Toxicological Evaluation and Limit Values for Nonylphenol, Nonylphenol Ethoxylates, Tricresyl, Phosphates and Benzoic Acid

2. Toxicokinetics

2. Toxicokinetics
2.1 Absorption, distribution
2.2 Elimination
2.3 Toxicological mechanisms

Inhalation

No data have been found for either NP or NPE.

However, on the basis that NP appears to be readily absorbed from the gastrointestinal tract and in view of its high partition coefficient (approximately 4.5) (EU-RAR 1998) it is assumed that significant absorption via the inhalation route will occur.

Oral intake

Knaak et al. (1966) administered ¹⁴C-labelled nonylphenol, ¹⁴C-labelled nonylphenol ethoxylate (9 ethylene oxide units), and ¹⁴C-labelled polyoxyethylene, orally or intraperitoneally to male rats (4 rats per group). Daily urine and faeces samples were collected and analysed for ¹⁴C over a 7-day period, while exhaled CO₂ samples were collected and analysed for ¹⁴C over a 4-day period. For NP and NPE, a similar pattern of excretion was found. About 70% of the administered radioactivity was excreted via faeces, and 20% via the urine. Most of the radioactivity was excreted within 4 days after administration. No radioactivity was detected in exhaled CO₂. The main part of the urinary NP and NPE metabolites were found to be acidic and were believed to be glucuronic acid conjugates of nonylphenol.

The toxicokinetic behaviour of radiolabelled nonylphenol was investigated in two male volunteers, aged 29 and 58 years (Müller 1997 - quoted in EU-RAR 1998). Ring ¹⁴C-labelled nonylphenol was administered to one volunteer as a single oral dose of 5 mg (66 µg/kg bodyweight) and to the second volunteer as a single intravenous dose of 1 mg (14 µg/kg). Blood, urine and faeces were collected from the first volunteer at intervals for up to 56 hours after administration. Blood samples only were taken from the second volunteer, for up 24 hours. The biological samples were analysed for nonylphenol and nonylphenol conjugates (glucuronide and sulphate) by gas chromatography/mass spectrometry (it is not clear why radiolabelled nonylphenol was used). Recovery experiments using spiked blood, urine, faeces and adipose tissue samples confirmed the efficiency of the analytical extraction technique. Following oral administration, the concentration of nonylphenol and nonylphenol present as conjugates in the blood both peaked at about 1 hour; peak concentration of nonylphenol present as a conjugate was 86 ng/g blood, which was some 100-fold greater than that of unconjugated nonylphenol. For intravenous administration, the highest concentrations of nonylphenol, at 0.6 and 0.2 ng/g blood for unconjugated and conjugated compound, respectively, were seen at the first sampling point of 30 minutes; at all time points the concentrations of unconjugated and conjugated nonylphenol were of the same order of magnitude. For both the oral and intravenous routes, the time courses of blood concentration were indicative of an initial phase of distribution from the blood to a second compartment (presumably the lipid compartment) followed by a slower elimination phase. Comparison of the AUCs for the oral and intravenous routes suggested that oral bioavailability of unconjugated nonylphenol was about 20%. Analysis of the urine samples showed that about 10% of the oral dose was excreted in urine as unconjugated or conjugated nonylphenol, most of which was eliminated within eight hours. Only about 1.5% of the oral dose was excreted in the faeces during the 56-hour collection period.

Müller (1997 - quoted in EU-RAR 1998) also measured the nonylphenol content of 25 samples of adipose tissue taken at autopsies of persons thought to have had no occupational exposure to alkyl phenols. The measured tissue concentrations were all within the range of background contamination found in the analytical "blank" samples. The author indicated that all reasonable precautions were taken to minimise contamination during analysis.

Dermal contact

No data have been found. On the basis that nonylphenol appears to be readily absorbed from the gastrointestinal tract, and in view of its high partition coefficient, and since dermal LD₅₀-values have been determined for NP and NPE, it is assumed that significant absorption via the dermal route will occur. The limited dermal toxicity data that are available indicate that the oral and dermal LD₅₀-values for nonylphenol are similar.

See above

2.3 Toxicological mechanisms

There are no data on toxicological mechanisms for either NP or NPE with the exception of oestrogenic effects of NP. NP is believed to interact directly with the oestrogen receptor (Odum et al. 1997).