Risk assessment plasticizers from erotic objects

Risk assessment plasticizers from erotic objects PJCM Janssen and HJ Bremmer. National Institute for Public Health and the Environment (RIVM) Centre for Substances and Integrated Risk Assessment (SIR) Date: 29 September 2010 In compliance with quality assurance procedures within RIVM/SIR, this assessment was reviewed by JE Delmaar, JGM van Engelen, AG Schuur. Kennisvraag nummer 9.1.30B Summary About one half of erotic objects as sampled by VWA from the Dutch market were found to be made of plasticized PVC. Both phthalates and other plasticizers used as replacements for phthalates (DINCH, DEHT, TXIB) were found in these objects. Based on migration measurements carried out by VWA according to a standardized method, we calculated worst case exposure, both for private and professional use of erotic objects. In absence of information on the actual use of erotic objects, we chose plausible worst case scenarios (i.e. the same as previously used in an RIVM risk assessment on cadmium in erotic objects). For private use, estimated worst case exposures indicated absence of any health risk. For the non-phthalate plasticizers that were identified, including DINCH and DEHT, the margins of safety were much larger than for phthalates, thus demonstrating the improved safety of these replacements. For professional use margins of safety for phthalates were below the usual minimum required in consumer risk assessments. In contrast for the non-phthalate plasticizers that were identified, including DINCH and DEHT, wide margins of safety were calculated, indicating absence of any health risk. The overall conclusion is that intensive use of erotic objects containing phthalates may lead to exposures in excess of safe levels. Objects containing common phthalate replacements are not associated with a similar risk.

1. Introduction As part of a market survey on erotic products, the Dutch Food and Consumer Product Safety Authority (VWA) investigated the composition of erotic objects such as vibrators and dildos. A total of 71 individual items were examined. Approximately one half of the products were found to be made of plasticized PVC. By far most of these PVC-objects were dildo s, vibrators or plugs. For all PVC products migration of plasticizers was measured using the standard method for plasticizers, the so-called head over heels method. Water was used as the migration matrix (VWA 2009). Several phthalate plasticizers were identified in the PVC- items, i.e. di(2- ethylhexyl)phthalate (DEHP, CAS 117-81-7), diisononylphthalate (DINP, CAS 68515-48-0 and 28553-12-0) and diisodecylphthalate (DIDP CAS 68515-49-1 and 26761-40-0). Non-phthalate plasticizers identified were diisononylcyclohexanoate (DINCH, CAS 166412-78-8), diethylhexyladipate (DEHA, CAS 103-23-1), diethylhexylterephthalate (DEHT, CAS 6422-86-2) nonylphenol (CAS 104-40-5) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB CAS 6846-50-0). Below in section 2 we briefly address toxicological data for these compounds. Since comprehensive toxicity reviews are available for all compounds, the discussion is limited to issues directly relevant for the present assessment. In section 3, we use the migration data as reported by VWA (2009) for an exposure assessment. In section 4 the risk assessment is presented. 2. Toxicology of plasticizers As indicated above, we will deal only with critical toxicological aspects here because comprehensive reviews are available for the plasticizers identified by VWA (SCF 1997; EU 2002, 2003a, 2003b and 2008; EFSA 2005a, 2005b, 2005c, 2006 and 2008; WHO 2004). 2.1 Relevance of effects A critical toxic effect for phthalates is on reproduction and development. DEHP has a higher toxic potency for these endpoints than have DINP and DIDP. The data indicate that male neonates are especially sensitive to the disruptive effect by DEHP on sexual development. Since for erotic objects use is envisaged for adults only, direct exposure of young children is not expected. Nevertheless in utero and perinatal exposure may occur via the mother. Therefore the reproductive and developmental effects as observed in the relevant studies with DEHP, DINP and DIDP are fully relevant for the present risk assessment (note that especially for DINP these effects occur at the higher tested dose levels only and were not critical in deriving an overall NOAEL).

