Practical exercises in physical hazard classification (Exercise ......Page 1 of 49 Practical...
Transcript of Practical exercises in physical hazard classification (Exercise ......Page 1 of 49 Practical...
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Practical exercises in physical hazard classification (Exercise set with answers)
General instructions:
Answer each of the following questions as instructed by the moderator for your session. Be prepared to provide your answer during the discussion session as well as to explain how you arrived at this answer. Please note that completing many of the exercises requires reference to the resource materials described at the end of the exercise so please read the exercise in full before attempting to answer the questions. Please also provide the pictogram (if appropriate) signal word and hazard statement for the classifications you have determined.
Exercise 1: What is the hazard? A substance is a mixture made up of the following components
Ammonium Nitrate 71% Water 16% Diesel fuel 8% An emulsifier composed of
Oleic Acid 3% Sodium Hydroxide (50% aq. soln.) 2%
The mixture has a paste like consistency which does not meet the GHS definition of a liquid. Question: Considering the components of this mixture, identify the possible physical hazard classifications for this mixture, providing reasons for your choice. Answer:
Possible classifications are
Explosive – will need to consider if the mixture is intended as an explosive and which
of the complex UN tests it passes or fails
Oxidising substance as a result of the ammonium nitrate component
Flammable solid ‐ consider whether or not the emulsified diesel fuel enable the substance to burn as specified in the UN tests (test are essentially apply a small amount of energy and determine whether a line of the substance would burn faster than 2.2m/s
Exercise 2: An explosive? You are provided with the following information about the mixture described in exercise 1.
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1. The substance as described is intended to provide one component of a substance which,
after other materials are added, will form part of an explosive chain (i.e. including a fuse, detonator material etc), but is itself not manufactured to produce an explosive or pyrotechnic effect.
2. The following results are obtained when the substance is subject to UN test series 8 (see figure 10.4 UNRTDG Manual of Tests and Criteria 4th Edn or Figure 2.1.4 GHS 3rd Edn)
a. Test 8(a) – substance is reported as thermally stable b. Test 8(b) (large scale gap test) – substance is reported as not too sensitive to shock
to be accepted as an oxidising liquid or oxidising solid c. Test 8(c) (Koenen test) – substance is reported as not too sensitive to heat under
confinement d. When tested using the UN standard test methods for oxidising solids the following
results were obtained
3. The mean burn time of the substance when mixed with cellulose and ignited as prescribed in UN Test Series O.1 is as follows
Greater than the mean burn time of a 3:2 mixture of potassium bromate and cellulose
Less than the mean burn time of 2:3 mixture of potassium bromate and cellulose
Question: Determine the physical hazard classification for the substance, explaining how you obtained the classification. Answer:
The mixture is not intended as explosive and test series 8 results show no explosive effect as
defined. The substance is therefore not an explosive
The mixture is not a liquid so it is tested to determine if it is an oxidising solid ‐see data set out
in 3 above and the criteria set out in chapter 2.14 GHS (supplied in resource material)
Conclusion: the mixture is classified as a category 2 oxidising solid
Label elements:
Symbol: flame over circle
Signal word: Danger
Hazard statement: May intensify fire: oxidiser
Discussion points:
Strictly following the test sequences in the UNRTDG Tests and criteria would not require that the test for and oxidising solid be performed. It is included in this exercise for training purposes.
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Resource material To help you complete this exercise please refer to the following resource material
Figure 2.1.4 GHS 4th Edition Chapter 2.14 GHS 4th Edition
Exercise 3: Classify articles A highway patrol officer presents you with a number of small round disks about 30mm in diameter apparently made of a soft metal of some sort. The disks are marked “railway fog signal.” The officer explains that the disks were picked up from the side of a main interprovincial highway and, considering the remnants of a similarly labelled cardboard box found nearby, appear to have fallen from a truck travelling at high speed. When shown a copy of the GHS ‘explosive’ pictogram, the officer agrees that part of the box found may have had a similar symbol on it. (The remnants of the box are not available to you.) Question: Classify these articles, explaining how you derived the classification. Answer:
These items presented are articles so only possible classification is as an explosive, a
classification already suggested by the patrol officer’s report.
1. Check to see if the items are listed articles in the UN Recommendations for the
Transport of Dangerous Goods alphabetical list. (NB: Also include check for similar
names.) Result: there are entries for “signals railway track explosive” with transport
classifications and UN numbers. Several UN numbers are found, 0192, 0492, 0193,
0493 but with different classes
2. Look up the UN number(s) found 0192, 0492, 0193, and 0493 in the dangerous goods list (part 3 volume 1) for further information. Possible classifications are class 1.1 class 1.3, class1.4
3. Consider the intended use of the articles ‐ fog signals are intended to be placed on a railway line to be run over by a train and produce a noise to warn of fog on the line ahead. Conclusion: these articles would exhibit very small blast and little or no projection hazard.
4. Classification is therefore Class: explosive Category: 1.4
Label elements:
Symbol: Exploding bomb (OR 1.4 on orange background (ex‐transport)
Signal word: warning
Hazard statement: Fire or projection hazard
Discussion points
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Classification for explosive articles requires information about the intended
(designed) use
Articles with similar descriptions require more information for effective classification.
(advanced) The GHS applies the classification from the UNRTDDG as packaged. Hazards (and so classification) can be different when these items are not packaged (see note to table 2.1.2 GHS 4th Edn)
Resource material To help you complete this exercise please refer to the following resource material
The alphabetical index of the UN Recommendations for the Transport of Dangerous Goods 16th Edition The UN Recommendations for the Transport of Dangerous Goods 16th Edition dangerous goods list Chapter 2.1 of the GHS
Exercise 4: The flammability of jet fuel Jet A and Jet A‐1 fuel are the commonest forms of jet aircraft fuel in general use. This fuel is virtually identical to kerosene or paraffin. Jet A/A1 fuel (paraffin) has the following flash point and boiling point ranges (these fuels are in practice mixtures with some variance in composition). Flash point 380C – 660C Boiling point 1600C ‐ 3000C In certain parts of the world Jet B fuel is used in aircraft operations. Jet B fuel has the following flash point and boiling point ranges Flash point < ‐310C Boiling point 500C ‐ 2700C Question: Classify Jet A fuel and Jet B for their physical hazards and comment on the consequences of the classifications you make. Answer:
Referring to the table of classes presented in physical hazards session 3
Jet fuel B is Class: flammable liquid Category 2.
Label elements:
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Symbol: flame
Signal word: Danger
Hazard statement: Highly flammable liquid and vapour
Jet fuel A/paraffin is Class: flammable liquid Category 3
Label elements:
Symbol: flame
Signal word: warning
Hazard statement: Flammable liquid and vapour
Discussion points
As the flashpoint is at a very low temperature, jet fuel B would be easily ignited while being
handled and so requires more precautions.
So why use Jet fuel B at all?
Jet fuel B is used where jet engines are required to be started at very cold temperatures. For
example Jet fuel B is used in Canada – especially in the winter.
Resource material Please refer to the section in the presentation material describing classification for flammable liquids. Reference can also be made to Chapter 2.6 in the GHS 4th Edn
Exercise 5: A flammable gas? You are provided with the following data about the substance TS2. Boiling point: ‐33°C Flammable range: 16% ‐ 25% in air at ambient temperature (20°C) and standard pressure
(101.3 kPa) Question: Classify the substance TS2 and explain your reasoning Answer:
Referring to the decision logic in section 2.2.4.1 GHS 4th Edn
The boiling point quoted means that TS2 is a gas
1. Does TS2 have a flammable range with air at 20 °C and a standard pressure of 101.3 kPa?
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Answer: Yes.
2. At 20 °C and a standard pressure of 101.3 kPa, does it:
(a) ignite when in a mixture of 13% or less by volume in air; or
(b) have a flammable range with air of at least 12 percentage points regardless of
the lower flammable limit?
