Reproductive and Developmental Toxicity

Little Pro on 2016-04-25

Reproductive toxicity is defined as adverse effects of a chemical substance on sexual function and fertility in adult males and females, as well as developmental toxicity in the offspring.

Developmental toxicity pertains to adverse toxic effects to the developing embryo or fetus. Chemicals cause developmental toxicity by two ways. They can act directly on cells of the embryo or fetus causing cell death or cell damage, leading to abnormal organ development. A chemical might also induce a mutation in a parent's germ cell which is transmitted to the fertilized ovum. Some mutated fertilized ova develop into abnormal embryos.

The 3 basic types of developmental toxicity are shown in the table below.

Embryolethality Failure to conceive, spontaneous abortion, or stillbirth
Embryotoxicity Growth retardation or delayed growth of specific organ system
Teratogenicity Irreversible conditions that leave permanent birth defects in live off spring

Dose Descriptor for Reproductive/Developmental Toxicity

Typically, a NOAEL or LOAEL can be obtained from reproductive/developmental toxicity studies. NOAEL/LOAEL can be further used for quantitative risk assessment.

  • No Observed Adverse Effect Level (NOAEL): The highest exposure level at which there are no biologically significant increases in the frequency or severity of adverse effect between the exposed population and its appropriate control; some effects may be produced at this level, but they are not considered adverse effects. 
  • Lowest Observed Adverse Effect Level (LOAEL): The lowest exposure level at which there are biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control group. 
  • The units of NOAEL or LOAEL: mg/kg/bw/day or ppm.

GHS Classification Criteria for Reproductive Toxicity

Category Criteria
Category 1A Known human reproductive toxicants

Mixtures containing ≥ 0.1% or ≥ 0.3 % of such a substance.

Category 1B  Presumed human reproductive toxicants - largly based on animal studies

Mixtures containing ≥ 0.1% or ≥ 0.3 % of such a substance.

Category 2 Suspected human reproductive toxicant - Evidence from animal and/or human studies is limited

Mixtures containing ≥ 0.1% or ≥ 3 % of such a substance.

Effects on via lactation Effects on via lactation

Toxicants which may interfere with lactation or which may be present in breast milk and may cause harm to breast-fed children 

Mixtures containing ≥ 0.1% or ≥ 0.3 % of such a substance.

Testing Guidelines for Reproductive/Developmental Toxicity

  • Reproductive/Developmental Toxicity Screening Assay (OECD TG 421)
  • Prenatal developmental toxicity test (OECD TG 414)
  • Two-generation reproduction toxicity study (OECD TG 416)
  • Extended one-generation reproductive toxicity study (EOGRTS; OECD TG 443)

In Europe, OECD TG 443 is preferred to OECD 416 because EOGRTS provides more info while using much less animals.


You have learned the definition of reproductive toxicity and developmental toxicity, dose descriptor for developmental/reproductive toxicity (NOAEL and LOAEL), GHS classification criteria for reproductive toxicant and  testing guidelines.

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 Tags: Topics - CRAToxicology and Health Risk Assessment