3.Polyvinyl
3.Polyvinyl chloride
Polyvinyl chloride is used in food containers, vinyl sheet, agricultural vinyl sheet
and building materials because its hardness is easily adjusted. This plastic is
generally formed by repeated polycondensation, using ethylene monomer andethylene dichloride as materials.

Polyvinyl chloride is originally hard, but can besoftened by adding di(2-ethylhexyl) phthalate (DEHP) or others as a plasticizer.
Phthalate used as plasticizer is suspected of being an endocrine disruptor.

TheJapan Toy Association has stated that teething rings and pacifiers made in Japando not contain polyvinyl chloride.
●Annual food-related use (investigated by Japan Hygienic Olefine and Styrene
Plastics Association, unit: 1,000 ton)
Production: 2,510; domestic sales: 2,510, including food-related use: 110;
volume of resin using diethylhexyl phthalate, for food-related use: 40(1) Elution of phthalate
Reportedly, phthalate is detected in dairy products and drinks.

Examination offoods packed in plastic containers showed di(2-ethylhexyl) phthalate (DEHP)
volumes to be approximately 10 to 100 ppb, as shown in Table 3*127*128.
In studies on phthalate contained in vinyl chloride toys, dibutyl phthalate, dioctyl
phthalate, dihepthyl phthalate and dinonyl phthalate ranged from 0.2 to 24%*129.
In another study, phthalates at concentrations from 10 to 40% were found using asimilar measuring method*130.

In a study of diisononyl phthalate (DINP) elusionfrom vinyl chloride toys into saliva, with the cooperation of 20 volunteers, DINP
levels were from 1.38 to 2.44 µg/min*131.
(2) Safety of phthalate
1.

Screeningz

In vitro study
Some studies reported ER-binding capacity in human mammary carcinoma cellline and rat uterus as follows:
1) Transcription activation capacities of phthalates (as mediated by ER in
human mammary carcinoma cell line (MCF-7)) were compared with the75maximum activity (10-8 to 10-9 M) in estradiol (E2). Dibutylbenzyl phthalate(10-6 to 10-4 M) and dibutylphthalate (10-5 to 10-4 M) increased in the activity,
but diethylhexyl phthalate (10-4 M) showed no such action*132.
2) In a study of estrogenic activity in terms of proliferation potency of humanmammary carcinoma cell line (MCF-7) dibutyl phthalate, diamyl phthalate,dimethyl isophthalate, dimethyl telephthalate and dinonyl phthalate wereevaluated to have no estrogenic activity, but the estrogenic activity ofbenzylbutyl phthalate was 0.0003 times that of estradiol (E2) as 100*119.
3) In a study using mouse peroxisome proliferation activity receptor,
monoethylhexyl phthalate (10-5 to 10-4 M), a metabolite of diethylhexyl
phthalate, showed increase in the activity, but diethylhexyl phthalate (10-5M) did not*133.
(Reference data)
In a study on binding to rat uterin ER, 50% inhibition concentration ofestradiol (E2) (a positive control) was 10-9 M, and dibutyl phthalate anddiisooctyl phthalate showed 9% and 15% inhibition respectively at 10-3 M, while
diisononyl phthalate, diisodecyl phthalate and dioctyl phthalate had noinfluence*134.
zIn vivo study
Utero-trophic assay etc. in phthalates have been reported.
In a study using male and female mice given diethylhexyl phthalate
subcutaneously (1 to 100 ml/kg, at days 1, 5 and 10), pregnancy ratio decreasedin groups given 10 ml/kg or more, and testis weight decreased in groups given
15 to 20 ml/kg. However, uterine weight did not change*135.
(Reference data)
In a study of ovariectomized female mice given the above chemical
subcutaneously (1,000 mg/kg, for 3 days), dibutyl phthalate and diisooctyl
phthalate exhibited 9% and 15% inhibition, respectively, at 10-3 M, while
diisononyl phthalate, diisodecyl phthalate and dioctyl phthalate did not show
any influence on uterine weight nor on amounts of progesteron receptor
volume*134.