Answer: No. Neither condition is met by TS2
Classification: TS 2 is classified as Flammable Gas Category 2.
Label elements:
Symbol: No symbol
Signal word: warning
Hazard statement: Flammable gas
Resource material
Please refer to section 2.2.4.1 GHS 4th Edn
Exercise 6: What sort of gas under pressure? You are provided with the following information about substance HG4.
Vapour pressure at 50 °C is greater than 410 kPa (4.1 bar) Substance when packaged under pressure is entirely gaseous at ‐50 °C HG4 has a critical temperature of ‐240.1 °C HG4 is normally contained in a receptacle which can contain gas at up to 200 bar and is stored at normal room temperature.
Question: To which group in the class gases under pressure does HG4 belong? Answer Following the decision logic of section 2.5.4.1 GHS 4th Edn
1. Is the gas contained in a receptacle at a pressure of 200kPa or more at 20 °C? ANSWER: Yes
2. Is the vapour pressure at 50 °C greater than 300 kPa (3 bar)? ANSWER: Yes.
3. Is the gas dissolved in a liquid solvent under pressure? ANSWER: No.
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4. Is the critical temperature above +65 °C? ANSWER: No.
5. Is the critical temperature between ‐50 °C and +65 °C? ANSWER: No.
6. Is the gas made partially liquid because of its low temperature? ANSWER: No.
7. Is the gas entirely in gaseous state at ‐50 °C? ANSWER: Yes. CLASSIFICATION: The gas is classified in group: compressed gas. Label elements:
Symbol: gas cylinder
Signal word: warning
Hazard statement: Contains gas under pressure; may explode if heated Resource material
Please refer to section 2.5.4 GHS 4th Edn
Exercise 7: A burning solid A yellow powder was tested using the test method prescribed in the UN Recommendations for the Transport of Dangerous Goods – Manual of Tests and Criteria Part III Sections 33.2.1. The tests showed that the powder burned during the test with the burn time being less than 45 seconds. It is known that the substance is not a powdered metal. Question: Classify the yellow solid using the information supplied, explaining how you arrived at your answer and any uncertainties that remain with the classification. Answer: Referring to the decision logic in section 2.7.4 of the GHS, we find that a burn time with the specified UN test of less than 45 seconds would suggest that the powder is a category 1 flammable solid. However no information is supplied about how the powder behaved with respect to the wetted zone in the test. Classification cannot therefore be completed and the required information should be obtained to complete classification. Resource material To help you complete this exercise please refer to the following resource material Section 2.7.4 GHS 4th Edition
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Exercise 8: A powder seen to give off gas A white powder when tested in accordance with UN test No. 5 as set out in Part III section 33.4.1.4 of the UN Recommendations for the Transport of Dangerous Goods Manual of Test and Criteria is shown to evolve gas at a maximum rate of 11 l/kg of the chemical per hour. The gas does not spontaneously ignite, but is flammable. Question: Identify the type of hazard exhibited and determine the physical hazard classification and the required hazard statement for this substance, including an explanation of how you classified the substance in your answer. Answer: The description of flammable gas evolution suggests this powder may belong to class of substances or mixtures which in contact with water emit flammable gas Comparing the data presented with the criteria in chapter 2.12 GHS shows that the powder is category 3 in this class. The criteria for Category 3 (>= 1l emitted gas/kg chemical/h) are fulfilled, but not the criteria for Category 2 (>20l/kg/h) Classification: Class 2.12, Category 3; Label elements:
Symbol: flame
Signal word: warning
Hazard statement: In contact with water releases flammable gas
Resource material To help you complete this exercise please refer to the following resource material Section 2.12.2 GHS 4th Edition
Exercise 9: Test results from a yellow powder A yellow powder was exposed to air at elevated temperatures using the test method No.4 of the UN Recommendations for the Transport of Dangerous Goods Manual of Test Criteria Part III Section 33.3.1.6 (“Burn test”). The following results were observed (results as defined by the test)
1. A positive result using a 100 mm sample cube at 140 °C. 2. A negative result using a 100 mm sample cube at 100 °C. 3. A negative result using a 25 mm sample cube at 140 °C.
Additional information: the powder is to be packed in containers with a volume: < 450 l Question: Identify the type of hazard shown by these results and determine the physical hazard classification, explaining how you arrived at the result.
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Answer:
The results presented suggest that the powder may be self‐heating substance or mixture.
Comparing the test results provided with the decision logic of chapter 2.11 of the GHS we find that
the powder should be considered for this class given test result 1
the powder is not Category 1, since test result 3 is negative
the powder is not category 2 since test result 2 is negative and it is to be packed at less than 450 l volume
The powder therefore cannot be classified as self‐heating and is not within the scope of the GHS based on this property.
Discussion point: remember that the powder may still have other hazardous properties (e.g. toxicity)
Resource material
To help you complete this exercise please refer to the following resource material (attached)
Section 2.11.4 GHS 4th Edition
Exercise 10: Organic peroxides – the effect of diluents
Benzoyl peroxide (IUPAC name dibenzoyl peroxide) is used widely in various formulations to
Initiate polymerisation reactions
Treat certain skin conditions As a bleach
The molecular structure of dibenzoyl peroxide is as shown Question1: Calculate the lowest concentration of this substance in an inert diluent which would be classified as an organic peroxide, explaining how you arrived at you answer. Answer: To perform this calculation, the formula in section 2.15.2 GHS 4th Edn is solved for the mass % concentration of organic peroxide using 1 (the threshold percentage of available oxygen as specified in this section) That is, solve 1 = 16 X C / (Molecular Weight benzoyl peroxide) for C
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C = mass concentration of organic peroxide Using the following atomic weights C = 12 O = 16 H = 1 The molecular weight of benzoyl peroxide is 242 Solution: the lowest concentration = 15.13% Question 2: Benzoyl peroxide is to be shipped as a 38% dispersion in water for use as a polymeriser in the fibre reinforced composite boat building industry. Determine its physical hazard classification, and explain how you arrived at this classification. Answer: Look up benzoyl peroxide in table of section 2.5.3.2.4 UNRTDG. (supplied in resource materials) On referring to this table we find that the 38% benzoyl peroxide described is referred to as < 42% stable dispersion in water. This gives this dispersion a UN number of 3109. Looking up this UN number in the table in the part 3 dangerous goods list of the UNRTDG we find that classification is organic peroxide type F. Label elements:
Symbol: flame
Signal word: warning
Hazard statement: Heating may cause fire
Resource material To help you complete this exercise please refer to the following resource material Section 2.15.2 GHS 3rd Edition The UN Recommendations for transport of Dangerous Goods 16th Edition Listing of Organic Peroxides The UN Recommendations for transport of Dangerous Goods 16th Edition Listing of UN Numbers
Exercise 11: Mass loss from a metal A chemical when brought in contact with aluminum sheets causes a mass loss from the aluminum of 21 % after 11 days at 55 +/‐ 1°C (conditions as specified in Part III Section 37.4 of the UN Recommendations for the Transport of Dangerous Goods ‐ Manual of Test and Criteria) Question: Using the above information, determine the physical hazard classification including the required Hazard statement for this substance. Your answer should explain your reasoning.
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Answer: The mass loss is due to corrosion by the chemical so the potential Hazard classis 2.16 Corrosive to Metals Using the table of equivalencies in the physical hazards presentation, (corrosion of metals section) we see after using an interpolation step, that the mass loss given is equivalent to a corrosion rate of more than 6.25mm /year. From the hazard classification of section 2.16 of the GHS the chemical is therefore Class: Corrosive to Metals Category 1 Label elements: Symbol: Corrosion symbol Signal wo d Warning Hazard statement May be corrosive to metals Resource material The material describing classification of substances corrosive to metals is given in the physical hazards presentation, section on the hazard class corrosive to metals.
