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Description of key information

Short description of key information on bioaccumulation potential result: 
The test substance does not undergo noticeable metabolism or appreciable degradation. Furthermore, toxicokinetic and metabolic data suggest no evidence of bioaccumulation (Jeffcoat, 1985). Experiments with finished textiles showed that formaldehyde or some breakdown product of DMDHEU could be released from the cloth treated with the textile finishing resin, but preferentially bound to the skin in small amounts and only poorly penetrated the epidermis, and that the absorption rate could be modified by surrounding conditions. In monkeys representing a more similar model of human skin no appreciable skin penetration could be demonstrated.

Key value for chemical safety assessment

Additional information

Several toxicokinetic studies with radiolabelled substance showed that oral and dermal absorption of the test substance takes place to a certain extent with dermal absorption being considerably lower than oral absorption. The substance does not undergo noticeable metabolism or appreciable degradation. Furthermore, toxicokinetic and metabolic data suggest no evidence of bioaccumulation.

Basic toxicokinetics:

The following evaluation of basic toxicokinetics is based on the assessment in course of the OECD SIDS program, 2002:

“Toxicokinetic studies were performed with DMDHEU still containing chemical by-products from chemical synthesis which were presumably identical to the two isomers of 1-(mono)methylol-4,5-dihydroxyethylene urea (MMDHEU):90% DMDHEU,10% MMDHEU). No attempts were made to isolate DMDHEU since no successful procedures were available (Jeffcoat, 1985).

After intravenous administration of ca. 50 mg/kg bw of 14C-DMDHEU (prepared from 14C urea) to male F-344 rats, excretion of 14C was rapid and almost entirely via the urine (Jeffcoat, 1985): Within 6 h some 85 %, after 24 h ca. 95%, and after 72 h about 96% of the radioactivity was recovered in the urine; minor amounts were found in the feces, accounting for some 2.2% in 24 h; less than 0.2% was exhaled as 14CO2 in 48 h. Within 0.5 h, an average of 26% of the dose was collected in the urinary bladder contents; tissues containing significant fractions of the dose after this period were the skin (13%), muscle (12%), blood (6%), liver (6%), and kidney (5%). These levels were reduced by a factor of 4 to 12 after 2 h p.a. By 72 h p.a., less than 0.5% of the dose remained in the tissues, most of it in the muscle (0.3%). Urinary analysis (HPLC radiochromatogram) revealed that the profile of the excreted components correlated approximately with the composition of the test material (see above), indicating to negligible or no metabolism or degradation.

After oral application of 14C-DMDHEU (by gavage) to rats, the percentage fraction absorbed from intestine, based on urinary excretion, was increased in relation to the dose for unexplained reasons (Jeffcoat, 1985): 17% at ca. 500 mg/kg bw, 28% at ca. 1000 mg/kg bw, and 38% at ca. 2000 mg/kg bw. The distribution pattern in the body was similar to that found after i.v. injection. More than 90% of the radioactivity that was recovered in the urine was excreted within 24 h. After 72 h, residual quantities of radioactivity (<10 μg DMDHEU equivalents/g tissue, except higher amounts in intestine and cecum) were still left in the tissues and eliminated in delayed fashion.

Dermal absorption in rats of14C-DMDHEU from a non-occluded dose site over a 144 h exposure period was ca. 5% of the applied dose for doses of 13 and 3.5 mg/cm² and ca. 1% of the applied dose for a dose of 0.3 mg/cm². Partial occlusion of the dose site resulted in a more than 4-fold increase in dermal absorption, probably due to increased hydration of the skin (Jeffcoat, 1985).

For the purpose of investigating dermal penetration from cotton-based fabrics, DMDHEU was prepared by two synthetic methods using 14C-labelled formaldehyde (Robbins and Norred, 1984).rabbits were treated for periods up to 48 h with fabric patches (10 x 12 cm) pretreated with defined quantities of the test material. Any interference with evaporations from the fabric was prevented by using a specially constructed housing chamber for the animals. Formaldehyde was studied in simultaneous groups for comparison. The levels of radioactivity recovered from the skin were small, yet varied with the degree of occlusion of the patch, presence or absence of perspiration, type of DMDHEU synthesis, and the type of fabric. After occlusive treatment 1 to 1.4 %, after semi-occlusive bandage only 0.1 to 0.12% of the applied dose was found, i.e. a factor of ca. 10 less than observed under stringent, i.e. occlusive conditions. Perspiration in combination with occlusion, i .e. the most severe conditions increased skin incorporation by a factor of 1.8 (2.6% of the total dose contained in the patches). In muscle tissues underlying this skin, and in other tissues only insignificant levels of radioactivity (0.001 up to 0.005% of the activity in cloth) could be detected. This indicates that the mate rial released from the treated textile is bound by skin and penetrates the dermis poorly, according to the authors. The highest amounts of exhaled CO2were below 0.02 %, but detectable. In none of these penetration studies it could be clarified where the radioactivity in tissues resulted either from DMDHEU, Formaldehyde or other degradation products.

A further study was conducted in rhesus monkey, which is according to the investigator ".....the model more closely resampling human skin…" (Jeffcoat, 1984). The application was performed with fabrics (96 cm²) treated with 14C-DMDHEU (prepared from 14C-formaldehyde) to monkeys over 48 hours at the skin of back either dry or with arteficial perspiration. Even though the level of radioactivity used was low, essentially all of the 14C activity was found to remain on the textile fabric following the exposure to monkey's skin; the level of 14C transferred from the fabric to the skin was at a level almost indistinguable from background. An average of 0.12 μCi of 14C (equivalent to 0.029%) of the activity could be detected in or on the skin lying underneath the fabric. In expired CO2, urine, feces, blood, muscle, adipose, liver, lung, kidneys, spleen, brain and testes no radioactivity (at or near background level) could be detected. Thus, no appreciable penetration from treated fabric could be demonstrated.”

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