................. 31

9.10.5.

Information Resources .............................................................................. 31

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GPS pilot study report
2010.01.22 Japan Chemical Industry Association

1. Preface
2. Legal Notice
2.1.

Disclaimer

2.2.

Antitrust and Competition Compliance

3. Background
4. ICCA Global Product Strategy (GPS) approach
5. Prioritization of substances for GPS risk assessment
Selected: Styrene
Rationale:(i)

The substance is of social concern. The substance is classified by IARC as Group2B (possible carcinogenic).

(ii) There is high degree of concern over exposure because styrene is manufactured
in large quantities (more than 1,000 tons annually) and consumed in large
quantities and has therefore been designated as a high production volume (HPV)
chemical by the OECD.

6. General guidance to tiered risk characterization

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7. GPS Risk characterization process
7.1.

Gathering Hazard and Exposure Information

7.1.1. Chemical Definition—Identification of Chemical/Application
Cases of exposure to styrene may be classified into 5 categories including (i)manufacturing styrene, (ii) formulating using styrene, (iii) molding the formulator, (iv)consumer’s uses, and (v) disposal. In this report, the risk assessment was carried out
for copolymer resins of unsaturated polyester with styrene, using a case of polystyrene
synthesis in our company’s plant as an example of occupational exposure and the casewhere styrene is used as a floor paint as an example of exposure to consumers.
Actual status of occupational exposure
Styrene monomer is used as a diluting agent or a monomer for polymerization during a
synthesis of unsaturated polyester resins. During this process, there seems to be low
worker exposure because closed reaction vessels and a local exhaust ventilation
system are furnished and all workers wear protective equipments (a gas mask, goggles,
long-sleeved clothes, etc.).
Actual status of consumer exposure
Floor paints are used as corrosion-proofing, antifouling and wear-resistance coating on
floors inside warehouses, etc.

Workers may be exposed to the vapor of the styrene

during painting the floors because the paints are polymerized and hardened on-site. .
However, the consumer exposure is considered to be very low at any site where
styrene is likely to be encountered by consumers. The most of the styrene ispolymerized, and residual monomers vaporize in the atmosphere. This sort of floor is
normally only used for business purposes, and t is not assumed that consumers will bewalking about on it in bare feet.
The influence on the environment, especially with regard to water pollution, etc., isconsidered to be small because of the high level of the efficiency of the
sewage-treatment plant operation.

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7.1.2. Establishing Knowledge Base
References(*1)

Initial Risk Evaluation of Chemical Substances: Styrene.

National Institute ofTechnology and Evaluation, Japan, August 2007(*2)

Integrated Risk Information System List of IRIS Substances: Styrene(*3)

European Union Risk Assessment Report, Styrene. Part. 1-environment, Final
2002, UK(*4)

European Union Risk Assessment Report, Styrene. Draft edition, June 2008, UK(*5)

Risk Assessment Report on Styrene. Scientific Committee on Health andEnvironmental Risks; May 2006(*6)

Annex XV Transitional Dossier, Styrene UK Competent Authority, November
2008
Legislative Restriction

Legislative information was gathered by searching the Chemical Risk Information
Platform provided by the National Institute of Technology and Evaluation, Japan.

7.2.

How to conduct the risk characterization

7.2.1. Hazard Evaluation
Hazard was evaluated by examining the documents cited in 7.1.2.

Read-acrossand QSAR analyses were not performed.

7.2.2. Exposure Evaluation
Exposure was evaluated using ECETOC-TRA (the European Centre for
Ecotoxicology and Toxicology of Chemicals—Targeted Risk Assessment), as
recommended by the Japan Chemical Industry Association.
Input data were obtained by calculation based on the data from sources
mentioned in 7.1.2. The calculation details are described in the appendix ECETOCTARGETED RISK ASSESSMENT MODEL.

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7.2.3. Is Information Sufficient to Complete a Risk Characterization?
The risk characterization carried out using ECETOC-TRA demonstrated that therisk of the present occupational conditions is controlled and can specify the use
conditions which can control the risk of consumer and environmental exposure.
Existing information is determined to be sufficient to complete a risk
characterization in accordance with the flow described in the chapter 9.7 of the risk
assessment guidance.

