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Laboratory testing should be
performed as the final option. Even for regulatory submission, attempts should be made to obtain data from
other sources and where such data is not available, you need to ask where testing is actually possible. And
if you still find that work is required to enable an adequate assessment of the chemical or that a regulatory agency demands
that such work should be performed, you are then faced with decisions on how to go about that testing.
Note that
for self-classification of substances and preprations and for justification of SDSs and Labelling, good scientifically sound
data is acceptable even if not conducted to the precise guidelines and if not performed to GLP. Denehurst can offer
advice on justification of data and will endeavour to avoid further testing.
Guidelines
and GLP Technical guidelines for testing have been agreed
by members of the Organisation for Economic Co-operation and Development (OECD). The same organisation
has also provided guidelines for Good Laboratory Practice (GLP) to provide a quality system for the testing.
However, following a test guideline and filling in the appropriate forms to claim GLP compliance is not necessarily
a substitute for good science and each study performed should be conducted in the best way to meet the objectives of that
study for that particular chemical. Guidelines are what they say: guidelines. They are
designed to help and not restrict the use of science.
List
of guidelines
The OECD Guidelines for the Testing of Chemicals
are available to buy from the OECD, either individually or as a set of two binders containing loose-leaf paper copies.
Alternatively, the Guidelines are also available on CD-ROM. Draft guidelines can be downloaded free
for consultation from the OECD web-site.
The EU Guidelines were published in Directive 92/69/EEC
as Annex V of Directive 67/548/EEC. Over the years since publication, amendments to these methods have
been made and new guidelines introduced. Most of the guidelines are transcripts of OECD guidelines (the
most notable exceptions being flammability and explosivity guidelines). The EU guidelines can be
downloaded for free from the ex-European Chemicals Bureau web-site http://ecb.jrc.ec.europa.eu/testing-methods/
Australian guidelines and those of many other countries are based firmly on OECD methods, although the US and Japan
notably have some restrictions on what they require. To overcome national differences, the OECD guidelines
are often with phrases such as ‘can be’ or ‘may be included’.
Good Laboratory Practice
(GLP) In
many ways, GLP is common sense. The basic theology of GLP is that thou shalt record everything and leave
a data trail for others to follow behind you. It is easy to get bogged down by GLP and make it the over-riding
criteria to follow when conducting laboratory work. However, it is important not to lose sight of science
and GLP has the potential to stifle open investigation.
Somewhere in the middle is a sound compromise. GLP
sets important standards for recording data, reporting, reviewing and maintaining records. It does not
guarantee the quality of the data being recorded and a balance between good science and good working practice is the goal
to aim for.
GLP is required for regulatory submissions around the World, although if you only intend to use the data for the
purposes of safety data sheets or labelling, the need to run the test to GLP standards must be questioned. The
main reason for questioning it is when a flash point study that takes about an hour to perform, can take up to a month to
report at a cost of up to € 1000 if performed to meet GLP.
OECD / EC Test Method index
OECD TG No. | EU Guideline | Study Description | 101 |
| UV-Vis Absorption spectra | 102 | A1 | Melting point | 103 | A2 | Boiling point | 104 | A4 | Vapour pressure | 105 | A6 | Water solubility | 106 | C18 | Adsorption / desorption in soils (batch
equilibrium method) | 107-117-122 | A8 | Partition coefficient (shake flask, HPLC,
pH-metric) | 108 |
| Complex formation
ability in water | 109 | A3 | Density | 110 |
| Particle size distribution | 111 | C7 | Hydrolysis as a function of pH | 112 |
| Dissociation constant | 113 |
| Screening
study for thermal stability in air | 114 |
| Viscosity
of liquids | 115 | A5 | Surface tension of aqueous solutions | 116 | A7 | Fat solubility | 118 | A18 | Polymer number-average molecular weight | 119 | A19 | Low molecular weight content of polymers | 120 | A20 | Solution/extraction
behaviour of polymers in water |
| A21 | Oxidising properties, liquids | 121 | C19 | Estimation of adsorption coefficient in sewage sludge by HPLC |
