Oral toxicity 28 days – OECD 407

OECD 407 testing evaluates the toxic effects of a substance administered orally daily for 28 days in rodents. It constitutes the first step in evaluating repeated-dose toxicity: where an acute toxicity test measures the consequences of a single exposure, OECD 407 highlights the effects that only appear with repetition—tissue accumulation, metabolic adaptation, progressive damage to a target organ.

This test identifies the organs affected, establishes a dose-response relationship and determines a NOAEL (no observed adverse effect dose), a central piece of data for any risk assessment and regulatory classification of a substance.

Objective of the analysis

The study pursues four complementary objectives:

• Identify the target organs of toxicity: liver, kidney, thyroid, hematopoietic system, nervous system.
• Characterize the dose-response relationship and determine the NOAEL as well as the LOAEL.
• To detect early functional effects, including neurobehavioral and endocrine effects.
• Assess the reversibility of the observed effects using a satellite group maintained without treatment after the exposure period.

The results also serve to calibrate the doses of a possible 90-day subchronic study, avoiding the selection of a high dose that would make the group uninterpretable.

OECD Methodology 407

The doses are selected so as to produce an observable toxic effect at the highest dose, without causing death or excessive suffering, and to generate no effect at the lowest dose.

Parameters evaluated

Clinical monitoring — daily observation of signs of toxicity, regular weighing, food and fluid consumption.

Functional observations — carried out in the fourth week: sensory reactivity to stimuli, grasping strength, motor activity.

Biological analyses — complete hematology and clinical biochemistry, performed at the end of exposure.

Endocrine parameters — the 2008 revision incorporated measures sensitive to endocrine function, with thyroid function being of particular concern. These parameters provide an early warning signal within a general toxicity study, but do not constitute a complete endocrine disruption test in themselves.

Necropsy and histopathology — weighing of organs followed by histopathological examination of an extensive list of tissues: brain, spinal cord, eye, stomach, intestines, liver, kidneys, adrenal glands, spleen, heart, thymus, thyroid, trachea, lungs, gonads and accessory sexual organs, bladder, lymph nodes, peripheral nerve, skeletal muscle, bone and bone marrow.

Interpretation and regulatory consequences

The NOAEL from the study is not just a report figure: it determines whether your substance will have to carry a STOT-RE (specific target organ toxicity, repeated exposure) hazard statement under the CLP regulation.

The CLP guideline values ​​are expressed for a 90-day study. For a 28-day study, they are multiplied by three :

Under REACH, a 28-day repeated-dose toxicity study becomes mandatory for quantities of 10 tonnes per year or more per registrant. The 100-tonne threshold triggers the requirement for a 90-day subchronic study.

OECD 407 or OECD 408: which one to choose?

This is the question that determines your budget and timeline, and the most costly arbitrage error we encounter.

Trial 407 is not an economical version of trial 408. Its reduced sample size and short duration give it less sensitivity: a negative result over 28 days does not allow us to conclude that there is no effect from prolonged exposure, and the authorities will not accept it as a substitute when the 90-day study is required by regulation.

OECD 407 is the right choice when your tonnage is between 10 and 100 tonnes per year, when you have no repeated dose data on the substance, or when you need to calibrate doses for an upcoming 90-day study.

Go directly to OECD 408 if your tonnage approaches or exceeds 100 tonnes per year: following up with a 407 and then a 408 costs more than ordering the subchronic study from the start.

For further information: OECD 408, 90-day subchronic oral toxicity study and our overview of subacute and subchronic toxicity trials.

Sectors and applications concerned

• Chemical industry — REACH registration of substances from 10 tonnes per year.
• Biocidal and phytopharmaceutical products — preparation of active substance approval dossiers.
• Nutraceuticals and food supplements — safety assessment of new ingredients.
• Animal feed and animal health — files on additives and premixes.
• Medical devices — biological evaluation within the framework of safety requirements.

The cosmetics sector is an exception: as animal testing is prohibited for the purposes of regulation 1223/2009, this test cannot be carried out for the purpose of assessing cosmetic safety in the European Union.

Why use YesWeLab?

A repeated-dose study requires a significant budget, several months of scheduling, and animal experimentation that no one wants to repeat. The choice of laboratory and the design of the study plan are not variables that can be adjusted.

We connect you with partner laboratories selected for their mastery of OECD guidelines. Our partners operate according to Good Laboratory Practices, a requirement for the study to be accepted in a regulatory dossier.

Our support begins with what determines the success of the study: choosing the exposure route, deciding between 28 and 90 days, and developing a dose plan tailored to your substance and your legal obligations. Our platform then centralizes your requests, quotes, and reports, with a single point of contact from start to finish.

Frequently Asked Questions

What is the expected timeframe for an OECD 407 test?

The exposure phase lasts four weeks, followed by preliminary analytical characterization, a possible dose-finding study, histopathology, and report writing. An overall timeframe of three to six months is realistic, depending on the complexity of the substance and the laboratory's availability.

Is test 407 sufficient for REACH registration?

It meets the requirement applicable to the 10 to 100 tonne per year range. Above 100 tonnes, the 90-day subchronic study becomes necessary and test 407 does not replace it.

Can this test be carried out by a route other than the oral route?

No. OECD 407 is specific to the oral route. For primarily respiratory exposure — powders, aerosols, volatile substances — the applicable guideline is OECD 412 over 28 days, or OECD 413 over 90 days.

Is the satellite group essential?

It is optional, but strongly recommended whenever an effect is expected at the high dose. Demonstrating that an adverse event regresses after fourteen days without exposure often carries significant weight in the final assessment of the risk.

See also

• Chronic toxicity study – OECD 452
• OECD acute toxicity tests: an overview of the guidelines
• Our complete catalogue of analyses