Screening for phthalates biomarkers and its potential role in infertility outcomes in Jordan.

BACKGROUND: Phthalates are endocrine disrupting chemicals that are used in plastic and personal care products. Phthalate exposure has been linked to reproductive and fertility outcomes. OBJECTIVES: This study aimed to assess the phthalate exposures using both urinary level of two DEHP metabolites in females and questionnaires. It also aimed to investigate the association between phthalate levels and reproductive and fertility outcomes. METHODS: 325 females with and without fertility problems at gynaecology clinics filled out a questionnaire and provided a urine sample. Urine samples were analyzed for two DEHP metabolites: MEHHP, mono (2-ethyl-5-hydroxyhexyl) phthalate; MEOHP, mono (2-ethyl-5-oxohexyl) phthalate, using an HPLC/MS/MS analytical method. RESULTS: We observed a significant difference between cases and controls in terms of heating plastic in the microwave and use of skin and eye make-up, sunscreen, and nail polish. Our findings showed that MEOHP exposure is significantly associated with infertility among Jordanian women (Adjusted OR = 1.66, 95% CI: 1.14, 2.40, p-value = 0.002). SIGNIFICANCE: To the best of our knowledge, our study is the first of its kind done in Jordan to screen for phthalate exposure and investigate its association with infertility. Our study demonstrated high exposure of the Jordanian population to DEHP. It confirms the association between DEHP exposure and infertility. IMPACT STATEMENT: We measured phthalates in infertile and fertile women, in a community unaware of phthalate sources or its impacts, and with no regulation limits set. We aimed to increase awareness to environmental exposure to phthalates, emphasize the importance of implementation of public health interventions to control and minimize the effects of phthalate exposure and provide a base for further studies and future research to aid in the formation of policies and guidelines for the manufacturing and use of phthalates.

Risk assessment of combined exposure to alkenylbenzenes through consumption of plant food supplements containing parsley and dill.

A risk assessment was performed of parsley- and dill-based plant food supplements (PFS) containing apiol and related alkenylbenzenes. First, the levels of the alkenylbenzenes in the PFS and the resulting estimated daily intake (EDI) resulting from use of the PFS were quantified. Since most PFS appeared to contain more than one alkenylbenzene, a combined risk assessment was performed based on equal potency or using a so-called toxic equivalency (TEQ) approach based on toxic equivalency factors (TEFs) for the different alkenylbenzenes. The EDIs resulting from daily PFS consumption amount to 0.74-125 µg kg-1 bw for the individual alkenylbenzenes, 0.74-160 µg kg-1 bw for the sum of the alkenylbenzenes, and 0.47-64 µg kg-1 bw for the sum of alkenylbenzenes when expressed in safrole equivalents. The margins of exposure (MOEs) obtained were generally below 10,000, indicating a priority for risk management if the PFS were to be consumed on a daily basis. Considering short-term use of the PFS, MOEs would increase above 10,000, indicating low priority for risk management. It is concluded that alkenylbenzene intake through consumption of parsley- and dill-based PFS is only of concern when these PFS are used for long periods of time.

Determination and risk assessment of naturally occurring genotoxic and carcinogenic alkenylbenzenes in nutmeg-based plant food supplements.

A risk assessment of nutmeg-based plant food supplements (PFS) containing different alkenylbenzenes was performed based on the alkenylbenzene levels quantified in a series of PFS collected via the online market. The estimated daily intake (EDI) of the alkenylbenzenes amounted to 0.3 to 312 µg kg-1 body weight (bw) for individual alkenylbenzenes, to 1.5 to 631 µg kg-1 bw when adding up the alkenylbenzene levels assuming equal potency, and to 0.4 to 295 µg kg-1 bw when expressed in safrole equivalents using toxic equivalency factors (TEFs). The margin of exposure approach (MOE) was used to evaluate the potential risks. Independent of the method used for the intake estimate, the MOE values obtained were generally lower than 10000 indicating a priority for risk management. When taking into account that PFS may be used for shorter periods of time and using Haber's rule to correct for shorter than lifetime exposure it was shown that limiting exposure to only 1 or 2 weeks would result in MOE values that would be, with the presently determined levels of alkenylbenzenes and proposed uses of the PFS, of low priority for risk management (MOE > 10000). It is concluded that the results of the present paper reveal that nutmeg-based PFS consumption following recommendations for daily intake especially for longer periods of time raise a concern. Copyright © 2017 John Wiley & Sons, Ltd.

Level of Alkenylbenzenes in Parsley and Dill Based Teas and Associated Risk Assessment Using the Margin of Exposure Approach.

Risk assessment of parsley and dill based teas that contain alkenylbenzenes was performed. To this end the estimated daily intake (EDI) of alkenylbenzenes resulting from use of the teas was quantified. Since most teas appeared to contain more than one alkenylbenzene, a combined risk assessment was performed based on equal potency of all alkenylbenzenes or using a so-called toxic equivalency (TEQ) approach through defining toxic equivalency factors (TEFs) for the different alkenylbenzenes. The EDI values resulting from consuming one cup of tea a day were 0.2-10.1 µg/kg bw for the individual alkenylbenzenes, 0.6-13.1 µg/kg bw for the sum of the alkenylbenzenes, and 0.3-10.7 µg safrole equiv/kg bw for the sum of alkenylbenzenes when expressed in safrole equivalents. The margin of exposure (MOE) values obtained were generally <10000, indicating a concern if the teas would be consumed on a daily basis over longer periods of time.

Mode of action based risk assessment of the botanical food-borne alkenylbenzene apiol from parsley using physiologically based kinetic (PBK) modelling and read-across from safrole.

The present study developed physiologically-based kinetic (PBK) models for the alkenylbenzene apiol in order to facilitate risk assessment based on read-across from the related alkenylbenzene safrole. Model predictions indicate that in rat liver the formation of the 1'-sulfoxy metabolite is about 3 times lower for apiol than for safrole. These data support that the lower confidence limit of the benchmark dose resulting in a 10% extra cancer incidence (BMDL10) that would be obtained in a rodent carcinogenicity study with apiol may be 3-fold higher for apiol than for safrole. These results enable a preliminary risk assessment for apiol, for which tumor data are not available, using a BMDL10 value of 3 times the BMDL10 for safrole. Based on an estimated BMDL10 for apiol of 5.7-15.3 mg/kg body wt per day and an estimated daily intake of 4 × 10(-5) mg/kg body wt per day, the margin of exposure (MOE) would amount to 140,000-385,000. This indicates a low priority for risk management. The present study shows how PBK modelling can contribute to the development of alternatives for animal testing, facilitating read-across from compounds for which in vivo toxicity studies on tumor formation are available to compounds for which these data are unavailable.