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Key Event: 1521
Key Event Title
Decrease, Growth
Short name
Biological Context
| Level of Biological Organization |
|---|
| Individual |
Event Components
| Process | Object | Action |
|---|---|---|
| growth | multicellular organism | decreased |
Key Event Overview
AOPs Including This Key Event
| AOP Name | Role of event in AOP | Point of Contact | Author Status | OECD Status |
|---|---|---|---|---|
| Uncoupling of OXPHOS leading to growth inhibition 1 | AdverseOutcome | You Song (send email) | Open for citation & comment | WPHA/WNT Endorsed |
| Mitochondrial ATP synthase antagonism leading to growth inhibition (1) | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | |
| Mitochondrial ATP synthase antagonism leading to growth inhibition (2) | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | |
| Mitochondrial complex III antagonism leading to growth inhibition (1) | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | |
| Mitochondrial complex III antagonism leading to growth inhibition (2) | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | |
| Reduction in photophosphorylation leading to growth inhibition in aquatic plants | AdverseOutcome | Knut Erik Tollefsen (send email) | Under development: Not open for comment. Do not cite | |
| Uncoupling of OXPHOS leading to growth inhibition 3 | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | Under Development |
| Uncoupling of OXPHOS leading to growth inhibition via ATP depletion associated cell death | AdverseOutcome | You Song (send email) | Open for citation & comment | Under Development |
| Uncoupling of OXPHOS leading to growth inhibition 4 | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | Under Development |
| Uncoupling of OXPHOS leading to growth inhibition 5 | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | Under Development |
| Uncoupling of OXPHOS leading to growth inhibition 6 | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | Under Development |
| Energy deposition from Ra226 decay lowers oxygen binding capacity of hemocyanin | AdverseOutcome | Danielle Beaton (send email) | Under development: Not open for comment. Do not cite | |
| ROS leading to growth inhibition via LPO and cell death | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | Under Development |
| ROS leading to growth inhibition via protein oxidation and cell injury/death | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | |
| ROS leading to growth inhibition via protein oxidation and reduced cell proliferation | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | |
| ROS leading to growth inhibition via fatty acid oxidation and cell injury/death | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | |
| ROS leading to growth inhibition via fatty acid oxidation and reduced cell growth | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | |
| ROS leading to growth inhibition via oxidative DNA damage | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | |
| ROS leading to growth inhibition via protein oxidation and cell cycle disruption | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | |
| ROS leading to growth inhibition via fatty acid oxidation and reduced cell proliferation | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | |
| Qb protein binding leading to decrease, population growth via PSII inhibition | AdverseOutcome | Li Xie (send email) | Under development: Not open for comment. Do not cite | |
| ROS leading to growth inhibition via oxidative DNA damage and cell cycle disruption | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | Under Development |
| ROS leading to growth inhibition via oxidative DNA damage and cell death | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | Under Development |
| ROS leading to growth inhibition via LPO and decreased cell proliferation | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | Under Development |
| ROS leading to growth inhibition via protein oxidation and decreased cell proliferation | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | Under Development |
| ROS leading to growth inhibition via protein oxidation and cell death | AdverseOutcome | You Song (send email) | Under development: Not open for comment. Do not cite | Under Development |
| ROS leading to growth inhibition moduleated by the Keap1–Nrf2 antioxidant response | AdverseOutcome | Ying Wang (send email) | Under development: Not open for comment. Do not cite |
Taxonomic Applicability
Life Stages
| Life stage | Evidence |
|---|---|
| Embryo | High |
| Juvenile | High |
Sex Applicability
| Term | Evidence |
|---|---|
| Unspecific | High |
Key Event Description
Decreased growth refers to a reduction in size and/or weight of a tissue, organ or individual organism. Growth is normally controlled by growth factors and mainly achieved through cell proliferation (Conlon 1999).
How It Is Measured or Detected
Growth can be indicated by measuring weight, length, total volume, and/or total area of a tissue, organ or individual organism.
Revised version (non-endorsed, added by You Song, 02/09/2026)
Growth can be measured as a change in size, mass, biomass, length, area, volume, or growth rate of a tissue, organ, or whole organism over a defined exposure period. The appropriate measurement depends on the biological system, life stage, and test species.
At the organism level, growth is commonly assessed by measuring body weight, wet weight, dry weight, body length, standard length, total length, shell length, shoot height, root length, frond number, frond area, cell density, biomass, or relative growth rate. Growth inhibition is typically expressed as a statistically significant reduction relative to the control, or as an effect concentration causing a defined percentage reduction in growth, such as ECx, ErCx, EyCx, LOEC, NOEC, or benchmark concentration/dose values.
For unicellular algae and cyanobacteria, growth is commonly quantified from changes in biomass over time. Biomass may be estimated using direct cell counts, electronic particle counters, microscopy, optical density, fluorescence, chlorophyll-related measurements, or other validated biomass proxies. Growth inhibition is commonly calculated from average specific growth rate and yield.
For aquatic macrophytes such as Lemna spp., growth is typically quantified using frond number and at least one additional growth-related variable, such as total frond area, dry weight, fresh weight, or image-based area measurements. Digital imaging, flatbed scanning, stereomicroscopy, or automated image-analysis tools can be used to quantify frond area and related morphological endpoints.
For terrestrial plants, growth can be measured using seedling emergence, survival, shoot height, root length, fresh or dry biomass, leaf area, and visual signs of phytotoxicity such as chlorosis, necrosis, deformation, or delayed development. Measurements may be made using rulers or calipers, analytical balances, scanners, digital imaging, or plant image-analysis software.
For aquatic invertebrates, growth may be assessed using body length, body area, wet weight, dry weight, developmental stage, or size at defined time points. In small organisms such as Daphnia, body length is often measured from microscope or stereomicroscope images using calibrated image-analysis software.
