Calcium lignosulphonate: Re-evaluation of relevant endpoints to re-confirm validity and NOAEL of a 90-day feeding study in rats

Anette Thiel, William Braun, Maurice G. Cary, Jeffery A. Engelhardt, Dawn G. Goodman, William C. Hall, Annette Romeike, Jerrold M. Ward

Research output: Contribution to journalArticle

Abstract

A 90-day feeding study in Han/Wistar rats with calcium lignosulphonate was evaluated by the EFSA. The study was considered to be inadequate due to potentially impaired health status of the animals based upon a high incidence of minimal lymphoid hyperplasia in mesenteric/mandibular lymph nodes and Peyer's patches, and minimal lymphoid cell infiltration in the liver in all animals. The EFSA Panel further disagreed with the conclusion that the treatment-related observation of foamy histiocytosis in mesenteric lymph nodes was non-adverse and asked whether this observation would progress to something more adverse over time. A PWG was convened to assess the sections of lymph nodes, Peyer's patches and liver. In addition, all lymphoid tissues were re-examined. The clinical pathology and animal colony health screening data were re-evaluated. The question whether the foamy histiocytosis could progress to an adverse finding with increasing exposure duration was addressed by read-across. In conclusion, the animals on the 90-day feeding study were in good health, the study was adequate for safety evaluation, and the foamy histiocytes in the mesenteric lymph nodes were not considered adverse, but rather an adaptive response that was considered unlikely to progress to an adverse condition with time. The NOAEL was re-affirmed to be 2000 mg/kg bw/d.

Original languageEnglish (US)
Pages (from-to)286-299
Number of pages14
JournalRegulatory Toxicology and Pharmacology
Volume66
Issue number3
DOIs
StatePublished - Aug 2013
Externally publishedYes

Fingerprint

No-Observed-Adverse-Effect Level
Rats
Animals
Lymph Nodes
Histiocytosis
Calcium
Peyer's Patches
Health
Liver
Clinical Pathology
Histiocytes
Lymphoid Tissue
Pathology
Infiltration
Health Status
Hyperplasia
Wistar Rats
Screening
Observation
Lymphocytes

Keywords

  • Histiocytosis
  • Ligninsulphonate
  • Lignosulphonate
  • PWG

ASJC Scopus subject areas

  • Toxicology

Cite this

Calcium lignosulphonate : Re-evaluation of relevant endpoints to re-confirm validity and NOAEL of a 90-day feeding study in rats. / Thiel, Anette; Braun, William; Cary, Maurice G.; Engelhardt, Jeffery A.; Goodman, Dawn G.; Hall, William C.; Romeike, Annette; Ward, Jerrold M.

In: Regulatory Toxicology and Pharmacology, Vol. 66, No. 3, 08.2013, p. 286-299.

Research output: Contribution to journalArticle

Thiel, Anette ; Braun, William ; Cary, Maurice G. ; Engelhardt, Jeffery A. ; Goodman, Dawn G. ; Hall, William C. ; Romeike, Annette ; Ward, Jerrold M. / Calcium lignosulphonate : Re-evaluation of relevant endpoints to re-confirm validity and NOAEL of a 90-day feeding study in rats. In: Regulatory Toxicology and Pharmacology. 2013 ; Vol. 66, No. 3. pp. 286-299.
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