7.2.4. Decision Point.See the chapter 9.7 in this document for the detail on the determination

7.2.5. Documentation of the risk assessment
7.2.5.1.

Company or value chain internal use

Relevant information has already been distributed as a MSDS.

7.2.5.2.

Elements of a product stewardship summary document forthe public

Relevant information has already been distributed as a MSDS.

8. Applying Appropriate Risk Management
Various risks can be adequately avoided by the appropriate selection of systems
and protective equipments.
Risk assessment reports will be published on a homepage, etc. or distributed tocustomers, together with MSDSs, as appropriate.
Thus, neither limiting the uses or the markets nor qualification nor training
customers are necessary at the present time.

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9. Annex 1
9.1.

GPS “Base Set of Information”

9.1.1. Standard Parameters to be evaluated for every substance
9.1.1.1.

Chemical Identity and use

CAS No.: 100-42-5
Name:

Styrene

Structural Formula:

Use Pattern:

SU12. Manufacture of plastics products, including compounding
and conversion (rationale for selecting this Sector of Use:meeting the business requirements of our company)

Source of Exposure: Three categories were considered: occupational(manufacture), consumers (use) and the environment (plant
effluent).

9.1.1.2.

Physical-Chemical Properties

Physical State:

Liquid(*3)

Melting Point:−30.6°C(*3)

Boiling Point:

145–146°C(*3)

Relative Density:

0.906 g/cm3 at 20°C(*3)

Vapor Pressure:

667 Pa at 20°C(*3)

Partition Co-efficient:2.95 (logKow)(*1)

Water Solubility:

300 mg/L at 20°C(*3)

Ignition Temperature (Flammability):

490°C

(*3)

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GPS_Pilot_JCIA_100122.doc

9.1.1.3.

Environmental Fate

Aerobic biodegradability: readily biodegradable (*1, p. 7)

9.1.1.4.

Environmental Toxicology

Acute toxicity (fish):96-hour LC50 fathead minnows, Flow-through:

4.02

mg/L
Reason for selection:

Data associated with the highest degree of risk was
selected. (*1, p. 21)

9.1.1.5.

Mammalian Toxicology (significant exposure)

Skin toxicity, the most significant exposure route was extrapolated from inhalation
toxicity.
LC50 in rats after inhalational exposure: 2800 ppm (4 hours) (*1, p. 38, Table 8-2).
Human toxicity has been evaluated by ECETOC-TRA (*7, See Appendix.)

9.1.2. Tiered information requirements depending on the hazard /exposure
9.1.2.1.

Tiered toxicological data requirements

The exposure for workers seems to be low using closed reaction vessels, a local
exhaust ventilation and wear protective equipments (a gas mask, goggles,
long-sleeved clothes, etc.).

The exposure for consumers also seems to be very low

because most of the styrene monomers are polymerized, almost all of the residual
monomers vaporize into the atmosphere and because this sort of floor (a typical use) is
normally only used for business purposes and consumers are unlikely to walk barefoot.
Therefore, Tier 2 (low-level exposure) was selected.

12GPS_Pilot_JCIA_100122.doc

9.1.2.2.

Tiered ecotoxicological data requirement

Tier 2 was selected because of only a low effect on the environment as follows:
LC50 in fathead minnows after 24 hours: 12 mg/L
LC50 in fathead minnows after 96 hours: 10 mg/L (*3, p. 57)

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9.1.3. Alternative source of information to fulfill the Information
An evaluation was performed using information corresponding to Klimisch Code 1 or 2.
Alternative information sources such as read-across analysis, a category approach,
QSAR analysis, in vitro methods, a WoE (weight of evidence) approach, etc. were notnecessary...

9.1.4. Adaptations to the tiered information requirements
Adaptation was not needed.

9.2.

Sorting Criteria

9.2.1. How to attribute a substance to a certain Tier (1-4)
9.2.1.1.

Toxicological sorting criteria(i)Flashpoint: 31°C = 87.8 F (*3, p. 10)(ii)

The rate constant for the atmospheric reaction between styrene and OH radicals is 5.8
× 10-11 cm3/molecule/second (25°C, measured value).