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Health Hazards Classification of Substances/ Mixtures Exercises/Examples: Questions
General instructions:
Answer each of the following questions as instructed by the moderator for your session. You will be given a group of exercises to complete and then the moderator for your session will ask the whole group to discuss the answers to these exercises. Be prepared to provide your answer during the discussion session as well as to explain how you arrived at this answer. Please note that completing many of the exercises requires reference to the resource materials given at the end of the exercise so please read the exercise in full before attempting to answer the questions. If you have any time after answering the questions please also provide the GHS label element for the classifications you have determined.
A. Substances (45 minutes)
Acute Toxicity:
Resource material : GHS Purple book (PB), 4rd rev. ed, Table 3.1.1, Annex 1
Substance 1
Acute Oral Toxicity
Test Data GHS Classification Rationale
Oral LD50 : 300 mg/kg bw (observed in a GLP‐compliant study in rats)
Category 3
LD50=300mg/kg bw is considered an Acute Toxicity Estimate (ATE) for classification purpose; according to the classification criteria for acute oral toxicity, 300mg/kg bw is the upper value for Category 3. Therefore, it is assigned Category 3 Acute Oral Toxicity classification
Danger
Toxic if swallowed
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Substance 2
Acute Oral Toxicity
Use of adequate and reliable human data allowing classification according to table 3.1.1. Animal data not appropriate.
Test Data GHS Classification Rationale
Toxicity Data:
Animal test data: oral LD50 (rat) > 5,000mg/kg bw (several values)
Human experience: lethal in relatively low dose range (ca. 300‐1,000mg/kg)
Category 3
.
Valid human data from a large data base (case studies) have precedence over animal data; the rat is in this case not the appropriate test species
Danger
Toxic if swallowed
Substance 3
Acute Dermal Toxicity
(Note use of non‐standard‐guideline test data)
Test Data GHS Classification Rationale
Animal data:
A study to evaluate the acute dermal toxicity was performed in rabbits. The following test data results were reported:
‐ At the dose level of 50 mg/kg bw: no mortality was observed
‐ At 200 mg/kg bw: 100% mortality
Therefore, LD50 was estimated to be between 50mg/kg bw and 200mg/kg
Category 2 Since the dermal LD50 is above 50 mg/kg bw and less than 200 mg/kg bw, Category 2 classification is warranted
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bw
Danger
Fatal in contact with skin
Substance 4
Acute Inhalation Toxicity: experimentally obtained LC50 value
Test Data GHS Classification Rationale
A gas
Animal data:
A GLP‐compliant test for acute inhalation toxicity (gaseous form) was performed in accordance with test guideline 403 in rats. The following LC50 was calculated: LC50: 4500ppm/4h
Category 4 LC50 = 4500 ppm is considered an Acute Toxicity Estimate (ATE) for classification purposes; according to the classification criteria for acute inhalation toxicity for gases, this value corresponds to Category 4. Therefore Category 4 Acute Inhalation Toxicity classification is warranted.
Warning
Harmful if inhaled
Substance 5
Acute Inhalation Toxicity (solid): Time extrapolation
Test Data GHS Classification Rationale
Solid substance Category 3 The classification criteria for acute inhalation toxicity refer to a 4h exposure
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Animal data:
The acute inhalation toxicity was studied in rats in a GLP compliant study performed in principle according to OECD Test Guideline 403, but with respect for transport only with 1‐h exposure. The LC50 (1‐h) of 3 mg/l was calculated.
time; therefore to classify a substance, existing inhalation toxicity data generated from 1‐hour exposure should be converted accordingly: 1hour LC50 values have to be converted by dividing by 4 (Haber’s rule/law, dusts and mists)
LC50 (4‐h) = (LC50 (1‐h) / 4) = (3 mg/l / 4) = 0.75 mg/l, thus Category 3 classification is warranted
Danger
Toxic if inhaled
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Skin Corrosion/Irritation
Resource material : GHS Purple book (PB), 4rd rev. ed, Tables 3.2.1, 3.3.2, Annex 1
Substance 6
Skin Corrosion/Irritation
Test Data GHS Classification Rationale
Toxicity data:
‐ No in vivo data available
‐ In vitro skin corrosion: Human skin model test (OECD 431): Positive
Other relevant information: determination of pH and acid/alkali reserve (buffering capacity) pH < 2 with low buffering capacity
Category 1
According to the criteria the valid positive in‐vitro test warrants classification in Cat 1 though buffering capacity is low.
Danger
Causes severe skin burns and eye damage
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Substance 7
Skin Corrosion
Test Data GHS Classification Rationale
In OECD Test 404 full necroses/irreversible skin damage after 4 h exposure within 14 d were observed in one animal
Cat 1/(1C) According to the classification criteria for Skin Corrosion/Irritation the production of irreversible damage to the skin after 4h exposure in at least one animal warrants classification in Category 1/1C.
Danger
Causes severe skin burns and eye damage
Substance 8
Skin Irritation
Test Data GHS Classification Rationale
According to OECD Test Guideline 404 test substance was applied for 1 hour and three minutes. No scars or other irreversible effects were found. The scoring results obtained after 4
hours application time are
Erythema/Eschar: 2.7, 3, 0.66
Oedema: 1.7, 2, 1
Skin Irritant Category 2
The classification is made on basis of 2 of 3 animals exceeding 2.3 mean score for erythema.
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Warning
Causes skin irritation
Eye Damage/Irritation
Resource material : GHS Purple book (PB), 4rd rev. ed, Tables 3.3.1, 3.3.2, Annex 1
Substance 9
Serious Eye Damage
Test Data GHS Classification Rationale
Toxicity data: neither in vivo data nor in vitro data available
Other relevant information: pH 1.9; no info on buffering capacity
Category 1
Based on a pH <2, the substance is a skin corrosive Cat 1 according to the evaluation strategy for skin corrosion and irritation potential and deemed to cause irreversible eye effects; according to the evaluation strategy for serious eye damage and eye irritation the substance is then also causes eye damage (irreversible effects on the eye) Cat 1.
.
Danger
Causes serious eye damage
Substance 10
Eye Irritation
Test Data GHS Classification Rationale
In an OECD Test Guideline 405 study the test substance was applied on the eyes
Eye irritant Category 2 The test results show:
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of three rabbits. The scoring results obtained are
Corneal opacity: 2, 2, 1.3
Iritis: 1, 1, 1
Conjunctival redness: 2, 1, 1
Conjunctival edema (chemosis): 3, 1.7, 2.3
Reversibility: The effects were reversible.
Cornea ≥ 1 (in all animals)
Iritis ≥ 1 (in all animals) Conjunctival redness ≥ 2 (in 1 animal)
Conjunctival edema ≥2 (in 2 of 3 animals)
The Category 2 criteria are fulfilled by the Cornea, Conjunctiva and Iris scores.
Warning
Causes serious eye irritation
Substance 11
Eye Irritation
Test Data GHS Classification Rationale
OECD Test Guideline 405: Acute Eye Irritation/Corrosion test results:
Corneal opacity: mean score 0.6
Iritis: mean score 1.3
Conjunctival redness: mean score 2.4 (from 2 of 3 animals)
Conjunctival edema (chemosis): mean score 1.4
Reversibility: The effects were fully reversible after 7 days
Category 2B Since the mean score for redness over 24, 48, and 72 hours in 2of 3 animals is 2.4 and therefore > 2.3, and the effects are fully reversible, the criteria for classification in Category 2B are fulfilled.
No pictogram Warning
Causes eye irritation
Substance 12
Serious Eye Damage SAR
Test Data GHS Classification Rationale
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The material is a new aliphatic secondary amine. No data is available. The test substance has Structure Activity Relationships (SAR) to substances with similar structure known to be corrosive to the skin.
