{"doi":"10.1016/j.reprotox.2007.04.068","title":"A retrospective analysis of the two-generation study: What is the added value of the second generation?","abstract":null,"journal":"Reproductive Toxicology","year":2007,"id":588877,"datarank":8.669735511128337,"base_score":4.2626798770413155,"endowment":4.2626798770413155,"self_citation_contribution":0.6394019815561974,"citation_network_contribution":8.03033352957214,"self_endowment_contribution":0.6394019815561974,"citer_contribution":8.03033352957214,"corpus_percentile":null,"corpus_rank":null,"citation_count":70,"citer_count":63,"citers_with_citation_signal":55,"citers_with_endowment":55,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1506653,"name":"Betty C. Hakkert","orcid":null,"position":1,"is_corresponding":false},{"id":1373780,"name":"Wout Slob","orcid":null,"position":2,"is_corresponding":false},{"id":1506654,"name":"Theo Vermeire","orcid":null,"position":3,"is_corresponding":false},{"id":1506655,"name":"Aldert H. Piersma","orcid":null,"position":4,"is_corresponding":false},{"id":900689,"name":"Gemma Janer","orcid":"0000-0001-6229-425X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A retrospective analysis of the two-generation study: What is the added value of the second generation?","abstract":"Increasing pressure is exerted by some stakeholders to reduce the two-generation study to a one-generation study, a measure that would considerably reduce the number of animals and other costs involved in these lengthy studies. The present study retrospectively evaluates 176 multi-generation studies to assess potential differences between the first and the second generation, both in terms of the types of effects observed and in terms of the effective doses. All substances classified as reproductive toxicants by the Directive 92/32/EEC or considered as toxic to fertility by the California EPA for which we found a multi-generation study were included (n=58 studies). The second generation in the two-generation studies considered affected neither the overall NOAEL nor the critical effect. Therefore, it had no impact on the ensuing risk assessment, nor on classification and labeling. However, several substances did show an increased sensitivity of the F(1) adults in comparison to the P(0). These results support the proposal of replacing the current two-generation study by a one-generation study with a more extensive assessment of parameters at F(1) adulthood.","is_dataset_classified":null,"base_score":4.2626798770413155,"endowment":4.2626798770413155,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17572063","pmcid":null,"openalex_id":"https://openalex.org/W2008106611","authors":[],"funders":[],"total_grants":0,"fwci":6.5431,"citation_percentile":0.97319846,"influential_citations":0,"citation_trend":[{"year":2012,"count":4},{"year":2013,"count":3},{"year":2014,"count":5},{"year":2015,"count":3},{"year":2016,"count":9},{"year":2017,"count":3},{"year":2018,"count":3},{"year":2019,"count":1},{"year":2020,"count":2},{"year":2023,"count":1},{"year":2024,"count":2}],"oa_status":"closed","license":"https://www.elsevier.com/legal/tdmrep-license","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0890623807001621?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0890623807001621?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.reprotox.2007.04.068","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/17572063","host_type":"repository"},{"url":"https://rivm.openrepository.com/handle/10029/641923","host_type":"repository"}],"fields_of_study":["Effects and risks of endocrine disrupting chemicals","Carcinogens and Genotoxicity Assessment","Genetically Modified Organisms Research"],"mesh_terms":["Animals","Body Weight","Dose-Response Relationship, Drug","Environmental Pollutants","Epididymis","Female","Fertility","Germ Cells","Litter Size","Male","Embryo Implantation","Pesticides","Population Dynamics","Reproduction","Retrospective Studies","Spermatozoa","Time Factors","Risk Assessment","No-Observed-Adverse-Effect Level","Toxicity Tests, Chronic","Growth and Development"],"keywords":["First generation","Generation time","Third generation","Directive","Value (mathematics)","Medicine","Toxicology","Statistics","Environmental health","Mathematics","Computer science","Biology","Population","Telecommunications"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-22T23:38:06.242367Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}