The half-life calculated

5

supposing that hydroxyl radical concentration of 5 × 10 to 1 × 106 molecules/cm3 is 4
to 7 hours. Styrene does not have any chemical binding liable to be hydrolyzed in water.
Therefore, styrene is not considered very reactive (*1: p. 6 SRC: AopWin, 2003).

14GPS_Pilot_JCIA_100122.doc(iii)

Oral LD50 (oLD50) for an acute toxicity study in rats is 5,000 mg/kg (*4, p. 97)
No data available for dermal LD50 (dLD50).
Inhalational LC50 (4 hours) in rats is 2,770 ppm = 11.80 mg/L (*4, p. 95)
The criteria given for inhalation are considered to be misprints.
(iv)

Irritation:
Animal skin = moderate irritantAnimal eye = irritant
Human eye = strong irritant (*4, pp.101-104)
Styrene is not corrosive but it is irritating (*1, p. 38).
Sensitization:
Styrene has no significant potential to cause this effect (*4). .
Mutagenicity:
Styrene has shown positive reactions in in vitro reverse mutation tests, chromosomal
aberration tests, sister chromatid exchange tests, etc. In vivo, the substance has
shown positive reactions in micronucleus tests, DNA strand break assays and15

GPS_Pilot_JCIA_100122.doc

unscheduled DNA synthesis tests. Based on these results, styrene is considered to
be a genotoxic substance.

(*1, p. 48)

Carcinogenicity:
No data available.

However, the substance has been classified into Group 2B(Possibly carcinogenic to humans) by the IARC (*1, p. 56).
(v)

Repeated dose toxicity:
No data was available for a 28-day repeated-dose study.
A NOAEL of 100 mg/kg/day from a 60-day study in rats was substituted. (*1 p. 39, p.
42)
Reproductive/developmental toxicity:
NOEL in an oral 3-generation study in rats: 125 ppm = 10.5 mg/kg/day (*1, p. 46)
Based on the above results, styrene can be assigned to Tier 3 for human toxicity.

9.2.1.2.

Ecotoxicological sorting criteria

LC50 in fathead minnows after 96 hours = 4.02 mg/L (*3: p. 57)
The acute aqueous toxicity classification is classified into Tier 2 since 1 < LC50 < 10.

16GPS_Pilot_JCIA_100122.doc

Chronic aqueous toxicity is not applicable because log Kow is not 4 or higher (although
the acute aqueous toxicity classification is classified into Tier 2).
Therefore, the ecotoxicological classification of styrene is classified into Tier 3.

Process category 5 (PROC5: blending and denaturation in the batch production ofdrugs) has been selected and the substance has been classified into Tier 2.

Styrene is classified into Category 1 because ERC 2 (Formulation of preparations) has
been selected.

9.3.

Hazard Identification (Human health / Environment)

9.3.1. Physico-chemical properties

17

GPS_Pilot_JCIA_100122.doc

Physicochemical properties are described in 9.1.1.2.

9.3.1.1.

Ignition temperature (Flammability)

9.3.1.2.

Boiling point

9.3.1.3.

Vapor pressure

9.3.1.4.

Water solubility

9.3.1.5.

Partition coefficient

It is assumed that styrene discharged into the atmosphere remains mainly in theatmosphere, that styrene discharged into water remains mainly in the water, and thatstyrene discharged into the soil remains mainly in the soil. Styrene discharged into
environmental water is considered to be eliminated from the water by volatilization into
the atmosphere and through biodegradation.

Styrene bound to soil particles, etc.

sinks to the bottom but is likely to be eliminated by anaerobic biodegradation. (*1: P.7
and 8)
Moreover, log Kow = 2.95, BCF = 37 (*1: p. 8).
Therefore, it is unlikely that styrene will become concentrated in any aquatic creatures;
therefore, is not applicable to any of the above classifications.

9.3.2. Endpoint-specific guidance
9.3.2.1.

Human Health Hazard Potential

9.3.2.2.

Tier 1: Minimal hazard potential

18GPS_Pilot_JCIA_100122.doc

9.3.2.2.1.

Acute toxicity

Oral:

LD50 in rats = 5000 mg/kg (*1: P. 38) (*4: P. 97)

Dermal:No data available (*1: P. 38) (*4: P. 97)

Gases:

LC50 in rats (2 hours) = 4930 ppm (*1: P. 38) (*4: P. 96)

Vapor:

LC50 in rats and guinea pigs (4 hours) = 2770 ppm = 11.8 mg/L (*4: P. 95)

Dust/mist:

No data available

Based on the above data, styrene can be classified into Tier 2.