For fish and amphibians, growth is commonly assessed using wet weight, dry weight, standard length, total length, snout–vent length, condition factor, developmental stage, and specific growth rate. Measurements may be obtained using balances, calipers, digital imaging, or stereomicroscopy, depending on organism size and life stage.
For mammals and other vertebrates in repeated-dose or reproductive/developmental toxicity studies, growth-related endpoints are typically evaluated using body weight, body-weight gain, food and water consumption, pup or offspring weight, litter growth, organ weight, and developmental landmarks. These endpoints are usually interpreted together with clinical observations, survival, pathology, and reproductive or developmental parameters.
Because growth is an integrative apical endpoint, measurement should be performed over a biologically appropriate time window and interpreted in relation to survival, developmental delay, nutritional status, reproductive output, and general toxicity. Direct measurements of organismal size, biomass, or growth rate provide the strongest evidence for this key event, whereas indirect indicators such as altered morphology, reduced condition factor, or reduced organ weight may provide supporting evidence depending on biological context.
Relevant OECD Test Guidelines include, but are not limited to:
-
OECD TG 201: Freshwater Alga and Cyanobacteria, Growth Inhibition Test. This guideline directly assesses inhibition of algal or cyanobacterial growth, typically using average specific growth rate and yield as response variables.
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OECD TG 208: Terrestrial Plant Test: Seedling Emergence and Seedling Growth Test. This guideline assesses effects on seedling emergence and early growth of terrestrial plants, including biomass, shoot height, and visible phytotoxic effects.
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OECD TG 211: Daphnia magna Reproduction Test. Although the primary endpoint is reproductive output, the test can provide chronic organism-level information relevant to population performance, and growth-related observations such as body size may be reported as supporting endpoints when included in the study design.
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OECD TG 212: Fish, Short-term Toxicity Test on Embryo and Sac-Fry Stages. This guideline assesses toxicity during early fish development from fertilized egg to the end of the sac-fry stage. Growth-related developmental observations may support interpretation of early-life-stage impairment.
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OECD TG 215: Fish, Juvenile Growth Test. This guideline directly evaluates effects on juvenile fish growth. Effects are expressed using growth rate, and concentration-response analysis can be used to estimate concentrations causing a defined percentage change in growth rate.
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OECD TG 221: Lemna sp. Growth Inhibition Test. This guideline directly assesses effects on vegetative growth of Lemna spp. using average specific growth rate and yield, commonly based on frond number and additional variables such as frond area or biomass.
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OECD TG 228: Determination of Developmental Toxicity to Dipteran Dung Flies. This guideline is relevant where chemical exposure affects development and growth-related performance in terrestrial invertebrates.
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OECD TG 241: Larval Amphibian Growth and Development Assay. This guideline evaluates growth and development in amphibians from fertilization through the early juvenile period.
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OECD TG 407: Repeated Dose 28-day Oral Toxicity Study in Rodents. This guideline includes body weight and food/water consumption measurements as part of the assessment of repeated-dose systemic toxicity.
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OECD TG 408: Repeated Dose 90-day Oral Toxicity Study in Rodents. This guideline includes body weight and related clinical observations as part of subchronic systemic toxicity assessment.
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OECD TG 416: Two-Generation Reproduction Toxicity. This guideline evaluates effects on reproduction as well as growth and development of offspring across generations.
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OECD TG 422: Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test. This guideline includes body weight, food/water consumption, offspring observations and measurements, and developmental parameters.
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OECD TG 443: Extended One-Generation Reproductive Toxicity Study. This guideline evaluates reproductive and developmental effects, including health, growth, development, and function of offspring following pre- and postnatal exposure.
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OECD TG 453: Combined Chronic Toxicity/Carcinogenicity Studies. This guideline includes body weight and body-weight gain as part of the evaluation of chronic systemic toxicity and carcinogenicity.
Domain of Applicability
Taxonomic applicability domain
This key event is in general applicable to all eukaryotes.
Life stage applicability domain
This key event is applicable to early life stages such as embryo and juvenile.
Sex applicability domain
This key event is sex-unspecific.
Regulatory Significance of the Adverse Outcome
Growth is a regulatory relevant chronic toxicity endpoint for almost all organisms. Multiple OECD test guidelines have included growth either as a main endpoint of concern, or as an additional endpoint to be considered in the toxicity assessments. Relevant test guidelines include, but not only limited to:
-Test No. 201: Freshwater Alga and Cyanobacteria, Growth Inhibition Test
-Test No. 208: Terrestrial Plant Test: Seedling Emergence and Seedling Growth Test
-Test No. 211: Daphnia magna Reproduction Test
-Test No. 212: Fish, Short-term Toxicity Test on Embryo and Sac-Fry Stages
-Test No. 215: Fish, Juvenile Growth Test
-Test No. 221: Lemna sp. Growth Inhibition Test
-Test No. 228: Determination of Developmental Toxicity to Dipteran Dung Flies (Scathophaga stercoraria L. (Scathophagidae), Musca autumnalis De Geer (Muscidae))
-Test No. 241: The Larval Amphibian Growth and Development Assay (LAGDA)
-Test No. 407: Repeated Dose 28-day Oral Toxicity Study in Rodents
-Test No. 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents
-Test No. 416: Two-Generation Reproduction Toxicity
-Test No. 422: Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test
-Test No. 443: Extended One-Generation Reproductive Toxicity Study
-Test No. 453: Combined Chronic Toxicity/Carcinogenicity Studies
References
Conlon I, Raff M. 1999. Size control in animal development. Cell 96:235-244. DOI: 10.1016/s0092-8674(00)80563-2.