The Threshold of Toxicological Concern for prenatal developmental toxicity in rats and rabbits

B. van Ravenzwaay, X. Jiang, T. Luechtefeld, Thomas Hartung

Research output: Contribution to journalArticle

Abstract

The Threshold Toxicological Concern (TTC) is based on the concept that in absence of experimental data reasonable assurance of safety can be given if exposure is sufficiently low. Using the REACH database the low 5th percentile of the NO(A)EL distribution, for prenatal developmental toxicity (OECD guideline 414) was determined. For rats, (434 NO(A)ELs values) for maternal toxicity, this value was 10 mg/kg-bw/day. For developmental toxicity (469 NO(A)ELs): 13 mg/kg-bw/day. For rabbits, (100 NO(A)ELs), the value for maternal toxicity was 4 mg/kg-bw/day, for developmental toxicity, (112 NO(A)EL values): 10 mg/kg-bw/day. The maternal organism may thus be slightly more sensitive than the fetus. Combining REACH- (industrial chemicals) and published BASF-data (mostly agrochemicals), 537 unique compounds with NO(A)EL values for developmental toxicity in rats and 150 in rabbits were evaluated. The low 5th percentile NO(A)EL for developmental toxicity in rats was 10 mg/kg-bw/day and 9.5 mg/kg-bw/day for rabbits. Using an assessment factor of 100, a TTC value for developmental toxicity of 100 μg/kg-bw/day for rats and 95 μg/kg-bw/day for rabbits is calculated. These values could serve as guidance whether or not to perform an animal experiment, if exposure is sufficiently low. In emergency situations this value may be useful for a first tier risk assessment.

Original languageEnglish (US)
Pages (from-to)157-172
Number of pages16
JournalRegulatory Toxicology and Pharmacology
Volume88
DOIs
StatePublished - Aug 1 2017

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Toxicology
Toxicity
Rats
Rabbits
Mothers
Agrochemicals
Fetus
Emergencies
Databases
Guidelines
Industrial chemicals
Safety
Risk assessment
Animals
Experiments

Keywords

  • Developmental toxicity
  • NOAEL
  • Rabbit
  • Rat
  • TTC

ASJC Scopus subject areas

  • Toxicology

Cite this

The Threshold of Toxicological Concern for prenatal developmental toxicity in rats and rabbits. / van Ravenzwaay, B.; Jiang, X.; Luechtefeld, T.; Hartung, Thomas.

In: Regulatory Toxicology and Pharmacology, Vol. 88, 01.08.2017, p. 157-172.

Research output: Contribution to journalArticle

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