1 Classification of substances and mixtures on the basis of health hazard Semira Hajrlahović...

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Classification of substances and mixtures on the basis of health hazard

Semira Hajrlahović Mehić, LL.M. Tatjana Humar – Jurič, M.Sc.

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Content

Introduction

Classification of substance Classification of mixture

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General information

Chemicals placed on the Serbian market shall be classified by using of:

1. Harmonised classifications

2. Self-classification by application of the criteria

3. Use of translation tables

4. Use of classification and labelling inventory

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General information

The classification criteria are in Part 2-5 of Annex I to CLP/GHS Rulebook!

For OLD system - Upostvo za klasufikacijo, pakovanje, obeležavanje i reklamiranje hemikalija (2010)

For NEW system - GHS (CLP/GHS system ) in practice- EU Guidances on CLP - EU Guidance on application of the CLP (= EU GHS) criteria - EU FAQ regarding CLP in EU and useful links

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Example: Classification of Substance- Health hazards Methanol Animal data:

LD50 rat > 5,000 (mg/kg) No specific target organ toxicity (impairment of seeing ability)

observed in rats, even in high doses Human experience:

Broad human experience from many case reports about blindness following oral intake.

Methanol is known to cause lethal intoxications in humans (mostly via ingestion) in relatively low doses: ” …minimal lethal dose in the absence of medical treatment is between 300 and 1000 mg/kg” (IPCS)

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Example: Classification steps

Use of adequate and reliable human data, where animal data are not appropriate

Independent classification for STOT-SE and Acute toxicity due to different effects

Task:Acute toxicity classificationSTOT (SE) classification

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Methanol : Acute toxicity

Animal data: The rat is known to be insensitive to the

toxicity of methanol and is thus not considered to be a good model for human effects (different effect/mode of action)

Classification not possible

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Methanol: Acute toxicity

Human experience Annex I: 3.1.2.1. Substances can be allocated to one of four

toxicity categories based on acute toxicity by the oral, dermal or inhalation route according to the numeric criteria shown in Table 3.1.1. Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or LC50 (inhalation) values or as acute toxicity estimates (ATE). Explanatory notes are shown following Table 3.1.1

See able 3.1.1. The minimum lethal dose reported of 300 mg/kg is used as

equivalent ATE; according to Table 3.1.1 the resulting classification is Category 3

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Methanol: STOT (SE)

Annex I , 3.8.2.2 Classification criteria for Categories 1 and 2

See Table 3.8.1 : Categories for specific target organ toxicity-single exposure

The classification criteria for Category 1 are fulfilled: clear human evidence of a specific target organ toxicity effect which is not covered by Acute toxicity

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Methanol - Conclusion

The standard animal species for single exposure (acute) tests, the rat, is not sensitive, i.e. no appropriate species for this specific target organ effect.

Methanol is classified independently for acute toxicity, since the impairment of vision is not causal for the lethality, i. e. there are different effects.

Methanol - Health hazards classification : Acute Tox. 3 STOT SE 1

Other hazards ?

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Classification of mixtures

CLP/GHS self-classification

Depending on the information available and on the hazard under consideration

you should classify using following approaches:

Using data on the mixture itself (not for CMR!) Classification based on the application of bridging principles Classification based on the concentration of individual ingredients,

NOTE: make sure that you choose the most appropriate method for your mixture for each hazard class or category!

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Bridging principles:

when data are not available for all components = used for classifying untested mixtures, but there are sufficient data on the

components and/or similar tested mixtures, these data can be used in accordance with the following bridging principles:

Diluting Batching Concentration of highly toxic mixtures Interpolation within one toxicity category Substantially similar mixtures Aerosols

All bridging principles do not apply to every health endpoint!

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Example 1Starting point:

Mixture X Mixture Y= ? Toxic Cat. 3 Tested

Two mixtures with several different ingredients (A, B, C) Both mixtures have one common ingredient (B) at the same

concentration The concentrations and toxicities (classifications) of the other (A, C)

ingredients are the same Mixture X is classified based on testing

A

B

C

B

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Example 1

Substantially similar mixtures:

Mixture X Mixture Y= Toxic Cat. 3 Toxic Cat. 3 Tested

The unknown mixture Y is classified in the same way as

the tested: Toxic Cat. 3

A

B

C

B

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Classification based on the concentration of individual ingredients:

When available data for all components

Calculations using formulas (acute toxicity) based on additivity

Concentration limits (tables; other hazard classes than acute toxicity)

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Classification of mixture

Cut-off values

Indicate when the presence of a substance needs to be taken into account for the purpose of classification of a substance or mixture containing that hazardous substance

Impurity, additive in a substance or individual constituent in a mixture: Specific concentration limits, SCL (List of classified substances,

Inventory) Generic concentration limits, GCL (Annex I) Generic cut-off values (Annex I, Table 1.1) M-Factors (enviromental hazard!)

New: SCL shall be set by the suppliers !

