Anti-androgenicity can only be evaluated using a weight of evidence approach.
Regul Toxicol Pharmacol
; 68(1): 175-92, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24184466
ABSTRACT
Preputial separation (PPS) is a commonly used external marker for the onset of male puberty in experimental animal studies. While treatment-related delays in PPS may be indicative of specific anti-androgenic activity, impaired general growth also alters the onset of puberty. To differentiate between specific and non-specific effects on the age at PPS--and thereby evaluate the validity of the endpoint PPS-two-generation toxicity studies of 23 substances were evaluated. The 23 substances were assessed regarding anti-androgenicity using all available data and external assessments in a weight-of-evidence evaluation (WoE). Correlation of individual pup body weight with age at PPS revealed that delays in pubertal development coincided with reduced pup body weight. After comparison with the WoE assessment, we concluded that inclusion of body weight analysis into the PPS evaluation of each study was able to correctly identify three compounds which specifically induced delayed PPS and 16 which only showed unspecific changes. A further two compounds which might be categorized as anti-androgens based on delayed PPS, were correctly regrouped using our refined methodology. Based on this analysis and in comparison to the WoE evaluation, it was found, that caution should be exercised when using the endpoint PPS in hazard assessment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Maturidade Sexual
/
Antagonistas de Androgênios
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article