4-(4-isopropoxyphenylsulfonyl)phenol

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Bisphenol A, Bisphenol S, and 4-Hydroxyphenyl 4 Isoprooxyphenylsulfone (BPSIP) in Urine and Blood of Cashiers

Author:

Thayer et al

Year:

2016

Bibliographic source:

Environmental Health Perspectives, Volume 124, No. 4

Materials and methods

Type of study / information:

The objective of the study was to determined whether handling receipt paper results in measurable absorption 4-hydroxyphenyl 4-isoprooxyphenylsulfone (BPSIP), BPA or BPS.

Endpoint addressed:

dermal absorption

Test guideline

Qualifier:

no guideline required

GLP compliance:

no

Method

Ethical approval:

confirmed, but no further information available

Details on study design:

The main objective of this study was to test the hypothesis that occupational exposure to thermal receipt paper results in increased urine and/or serum levels of BPA or its analogues in cashiers when measured shortly after they complete a work shift compared with levels measured > 24 hr after completing a shift. The analyses of biospecimens from cashiers were matched with analyses of receipt paper samples provided by the cashiers. The levels of BPA,BPS and BPSIP were compared in urine from cashiers with those in urine from non-cashiers. A total of 77 cashiers were included in the analysis. Cashiers were grouped into receipt categories based on the dominant analyte detected in the paper (BPA = 33, BPS = 32, BPSIP = 12). Urine samples were also collected from 25 non-cashiers.

Receipt, blood, and urine sample collection:
Care was taken to avoid possible BPA contamination from laboratory materials and equipment by using glass pipets and polypropylene containers, including water blanks for blood and urine collection and processing procedures, and providing special instructions to CRU staff. Each cashier provided a receipt sample from her/his place of employment that was at least 12 in long and was stored in a Ziploc1 bag (these bags do not contain BPA). Two sets of samples were collected from each cashier, one “post-shift” sample collected within 2 hr of completing a work shift, and one “preshift” sample collected at least 24 hr after a work shift had been completed.
Urine samples were collected in polypropylene collection cups (Andwin Scientific). Water blanks using high-performance liquid chromatography (HPLC)-grade water were prepared in the same manner and collection containers as the blood and urine samples.
One-milliliter samples of serum, urine, and two water blanks (one for blood, one for urine) were aliquoted into four 1.5-mL polypropylene microcentrifuge tubes (Sarstedt) for storage. Samples were stored at -80°C, shipped on dry ice to NCTR for analysis, and stored at -60°C until analyzed.
LC/MS/MS determinations in urine and serum:
BPSIP was analyzed in urine and serum using the LC. Concentrations of BPSIP were initially evaluated using 13C12-BPA as a surrogate internal standard. The method performance was evaluated during the BPS validation procedure using control and spiked matrices. The validation procedure produced acceptable precision and accuracy ranges. However, when actual cashier serum or urine was analyzed, the method failed because of the wide range of suppression observed on the13C12-BPA, which did not affect the BPSIP. Because no other suitable internal standard could be identified for quantification of BPSIP, semi-quantitative results were evaluated as either above or below the LOD for urine (0.01—0.02 ng/mL) and serum (0.005-0.008 ng/mL). Subsequently, all urine samples containing total BPSIP above the daily limit of quantitation (LOQ) (0.03—0.06 ng/mL) were quantified using the method of standard addition, where two aliquots of each sample were analyzed: One aliquot was spiked with a known amount of BPSIP matched to the target concentration, which was based on the value estimated from the original analysis; the other aliquot was not spiked. The control human urine sample from the laboratory volunteer was also analyzed in duplicate with standard addition to provide a background value of contamination during sample preparation. The amount of BPSIP was quantified by dividing the area under the chromatographic peak of the unspiked sample with the area under the chromatographic peak of the spiked sample minus the area of the unspiked sample and multiplying by the amount of BPSIP added in ng/mL. The background value generated from the control urine was subtracted from each sample before results were reported. All serum samples contained total BPSIP below the LOQ (0.015-0.024 ng/mL) and were not analyzed further.

Exposure assessment:

measured

Remarks:

LC/MS/MS

Details on exposure:

TYPE OF EXPOSURE: occupational

TYPE OF EXPOSURE MEASUREMENT: Biomonitoring (urine) / Biomonitoring blood

EXPOSURE PERIOD: 8 h during shift

DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES:
Cashiers (required to be > 18 years old, not pregnant, and working at a cash register for at least 20 hr/week) and non-cashiers were recruited by open advertisement from the Raleigh—Durham-Chapel Hill region of North Carolina during June 2011-September 2013. Cashiers were asked to provide proof of employment as a cashier, and all participants were asked to provide a medical history including disease status, current medications, alcohol and cigarette use, and food and drink
consumption during the previous 24 hr (yes/no) at study enrollment. A post-shift questionnaire was. administered to a subset of cashiers to assess hours worked at a register, average number of transactions, consumption of food or beverage from metal containers, use of polycarbonate plastic, frequency of hand washing, and use of gloves and hand creams during work. All human subject research activities were conducted at the National Institute of Environmental Health Sciences (NIEHS) Clinical Research Unit (CRU) in accordance with protocols approved by the NIEHS Institutional Review Board (IRB #10-E-0063), and all participants gave written informed consent before providing their medical history and donating samples. Participation of the National Center for Toxicological Research (NCTR) laboratory was reviewed and approved by the U.S. Food and Drug Administration (FDA) Research Involving Human Subjects Committee (RIHSC #11-067T).

