Nonylphenol

Molecular Formula. C₁₅H₂₄O
M = 220.39
CAS No  25154-52-3
                84852-15-3
RTECS No SM5600000
Abbreviation. NP.

Synonym and Trade Name. 2,6-Dimethyl-4-heptylphenol; p-Nonylphenol, branched.

Composition. Mixture of monoalkyl phenols, predominantly p-substituted.

Properties. Thick, light yellow, straw color liquid with slight characteristic phenolic odor. Poorly soluble in water; soluble in alcohols.

Applications. Chemical intermediate for antioxidants for rubber and plastics, phenolic resins, rubber processing chemicals, nonionic and anionic surfactants, and polyvinyl chloride plasticizers. Antioxidant in the manufacture of polystyrene.

Migration Data. NP was released from plastic centrifuge tubes.

Acute Toxicity. LD₅₀ is 1.3 g/kg BW. Poisoning decreased weight gain, caused changes in the liver, hemorrhages.

Clastogenic Effects. Has been shown to have estrogenic properties. Estrogen-like activity of NP was observed in vitro. NP induced both cell proliferation and progesterone receptor in human estrogen-sensitive MCF7 breast tumor cells. It also triggered mitotic activity in rat endometrium.^1,2

Short-term Toxicity. Rats were exposed to 200, 650, or 2000 ppm NP in their diet for 3 months. The treatment caused a small decrease in BW and food consumption in the 2000 ppm dose group. No treatment-related clinical or histopathaological changes, including effects on endocrine organs, estrous cycling, or sperm measurements were noted up to 2000 ppm exposure. The NOAEL is considered to be 650 ppm NP in the diet (approximately 50 mg/kg B W)_.3

NP was shown to increase uterine weight in the standard uterotrophic assays. The oral NOEL ranged from approximately 50 to 100 mg/kg BW (Maoffat, 1996; Cervan, 1997).³

Embryo- and Gonadotoxicity. Sprague-Dawley rats were exposured to NP by treating via diet at 200, 650, and 2000 ppm. BW gain was reduced by 8 to 10% in the 650 and 2000 ppm groups. Vaginal opening was accelerated by approximately 2 days (650 ppm) and approximately 6 days (2000 ppm) in F₁, F₂, and F₃ generations. No consistent changes were seen in pup number, weight or viability, litter indices, or other functional reproductive parameters. Sperm indices were unchanged in F₀ and F, males. Testis and epididymis weights were unchanged. These data show that NP had limited effects on the reproductive system in the presence of measurable nephrotoxicity.⁴

Allergenic Effect. Caused skin sensitization reaction (Gaworski, 1979).

Chemobiokinetics. Only about 1.0% of the oral dose entered circulation.5⁴

Recommendations. Non-occupational exposure does not pose any risk for humans. Safe level in drinking water is likely to be 0.001 mg/l (ADI - 55 µg/kg BW).⁵

EU (1990). NP is available in the List of authorized monomers and other starting substances which may continue to be used for the manufacture of plastic materials and articles intended to come into contact with foodstuffs pending a decision on inclusion in Section A (Section B).

U.S. FDA (1998) approved the use of NP (1) in adhesives as a component of articles intended for use in packaging, transporting, or holding food in accordance with the conditions prescribed in 21 CFR part 175.105; (2) as a component of a defoaming agent intended for articles which may be used in producing, manufacturing, packing, processing, preparing, treating, packaging, transporting, or holding food in accordance with the conditions prescribed in 21 CFR part 176.200; as (3) a defoaming agent in the manufacture of paper and paperboard intended for use in packaging, transporting, or holding food in accordance with the conditions prescribed in 21 CFR part 176.210; and (4) in the manufacture of resinous and polymeric coatings for the food-contact surface of articles intended for use in producing, manufacturing, packing, processing, preparing, treating, packaging, transporting, or holding food in accordance with the conditions prescribed in 21 CFR part 175.300.

1. Soto, A. M., Justicia, H., Wray, J. W., and Sonnenschein, C., p-Nonylphenol: an estrogenic xenobiotic released from "modified" polystyrene, Environ. Health Perspect., 92, 167, 1991.

2. White, R., Jobling, S., Hoare, S. A., Sumpter, J. P., and Parker, M. G., Environmentally persistent alkylphenolic compounds are estrogenic, Endocrinology, 135, 175, 1994.

3. Cunny, H. C., Mayes, B. A., Rosica, K. A., Trutter, J. A., and Van Miller, J. P., Subchronic toxicity (90-day) study with para-nonylphenol in rats, Regul. Toxicol. Pharmacol., 26, 172, 1997.

4. Chapin, R. E., Delaney, J., Wang, Y., Lanning, L., Davis, B., Collins, B., Mintz, N., and Wolfe, G., The effects of 4-nonylphenol in rats: a multigeneration reproduction study, Toxicol, Sci., 52, 80, 1999.

5. Schlatter, C., Human health risk assessment for the xeno-oestrogen nonylphenol, Commun. to seminar Mechanistic and Regulatory Aspects of Risk Assessment, Jerusalem, January 11, 1998.

source: Sheftel, Victor O., Indirect Food Additives and Polymers: Migration and Toxicology.  Lewis Publishers, Boca Raton, 2000, 970.