9.3.2.2.2.

(Eye / Skin) Irritation

9.3.2.2.3.

Corrosion

A 4-week skin irritation study in rabbits reported blisters on the skin and loss of fur (*1:
p. 39)

9.3.2.3.

Tier 2: Low hazard potential

9.3.2.3.1.

Genotoxicity

Styrene has shown positive reactions in reverse mutation tests, chromosomal
aberration tests, sister chromatid exchange tests, etc.
In vivo, the substance has shown positive reactions in micronucleus tests, DNA strand
break assays and unscheduled DNA synthesis tests. Based on these results, styrene
can be considered genotoxic.

9.3.2.3.2.

(*1: p. 48)

Skin sensitization (in case of structural alert)19GPS_Pilot_JCIA_100122.doc

No data available (*1: p. 39)

9.3.2.4.

Tier 3: Medium hazard potential

9.3.2.4.1.

Repeated dose toxicity (e.g. a 28-days study)

No data is available concerning any 28-day repeated-dose study.
NOAEL in rats after 60 days: 100 mg/kg/day (*1: p. 39 and p. 42)

9.3.2.5.

Tier 4: High hazard potential

9.3.2.5.1.

Reproductive and developmental toxicity

In inhalational exposure studies in mice and hamsters, increased embryonic/fetal death
rates and skeletal anomalies have been reported.

However, fetal death orteratogenicity has not been reported in any oral or inhalational studies in rats, evenwhen dams were exposed to the test substance at a dose large enough to affect bodyweight.

In a 3-generation proliferation study, no reproductive toxicity associated withthe administration of styrene was observed and the NOAEL was found to be 250 ppm.
(*1: p. 44 to 47)

9.3.3. Environmental Hazard Potential
9.3.3.1.

Tier 1: Minimal hazard potential

9.3.3.1.1.

Degradation/biodegradation

Percentage degradation of styrene in a wastewater treatment plant (estimated by
EUSES)
Specific biodegradability: 58.3%
Aerobic biodegradability: 31.4%
Biodegradation in seawater: 7.2%
Non-biological changes: 3.1% (*3: p. 41)
Therefore, styrene can be considered readily biodegradable.

9.3.3.2.

Tier 2-3: Low to medium hazard potential

20GPS_Pilot_JCIA_100122.doc

9.3.3.2.1.

Aquatic toxicity (algae, daphnia, fish)(*1: pp. 18 to 20, *3: pp. 56 to 62)
Algae
EC50 in Selenastrum capricornutum after 72 to 96 hours was 0.72 to 1.4 mg/L in termsof biomass calculation, and 4.9 to 6.3 mg/L in terms of growth rate. (*1: p. 18)
Daphnia
The lowest toxicity value in studies taking into account volatilization was an EC50
(Immobilization, 48 hours) of 4.7 mg/L for Daphia magna.

No report has been madeconcerning long term toxicity. (*1 p. 19)
Fish
The lowest toxicity value in studies under flow-through conditions and taking into
account volatilization is and LC50 was 4.02 mg/L (mean measured concentration) for
fathead minnows. (*1 p. 20)

9.3.3.3.

Tier 4: High hazard potential

9.3.3.3.1.

Chronic toxicity (daphnia, fish)

Daphnia: No report has been made concerning long-term toxicity.
Algae:The EC10 acting an indicator in a long-term study was 0.13 mg/L
(biomass method).

Fish:

9.4.

This was similar to the NOEC. (*1: p. 18)

No data available

Dose-Response Assessment

9.4.1. Metabolism and Pharmacokinetics
9.4.2. Potency
9.4.3. NOAEL / LOAEL approach
9.4.4. MOS approachCalculation was impossible because the amount of exposure was unknown.

21GPS_Pilot_JCIA_100122.doc

9.5.

Exposure assessment

9.5.1. General Use Pattern
9.5.1.1.

Use categories

No sector of use is mentioned in the guidance material provided.