Category 1 Based on expert judgment using SAR information the classifier concluded that Category 1 is justified, since there is a much data on aliphatic amines which are skin corrosives Category 1 and thus deemed to cause irreversible eye effects resulting in Serious Eye Damage Category 1 according to the evaluation strategy.
Danger
Causes serious eye damage
Sensitization
Resource material : GHS Purple book (PB), 4rd rev. ed, Tables 3.4.1, 3.4.2, Annex 1
Substance 13
Respiratory Sensitizer Enzymes
Test Data GHS Classification Rationale
The material is an enzyme with many well‐documented human case studies for respiratory sensitization occurring in workers exposed during the manufacturing process.
Respiratory Sensitizer
Category 1
Because of the clear evidence from valid human studies, classification for respiratory sensitization was warranted.
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Danger
May cause allergy or asthma symptoms or breathing difficulties if inhaled
Substance 14
Skin Sensitization
Test Data GHS Classification Rationale
Toxicity data: There are many well documented human case reports on contact sensitization at very low concentrations and in addition positive animal study results showing a high potency
Skin Sensitizer, Category 1A
The classification criteria are clearly fulfilled based both on human and animal evidence.
.
Warning
May cause an allergic skin reaction
Germ Cell Mutagenicity:
Resource material : GHS Purple book (PB), 4rd rev. ed, Figure 3.5.1, Annex 1
Substance 15
Germ Cell Mutagenicity
Test Data GHS Classification Rationale
Positive result in vivo in the Mammalian Bone Marrow Chromosome Aberration Test (OECD Test Guideline 475) and also positive in several in vitro tests for mutagenicity
Category 2 The test result fulfills the Germ Cell Mutagenicity Category 2 classification criteria of positive evidence obtained from a somatic cell mutagenicity tests in vivo in mammals
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Warning
Suspected of causing genetic defects (state route of exposure if it is conclusively
proven that no other routes of exposure cause the hazard)
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Carcinogenicity:
Resource material : GHS Purple book (PB), 4rd rev. ed, Figure 3.6.1, Annex 1
Substance 16
Carcinogenicity
Test Data GHS Classification Rationale
Occupational exposure has been strongly associated with bladder cancer in numerous case reports from many countries. The association has also been observed in several epidemiological studies. In one extreme instance, all five of a group of workers continuously employed in manufacture of the substance for 15 years or more developed bladder cancer.
The substance was tested in mice, rats and hamsters by oral administration, in mice and rats by subcutaneous administration and in rats by inhalation and intraperitoneally. Following its oral administration to mice of different strains, both sexes, newborn and adult, and following its subcutaneous administration, it significantly increased the incidence of liver‐cell tumors (benign and malignant). In female rats, it markedly increased the incidence of mammary tumors; and in male and female hamsters, it increased the incidence of liver tumors following its oral administration. It also induced bladder carcinomas in dogs.
The substance gave positive results in several in vitro and one in vivo genotoxicity studies, no data were available on the genetic and related effects in humans.
Category 1A There is sufficient evidence that the substance is carcinogenic to mice, rats, hamsters and dogs and there is sufficient evidence that S32 is carcinogenic to humans.
Sufficient human evidence demonstrates causality between human exposure and the development of cancer, and sufficient evidence in animals shows a causal relationship between the substance and an increased incidence of tumors.
Danger
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May cause cancer (state route of exposure if it is conclusively proven that no other
routes of exposure cause the hazard)
Substance 17
Carcinogenicity (Derivation of classification from lists)
Test Data GHS Classification Rationale
Classified as Group 3: Not Classifiable as to Carcinogenicity to Humans by IARC (1999)
Classified as Category A4: Not Classifiable as a Human Carcinogen by ACGIH (2001)
Classified as Category D: Not Classifiable as to Human Carcinogenicity by EPA (1995)
Not classified Due to the fact that the substance is classified as Group 3 by IARC (1999), Category A4 by ACGIH (2001) and Category D by EPA (1995).
No hazard communication
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Reproductive Toxicity:
Resource material : GHS Purple book (PB), 4rd rev. ed, Figure 3.7.1, Annex 1
Substance 18
Reproductive Toxicity
Test Data GHS Classification Rationale
Human epidemiological studies in IRIS Toxicological review (2005) and ATSDR (2000), describe increased incidence of natural abortion after exposure, abnormal development and malformation of newborns caused by prenatal abuse and decreased plasma concentrations of luteinizing hormone and testosterone after exposure.
Increased risk of late spontaneous abortions associated with exposure at levels around 88 ppm (range 50‐150 ppm).
Evidence of increased incidences of fetal death and delayed ossification, a decrease and unossification of sternebrae, a shift in rib profile, excess ribs, retarded skeletal development, delayed reflex response, learning disability and early vaginal opening and testes descent at dosing levels not toxic to dams from rat and mouse teratogenicity tests.
Category 1A Evidence of adverse effects on development in humans and in animal studies
Danger
May damage fertility of the unborn child (state specific effect if known)(state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard)
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Specific Target Organ Toxicity – Single and Repeated Exposure:
Resource material : GHS Purple book (PB), 4rd rev. ed, Figures 3.8.1, 3.9.1, Annex 1
Substance 19
STOT‐SE Human Experience
Test Data GHS Classification Rationale
There is broad human experience from many case reports of blindness following oral ingestion of a single dose.
Acute oral toxicity in rats is low (LD50 values > 7,000 mg/kg body weight with no evidence of specific target organ toxicity observed in rats).
STOT‐SE
Category 1
The classification criteria for STOT‐SE Category 1 are fulfilled, as there is clear human evidence of a specific target organ toxicity effect. The rat is the standard animal species for single exposure tests and is not sensitive as it did not predict the specific target organ toxicity potential seen in humans.
Danger
Causes damage to organs (or state all organs affected if known)(state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard)
Substance 20
STOT‐RE
Test Data GHS Classification Rationale
Human evidence including "hemolytic anemia, a decrease in white blood cell count" (ACGIH (7th, 2001)), and evidence from animal studies including "a decrease in mean corpuscular hemoglobin, hemoglobin concentrations, red blood cell count and hematocrit levels," and "adrenal degeneration" (MOE Risk Assessment Vol.3 (2004)).
Category 1 (adrenal, blood system)
The effects on experimental animals were observed at dosing levels within the guidance value ranges for Category 1
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Danger
Causes damage to organs (state all organs affected, if known) through prolonged or repeated exposure (state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard)
Substance 21
STOT
Test Data GHS Classification Rationale
In valid animal experiments narcotic effects (transient effect on the nervous system including lethargy, lack of coordination and narcosis) were observed following a single inhalation exposure at ≥ 8 mg/l.
STOT Category 3
Narcotic effects
The classification criteria for narcotic effects STOT Category 3 are fulfilled based on results in an animal experiment.
Warning
May cause drowsiness or dizziness
Aspiration Hazard:
Substance 22
Page 28 of 49
Aspiration Hazard
Test Data GHS Classification Rationale
The material is a hydrocarbon and has a kinematic viscosity of 0.74mm3/s at
25 .
Case reports of human symptoms "May cause pulmonary edema if inhaled and chemical pneumonia if swallowed." (ATSDR (2001)).
Category 1 Fulfills criteria
it is a hydrocarbon and has a kinematic viscosity ≤ 20.5 mm2/s, measured at 40° C.
Also based on the description in reports of human symptoms, the Category 1 critera are fulfilled:
Danger
May be fatal if swallowed and enters airways
Page 29 of 49
B. Mixtures (1 hour)
Exercise 1 (=PCI Example 1)
Acute oral toxicity of a mixture
The following example demonstrates the application of data when the available range data spans
more than one acute toxicity range estimate in Table 3.1.2.