Results and discussion

Results:

Urine levels of total BPSIP:
In the 12 cashiers who handled BPSIP containing receipts, the proportion of samples with detectable BPSIP was similar in pre- and post-shift samples (10/12, 83% and 9/12, 75%, respectively; p = 0.65). BPSIP was detected more frequently in cashiers in the BPSIP group pre- and postshift than in cashiers in the other receipt groups, where the pre- and post-shift detection frequency ranged from 12.1 to 28.2% (p < 0.02). BPSIP was also detected significantly less often in non-cashiers [32% (8/25); p < 0.02]. BPSIP concentrations were > LOQ in 58% and 67% of pre- and post-shift samples from the BPSIP cashier group, respectively, compared with 0-16% of samples from other cashier groups and from non-cashiers.

Serum levels:
Serum BPSIP was detected in cashiers from the BPSIP-receipt paper group at levels between the LOD and LOQ, but the detection frequency did not differ between pre- and post-shift samples (7/12 or 58.3% post-shift vs. 6/12 or 50% pre-shift). BPSIP was also detected in 33-44% of samples from cashiers in the BPA- and BPS-receipt paper groups. Furthermore, BPSIP was more consistently detected in a greater percentage of samples in cashier groups (33-58.3%) than was BPA (0-33%) or BPS (8.3-40.6%).
BPSIP or the other compounds were not detected in serum samples from non-cashiers

Limitations:
There are limitations to this study. Sample sizes were small in each group, and our study was not designed to discern which routes of exposure might account for the observed patterns in cashiers, that is, dermal, oral, and/or inhalational, or to rule out exposure from other sources.
The time interval between last receipt handling and sample collection in the post-shift samples was not known, and it is possible that 24 hr of not handling receipts before pre-shift sample collection may not be a sufficient washout period for BPA levels to return to baseline. Furthermore, it was not known how many hours were worked during the workweek preceding the post-shift visit.

Any other information on results incl. tables

Table 4. Serum total BPA, BPS, and BPSIP in cashiers.
	BPA receipts	BPS receipts	BPSIP receipts (number
Compound	(number > LOD)	(number > LOD)	> LOD)
BPA serum
Pre-shift	7/33 [21.2%)	4/32(12.5%)	4/12(33.3%)
Post-shift	7/33(21.2%)	4/32(12.5%)	0/12(0%)
BPS serum
Pre-shift	9/33(27.3%)	5/32 (15.6%)	2/12(16.7%)
Post-shift	5/33(15.2%)	13/32(40.6%}*	1/12(8.3%)
BPSIP serum
Pre-shift	9/21 (42.9%)	5/15(333%)	7/12(583%)
Post-shift	6/17(35.3%)	7/16(43.8%)	6/12(50.0%)

Abbreviations: BPA, bisphenol A; BPS, bisphenol S; BPSIP, 4-hydroxyphenyl 4 isoprooxyphenylsulfone; LOD, limit of detection. Serum LODs: BPA, 0.045-0.35 ng/mL; BPS, (0.002-0.01 ng/mL; BPSIP, 0.005-0.008 ng/mL.*p = 0.02, significant difference between pre-shift and post-shift.

Applicant's summary and conclusion

Conclusions:

Thermal receipt paper is a potential source of occupational exposure to BPA, BPS, and BPSIP.

Executive summary:

Cashiers (n = 77) and non-cashiers (n = 25) were recruited from the Raleigh-Durham-Chapel Hill region of North Carolina during 2011-2013. Receipts were analyzed for the presence of BPA or alternatives considered for use in thermal paper. In cashiers, total urine and serum BPA, BPS, and BPSIP levels in post-shift samples (collected < 2 hr after completing a shift) were compared with pre-shift samples. Levels of these compounds in urine from cashiers were compared to levels in urine from non-cashiers.

Each receipt contained 1-2% by weight of the paper of BPA, BPS, or BPSIP. The postshift geometric mean total urinary BPS concentration was significantly higher than the pre-shift mean in 33 cashiers who handled receipts containing BPS. The mean urine BPA concentrations in 31 cashiers who handled BPA receipts were as likely to decrease as to increase after a shift, but the mean post-shift concentrations were significantly higher than those in non-cashiers. BPSIP was detected more frequently in the urine of cashiers handling BPSIP receipts than in the urine of noncashiers. Only a few cashiers had detectable levels of total BPA or BPS in serum, whereas BPSIP tended to be detected more frequently.