If a sector of use

specific to an exposure assessment tool is applied, this must be clearly stated.
Moreover, the range of uses included as examples does not provide sufficient choiceand none are applicable.
Here, the SU12 (Manufacture of plastics products) sector (ECETOC-TRA) was used.

9.5.1.1.1.

Isolated intermediate used/stored off site

9.5.1.1.2.

Substance that is included into or onto a matrix

9.5.1.1.3. Non-dispersive use – Professional (industry
point-sources)
9.5.1.1.4.

Wide dispersive use

9.5.2. Considerations and uncertainties
9.5.3. General exposure assessment guidance
9.5.4. Occupational exposure estimation assessment
9.5.4.1.

Measurements

9.5.4.2.

Modeling approaches

9.5.4.3.

Inhalation

9.5.4.4.

Dermal

9.5.4.5.

Oral

9.5.5. Consumer exposure estimation
9.5.5.1.

Inhalation

22GPS_Pilot_JCIA_100122.doc

9.5.5.2.

Dermal, two options:9.5.5.3.

Oral, two options:9.5.6. Environmental exposure assessment
9.5.7. Generic Supply Chain Exposure Assessment
9.5.7.1.

Information on the safe use of substances in the supply
chain

9.5.8. Exposure Assessment
9.5.8.1.

Tools

ECETOC-TRA was used as the initial step evaluation tool.

9.5.8.2.

Functioning of the Tier-One Tools preferred by industry: stop

9.5.9. Industry Input to exposure assessment
See (Annex: ECETOC TARGETED RISK ASSESSMENT MODEL Supplement).

9.5.10.

Downstream User Activities

Upgrading of the ERC classification, which is highly versatile, by the Synthetic Resin
Industry Association, is anticipated.

9.5.11.

Industry Strategy

Establishment of a detailed risk assessment is anticipated at the meeting of theSynthetic Resin Industry Association.

9.5.12.

Generic Environmental Exposure Assessment

ERC2: Production of Preparation has been selected as the most appropriate category.

9.5.13.

Exposure assessment as input to risk characterization

In this assessment, a PEC-derived model was not used because it was possible tosimply extract PEC values from available references.

23(*7 See Annex.)

GPS_Pilot_JCIA_100122.doc

9.5.14.

Exposure assessment in defining conditions of safe use

Risks were evaluated using an evaluation tool (ECETOC-TRA).
A risk is considered to be under control if the annual production is less than 90 tons.
At present, it is likely that an adequate level of risk control can be achieved even if
annual production exceeds 90 tons, provided that adequate effluent treatment facilities
are available and wastewater is fully controlled.(*7 See Annex.)

9.5.15.

Environmental risk assessment with base set information:

Environmental risks were assessed using the essential items entered in ECETOC-TRA(yellow parts of the sheet).

9.5.16.

(*7 See Annex.)

Environmental modeling tools

No environmental modeling tool was used because existing data, such as that found in
the initial risk assessment reports, etc., was cited.

9.6.

Risk characterization

9.6.1. Conclusion in situations where no LOAEL has been identified
Not applicable (because the LOAEL has been specified).

9.7.

Triggers for additional data requirements24GPS_Pilot_JCIA_100122.doc

Rationale:
There was no obvious skin irritability after a single exposure but the substance acted
as an irritant when exposures were repeated (*4: p. 104).
NOAEC for irritation (eye): 216 ppm/1 hr, no irritability
100 ppm/7 hrs, slightly irritating (*4: pp. 102 and 103)NOAEC (skin): No data available
oLD50 = 5000 mg/kg (*4: p. 97), iLC50 = 11.8 mg/L (*4: p. 95)
Therefore, styrene can be classified into category 3.
If the exposure potential is assumed to be low, additional data on skin sensitizationand genotoxicity will be required.
No data on skin sensitization was found in the initial risk evaluation reports, etc.

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The company cannot evaluate these parameters because DEREK (Deductive
Estimation of Risk from Existing Knowledge, Lhasa Limited, UK), which can be used asa QSAR tool for the evaluation items concerned, is not available.