Ingredient information:
Ingredient Wt% Test Data
Ingredient 1 16 Oral LD50: 1,600 mg/kg
Ingredient 2 4 Acute oral toxicity range estimate: 200 < LD50 < 2,000
Ingredient 3 80 Oral LD50: 3,450 mg/kg
Answer:
Apply the equation in paragraph 3.1.3.6.1:
nmixture ATEi
Ci
ATE
100
450,3
80
200
4
600,1
16100
mixtureATE
Therefore: ATEmixture = 1,880 mg/kg, Category 4
Page 30 of 49
Warning
Harmful if swallowed
Rationale:
(a) Classification via application of substance criteria is not possible since acute toxicity test data
was not provided for the mixture (paragraph 3.1.3.4);
(b) Classification via the application of bridging principles is not possible since data on a similar
mixture was not provided (paragraph 3.1.3.5.1);
(c) Classification of the mixture based on ingredient data can be considered (paragraph 3.1.3.6);
(d) Applying the “relevant ingredients” concept from paragraph 3.1.3.3(a) means that all
ingredients will be considered when applying criteria in paragraph 3.1.3.6;
(e) Data is available for all ingredients so criteria in paragraph 3.1.3.6.1 apply;
(f) Ingredients 1, 2 and 3 are all included in the ATEmixture calculation because they have data that
fall within a GHS acute toxicity category [paragraph 3.1.3.6.1 (a)].
(g) Applying the guidance in Note (a) to Table 3.1.1:
(i) The LD50 data for ingredients 1 and 3 are used in the ATEmixture calculation since data are
available;
(ii) The use of expert judgment is needed to determine what value to use in the ATEmixture
calculation for ingredient 2. Since the experimentally obtained acute toxicity range
estimate of 200 < LD50 < 2,000 for ingredient 2 is existing data developed prior to
development of the GHS criteria it does not match up with the ranges provided in Table
3.1.2. The lower end of the range falls within the Category 3 range of 50 – 300 mg/kg and
the converted acute toxicity point estimate for an Oral Category 3 ingredient is 100. Given
that the converted point estimate is lower than the experimentally determined value of >
200 mg/kg it does not make sense to use the converted point estimate. In this case, one
should apply the known information, and 200 mg/kg should be used in the ATEmixture
calculation.
Exercise 2 (=PCI Example 2)
Acute oral toxicity of a mixture
The following example demonstrates the application of the “relevant ingredients” criteria in
paragraph 3.1.3.3.
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Ingredient information:
Ingredient Wt% Classification Test Data
Ingredient 1 4 Oral Category 3 LD50: 125 mg/kg
Ingredient 2 92 ‐ No data available
Ingredient 3 3 Oral Category 4 LD50: 1500 mg/kg
Ingredient 4 0.9 ‐ No data available
Ingredient 5 0.1 Oral Category 2 LD50: 10 mg/kg
Answer:
Apply the equation in paragraph 3.1.3.6.2.3:
n i
i
mixture
unknown
ATE
C
ATE
ifC %10100
1500
3
125
4)92(100
mixtureATE
Therefore: ATEmixture = 235 mg/kg, Category 3, and
“92% of the mixture consists of an ingredient of unknown toxicity.”
Danger
Toxic if swallowed
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Rationale:
(a) Classification via application of substance criteria is not possible since acute toxicity test
data was not provided for the mixture (paragraph 3.1.3.4);
(b) Classification via the application of bridging principles is not possible since data on a
similar mixture was not provided (paragraph 3.1.3.5.1);
(c) Classification of the mixture based on ingredient data can be considered (paragraph
3.1.3.6);
(d) Applying the “relevant ingredients” concept from paragraph 3.1.3.3 (a) means that
ingredient 4 could be excluded from both the ATEmixture calculations. This is true for the
calculation in either paragraph 3.1.3.6.1 or 3.1.3.6.2.3. This same reasoning could also
apply to ingredient 5, as it is below the “relevant ingredients” threshold; however, the use
of expert judgment is necessary to make this decision for ingredient 5 as it is classified in
Category 2. For this example, it was decided that since the percentage of this ingredient is
well below the threshold (i.e. 0.1%) and the ingredient is classified in Category 2, it would
be excluded from the ATE calculation;
(e) The total concentration of ingredients with unknown acute toxicity (i.e. ingredient 2) is
92%, therefore, the ATEmixture equation in paragraph 3.1.3.6.2.3 must be used. This
calculation corrects for ingredients with unknown acute toxicity above 10% of the mixture;
(f) Ingredients 1 and 3 are included in the ATEmixture calculation because they have data that
fall within a GHS acute toxicity category [Paragraph 3.1.3.6.1 (a)];
(g) Applying the guidance in Note (a) to Table 3.1.1 results in using the LD50 data for
Ingredients 1 and 3 in the ATEmixture calculation since data are available;
(h) Ingredient 2 does not have any useable information for the oral route ATEmixture calculation
and is in the mixture at a concentration 1% so an additional statement is included
(paragraph 3.1.3.6.2.2.);
Exercise 3 (= PCI example 5)
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The following example demonstrates application of data for skin corrosion/irritation for mixtures
when additivity may not apply (paragraphs 3.2.3.3.4 and 3.3.3.3.4). A similar approach would be
used for serious eye damage/irritation.
Ingredient information:
Ingredient Wt% Classification Ingredient information
Ingredient 1 4 Skin Category 1 pH = 1.8
Ingredient 2 5 Skin Category 2 ‐
Ingredient 3 5 Skin Category 3 ‐
Ingredient 4 86 ‐ No data available
Mixture information: Mixture pH = 4.0
Answer:
For this mixture, the classification was assigned as a Category 1 because ingredient 1 (Category 1) is
in the mixture at 1%
Danger
Causes severe skin burns and eye damage
Rationale:
(a) Classification via application of substance criteria is not possible since test data (other
than a pH) was not provided for the mixture (paragraph 3.2.3.1.1);
(b) The overall mixture pH of 4.0 does not result in classification in Category 1 since this
does not fall within the criteria of pH 2 or pH 11.5 ( paragraph 3.2.3.1.2);
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(c) Classification via the application of bridging principles is not possible since data on a
similar mixture was not provided (paragraph 3.2.3.2.1);
(d) Classification of the mixture based on ingredient data can be considered (paragraph
3.2.3.3);
(e) Ingredient 1 with a pH = 1.8 is an ingredient for which additivity might not apply as
described in paragraph 3.2.3.3.4 and summarized in Table 3.2.4. Expert judgment would
be needed to determine whether or not additivity applies. Knowledge of the
components is important. Given the limited information in this example, the classifier of
this mixture chose to apply non‐additivity for a conservative approach. Without
information on the mode of action of Ingredient 1, the mixture could be corrosive
regardless of the overall pH. Therefore, the criteria described in paragraph 3.2.3.3.4
were applied (i.e. “A mixture containing corrosive or irritant ingredients that cannot be
classified based on the additivity approach shown in Table 3.2.3, due to chemical
characteristics that make this approach unworkable, should be classified as skin
Category 1 if it contains ≥ 1% of a corrosive ingredient and as skin Category 2/3 when it
contains ≥ 3% of an irritant ingredient”).
Exercise 4 Classification of “AllRound”: a pesticide mixture used for crop protection The Table below provides compositional information on “Allround”, which is a mixture of three different
commercial pesticide formulations, an unknown ingredient and two different solvents, plus water. The
toxicological data/classifications for the different ingredients of the mixture are provided in the Table. The
data in the table are generally based on Safety Data Sheets and other information in the Internet. There are
no test data on the mixture as a whole. There are no test data on similar tested mixtures.
