Phenol

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

In the EU-RAR (2006) toxicity to reproduction was documented in Section 4.1.2.9. Data on fertility impairment (page 128ff) indicated no impairment of reproductive capability (but systemic toxicity in parenteral animals) even at a dose of 5000 mg/l in a drinking water study.

 

Phenol was investigated for effects on reproductive performance and fertility in a valid two generation reproductive toxicity study in Sprague-Dawley rats (Ryan et al., 2001; see robust study summary in IUCLID Section 7.8.1). P1 and F1 rats were exposed via the drinking water to 0, 200, 1000, 5000 mg/l (calculated to be 0, 14, 70, and 310 mg/kg bw/day for males and 0, 20, 93, and 350 mg/kg bw/day for females in both generations). At 5000 mg/l, a dose level which led to reduced water intake and consequently decreased body weight and body weight gain in the animals, no impairment of reproductive capability and fertility was detected. However, postnatal litter survival and offspring body weights at birth and during the period of lactation were reduced at 5000 mg/l in F1 and F2 generation. Furthermore, signs of impaired offspring development were observed in F1 like delay in sexual maturation. However, all effects in progeny were found at a dose level that clearly indicated systemic toxicity in parental animals. From the findings of reduced water intake (which is considered secondary to an aversion to the flavour of phenol), body weight and organ weight impairment in the P0 and F1 generation at 5000 mg/l a NOAEL for general, systemic toxicity of 1000 mg/l (corresponding to 70 mg/kg bw/day for males and 93 mg/kg bw/day for females) can be derived. The observed impairment of development at the higher concentration levels may be considered to be secondary to the overall reduced state of health at 5000 mg/l.

 

In a long-term drinking water study in rats and mice mammary gland, prostate or uterus, testis or ovary were examined by histopathological methods and no effects on reproductive organs were detected (NIH, 1980; see IUCLID Section 7.7).

 

The reports from an early study (Heller and Purcell, 1938) are considered not to be valid for assessment due to insufficient documentation.

Short description of key information:
Reported effects in a two generation reproduction toxicity study were considered secondary to water avoidance due to an flavour aversion to phenol. The NOAEL of phenol in drinking water is 1000 mg/l (70 mg/kg bw/day for males and 93 mg/kg bw/day for females), the LOAEL is 5000 mg/l. No impairment of reproductive capability and fertility was found at 5000 mg/l. There is no need for classification and labelling.

Effects on developmental toxicity

Description of key information

In gavage studies phenol was evaluated for maternal and developmental toxicity in valid teratology studies with rats and mice. Data on developmental toxicity are also available from a 2 generation drinking water study. Oral exposure to phenol resulted in growth retardation of the offspring and impaired postnatal viability and growth. However, these effects were found at dose levels that were also toxic to the dams. Therefore, phenol is not considered to have specific embryo- or fetotoxic effects. The NOAEL for developmental toxicity is 93 mg/kg bw/day. There is no need for classification and labelling.

Additional information

From the assessment of the data from the teratology studies with mice and rats it was concluded in the EU-RAR (2006; page 131ff) that phenol does not seem to have any specific embryotoxic or teratogenic properties.

In a valid developmental study (Jones-Price et al., 1983; see robust study summary in IUCLID Section 7.8.2) CD-1 mice received via gavage 0, 70, 140, and 280 mg/kg bw daily during gestation days (GD) 6 -15. Maternal toxicity was observed at the high dose level including increased mortality, reduced body weight and reduced weight gain as well as clinical signs like tremor and ataxia. No effects were detected on prenatal mortality or the incidence of teratogenic effects in any of the dosed groups, except for an increase in cleft palate at the highest dose level, a malformation for which the CD-1 mouse is predisposed under conditions of maternal stress. At 280 mg phenol/kg bw the mean gravid uterine weight and the average fetal body weight per litter was statistically significantly reduced. In this study development effects were detected at dosages of 280 mg/kg bw/day that also led to maternal toxicity. The NOAEL for developmental and maternal effects is 140 mg/kg bw/day.

 

Pregnant Sprague-Dawley rats received on gestation day 6 -15 via gavage 0, 60, 120, 360 mg/kg bw. Dams of the high dose group revealed excess salivation and respiratory distress (tachypnea) as well as significantly reduced maternal body weight and body weight gain at 360 mg/kg bw/day. At 120 mg/kg bw/day also statistically significant effects on body weight gain were detected. No maternal effects were recorded in the low dose group. No developmental effects were reported except slight (but significant) reduction of fetal body weight and delayed ossifications (in metatarsals) at 360 mg/kg bw/day. From the results of this study the NOAEL for maternal toxicity is 60 mg/kg bw/day and the NOAEL for developmental toxicity is 120 mg/kg bw/day (Proctor&Gamble, 1997; see robust study summary in IUCLID Section 7.8.2).

 

In the 2 generation reproduction study described above (Ryan et al., 2001; see also IUCLID Section 7.8.1) pre- and postnatal developmental effects as well as maternal toxicity have been reported at 5000 mg/l, the NOAEL was 1000 mg/l corresponding to mean daily intake of 93 mg/kg bw/day for the dams.

Justification for classification or non-classification

The available data indicated that classification is not warranted for developmental toxicity and teratogenicity as well as for reproduction.