Registration Dossier

Toxicological information

Health surveillance data

Currently viewing:

Administrative data

Endpoint:
health surveillance data
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented. Sampling and analytical method sufficiently documented. Little statistical meaning. Minority population investigated. But based on accepted scientific principles.

Data source

Reference
Reference Type:
publication
Title:
Intra- and inter-individual variability of urinary phthalate metabolite concentrations in Hmong women of reproductive age
Author:
Peck J. D., Sweeney A. M., Symanski E., Gardiner J. and Schantz S. L.
Year:
2010
Bibliographic source:
Journal of Exposure Science and Environmental Epidemiology, 20, 90-100

Materials and methods

Study type:
biological exposure monitoring
Principles of method if other than guideline:
Intra- and inter-individual variability of urinary phthalate metabolite concentrations in Hmong women of reproductive age.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Type of population:
general
Ethical approval:
confirmed, but no further information available
Details on study design:
Forty-five Hmong women and their 20 spouses from Green Bay, Wisconsin, who were enrolled in the Fox River Environment and Diet Study (FRIENDS) between September 1999 and November 2005, were recruited to participate in a sub-study for evaluating phthalate exposures. This sub-study had two primary goals. The first objective was to describe the distribution of urinary concentrations of phthalate metabolites among Hmong couples of reproductive age, and to explore the variability of the phthalate metabolite concentrations within households. The second objective was to evaluate the intra- and inter-individual variability in urinary metabolite concentrations. Recruitment occurred between May and November 2005, and all participants were asked to provide a first-morning urine sample and to complete an exposure assessment questionnaire.

Results and discussion

Results:
Urine samples were collected between May and November of 2005, with 66% (n= 61) obtained during the fall months (September through November). Twenty women provided a single urine sample, three women provided two samples and 22 women provided three samples. The authors observed a large degree of variability in phthalate metabolite concentrations across all samples. The rank order of geometric mean concentrations was identical for creatinine-adjusted and unadjusted values. No significant difference was noted on urinary metabolites of DEHP between different subsets of the investigated population according to the age, the body mass index, the education and the season. Only smoking status and incomes of the study population showed to have an impact on the metabolite concentrations. Besides, DEHP metabolites concentrations proved to be more consistent when three urine samples were given over a month period. These elements prove that there is potential variability of DEHP excretion over the day time that was not fully avoided by taking the first morning urine.
cf remarks for detailled results.

Any other information on results incl. tables

Detailled results of urinary phthalate metabolites concentrations:

Distribution of creatinine-adjusted (µg/g creatinine) (in bold)
and unadjusted (µg/l) phthalate metabolite concentrations in urine
samples from 45 women
% > LOD Geometric mean Geometric standard deviation Percentiles
25 th 50 th 75 th 95 th Min Max

MEHP

 
81 3.4 2.4 2.3 3.5 9.1 21.3 0.5 36.0
  3.6 2.6 2.6 4.5 7.7 22.2 0.6 30.8

MECPP

100 29.5 2.2 17.5 32.6 52.7 164.4 6.3 243.4
  31.7 2.5 16.9 36.0 82.5 192.7 6.2 226.5

MEHHP

100 19.5 2.2 10.7 20.3 36.8 138.4 3.9 251.3
  20.9 2.4 11.3 21.4 51.6 156.6 4.6 268.2

MEOHP

100 13.0 2.1 7.6 13.4 25.3 83.1 3.1 103.9
  13.9 2.4 8.6 13.5 36.5 84.1 2.6 164.3

Sum of DEHP

  67.3 2.1 41.0 68.9 128.7 462.1 14.5 540.9
  72.1 2.4 41.2 71.6 180.6 452.9 14.5 686.5

Applicant's summary and conclusion

Conclusions:
Urinary metabolites concentrations of phthalates, especially DEHP, were controlled in a small cohort of Hmong women. In the test conditions, the authors found that 95 % percent of these Hmong women exhibited less than 462.1 ug/g creatinine of the sum of the four investigated urinary metabolites associated to DEHP exposure.
Executive summary:

Forty-five Hmong women and their 20 spouses from Green Bay, Wisconsin, who were enrolled in the Fox River Environment and Diet Study (FRIENDS) between September 1999 and November 2005, were recruited to participate in a sub-study for evaluating phthalate exposures. This sub-study had two primary goals. The first objective was to describe the distribution of urinary concentrations of phthalate metabolites among Hmong couples of reproductive age, and to explore the variability of the phthalate metabolite concentrations within households. The second objective was to evaluate the intra- and inter-individual variability in urinary metabolite concentrations. Recruitment occurred between May and November 2005, and all participants were asked to provide a first-morning urine sample and to complete an exposure assessment questionnaire.

Participants were provided with a urine collection kit containing instructions for the collection of a first-morning void and a polypropylene plastic urine collection cup that had been prescreened for phthalate metabolites. Participants were instructed to record the time of collection, place the

sample immediately in the freezer and call the research staff on the day of collection to arrange for sample pickup. When the research staff member visited the home to retrieve the urine specimen, an exposure assessment questionnaire was administered.

In brief, the analytical methodology of the urinary metabolites involved enzymatic deconjugation of the phthalate metabolites from their glucuronidated form, followed by an online solid-phase extraction, separation with high performance liquid chromatography and detection by isotope-dilution tandem mass spectrometry. Limits of detection were for MEHP, 0.9 mg/l; for MEOHP, 0.45 mg/l; for MEHHP, 0.32 mg/l; and for MECPP, 0.25 mg/l.

Hence, in the test conditions, urine samples were collected between May and November of 2005, with 66% (n= 61) obtained during the fall months (September through November). Twenty women provided a single urine sample, three women provided two samples and 22 women provided three samples. The authors observed a large degree of variability in phthalate metabolite concentrations across all samples. The rank order of geometric mean concentrations was identical for creatinine-adjusted and unadjusted values. No significant difference was noted on urinary metabolites of DEHP between different subsets of the investigated population according to the age, the body mass index, the education and the season. Only smoking status and incomes of the study population showed to have an impact on the metabolite concentrations. Furthermore, the authors found that 95 % percent of these Hmong women exhibited less than 462.1 ug/g creatinine (452.9 µg/L) of the sum of the four investigated urinary metabolites associated to DEHP exposure. These results show evidences that consumers are exposed to DEHPat rather low levels.

Thus, this study is well documented. Besides, even if sample size id restricted, if some bias could be introduced by the sampling method and even if the investigated population is a minority population, the study is based on generally accepted scientific principles. Analytical and sampling method are sufficiently documented. Therefore, this study should be considered as reliable with acceptable restrictions.