Ingredients % AT oraL
LD50 ...mg/kg/ Classification
AT dermal LD50.mg/kg /Clas‐ sification
AT Inhal‐ ation LC50 Mg/l/4h
Skin Corr./Irr
Eye damage/ Irritation (EI)
Sensitization Carc Mut Repro‐ ductive toxicity
1. Pesticide formulation A Fungicide
7.2 NC >5,000
NC >5,000
NC Tested at max. conc
NC Cat 2 Respiratory: NC Skin: Cat 1
NC NC Cat 2
2. Pesticide formulation B Insecticide
35 Cat 4 LD>2000 1.62 mg/l/4h
NC „May cause slight EI NC
NC Negative
NC NC
3. Pesticide formulation C Herbicide
12 NC >5,000
NC >5,000
NC Tested at max.conc.
Cat 2 Cat 2 Negative
Neg. Neg Neg.
4. Ingredient (Unknown)
0.8 No data No data No data No data No data No data No data
No data
No data
5.Ingredient (a solvent)
11 NC NC Unknown NC NC NC NC NC NC
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6. Solvent : 1,2 Propyleneglycol
16 NC NC NC NC NC NC NC NC NC
7. Water 18 NC NC NC NC NC NC NC NC NC
Question 1: Which procedure for mixture classification has to be used?
Question 2: Which Hazard classes/differentiations have to be taken into consideration?
Question 3: Are there any ingredients which can be totally neglected in the mixture classification
procedure? If any, why?
Question 4: Determine for each respective Hazard class/differentiation which ingredients have to
be taken into account (“Cut‐off values)”.
Question 5: What is the classification of the mixture? Rationale?
Question 6: The manufacturer of the pesticide wants a formulation classified in Acute oral toxicity
Cat 5. What is the maximum concentration of the relevant ingredient?
Resource material Excerpts from Chapter 3.1, 3.2, 3.3, 3.4 and 3.7 GHS 3rd Edition
Category 5 Acute Oral Toxicity
No pictogram Warning
May be harmful if swallowed
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Hazardous to the aquatic environment
Exercise/Examples: Answers with Questions General instructions:
Answer each of the following questions as instructed by the moderator for your session. You will be given a group of exercises to complete and then the moderator for your session will ask the whole group to discuss the answers to these exercises. Be prepared to provide your answer during the discussion session as well as to explain how you arrived at this answer. Please note that completing many of the exercises requires reference to the resource materials given at the end of the exercise so please read the exercise in full before attempting to answer the questions. Please also provide the GHS label elements (pictogram, signal word, and hazard statement) for the classifications you have determined.
A. Substances
Exercise 1: Potential Acute (short‐term) aquatic hazard?
A substance has been tested with respect to acute aquatic toxicity with the following results:
‐ Daphnia EC50 5.6mg/l/48h
‐ Algae ErC50 99mg/l/72h
Question: Determine the classification including the pictogram, signal word, and hazard statement (as appropriate)
Answer:
Classification: Acute aquatic toxicity Category 2 (see Table 4.1.1.) No pictogram No signal word Hazard statement: H401=Toxic to aquatic life Rationale for classification: The L(E)C50 for the most sensitive species (daphnia) in a valid study is > 1mg/l but =< 10 mg/l, and thus the criteria for Category 2 are clearly fulfilled. The algae data are not taken anymore into consideration. Resource material
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GHS Purple book, 3rd rev. ed, Tables 4.1.1 and 4.1.6 Exercise 2:
A substance has been tested in all representative aquatic species with respect to acute toxicity with
the following results:
‐ Fish LC50 0.002mg/l/96 h
‐ Daphnia EC50 4.6mg/l/48h
‐ Algae ErC50 88mg/l/72h
Question: Determine the classification including the harmonized label elements and, if applicable, the Multiplying factor (M factor) Answer:
Classification: Acute aquatic toxicity Category 1 (see Table 4.1.1.) M‐factor: 100 (s. Table 4.1.5) Environmental pictogram Warning Hazard statement: H400=Very toxic to aquatic life Rationale for classification: The L(E)C50 for the most sensitive species (fish) in a valid study is below the cut‐off level of <= 1 mg/l for Category 1, and thus the criteria are clearly fulfilled Resource material GHS Purple book, 3rd rev.ed, Tables 4.1.1 and 4.1.5 Exercise 3: Potential acute aquatic hazard A mixture has been tested in all representative aquatic species with respect to acute toxicity with
the following results:
‐ Fish LC50 0.8 mg/l/96 h (study with flaws)
‐ Daphnia EC50 10 mg/l/48h
‐ Algae ErC50 88mg/l/72h
Question: Which classification is appropriate? Discuss the crucial point and show options for solutions. Answer:
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Classification: Acute Cat 2 No pictogram or signal word; Toxic to aquatic life NB: Application of a very conservative approach would lead to Cat 1 Rationale: Based on the lowest valid value of 10 mg/l for daphnia the criteria for Cat 2 are fulfilled. Based on expert judgement on the total weight of evidence the invalid study has not been used for classification. Other options: ‐ Request the full fish study report and have it evaluated in order to decide if it is really in total invalid and not usable even in part (expert judgement) ‐ Perform a new fish study in order to clarify the toxicity in this species (Not required by GHS) Resource material GHS Table 4.1.1 and chapter 1.3.2.4.2, 1.3.2.4.8 and 1.3.2.4.9.2 (excerpts) Exercise 4: Potential aquatic hazard of an organic substance? A substance has been tested with the following results. ‐ Fish early life stage: NOEC 0.75 mg/l
‐ Daphnia reproduction: NOEC 1.6 mg/l
‐ Degradation: OECD test No. 301 > 70% biodegradability in 28days Question 1: Which kind(s) of aquatic hazards can be assessed on the basis of the available data? Question 2: Determine the classification including the label elements and if applicable the Multiplying factor (M factor) Answers:
1: Since no data with respect to acute toxicity are available, only chronic aquatic hazards can be determined 2. Classification: Chronic Cat 3; there is no specific M factor , since the NOEC is < 0.001 mg/l No pictogram No signal word Harmful to aquatic life with long lasting effects Rationale: The substance is rapidly degradable. Since there are adequate chronic data available, Table s. 4.1.1 b. ii applies for classification. The lowest valid chronic NOEC is > 0.1 mg/l and <= 1 mg/l, therefore Cat Chronic 3; H 412=Harmful to aquatic life with long lasting effects According to Table 4.1.5 there is no specific M factor
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Resource material GHS Table 4.1.1, 4.1.5 and 4.1.6 Exercise 5: Potential aquatic hazard? A substance has been tested with the following results. ‐ Fish early life stage: NOEC 0.045 mg/l
‐ Daphnia reproduction: NOEC 1.6 mg/l
‐ Rapid biodegradation: no useful data available Question 1: What is the classification including the label elements? Question 2: Discuss the consequence of the lack of data on degradation Answer: Classification: Cat 1 Environmental pictogram Warning H 410=Very toxic to aquatic life with long lasting effects Rationale: Assumption not readily biodegradable; see Note 4 to Table 4.1.1. Therefore Table 4.1.1(b) i has to be applied. Consequence: It’s one of the cases, where data gaps can lead to a more stringent classification (Cat 1 rather than Cat 2) Resource material: GHS Tables 4.1.1 and 4.1.6 Exercise 6: Potential aquatic hazard? A substance has been tested with the following test results:
Data:
‐ Fish LC50 8.2 mg/l
‐ Daphnia EC50 56 mg/l
‐ Algae ErC50 122 mg/l
‐ Biodegradability <5%
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‐ log Kow 2.1
Question: Identify the type of hazard exhibited and determine the environmental hazard classification and the required label elements for this substance, include an explanation of how you classified the substance. Answer: There is relevant acute and chronic aquatic toxicity
Classification: Acute and chronic aquatic toxicity Cat 2
Environmental pictogram
No signal word
Toxic to aquatic life with long lasting effects
Rationale:
Acute toxicity Cat 2, since EC50 >1 and <=10 mg/l (Table 4.1.1 a)
No adequate chronic toxicity data available, therefore Table 4.1.1b (iii)
Not readily biodegradable, Log Kow not taken into account
Resource material: GHS Table 4.1.1 Exercise 7: Potential aquatic hazard of a green powder? A substance has been tested with the following test results: ‐ Fish LC50 8.2 mg/l
‐ Daphnia EC50 56 mg/l
‐ Algae ErC50 122 mg/l
‐ Daphnia reproduction NOEC > 1mg/l
‐ Biodegradability <5%
‐ log Kow 2.1
Question: What is the classification including the label elements? Answer: Classification: Acute and chronic Cat 2
Environmental pictogram
No signal word
Toxic to aquatic life with long lasting effects
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Rationale:
Acute Cat 2 from Fish data according to Table 4.1.1a
Not readily degradable; this information combined with acute data for fish gives chronic 2 ( s. Table
4.1.1 b (iii)
No BCF; log Kow not taken into account
Chronic data NOEC > 1mg/l (daphnia) cannot be used for non‐classification since not from the same
species for which acute classification is based on (fish)
Resource material: GHS Table 4.1.1 Exercise 8: Potential aquatic hazard? A substance has been tested with the following test results ‐ Fish LC50, Daphnia EC50, Algae ErC50 all > water solubility
‐ Water solubility 35 mg/l
‐ Biodegradability <5%
‐ log Kow 2.1
Question1: Determine the classification for acute and chronic aquatic toxicity and label elements Answer:
Acute and chronic no classification No hazard communication Rationale: ‐ Acute toxicity values > water solubility ‐ Not readily degradable, but log Kow< 4; no BCF ‐ No chronic data Therefore no classification according to criteria in Table 4.1.1 (c) Resource material: GHS Table 4.1.1
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B. Mixtures
Exercise 9 (=PCI Example 1)
The following example demonstrates application of the summation methods when classification information is available for some or all of the ingredients of a mixture.