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Generic cut-off values

Hazard class

Acute Toxicity:

- Category 1 - 3

- Category 4 Skin corrosion/irritation

Serious damage to eyes/eye irritation

Generic cut-off values to be

taken into account

0,1 %

1 %

1 %

1 %

These values are minimum concentration for substances to be taken into account for

classification (even they do NOT trigger classification of the mixture directly)

– if is concentration of sub. > generic cut-off value then contribute to the classification

Table 1.1 (Annex I)

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Data available for all ingredients: A hazardous substance needs to be taken into account for the purpose of

classification of a mixture if it is present in the mixture above the cutt-off value Each of these substances contribute to the hazardous properties of the mixture Use the additivity formula: if the sum of the concentrations is above the limit values -

> mixture is classified for that hazard class

Using additivity formula: Acute Toxicity Using the additivity aproch Skin corrosion/irritation Serious eye damage/eye irritation

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Classification of mixtureCalculations using formulas (acute toxicity) based on additivity

Additivity formula

The ATE of the mixture is determined by calculation from the ATE values for the relevant

ingredients (for all three routs of exposure)

Ci = concentration of ingredient i i = the individual ingredient from 1 to n n = the number of ingredients ATEi = Acute Toxicity Estimate of ingredient

in imix ATE

C

ATE

100

ATE:

- LD50 or LC50-value, or

- Converted value (point estimate) for

acute toxicity from Table 3.1.2 in Annex I,

relating to a value from a range test or to

a classification category

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Acute toxicity

LD50 or LC50-value

or Converted value (point estimate) for acute

toxicity from Table 3.1.2 in Annex I, relating to a value from a range test or to a classification category

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Classification based on the concentration of individual ingredients

Additive concentration limits Skin corrosion/irritation Serious eye damage/eye irritation STOT SE, Cat. 3

Non- additive concentration limits Sensitisers (respiratory and skin) CMR STOT SE and RE, Cat 1-2 Aspiration hazard

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Sum of ingredientsclassified as:

Concentration triggering classification of a mixture as:

Skin Corrosive Skin Irritant

Category 1 Category 2

Skin Corrosive Categories 1A, 1B, 1C

5 % 1 % but < 5 %

Skin irritant Category 2

10 %

(10* x Skin Corrosive Category 1A, 1B, 1C) + Skin irritant Category 2

10 %

Example of generic concentration limits for skin corrosion/irritation

•Additivity approach applies •Generic concentration limits of ingredients classified that trigger classification of the mixture- Table 3.2.3 of Annex I

* Weighing factor of 10 if Category 1 component ≥ 1% but ≤ 5% in a mixture

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Ingredientclassified as:

Concentration triggering classification of a mixture as:

Repro cat. 1A Repro cat. 1B Repro cat.2 Effects on or via lactation

Repro cat. 1A 0,3 %

Repro cat. 1B 0,3 %

Repro cat. 2 3,0 %

Effects on or via lactation 0,3 %

Example generic concentration limits for reproduction toxicity/Effects on or via lactation:

• Non-Additivity approach applies• Generic concentration limits of ingredients classified that trigger classification of the mixture- Table 3.7.2 of Annex I

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Exposure route Classification category or

experimentally obtained acute

toxicity range estimate

Converted acute

toxicity point

estimate

Oral(mg/kg bw)

0 < category 1 ≤ 55 < category 2 ≤ 50


0,55

100500

Table 3.1.2

Conversion values

Where an ATE is not available for an ingredient of a mixture, but available information can provide a value derived from the conversion table, this conversion value may be used for calculation.Conversion from experiementally obtained acute toxicity range values (or acute toxicity hazard categories) to acute toxicity point estimates for classification of the respective routes of exposure

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Example 2

How is classified mixture A?

MIXTURE A Concentration LD50 oral Classification

Substance 1 1% 225 mg/kg


Substance 3 10% Acute tox. category 3, oral

Water 76%

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Conversion from hazard category to point estimate:

Table 3.1.2




Converted acute

toxicity point

estimate

Oral(mg/kg bw)



0,55

100500

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Classification of a mixture

100

ATEmixture

=∑Ci

ATEin

Concentration LD50 oral Classification



Substance 3 10% Acute tox, cat 3

Water 76%

100

ATEmixture

1

225+

3

100+

10

100ATEmixture = 743 mg/kg bw=

ATE: 100

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Conversion from hazard category to point estimate:

Table 3.1.2




Converted acute

toxicity point

estimate

Oral(mg/kg bw)



0,55

100500

ATEmixture = 743 mg/kg bw

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Classification of a mixture

100

ATEmixture

=∑Ci

ATEin

Concentration LD50 oral Classification



Substance 3 10% Acute tox, cat 3

Water 76%

100

ATEmixture

1

225+

3

100+

10

100ATEmixture = 743 mg/kg bw=

Classification: Acute tox. cat 4, oral

ATE: 100

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Result of example 2:

According to table 3.1.1 and Table 3.1.3 (Annex I of CLP/GHS Rulebook) is result: Acute oral tox. 4, H302

Labellling:

Warning

H302 Harmful if swallowed

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Thank you!

Thank you!

1 Classification of substances and mixtures on the basis of health hazard Semira Hajrlahović...

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