p-Tert-Butylphenol - UNEP Chemicals

OECD SIDS P-TERT-BUTYLPHENOL
p-t-Butylphenol induced structural chromosome aberration in CHL/IU cells with exogenous
metabolic activation by short term treatment in 6.5-12.0 % of cells at all concentrations studied
(OECD TG 473). This chemical also induced polyploidy with and without exogenous metabolic
activation system. The high incidences of polyploidy cell were observed after 48 hr continuous
treatment even though this chemical showed approximately 20% cytotoxicity (= 80 % cell growth
of control culture) at the two high concentrations. Based on these results, there is no doubt to
conclude that p-t-butylphenol induces both structural and numerical chromosome aberrations in
vitro. (MHW, Japan: 1996)
Two other chromosomal aberration tests were conducted. In one study, this chemical induced
neither clastogenicity nor polyploidy in rat lymphocytes by 20 or 30 hours treatment with and
without exogenous metabolic activation (OECD TG 473). (Safepharm Laboratories Ltd.: 1992b) In
another study, this chemical did not induce chromosomal aberration in rat liver epithelial-type cells
by 24 hours treatment without exogenous metabolic activation at the higher concentrations than the
above studies. As for polyploidy, it is not mentioned. (Dean et al.: 1985)
This chemical was not mutagenic to L5178Y mouse lymphoma cells at the thymidine kinase TK +/-
locus with and without exogenous metabolic activation. (Safepharm Laboratories Ltd.: 1992c)
Genetic toxicity in vivo
There was no available data for evaluation.
In summary, p-t-butylphenol showed clear negative results in several gene mutation tests but one
chromosomal aberration study indicated structural chromosome aberration and polyploidy with
metabolic activation in CHL/IU cells in spite of negative results in rat lymphocytes and rat liver
epithelial-type cells. Therefore, the possibility of in vivo genotoxicity should be considered.
h) Carcinogenecity
There was no sufficient carcinogenicity study but a two-stage promoting study was conducted.
N-Methyl-N’-nitro-N-nitrosoguanidine (MNNG) was used as an initiator. Male Fischer rats were
administered with or without MNNG at a dose of 150 mg/kg b.w. by stomach tube. After a week,
rats were given diet containing 15 g/kg p-t-butylphenol (calculated dose: 1.07 g/kg b.w.) or basal
diet for 51 weeks. (Hirose et al.: 1988)
Without MNNG, histological change observed in the forestomach was hyperplasia (14/15, 0/10 for
treated and control) but papilloma (1/14, 1/15), carcinoma in situ (0/15, 0/15) and squamous cell
carcinoma (0/15, 0/10) were no changes. No tumors were observed in the other organs examined
such as the esophagus and intestines.
With MNNG, grossly, small papillary or polypoid tumours were found in the forestomach of control
rats, while very large single or multiple tumor masses occupied the forestomach in treated rats.
Histological changes observed in the forestomach were hyperplasia (20/20, 19/19 for treated and
control rats, respectively), papilloma (19/20, 13/19), carcinoma in situ (8/20, 11/19), and squamous
cell carcinoma (15/20, 5/19). Squamous cell carcinoma in treated group was significant change,
compared to control group. Leiomyosarcoma was induced in one treated rat with MNNG treatment.
As histological change of the glandular stomach, adenocarcinoma of fundic region was only
observed in one of treated rats. No tumors were observed in the other organs examined such as the
esophagus and intestines.
UNEP Publications 77