Ingredient information:
Ingredient Wt% Acute classification
(M‐factor)
Chronic classification
(M‐factor)
Ingredient 1 0.01 Acute 1
(M‐factor: 10)
Chronic 1
(M‐factor: 10)
Ingredient 2 1.0 Acute 2 Chronic 2
Ingredient 3 25.0 Not classified Chronic 4
Ingredient 4 68.76 Not classified Not classified
Answer:
Acute Classification - Not classified because:
Acute 1: (Acute 1) x M 25%
using data from ingredients of the mixture:
(0.01% x 10) = 0.1% (Not classified)
Acute 2: (M x 10 x Acute 1) + Acute 2 25%
using data from ingredients of the mixture:
(10 x 10 x 0.01%) + 1.0% = 2.0% (Not classified)
Acute 3: (M x 100 x Acute 1) + (10 x Acute 2) + Acute 3 ≥ 25%
using data from ingredients of the mixture:
(10 x 100 x 0.01%) + (10 x 1.0) = 20% (Not classified)
Chronic Classification - Category 4 because:
Chronic 1: (Chronic 1) x M 25%
using data from ingredients of the mixture:
0.01% x 10 = 0.1% (Not classified)
Chronic 2: (M x 10 x Chronic 1) + Chronic 2 25%
using data from ingredients of the mixture:
(10 x 10 x 0.01%) + 1.0% = 2% (Not classified)
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Chronic 3: (M x 100 x Chronic 1) + (10 x Chronic 2) + Chronic 3 ≥ 25%
using data from ingredients of the mixture:
(10 x 100 x 0.01%) + (10 x 1.0%) = 20% (Not classified)
Chronic 4: Chronic 1 + Chronic 2 + Chronic 3 + Chronic 4 ≥ 25%
using data from ingredients of the mixture:
0.01% + 1.0% + 25.0% = 26.01% (Classified)
Rationale:
(a) Classification via application of substance criteria is not possible since aquatic toxicity test data was not provided for the mixture (paragraph 4.1.3.3);
(b) Classification via the application of bridging principles is not possible since data on a similar mixture was not provided (paragraph 4.1.3.4);
(c) Classification based on ingredient data for the mixture can be considered (paragraph 4.1.3.5);
(d) Acute and chronic classification data is available for some of the ingredients of the mixture and the percentage of these ingredients classified as “Acute” or “Chronic” will feed straight into the summation method (paragraph 4.1.3.5.51);
(e) Adequate toxicity data is not available so the additivity formula cannot be considered (paragraph 4.1.3.5.2)
Acute classification:
(f) Applying the “relevant ingredients” concept from paragraph 4.1.3.1 means that:
(i) The use of expert judgment is necessary to make the “relevant ingredient” decision for ingredient 1 since it is a highly toxic ingredient with an M-factor of 10. In this case it was decided to include the ingredient because its concentration in the mixture (i.e., 0.01%) is still significant given the M factor and the constants used in the Acute 2 and 3 calculations for Acute 1 ingredients;
(ii) Ingredient 2 will be included in the calculation because it is in the mixture at a concentration 1%;
(g) The summation method approach described in paragraph 4.1.3.5.5.3 applies and the cut-off value/concentration limits provided in Table 4.1.3 are used for classification.
Chronic classification:
(h) Applying the “relevant ingredients” concept from paragraph 4.1.3.1 means that:
(i) The use of expert judgment is necessary to make the “relevant ingredient” decision for ingredient 1 since it is a highly toxic ingredient with an M-factor of 10. In this case it was decided to include the ingredient because its concentration in the mixture (i.e., 0.01%) is still significant given the M factor and the constants used in the Chronic 2 and 3 calculations for Chronic 1 ingredients.
(ii) Ingredients 2 and 3 will be included in the calculation because they are in the mixture at a concentration 1%.
(i) The summation method approach described in paragraph 4.1.3.5.5.4 applies and the cut-off value/concentration limits provided in Table 4.1.4 are used for classification.
(End of example 1)
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Exercise 10 (=PCI 2)
The following example demonstrates application of a stepped approach where the additivity formula is used for the part of the mixture that has chronic toxicity data and passing that result into the summation method.
Ingredient information:
Ingredient Wt% Chronic toxicity data NOEC
or ECx
Rapidly
degradabl
e
Classification
NOEC (28 day for fish) 4.1
Ingredient 1 15 NOEC (21 day for
crustacea)
0.13 Yes ‐
Ingredient 2 5 NOEC (for algae) 0.8 No ‐
Ingredient 3 80 ‐ Chronic 3
Answer:
Mixture is Chronic Category 3
Step 1:
Applying the additivity formula based on chronic toxicity from 4.1.3.5.2 (b):
nnm NOECj1.0
Cj
NOECi
Ci
EqNOEC
CjCi
where:
Ci = concentration of ingredient i (weight percentage) covering the rapidly
degradable ingredients;
Cj = concentration of ingredient j (weight percentage) covering the non‐
rapidly degradable ingredients;
NOECi = NOEC (or other recognized measures for chronic toxicity) for
ingredient i covering the rapidly degradable ingredients, in mg/l;
NOECj = NOEC (or other recognized measures for chronic toxicity) for
ingredient j covering the non‐rapidly degradable ingredients, in mg/l;
N = number of ingredients, and i and j are running from 1 to n;
EqNOECm = Equivalent NOEC of the part of the mixture with test data;
EqNOECm = 20/((15/0.13) + 5/(0.1x 0.8)) = 0.11 mg/l
The part of the mixture (i.e., 20%) with Chronic toxicity data (i.e., ingredients 1 and 2) has an EqNOECm of 0.11 mg/l. As the NOEC of the ingredients that are considered not-rapidly degradable have already been multiplied with the factor 0.1
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the EqNOECm can now be applied to table 4.1 b (ii) resulting in a classification of Chronic 3.