The critical effects for plasticizers other than DEHP, as listed in Table 2 (section 2.3 below), all are relevant for exposure of adults and accordingly there is no reason to select other critical endpoints for the current evaluation. 2.2. Toxicokinetic considerations Possible effect of first-pass metabolism In the present case exposure is vaginal or anal. Plasticizers absorbed via these routes will enter the bloodstream and then be available systemically. In contrast, after oral absorption there is the possible step of first-pass metabolism in the liver. This difference may render the use of oral data problematic. Given the scarcity of toxicity data for non-oral exposure routes for the plasticizers dealt with here, this issue can only be explored to a limited extent based on the available toxicokinetic and -dynamic information. As to phthalates, DEHP is by far the most data-rich chemical. For DEHP a number of intravenous toxicity studies are available, summarised in a draft ISOdocument from 2007 (ISO 2007). A crucial step in the induction of reprotoxicity by DEHP is conversion to the mono-ester MEHP. After oral intake this conversion takes place under influence of the lipases in the GI-tract. Lipases are also present in blood and the blood vessel endothelium, allowing for formation of MEHP after intravenous or intravaginal/intra-anal uptake. In a short-term toxicity study in neonatal rats, Cammack et al. (2003) studied testis effects both after intravenous and oral administration and found testicular toxicity at 300 mg/kg bw for both routes. The effect was more severe after oral dosing, indicating a somewhat lower toxic potential for the intravenous route. For DINP and DIDP no intravenous toxicity studies are available. In conclusion, data on DEHP indicate a somewhat lower potency via the intravenous route compared to the oral route. Based on testes weight decrease, the effect was 15-24% greater after oral dosing. Within the margins of the current risk assessment this is a minor difference only. We therefore choose to use oral toxicity data for phthalates as relevant for the current exposure situation of the use of erotic objects. For DINCH the toxicokinetic data indicate similar biotransformation after intravenous uptake compared to oral uptake (RIVM 2009). Thus for this compound use of oral data is appropriate based on the data. For nonylphenol first-pass metabolism was concluded to be extensive and it was proposed (taking into account a toxicokinetically determined biovailability of only 10-20% after oral intake study) to reduce the oral LOAEL with a factor of 10 when using these data for assessing dermal and inhalation risks (EU 2002). This proposal is followed here for the exposure situation of use of erotic objects. For the remaining plasticizers (TXIB, DEHA, DEHT) only oral data are available, precluding a comparison between routes. In the absence of evidence indicating otherwise, we assume that oral toxicity data are relevant for these chemicals as well for the current exposure situation of the use of erotic objects.

Correction for absorption In the previous assessment for cadmium in vibrators it was concluded that no data were available on intravaginal and -anal absorption. An absorption of 100% was assumed given the fact that the vaginal and anal mucous membranes are well-perfused tissues. Similarly, for the plasticizers dealt with in the present report no data on vaginal and anal absorption are available. As an a priori reasonable approach we assume that vaginal and anal absorption will be equal to absorption from the GI-tract. Thus we can use oral NOAELs without adjustments. 2.3 NOAELs and toxicological limit values for plasticizers In Table 1 NOAELs and TDIs are summarized for the plasticizers as found in erotic objects. Table 1. NOAEL and TDIs for different phthalate and non-phthalate plasticizers. Compound TDI NOAEL Critical effect Reference (mg/kg bw/day) (mg/kg bw/day) DEHP 0.05 5 Reproductive and developmental EFSA 2005a toxicity in rat 3-generation reproduction study DINP 0.15 15 Hepatotoxicity and renal toxicity in EFSA 2005b chronic rat study DIDP 0.15 15 Slight hepatotoxicity in semichronic EFSA 2005c dog study, decreased pup survival in rat 2-generation reproduction study DINCH 1 100 Renal toxicity in semichronic rat study EFSA 2006 and 2-generation rat study TXIB not available 30 Hepatotoxicity in semichronic rat study RIVM 2009 and 28-day reproduction screening test DEHA 0.3 28 Foetotoxicity in 28-days study rat SCF 1997, WHO 2004 nonylphenol not available 1.5 (LOAEL) Renal toxicity in 2-generation rat EU 2002 reproduction study DEHT 1 79 Decreased growth and feed EFSA 2008 consumption, increased incidence of eye lens opacity in chronic rat study Similar to the approach in our previous risk assessment for non-phthalate plasticizers in toys (RIVM 2009), we will use the above NOAELs for calculating the Margin of Safety. 3. Exposure estimation In agreement with the previous RIVM risk assessment on cadmium in erotic objects (RIVM 2002), in the exposure scenario we assume use of erotic objects during 2

