4-nitrophenol

Endpoint summary

Additional information

According to regulation (EC) 1907/2006 of the European parliament and the council of 18 December 2006 (Article 18),

repeated dose toxicity on transported isolated intermediates needs to be described, if data on this endpoint are available,

but no chemical safety assessment is necessary. Therefore, publicly available data on repeated dose toxicity of 4 -Nitrophenol

is summarized in the following, but no key values were defined for 4 -Nitrophenol.

In the Concise International Chemical Assessment Document (CICAD) as well as in the BUA report, information on repeated dose toxicity of PNF is reviewed.
CICAD:
In a 13-week gavage study, Sprague-Dawley rats (20 per sex per dose group) were given 0, 25, 70, or 140 mg 4-nitrophenol/kg bwin water 
5 days/week. Premature deaths were seen in animals dosed at 70 and 140 mg/kg bw (1 male and 1 female at 70 mg/kg bwand 15 males and 
6 females at 140 mg/kg bw); these were usually preceded by clinical signs, including pale appearance, languid behaviour, prostration, wheezing, 
and dyspnoea, shortly after dosing. The histopathological examination of these animals revealed minimal to moderately  severe congestion in the 
lung, liver, kidney, adrenal cortex, and pituitary; in surviving animals, no treatment-related changes compared to controls were report ed. Only a 
provisional NO(A)EL based on changes in liver, kidneys, and lungs of 25 mg/kg bw can be derived from this study (Hazleton Lab., 1989).Dermal 
application of 4-nitrophenol to Swiss-Webster mice (10 per sex and dose group; given 0, 22, 44, 88, 175, or 350 mg/kg bw in acetone, 3 times per
 week over 13 weeks) resulted in dose-dependent mortality as well as skin irritation/inflammation and necrosis at > 175 mg/kg bw (cited from NTP).
In a long-term study with Swiss-Webster mice (50 per sex per dose group), 4-nitrophenol in acetone was applied to the interscapular skin at doses of 
0, 40, 80, or 160 mg/kg body weight, 3 days/week for 78 weeks. At termination of the study, the survival rates were 29/60, 17/60, 26/60 and 24/60 for 
males and 35/60, 26/60, 33/60 and 27/60 for females. The increased mortality after 60 weeks was due to a generalized amyloidosis (the severity 
of the amyloidosis  was similar among dosed and control animals) and secondary kidney failure. The final mean body weights of the dosed animals 
were similar to those of the controls. NTP (1993) stated that there were no substance-related neoplastic or non-neoplastic effects associated with the 
dermal administration of 4-nitrophenol and that there was no evidence of a carcinogenic activity of the substance in male or female mice.

BUA report:
Administration of 0, 62.5, 125, 250, 500 or 1000 mg/kg bw/d of 4 -nitrophenol in corn oil to CD-1 mice over a period of 8 days by gavage resulted in an 
LD50 value of 626 mg/kg bw with a 95% confidence interval of 456 -895 mg/kg bw (Plasterer et al, 1985).In a 28 -day subchronic toxicity test according 
to OECD guidelines, male and female Sprague-Dawley rats (10/dose group) were administered daily dosages of 70, 210 or 630 mg 
4 -nitrophenol/kg/d by gavage (Andrae et al, 1981). According to the report of Leuschner, 1980, motoric inhibition, which lasted for up to 2 hours, 
was seen in the animals of the two highest dosage groups immediately after administration. One male of the middle dose group and 4 males and 
6 females of the highest dose group died. In the lowest dose group, pale liver and fatty degenreation of liver were observed; the latter of which was 
also seen at 210 mg, but due to the early mortality not at the highest dose group. All of the animals which died prematurely, showed vascular 
congestion. In addition, nephrosis, testicular athrophy, inhibition of spermatogenesis and follicular atresia in the ovaries were seen. No NOEL 
can be derived from the study, as at the lowest dosage group tested, effects of treatment were observed. It is pointed out, that the dosage levels 
chosen were at leasdt in part in the range of acute toxicity.