p-Tert-Butylphenol - UNEP Chemicals

OECD SIDS P-TERT-BUTYLPHENOL
Ito et al. (1986) showed BHA enhanced forestomach carcinogenesis initiated in rats by N-methyl-
N'-nitro-N-nitrosoguanidine or N-methylnitrosourea (MNU) and enhanced urinary bladder
carcinogenesis initiated by MNU or N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). BHT (2,6-bistert-butyl-methoxyphenol)
(CAS 128-37-0) promoted urinary bladder carcinogenesis initiated by
BBN or MNU and thyroid carcinogenesis initiated by MNU. Hirose et al. (1988) investigated
promoting effects of phenolic compounds on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)initiated
forestomach and glandular stomach carcinogenesis in male F344 rats. The incidence of
squamous cell carcinoma of the forestomach in MNNG-treated animals was significantly elevated
by catechol (2-hydroxyphenol) (CAS 120-80-9), TBMP and p-t-butylphenol.
4.3 Initial Assessment for Human Health
Acute toxicity of p-t-butylphenol is low via any administration routes. This chemical is considered
as an irritant to the skin, eyes and respiratory tract. Animal experiment (OECD TG 406) indicated
no skin sensitization but some positive results were reported in human patch tests. The
depigmentation was observed on the skin of various animals and human exposed to this chemical.
The depigmentation was observed on the skin of various animals and human exposed to this
chemical. This change was likely induced by exposure to this chemical not only via direct contact but
also via inhalation or ingestion route. In OECD combined repeat dose and
reproductive/developmental screening toxicity test of rats by gavage, this chemical showed neither
systemic toxicity nor reproductive toxicity even at the highest dose of 200 mg/kg/day. Although a
noisy respiratory sound was induced in a few females at 200 mg/kg/day, it is considered due to
irritation of this chemical to respiratory tract. In a dose-finding study (14 days), this became to
respiratory difficulty, especially at 1,000 mg/kg/day. In other studies by the longer and higher
exposure in diet, forestomach hyperplasia was induced. This chemical showed negative result in
gene mutation test. In chromosomal aberration study, CHL/IU cells indicated structural
chromosome aberration and polyploidy with metabolic activation although two other studies in rat
lymphocytes and in rat liver epithelial-type cells showed negative results. As a two-stage
carcinogenicity study indicated this chemical has promoting activity of forestomach carcinogenesis
(papilloma and squamous carcinoma) in rats treated with N-methyl-N’-nitro-N-nitrosoguanidine
(MNNG), a carcinogenic potential of this chemical could not be ruled out. In transcriptional assay
using transfected yeast, this chemical showed very weakly estrogenic activity.
Occupational exposure
p-t-Butylphenol is used as an intermediate in a closed system at industries, and workers wear
protective gloves and respiratory protective equipments during operation in present time. The
major exposure route is an inhalation and skin in limited workers. The daily intake through
inhalation in occupational situation is calculated as 0.087 mg/kg/day as the worst case. As for
systemic toxicity, occupational risk is presumably low because the margin of safety is 2.30 x 10 3 .
However, many reports indicated depigmentation on skin occurred by occupational exposure.
Therefore, irritation and sensitisation in addition to depigmentation on skin might be concerned to be
risk at work place.
Consumer exposure
Consumer exposure is expected to be low because of its use pattern.
Indirect exposure via environment
As for indirect exposure via environment, PEClocal of 5.8 x 10 -3 mg/l from local exposure scenario
was used for the estimation. The daily intake through drinking water or fish is calculated as 1.9 x
10 -4 mg/kg/day or 1.0 x 10 -3 mg/kg/day. Therefore, health risk via environment is presumably low,
UNEP Publications 81