A category approach for reproductive effects of phthalates.
In regulatory toxicology, the experimental assessment of reproductive toxicity is one of the most costly endpoints to perform. Categorizing chemicals is an approach that can be used to reduce animal tests in risk assessments of chemicals, for example, via REACH (Registration, Evaluation, and Authorization of Chemicals). The category approach was tested for reproductive toxicity with a group of 10 ortho-phthalate esters, with different side chain lengths. Three ortho-phthalates were used for testing the category. Phthalates with side-chain lengths C4 to C6 that are commonly known to cause reproductive effects were included, as well as the recently discovered mechanism that indicates antiandrogenic effects. The differences in physicochemical properties, absorption rates, and metabolism between the phthalates investigated could not fully explain the difference in reproductive toxicity. It was concluded that phthalates with the alkyl side-chain length from C4 to C6 produce similar severe reproductive effects in experimental animals. It is expected that phthalates included in the tight boundaries of the proposed category would all show severe reproductive effects, especially the antiandrogenic effects. Further testing might not be needed for phthalates within these boundaries. If necessary, limited testing could focus on the critical endpoints. Detailed mechanistic information is needed on phthalates to apply the categories for regulatory toxicology.
Fabjan
Evelin
E
Utrecht University, Institute for Risk Assessment Sciences, Utrecht, The Netherlands.
Hulzebos
Etje
E
Mennes
W
W
Piersma
A H
AH
D000826:Animal Testing Alternatives; D000818:Animals; D006801:Humans; D010795:Phthalic Acids / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D021281:Quantitative Structure-Activity Relationship; D012098:Reproduction / Q000187:drug effects*; D018570:Risk Assessment / Q000379:methods*; D018675:Toxicity Tests / Q000379:methods*
D010795:Phthalic Acids