2.

Repeat dose tests etc.

76

As regards diethylhexyl phthalate, etc., subchronic toxicity studies in mice andrats have been reported:
1) In a 4-week oral dose study in mice given a mixture of diocyl phthalate andstyrene (13:1, 0.02, 0.03, 0.05 × LD50), the immune system was influenced,
e.g., decrease in numbers of lymphoid cells and monocytes in the spleen*136.
2) In both single oral dose (5,000 mg/kg) and 14-day repeat oral dose (1,500mg/kg)

toxicitystudies

inneurotoxicity was not detected

rats
*137

withdiethylhexylphthalate,any.

3) In a 12-day toxicity study in adult rats fed a mixed diet containing
diethylhexyl phthalate (2 g/kg), prolonged estrous cycle, inhibition ofovulation and decrease in serum estradiol were found*138.
4) In a 10-day repeat oral dose toxicity study in male rats aged 4 and 15 weeks
with diethylhexyl phthalate (2,800 mg/kg), atrophy of the seminiferous
tubules and decrease in the prostate weight were found in 4-week group,
whereas there was no alteration in 15-week group*139.
5) In a mid-term hepatic carcinogenicity study in rats fed a mixed dietcontaining diethylhexyl phthalate (30, 300, 3,000 and 12,000 ppm), at 48
weeks hyperplastic nodules developed in 3,000- and 12,000-ppm dose groups.
At 52 weeks, the hyperplastic nodules had developed in all animals of the12,000-ppm dose group, with hepatocellular carcinoma in 9 of 12 cases*140.
(Reference data)
In a 13-week oral dose study in marmosets (the primate) with diethylhexyl
phthalate (100, 500 and 2,500 mg/kg), decrease in body weight gain was foundin 2,500-mg/kg dose group, and increases in liver microsome protein and p-450
content per unit of weight were found in male 500- and 2,500-mg/kg dosegroups.
3.

Testicular atrophy was not found*141.

Pharmacodynamics(Reference data)
A distribution study on testis was performed with radio-labelled diethylhexyl
phthalate.

In a single oral dose testis toxicity study in rats with oral

diethylhexyl

phthalatedegenerationofthe(700,1,000,spermatocyte

1,400,and2,000and2,800mg/kg),

expansionofsmooth-surfaced

endoplasmic reticulum in the junction of Sertoli cells etc. were found in 2,800mg/kg group.

Slight expansion of smooth-surfaced endoplasmic reticulum was77observed also in the groups with 700- and 1,000-mg/kg. In a single oral dosestudy with the 3H labelled diethylhexyl phthalate, testis and liver distribution
were examined, and it was revealed that diethylhexyl phthalate affected
localization of β-actin in Sertoli cells in the testis*142.
(3) Conclusion
ER-binding capacity of phthalates differed with the kind of ester; it has beenreported that diethylhexyl phthalate did not bind to ER at a low concentration.
In another report concerning utero-trophic assay in rats, uterine hypertrophy was
not found.
As shown above, we do not have scientific information that diethylhexyl phthalate
at the level eluting from polyvinyl chloride seriously influences human health;therefore, it would not be necessary to prohibit use of polyvinyl chloride at present.
However, in a 10-day repeat dose toxicity study in rats, atrophy of theseminiferous tubule and decrease in prostate weight were found.

Therefore, weshould conduct further researches such as two-generation reproductive studies.
Safety performance should be assessed on the basis of examination of exposurelevels of tableware and toys infants may take into their mouth as well asinternational trends.
(4) Future researchz

Two-generation reproductive study in rats; pharmaco-dynamic study in rats
etc. (bioaccumulation, transfer to fetus and milk)zConcentration research in human umbilical cord blood and breast milk andresearch for organ distributionz

Research for elution volumes from tableware and toys78