Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

Additional information

In vitro studies

Study design

Critical effect

Reference

NPE-2

Estrogen dependent cell proliferation assay

Estrogen sensitive human breast tumor MCF-7 and ZR-75 cells cultured in presence of fetal calf serum stripped of hormones. Estrogens overcome this inhibition and the proliferative effect measured. NPE-2 concentrations ranged from 0.1 nM to 10 µM.

NPE-2 at concentrations of ≤ 100 nM produced no estrogenic activity. NPE-2 at 1 and 10 μM produced proliferative response which at the higher concentration was similar to that produced by estradiol. 17β-estradiol was 1000 times more potent.

White R et al. (1994)

 

NPE-2

Transcriptional activity of ER directly

MCF-7 and chicken embryo fibroblasts (CEF) cells transfected with reporter gene pEREBLCAT and a mouse estrogen receptor.

NPE-2 stimulated transcription at culture concentrations of 1 and
10 μM.

White R et al. (1994)

 

In vivo studies

Study design

Critical effect

Reference

NPE-4

Female rats; oral exposure; up to 1000 mg/kg bw/d; 3 or 4 days;

Lack of uterine growth

Bakke D (2003)

NPE-9

Sperm study

Male mice; IP doses of 20, 40, 50, 60 mg/kg bw/d; 5 days

NOAEL > 60 mg/kg bw/d. No increase in frequency of morphologically abnormal sperm.

Buttar HS et al. (1986)

NPE-9

Female rats; oral exposure; up to 1000 mg/kg bw/d; 3 or 4 days

Lack of uterine growth

Bakke D (2003)

NPE-9

Humans- intravaginal application;
14 days; 125 mg/day (approximately 2

mg/kg bw/d)

No effects on blood chemistries or on hepatic function.

Malyk B (1981, 1984)

NP and NPEs are frequently discussed as endocrine disrupters. Due to pending disagreements with or interpretation of the definition of an endocrine disrupter, this view is, however, contentious. While NP and shorter chain NPEs undoubtedly show endocrine activity (particularly estrogenicity) in various in vitro and in vivo screening assays, this did for example not manifest itself in endocrine toxicity in Level 5in vivoassays for NP. The EU risk assessment report stated that the estrogenic activity of NP and NPEs with ethoxylation degrees ≤ 3 is approximately 3-6 orders of magnitude less than that of estradiol (EU RAR, 2002). Beyond an ethoxylation degree of 4 and with increasing degree of ethoxylation, the estrogenicity of nonylphenol ethoxylates disappears. In the absence of evidence of specific endocrine-mediated toxicity and the low level of estrogenicity of nonyl phenol ethoxylates, DNELs established based on chronic toxicity data for NPE are considered protective for the NPEO uses considered in this CSR for workers, professional users and consumers.