hours per week (private use) or 10 hours per week (professional use). These time periods represent estimates only and are not based on research. They should be viewed as worst case assumptions. Probably the real time periods will be smaller than the stated values. We assume that exposure will be only to one plasticizer at a time (according to the scenario specified). This is based on the pattern of occurrence of the different plasticizers as found by VWA. In products in which plasticizers were present, in most cases only one plasticizer was present and where two or three were present, one usually clearly was dominant as to content. In view of this, we consider there to be no need for special evaluation of mixture effects, as would be possible by applying dose addition by using the so-called fraction method (summing the parts of the individual TDIs filled up by the respective simultaneously present plasticizers). The head over heels measurement of migration is done on isolated parts of the object. Migration during the measurement will be from all sides of the material. This differs from the situation of consumer use of the intact object in which migration will take place from the outside surface only. To correct for this we will apply a factor of 0.5 in the exposure calculation. Calculation The exposure to individual plasticizers from erotic objects is calculated using the following assumptions. Scenario 1: use intravaginally (or anally) two times per week during one hour. Scenario 2: worst-case situation for professional use, daily use during two hours, five days per week. Contact surface with well-perfused tissue: 125 cm 2 The exposure to lesser-perfused tissues is neglected with respect to wellperfused tissue Correction factor for one-sided contact in practical use situation: 0.5 We based our exposure calculation on the maximum concentration found for the plasticizers. This simple approach was considered adequate given the large uncertainties concerning the exposure scenario and given the limited number of measurements for individual plasticizers. The results should be viewed as a worst case estimate based on limited data. The results of the migration experiments, as reported by VWA (2009), are presented in Table 2.

Table 2: Migration of plasticizers from erotic articles (results from VWA 2009) Type of plasticizer (number of positives) 1 DEHP (18) DINP (14) DIDP (6) migration [µg/10 cm 2 /min] DINCH (5) TIXB (3) DEHA (3) Nonylphenol (1) 50-percentile 2 12.1 3.4 22 6.2 1 0 1.4 2.1 75-percentile 16.9 13.5 36.1 8.8 1.1 0.7 1.4 2.1 maximum 23.9 37.4 55.4 8.9 1.1 1.4 1.4 2.1 1 The total number of products sampled was 71, approximately one half of these products were made of plasticized PVC. 2 Of positive samples DEHT (1) In Tables 3 and 4 the results of the exposure calculations are described for scenarios 1 and 2 respectively. As an example the exposure calculation for DEHP is described below. Migration DEHP (maximum): 23.9 µg/10 cm 2 /min (see: Table 2) Exposure scenario 1 2 hours per week, contact surface 125 cm 2. 23.9 [µg/10 cm 2 /min] x 12.5 [10 cm 2 ] x 60 [min/ day] / 60 [kg bw] x 2/7 [day/day] x 0.5 = 43 µg / (kg bw x day) = 0.043 mg / (kg bw x day). Exposure scenario 2 10 hours per week, contact surface 125 cm 2. 23.9 [µg/10 cm 2 /min] x 12.5 [10 cm 2 ] x 120 [min/day] / 60 [kg bw] x 5/7 [day/day] x 0.5 = 213 µg / (kg bw x day) = 0.21 mg / (kg bw x day) 4. Risk assessment In Table 3 the results of the exposure calculations are presented for scenario 1. The final column gives the margins of safety. Table 3: Exposure to plasticizers in scenario 1(private use) plasticizer NOAEL (mg/kg migration 1 exposure Margin of safety bw/day) µg/ 10 cm 2 /min mg/(kg bw x day) (rounded value) DEHP 5 23.9 0.043 120 DINP 15 37.4 0.067 220 DIDP 15 55.4 0.10 150 DINCH 100 8.9 0.016 6200 TXIB 30 1.1 0.002 15000 DEHA 28 1.4 0.0025 11000 nonylphenol 1.5 (LOAEL) 1.4 0.0025 600 DEHT 79 2.1 0.004 20000 1 Maximum value found As can be seen from Table 3, within scenario 1 for all plasticizers the calculated margin of safety is above 100, the usual minimum required in consumer risk assessments. Thus, based on a worst case exposure estimate using the available

