Help us gain a ban on the LD50

What is the LD50?

The LD50 stands for ‘Lethal Dose 50%’. It is the amount of a substance which is predicted to kill half of a group of animals.  The LD50 test sees groups of animals being given increasing doses of a substance and the number of animals who die is recorded. The LD50 was devised in 1927 as a way to compare toxic substances, to measure the relative ‘lethality’. If one compound was attacking the kidneys but another targeted the liver, the LD50 was devised as a way to compare the two toxic compounds using the same measure – death of an animal.

How many animals are used in LD50 tests?

In Great Britain, the ‘annual statistics’ provide data on the animals used in ‘scientific procedures’ . This report gives one figure for the number procedures conducted for both LD50 and LC50 tests. The LC50 attempts to measure the same endpoint as the LD50, but the LD50 typically uses the oral or dermal route (through the skin) whereas the LC50 is the lethal concentration which is fatal to half of the group of animals. This is the amount of the substance which animals have inhaled.

According to the most recent statistics for Great Britain, in 2023, there were 11,519 procedures for LC and LD50.  The latest statistics for the 27 EU Member States and Norway, state there were 18,560 uses for 2022.

Which laws require the LD50?

An FOI request to the Home Office clarified that, of the 11,519 procedures, 10 were for ‘legislation on industrial chemicals’ (to comply with UK REACH or REACH (EU)). The remaining 11,509 were for ‘legislation on medicinal products for veterinary use and their residues’ to comply with ‘individual Marketing Authorisations required by the legislation regulated by the VMD (UK) or EMA (EU) ‘

Which animals are used in the LD50?

The most recent statistics for Great Britain outline how 11,509 procedures involved mice and 10 involved rats. However, the OECD* Test Guidelines describe how the ‘preferred rodent species is the rat’. Also that female rats are expected to be used and they should be aged 8-12 weeks and not pregnant. They state that after dosing, the animals should be monitored.

What suffering do they undergo?

The OECD ‘Guidance Document on the Recognition, Assessment and Use of Clinical Signs as Human Endpoints for Experimental Animals Used in Safety Evaluation’ states: ‘Current OECD Test Guidelines generally state that animals that are moribund or obviously in pain and showing signs of severe and enduring distress should be humanely killed. The objective of the Guidance Document is to provide useful guidance and criteria for determining when an animal is in a moribund condition, or expected to become moribund, or experiencing significant pain and distress, and should therefore be euthanised.’.

It continues ‘The following clinical signs may indicate that an animal is experiencing significant pain and distress. Pain and distress should be alleviated with appropriate treatment if it does not interfere with the conduct or the objectives of the study, or the animal should be humanely killed if there are signs of severe pain and distress, such as: ‘abnormal vocalisation; abnormal aggressiveness; abnormal posture; abnormal reaction to handling; abnormal movements; self-induced trauma; open wounds or skin ulceration; difficulties in respiration; corneal ulceration (the cornea is very sensitive to pain, and according to some, stages that precede ulceration are painful, but not the ulceration itself); bone fractures; reluctance to move; abnormal external appearance; rapid weight loss or emaciation or severe dehydration; significant bleeding or any other factor that suggests that the animal may be in pain or distress.’

Scientific unreliability of the LD50-type tests.

We are not 70kg rodents! Data from animal experiments cannot be reliably translated to an effect on humans and this is also the case with the LD50. Not only do these tests seek to quantify an unlikely scenario – people do not accidentally drink huge quantities of a substance – animals are very different to humans. For many years, the LD50 has been criticised, not only for what the animals are subjected to, but also the data which are generated:

A paper from 2022 stated, that when evaluating the variability across acute oral toxicity studies in rats: ‘Conditional probability analyses reveal that replicate studies only result in the same hazard categorization on average at 60% likelihood.’ i.e. categorized the hazard presented by a substance incorrectly 40% of the time!

A paper from 2020, stated: ‘Rodent LD50 values have been used for almost a century as a measure of potential human toxicity from drugs and other chemicals. However, they have been found not, on the whole, to be good models for human toxicity.’

What can replace the animal-based LD50?

Clearly things have moved on since the LD50 was devised in 1927. There are NA-NAMs (non-animal new-approach methodologies) available, including AcutoX. AcutoX was developed by a UK laboratory to replace the oral LD50. The very simplest explanation of AcutoX is that instead of using animals to try to determine what is poisonous to humans, AcutoX exposes ethically sourced, human skin cells to increasing doses of a test chemical, to learn how damaged the cells are. The more damaged the cells, the more toxic the chemical.

What can you do as an MP?

• The government is due to publish a roadmap soon and we would like to see an immediate ban on the LD50, and other lethal dose animal tests as one of the short-term priorities of the roadmap.  A ban on such a cruel and unreliable test would align with the government’s manifesto and would see an end to a test which has been widely criticised and for which there is a non-animal replacement.
• Show your support for a ban on the LD50 and the transition towards human-relevant sciences by hosting a Westminster Hall debate.
• Table Oral or Written Questions for DEFRA, DSIT and the Home Office on the issue of the LD50 and its non-animal replacement tests. Animal Aid can provide support on all Parliamentary Questions – jessamy@animalaid.org.uk

* OECD is the ‘Organisation for Economic Co-operation and Development’. They describe themselves as ‘an international organisation that works with policy makers, stakeholders and citizens to establish evidence-based international standards and to find solutions to social, economic and environmental challenges.’