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Rationale
In vitro(i)

Reverse mutation test: The plate method using Salmonella typhimurium,
52 μg/mL < 5 mg (*1: p. 49)(ii) Chromosomal aberration test (CHL cells): 250 μg/mL < 1 mM (*1: p. 49)
In vivo(iii)

NOEL = 21 mg/kg, MOE = 700 (*1: p. 59)

Based on the above results, it can be seen that further evaluation of genotoxicity andcarcinogenicity is required, taking repeated dose administration and additional studies
into consideration.
With regard to carcinogenicity, the incidence of lung adenoma/cancer increased in a27

GPS_Pilot_JCIA_100122.doc

78-week oral study in mice, although the relationship between the amount of exposureand the increase in the incidence of tumors was not clear when background data wasalso taken into consideration.

An increase in the incidence of lung tumors wasobserved in a study in which styrene was administered transplacentally in female
pregnant mice and orally in their neonates, from weaning through to 16 weeks, but thisincrease was not observed in rats and, therefore, the presence or absence of
carcinogenicity cannot be clearly determined.
An increase in the incidence of breast tumors was observed in a 52-week inhalational
exposure study in rats, indicating a relationship between exposure to styrene and theoccurrence of breast tumors, but details regarding the methodology and the data areunavailable and the relationship with spontaneous tumors is also unclear.
The carcinogenicity of styrene cannot, therefore, be determined on the basis of theabove results obtained from animal experimentation.

The IARC has classified styrene

into Group 2B (Possibly carcinogenic to humans) on the basis of its mechanism ofaction with regard to genotoxicity and the observation of chromosomal aberrations inhumans, although there is still only limited evidence available for carcinogenesis inexperimental animals.

(*1: p. 58)

Styrene has shown a positive reaction in an in vitro genotoxicity study.

Both negativeand positive reactions were observed in vivo while a positive reaction was observed for
DNA damage.

Based on these results, it can be concluded that styrene is genotoxic.

(*4: p. 218)

9.8.

Examples of Possible Risk Management Actions to Consider
A. Chemical substance1

Manufacturing specifications: Product specificities (as a preparation) are
shown in the MSDS.

2

Product hazard classification: The hazard classification is stated on the
product and in the MSDS, in accordance with various relevant laws andregulations.

3(Material) Safety Data Sheets: Preparation has been completed in accordancewith the GHS

4Classification and packaging labels: GHS has been adopted.

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B. R&D
1

Sourcing of alternative raw materials. There is no need to obtain alternative
materials at present because risks are not predicted, provided that theprescribed conditions are met.

2

Changes to product physical form to reduce exposure potential: Not
needed (for the same reasons given above).
C. Purchase1

Supplier materials contracts: A delivery specification has been exchanged
with the supplier.

2

Switching suppliers. No needs to change suppliers as risks are predicted, atpresent.
D. Manufacturing

1

Legislation and operating permits: Controllable using the current in-house
rules

2

Engineering control: The manufacturing formulation and process sheet arehighly controlled.

3

Personal protective devices: Wearing of protective devices is compulsory inaccordance with in-house rules.
E. Contractors

1

Toll-manufacturing contracts: No applicable example

2

Audits: No applicable example
F. Marketing

1

Voluntary restrictions on applications and uses. In accordance with thepolicy of voluntary restrictions by industry groups.
G. Sales1

Customer assistance: To be provided, as necessary.

2

Assessment of customer’s safe handling of chemicals.: To be conducted,
as necessary

3

Provision of advice, possibly equipment: To be provided, as necessary.

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4Halt sales: To be decided on the basis of the purpose of use, construction
conditions, etc.
H. Distributors

1

Product stewardship agreements: Education and training, as well as theprovision of yellow cards.

2

Distributor training: To be conducted, as necessary.

3

Assessment and Audits: To be conducted, as necessary.
I. Recycling and disposal

1

Feasibility of recycling or reusing used and unused product or packaging:
Feasible.

2

Labels, safety data sheets and other relevant guidance contain adequate
disposal information: Preparation completed.

3

Expertise available to advice on product & packaging disposal: To be dealt
with by the sales representatives and researchers.
J. Transportation

9.9.

Process of Setting Priorities for CSA

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9.10.

Frequently Asked Questions on ICCA Implementation of the
Global Product Strategy (GPS)9.10.1.

GPS Background9.10.2.

GPS & Responsible Care®

9.10.3.

GPS & Other Programs (REACH, HPV)

9.10.4.

Product Stewardship Summaries

9.10.5.

Information Resources31