migration data, we assess that private use of erotic articles made of PVC containing phthalates does not lead to a health risk for consumers. In Table 4 the results of the exposure calculations are presented for scenario 2. The final column gives the margins of safety. Table 4: Exposure to plasticizers in scenario 2 (professional use) plasticizer NOAEL (mg/kg migration 1 exposure Margin of safety bw/day) µg/ 10 cm 2 /min mg/(kg bw x day) (rounded value) DEHP 5 23.9 0.21 20 DINP 15 37.4 0.33 50 DIDP 15 55.4 0.5 30 DINCH 100 8.9 0.08 1300 TXIB 30 1.1 0.010 3000 DEHA 28 1.4 0.012 2300 nonylphenol 1.5 (LOAEL) 1.4 0.012 130 DEHT 79 2.1 0.019 4200 1 Maximum value found As can be seen from Table 4, within scenario 2 for phthalates the margin of safety may be considerably below 100, the usual minimum required in consumer risk assessments. Thus based on the available migration data, we assess that intensive professional use of erotic articles made of PVC containing phthalates may lead to a health risk. For nonylphenol also a possible risk was found (relatively low margin of safety compared to LOAEL). This however was based on a single measurement only. For other non-phthalate plasticizers including DINCH and DEHT wide margins of safety were found indicating absence of any health risk even in the scenario of intensive professional use. The above calculation of margins of safety represents a screening for possible health effects based on worst case estimate of exposure. Where margins of safety are below 100 this indicates a possible risk. Major uncertainties in this risk assessment are the lack of reliable information on the use pattern by consumers and professionals of these products and the limited number of measurements made. There is also uncertainty about the relevance of the migration measurement method used for the vaginal and anal exposure situations and about the degree of vaginal and anal absorption of the plasticizers. Determining the likelihood of an actual risk and its size would require more in-depth risk analysis including further research concerning the exposure situation, primarily concerning the pattern of use of these products by consumers and professionals.

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RIVM (2009) Risk assessment non-phthalate plasticizers in toys. Report dated: 9 November 2009. Report to the Dutch Food and Consumer Product Safety Authority (VWA). SCF (Scientific Committee for Food). Report of the Scientific Committee for Food on di-2-ethylhexyladipate; opinion expressed the 16 December 1994; (1997). http://ec.europa.eu/food/fs/sc/scf/reports/scf_reports_36.pdf (Retrieved on 2 June 2010) VWA (2009) Consumentenproducten in de eroticabranche. Factsheet. Deelprojectnummer Marktkennis ND08181A Thema: Cosmetische producten en Lichaamsverzorging. Voedsel en Waren Autoriteit, Afdeling Signalering en Ontwikkeling, Regio Noord. Report dated June 2009. [In Dutch] WHO (2004) Di(2-ethylhexyl)adipate in Drinking-water. Background document for development of WHO Guidelines for Drinking-water Quality. WHO/SDE/WSH/03.04/68 English only.