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Description of key information

A primary dermal irritation study according OECD 404 was conducted on Small White Russian Rabbits (Hüls 0584). Iso-nonylphenol was considered corrosive based on the induction of necrosis after 60 min exposure. A second OECD 404 study was conducted by HRC (1987) using New Zealand White strain rabbits. NP was found to be irritating but damages were not irreversible. This result contradicts the Hüls 0584 report. The EU Risk Assessment Report (2002) cites additional studies of variable reliability and variable results.

In a primary eye irritation study according OECD 405 (Hüls 0585) conducted in Small White Russian Rabbits Nonylphenol was considered corrosive to the eye based on irreversible damage.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation has been investigated in a number of studies both, using guidelines equivalent to OECD 404 and non-standard methods. In a primary dermal irritation study, three female Small White Russia rabbits were dermally exposed to 0.5 ccm undiluted isononylphenol for 4 hours to 6 sq.cm skin. In this study, isononylphenol was found to be corrosive based on the induction of necrosis after 60 min exposure (Hüls 0584). A second OECD 404 study was conducted by HRC (1987) using New Zealand White strain rabbits. NP was found to be irritating but damages were not irreversible.

Union Carbide (1992) tested "nonylphenol S" and "nonylphenol RNH" and found severe irritation including full-thickness necrosis and ulceration within 24 hours of either a 1 or 4 hour application. In a GLP guideline study (EniChem 1992), all rabbits showed skin reactions described as erythema grade 2 and oedema grade 3 at 24, 48 and 72 hours, progressing to eschar formation grade 4 at termination of the study on day 8, suggesting corrosion.
Another GLP guideline study conducted by Berol Kemi AB (1987) reports severe but reversible skin reactions, graded as 2 for erythema and 1-3 for oedema at the 24-, 48- and 72-hour. Several other studies show less severe effects. Gaworski et al.,(1979) reported no signs of irritation following a 24-hour application of 0.5 ml nonylphenol to the skin of rabbits. ICI (1982) reported sensitivity to touch, severe erythema and thickening, wrinkling and hardening of the skin at the application site immediately after a 24-hour contact with 0.1 ml nonylphenol in a rat study. In an earlier ICI (1979) study a single applications of nonylphenol from two different sources caused slight erythema together with wrinkling and thickening of the skin at the application site in rats; the amount of test substance applied and contact time were not reported.

ICI Chemicals and Polymers Ltd (1995) investigated the sensory irritation potential of Nonylphenol using saturated vapour concentration (3636 mg/m3,400 ppm) and one tenth saturated vapour concentration (267 mg/m3,30 ppm) [Section 7.9.3]. Groups of five female CD-1 mice were exposed, nose only, to each concentration and the respiration rate was monitored using pressure plethysmography. The duration of exposure was not reported. The proportion of liquid particulate material in the test atmospheres was determined, and found to be approximately 1% of the nominal concentration, an amount considered unlikely to have a significant influence on the results. At 3636 mg/m3a mean respiratory rate depression of about 25% was found during exposure. However, at 267 mg/m3there were no changes in the respiratory rate. These results suggest that nonylphenol can cause mild sensory irritation to the respiratory tract at high exposure levels.

 

The results of these animal studies suggest that the irritant properties of nonylphenol may vary, depending on the source of the test sample. However, since full thickness destruction or skin necrosis were seen in some studies it is reasonable to consider nonylphenol to be corrosive on contact with skin.

 

According Regulation (EC) No 1272/2008 skin corrosive substances shall be considered as leading to serious damage to the eyes as well (Category 1). This is supported by a primary eye irritation study. 0.1 cm³ of ≥ 98 % (w/w) iso-Nonylphenol (undiluted) was instilled into the conjunctival sac of the right eye of 3 female Small White Russian rabbits for 72 hours. The irritation index was 38,42/110. Irritation was irreversible. In this study, nonylphenol is corrosive to the eye.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Effect level: empty Endpoint conclusion: Adverse effect observed

Justification for classification or non-classification

Nonylphenol is corrosive to the skin (Category 1B) based on the induction of necrosis after 60 min exposure. According Regulation (EC) No 1272/2008 skin corrosive substances shall be considered as leading to serious damage to the eyes as well (Category 1). This classification is supported by a primary eye irritation study.