http://www.rsc.org/pdf/ehsc/ld50.pdf
This Note was produced by a Working Party of the Environment, Health and Safety
Committee [EHSC] of the Royal Society of Chemistry with expert input from the
Society’s Occupational and Environmental Toxicology Group.
Environment, Health and Safety Committee [EHSC]
Note On
“ LD50 ” [ LETHAL DOSE 50% ]
This Note is designed to provide guidance to RSC members, though it
may also be useful to others with a particular interest in the subject. It
is an update of the original version which was issued in 1996.
The LD50 test and its variants were often undertaken as a result of
legislative requirements. These tests are now considered obsolete
and nowadays they would rarely if ever be performed in the United
Kingdom and many other countries. Internationally accepted
alternative tests have been developed. These use fewer animals and
“absence of evident toxicity”, rather than death, as their criterion. They
have been accepted by most regulators as valid alternatives to LD50
testing.
Nonetheless LD50 values are still quoted and enquiries received by the
Royal Society of Chemistry suggest that there is still a need for
information about their meaning. This Note aims to provide basic
information about LD50 but does not pretend to be a full or definitive
explanation. Readers are urged to obtain more detailed information if
this is required. Also this paper does not address the complex ethical
arguments surrounding the use of animal experiments to obtain LD50
and related data.
WHAT IS AN LD50?
“LD50” is an abbreviation for “Lethal Dose 50%.” It is sometimes also
referred to as the “Median Lethal Dose”. Although the LD50 is no
longer the only measure available for assessing the acute toxicity of
single doses of a substance, for historical reasons it is probably still
the most commonly cited measure.
The LD50 for a particular substance is essentially the amount that can
be expected to cause death in half (ie 50%) of a group of some
particular animal species, usually rats or mice, when entering the
animal’s body by a particular route. For example if the substance is
swallowed the figure is an ‘oral LD50’ whereas if its absorbed through
the skin it’s a ‘dermal LD50 ‘. LD50 figures are derived by mathematical
calculation from the results of tests on animals and hence should not
be regarded as biologically precise values. In general the amounts of
a substance required to kill animals from different species are
approximately related to the animals’ body weights. Therefore LD50
figures are usually reported in units of milligrams of the substance per
kilogram body weight for the animal species concerned.
The LC(t)50 (lethal concentration 50% for exposure time t) is a similar
and widely used measure for acute toxicity by inhalation. The LC(t)50 is
essentially the concentration of a substance that can be expected to
cause death in half [ie 50%] of a group of some particular species
when entering the body over the specified period of time. “LC(t)50” figures are
usually reported as
milligrams of the substance per cubic metre (or litre) of the atmosphere to
which the animal is
exposed for the specified time [ t ]. Generally, no account is taken of body
weight when comparing
values for different species.
Conventionally, the median lethal dose (MLD) is quoted as an LD50 when the
exposure is by
swallowing, skin contact or injection and as an LC(t)50 when exposure is by
breathing it in. When
quoting an LD50 the information must include the substance, the route of entry
and the animal
species. For example sodium cyanide has an oral LD50 of 15 mg/kg in rats. The
LC(t)50 of a
substance should state the duration [ t ] and species.
From the above it will be clear that the smaller the LD50 or LC(t)50 figure the
less the amount of the
substance needed to cause death.
In environmental toxicology the concentration of a substance which may be lethal
to wildlife may also
be expressed as LC(t)50 figures where the concentration [ c ] refers to the
concentration in the
relevant environmental medium. Perhaps the most common such use is LC(t)50 in
water to indicate
aquatic concentrations lethal to fish species. However LC(t)50 values can also
be given for a
substance in soil or other materials.
WHAT USE IS AN LD50 FIGURE?
Most users of a substance will need to know its toxicity to humans. It requires
expert judgement to
assess the relevance to humans of toxicity data derived from animals, including
LD50 figures. Under
European law the supplier of a chemical substance must assign it to a defined
toxic hazard category
using criteria set out in the legislation. The supplier may use LD50 figures,
among other data, when
deciding how to categorise the substance. Alternatively they can use a
categorisation system based
on a lack of “evident toxicity”.
Information from either procedure may be used to classify the acute lethal
hazard of a substance as
set out in the regulatory requirements (eg “very toxic if swallowed”). LD50 and
LC(t)50 values
themselves give no information about other, non-lethal, effects of the
substance, nor about
cumulative, chronic, reproductive or irritant effects.
The law requires that the supplier of a substance must classify and label it to
show the hazard
categories to which it belongs and provide a material safety data sheet (MSDS)
that gives, amongst
other things, the hazard categories that apply to the substance. The relevant
MSDSs will provide
much, but not all, of the information that must be taken into account when
making a COSHH
assessment and deciding on appropriate control measures for use in the
workplace. [Information will
also be needed on the circumstances of use and hence the likely exposures.] The
MSDS also
provides information needed when classifying wastes as “special wastes”.
Information on the LC(t)50
values can also be used when preparing safety reports for toxic major accident
hazards.
Some people have doubts about the ethics of using animals to obtain toxicity
data. The complex
ethical, legal and scientific issues involved are beyond the scope of this
paper. However,
toxicologists have developed new procedures that reduce the numbers of animals
used for acute
toxicity testing and they continue to seek alternative, non-animal based
procedures for assessing
acute toxicity.

FURTHER READING
· Hayes, A., 'Principles and Methods of Toxicology', Taylor and Francis, 4th Ed,
2001, Chapter 18
· Gad, S., 'Acute Toxicology Testing', The Telford Press, 1988, Chapter 7
· The British Toxicology Society, 'A New Approach to Classification of
Substances and
Preparations on the Basis of their Acute Toxicology', 1984, Human Toxicol., Vol
3, 85-92
This Note was prepared by a Working Party of the RSC Environment, Health and
Safety Committee
[EHSC]. The members of the Working Party were :
Dr G V McHattie [Co-chairman]
Dr I Wrightson [Co-chairman]
Mr T G R Farthing
Dr C L Grundy
Dr D H Lohmann
Mr D M Sanderson
Mr H G E Wilson
Mr P Whitehead
Mr R W Hazell [Secretary]
The Working Party gratefully acknowledges the expert assistance of the Society’s
Occupational and
Environmental Toxicology Group and of Dr P Illing in particular. However
responsibility
The Society is a registered Charity. Its Royal Charter obliges it to serve
the public interest by acting in an independent advisory capacity. In order to
meet this obligation the members of the EHSC are drawn from a wide range of
backgrounds and serve on the committee as individual experts and not as
representatives of their employer.
Wishing You Success & God's Blessing,
Zach Thompson
zcthompson@...

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