| A9 | Flash point |
| A10-A11 | Flammability, solids / gasses |
| A12 | Flammability in contact with water |
| A13 | Spontaneous combustion |
| A14 | Explosivity |
| A15 | Auto-ignition, liquids |
| A16 | Auto flammability, solids |
| A17 | Oxidising properties |
| A21 | Oxidising properties, liquid |
OECD TG No. | EU Guideline | Study Description | 201 | C3 | Algal growth inhibition | 202 | C2 | Daphnia immobilisation | 203 | C1 | Acute fish toxicity | 204 |
| Prolonged
toxicity to fish | 205 |
| Acute bird
dietary toxicity | 206 |
| Bird reproduction
| 207 | C8 | Earthworm toxicity | 208 |
| Higher plant toxicity | 209 | C11 | Activated sludge respiration inhibition | 210 |
| Fish, early life stage | 211 | C20 | Daphnia reproduction toxicity | 212 | C15 | Fish, short-term test on embryo / sac-fry | 213 | C16 | Bees, acute
oral toxicity | 214 | C17 | Bees, acute contact toxicity | 215 | C14 | Fish, Juvenile growth test | 216 |
| Soil micro-organisms | 217 |
| Soil micro-organisms carbon transformation | 218 |
| Sediment-water
chironomid toxicity (spiked sediment) | 219 |
| Sediment-water
chironomid toxicity (spiked water) | 220 |
| Enchytraedae reproduction | 221 |
| Lemna growth inhibition |
OECD TG No. | EU Guideline | Study Description | 301A | C4a | Ready biodegradation, DOC die-away | 301B | C4c | Ready biodegradation, CO2 evolution
test | 301C | C4f | Ready biodegradation, modified MITI, CO2 evolution
test | 301D | C4e | Ready biodegradation, closed-bottle test | 301E | C4b | Ready biodegradation, CO2 evolution test | 301F | C4d | Ready biodegradation, manometric |
| C5 | BOD |
| C6 | COD | 302A | C12 | Inherent biodegradation, SCAS | 302B | C9 | Inherent biodegradation, Zahn Wellens | 302C |
| Modified MITI (part ii) | 303A | C10 | Inherent biodegradation, simulation (activated
sludge) | 303B |
| Inherent biodegradation,
simulation (biofilms) | 304A |
| Inherent biodegradation
in soil | 305 | C13 | Bioconcentration in fish | 306 |
| Biodegradation in seawater | 307 |
| Transformation
in soil | 308 |
| Transformation
in aquatic sediments |
OECD TG No. | EU Guideline | Study Description | 401 | withdrawn | Acute oral
toxicity, LD50 (now banned in EU) | 402 | B3 | Acute dermal toxicity | 403 | B2 | Acute inhalation toxicity | 404 | B4, B40 | Acute dermal irritation / corrosion | 405 | B5 | Acute eye irritation | 406 | B6 | Skin sensitisation | 407 | B7 | Repeat dose oral toxicity (28 days), rodents | 408 | B26 | Repeat dose oral toxicity (90 days), rodents | 409 | B27 | Repeat dose oral toxicity (90 days), non-rodents | 410 | B8 | Repeat dose dermal toxicity (21/28 days), rodents | 411 | B28 | Repeat dose dermal toxicity (90 days), rodents | 412 | B9 | Repeat dose inhalation toxicity (28 days),
rodents | 413 | B29 | Repeat dose inhalation toxicity (90 days),
rodents | 414 | B31 | Prenatal development toxicity (teratogenicity) | 415 | B34 | One generation reproduction toxicity | 416 | B35 | Two generation
reproduction toxicity | 417 | B36 | Toxicokinetics | 418 | B37 | Delayed neurotoxicity of organophosphates (acute) | 419 | B38 | Delayed neurotoxicity of organophosphates (28 day repeat dose) | 420 | B1 (bis) | Acute
oral toxicity, fixed dose method | 421 |
| Reproduction
/ developmental toxicity screening study | 422 |
| Combined repeat
dose with reproduction / developmental screening | 423 | B1 (tris) | Acute oral
toxicity, toxic class method | 424 |
| Neurotoxicity
in rodents | 425 |
| Acute oral
toxicity, up and down method | 426 |
| Developmental
neurotoxicity |
|
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| 451 | B32 | Carcinogenicity | 452 |
| Chronic toxicity | 453 | B33 | Combined chronic / carcinogenicity |
|
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| 471 | B13, B14 | Bacterial
reverse mutation (Ames) | 473 | B10 | In vitro mammalian chromosomal aberration | 474 | B12 | Mammalian erythrocyte micronucleus | 475 | B11 | Mammalian
bone marrow chromosomal aberration | 476 | B17 | In vitro mammalian cell gene mutation (mouse TK) | 477 | B20 | Sex-linked recessive lethal test in Drosophila | 478 | B22 | Rodent dominant lethal | 479 | B19 | In vitro sister chromatid exchange in mammalian
cells | 480 | B15 | Yeast gene mutation | 481 | B16 | Yeast mitotic recombination | 482 | B18 | Unscheduled DNA synthesis, mammalian
cells in vitro | 483 | B23 | Mammalian spermatogonial chromosome aberration | 484 | B24 | Mouse spot test | 485 | B25 | Mouse heritable translocation | 486 | B39 | Unscheduled DNA synthesis, liver cells in vivo |
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