Step 2:
Ingredient information going into the summation method calculations:
Ingredient Wt % Classification
Additivity result – part of mixture with only
toxicity data
20 Chronic 3
Ingredient 3 80 Chronic 3
Chronic 1: (Chronic 1) x M 25%
0% (Not classified)
Chronic 2: (M x 10 x Chronic 1) + Chronic 2 25%
using data from the additivity result & ingredients of the mixture:
(10 x 0%) + 0% = 0% (Not classified)
Chronic 3: (M x 100 x Chronic 1) + (10 x Chronic 2) + Chronic 3 ≥ 25%
using data from the additivity result & ingredients of the mixture:
(100 x 0%) + (10 x 0%) + 20% + 80% = 100% (Classified)
Alternatively apply summation method straight away.
Rationale:
(a) Classification via application of substance criteria is not possible since acute aquatic toxicity test data was not provided for the mixture (paragraph 4.1.3.3);
(b) Classification via the application of bridging principles is not possible since data on a similar mixture was not provided (paragraph 4.1.3.4);
(c) Classification based on ingredient data for the mixture can be considered (paragraph 4.1.3.5);
(d) The percentage of the ingredient classified as Chronic 3 will feed straight into the summation method (paragraph 4.1.3.5.1);
(e) Adequate toxicity data for the other ingredients are available so the additivity formula in combination with the summation method can be considered (paragraphs 4.1.3.5.2 & 4.1.3.5.5.4);
(f) Applying the “relevant ingredients” concept from paragraph 4.1.3.1 means that ingredients 1, 2, and 3 will be considered in the calculations (paragraph 4.1.3.5.2 (b));
(g) When applying the additivity formula the preferred method is to calculate the toxicity of this part of the mixture for each ingredient toxicity values that relate to the same taxonomic group (i.e. fish, crustacean or algae) and then to use the highest toxicity obtained (i.e., use the most sensitive of the three groups). However, when toxicity data for each ingredient are not available in the same taxonomic group the data from the most sensitive test organism should be used (paragraph 4.1.3.5.3). In this case ingredient 1’s toxicity data for Crustacea is used because it is has the lowest value (i.e. highest toxicity) and ingredient 2’s Algae data is used;
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(h) Application of the chronic additivity formula results in 20% of the mixture being classified at Chronic Category 3, which is used in the summation method with the classification information provided for ingredient 3;
(i) If the mixture is classified in more than one way, the method yielding the more conservative result is valid (GHS 4.1.3.5.4);
Exercise 11 (PCI 3)
The following example demonstrates application of the tiered approach to determining the mixture’s classification where acute toxicity data is available on the mixture as a wholeas well as on the ingredients, and chronic classification information is only available on the ingredients.
Ingredient information:
Ingredient Wt% Acute toxicity data L(E)C50 mg/l Chronic classification
LC50 (for fish) 12
EC50 (for crustacea) 18
Ingredient 1
5
ErC50 (algae) 0.9
Chronic 1
(M Factor: 1)
LC50 (for fish) 40
EC50 (for crustacea) 25
Ingredient 2 1.5
ErC50 (algae) 9.5
Chronic 2
LC50 (for fish) > 100
EC50 (for crustacea) > 100
Ingredient 3 93.5
ErC50 (algae) > 100
Chronic 4
Information on tested mixture:
Acute toxicity data L(E)C50 mg/l
LC50 (for fish) 68
EC50 (for crustacea) 90
ErC50 (algae) 12.5
Answer:
Acute classification - Category 3
Chronic classification - Category 2 because:
Chronic 1: (Chronic 1) x M 25%
5% x 1 = 5% (Not classified)
Chronic 2: (M x 10 x Chronic 1) + Chronic 2 25%
using data from the ingredients of the mixture:
(1 x 10 x 5%) + 1.5% = 51.5% (Classified)
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Rationale:
Acute classification:
(a) Classification via application of substance criteria is possible for acute toxicity since acute aquatic toxicity test data was provided for the mixture as a whole (paragraph 4.1.3.3);
(b) The higher toxicity value (from the most sensitive test organism) which in this case is Algae or other aquatic plants is used to classify the tested mixture (paragraph 4.1.3.3.3 (a));
Chronic classification:
(c) Classification via application of substance criteria is not possible since chronic aquatic toxicity test data was not provided for the mixture as a whole(paragraph 4.1.3.3.4 (a));
(d) Classification via the application of bridging principles is not possible since data on a similar mixture was not provided (paragraph 4.1.3.4);
(e) Chronic classification data is available for some or in this case all of the ingredients of the mixture and the percentage of these ingredients will feed straight into the summation method (paragraph 4.1.3.5.1);
(f) Adequate chronic toxicity data is not available so the additivity formula cannot be considered (paragraph 4.1.3.5.2);
(g) Applying the “relevant ingredients” concept from paragraph 4.1.3.1 means that ingredients 1, 2, and 3 will be considered when applying criteria in paragraph 4.1.3.5.5;
(h) The chronic summation method approach described in paragraph 4.1.3.5.5.4 applies and the cut-off value/concentration limits provided in Table 4.1.4 are used for classification.
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Exercise 12 Mixture classification: acute and chronic hazards based on classification of ingredients Available information:
Ingredient % GHS‐Classification of ingredient
Relevant ingredient/ Ingredient to be taken into account
M‐Factor (M) On basis of avail‐able information
Ingredient 1 0.2 Aqu.chron. Cat 3; H 412 No; < 1% NA*
Ingredient 2 0.15 Aqu. akut Cat 1; H 400 Aqu. chron. Cat 1; H 410
Yes; > 0.1 % Yes; < 0.1 %
1 1
Ingredient 3 0.4 Aqu. chron. Cat 2; H 411 No; < 1% NA*
Ingredient 4 5.5 Aqu. chron. Cat 3; H 412 Yes; > 1% NA*
Ingredient 5 24.9 Aqu. acute Cat 1; H 400 Yes; > 0.1 % 1
Ingredient 6 21 Aqu. chron. Cat 4; H 413 Yes; > 1% NA*
Ingredient 7 47.85
*NA= Not applicable since not classified in Cat 1
Question 1: Which method is applicable? Why? Question 2: Apply the chosen method and classify the mixture Answer: Answer 1:
‐ No test data for the mixture as a whole, thus direct classification not possible
‐ No test data for similar mixtures, therefore Bridging principles not applicable
‐ No complete data sets for the ingredients, therefore Additivity formula not applicable
Summation method (§ 4.1.3.5.5) on basis of classified ingredients
Answer 2:
1. Acute aquatic toxicity (Table 4.1.3 ):
Cat 1; Criteria: Sum relevant Cat 1‐ ingredients x M) >= 25%:
0. x1 + 24,9%x1 = 25,05%
Cat 1
Remark: other Cats can be disregarded
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2. Chronic aquatic toxicity (Table 4.1.4):
Cat 1; Criteria: Sum (relevant chronic Cat 1‐ ingredients x M )>= 25%:
0.15x1 < 25%
No Classification (NC)
Cat 2; Criteria: Sum (M x 10x rel. chron. Cat 1‐ingredients) + rel. chron. Cat2‐ingredients >= 25%:
1x10x0.15 + 0= 1.5 < 25%
NC
Cat 3; Criteria: Sum ( M x 100 x rel. Chron. Cat 1‐ingredients)+ (10x rel. chron. Cat2‐ingredients)
+ rel. chron. Cat 3‐ingredients):
1 x 100 x 0.15 +0+5.5 = 20,5 < 25%
NC
Cat 4; Criteria: Rel. chron. Cat 1‐ingredients+ rel. chron. Cat 2‐ingrdients + rel. chron. Cat 3‐
ingredients
rel. chron. Cat 4‐ingredients:
0.15 + 0 + 5.5 + 21 = 26.65 >25%
Cat 4
Resource material
PB Tables 4.1.3 and 4.1.4