Pesticide residues in food — 2006: Toxicological ... - ipcs inchem

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In order to follow the fate of cyromazine in the skin more closely, the skin was fractionated
by tape-stripping the stratum corneum. At all doses the radioactivity remained in/on the treated skin
area and was associated with the stratum corneum, i.e. 11–18% of the lowest dose, 12–16% of the
intermediate dose, and 1–3% of the highest dose. The lower skin layers after skin-stripping, i.e. corium
and subcutis, showed insignificant concentrations of radioactivity, indicating that the radioactivity
present in the stratum corneum was not available for further penetration into the lower skin layers.
The systemically absorbed dose was rapidly eliminated mainly via the urine. Elimination via the
faeces was only a minor route of excretion (Hassler, 2002a).
Penetration of [U- 14 C triazine]cyromazine (specific activity, 2590 kBq/mg, for the highest
dose, the labelled test substance was diluted with non-labelled cyromazine to a specific activity of
70 kBq/mg; radiochemical purity, 98%), formulated as a WP containing 7.5% active substance,
through rat and human epidermis was compared in vitro. The epidermal membranes were mounted
to flow-through cells and each diffusion cell received a 6 μl aliquot of the application solution.
Cyromazine was applied at a concentration of 1.1, 22 or 834 μg/cm 2 to rat or human epidermis for
6 h (Table 19). The two lowest doses reflected typical concentrations recommended for the use in the
field, while the highest dose represented the concentrate formulation (active ingredient, 75 g/l).
Table 19. Dermal penetration of cyromazine through rat and human epidermis in vitro
Species Dose Applied dose Concentration
mg/cell a mg·cm −2a KBq/cell (mg·cm -3 ) a
Lowest 0.7 1.1 1.9 0.12
Rat
Intermediate 14 22 37 2.4
Highest 534 834 37 89
Lowest 0.7 1.1 1.9 0.12
Human Intermediate 14 22 37 2.4
Highest 534 834 37 89
a
Expressed as cyromazine
From Hassler (2002b)
Rat epidermis was prepared from male HanBrl:WIST (SPF) rats aged about 9 weeks. Human
epidermis was prepared from abdominal cadaver skin from Caucasian donors. Perfusates were
collected at defined time-points. Twenty-four hours after application, the skin membrane surface
was rinsed with ethanol (10 ml) and the radioactivity in the skin rinse was determined by LSC. The
skin membrane was removed from the in-line cells and dissolved in tissue solubilizer before LSC.
The receptor chamber was washed with ethanol and radioactivity determined by LSC. The study was
conducted according to the principles and practices of GLP (with QA certificate) and the protocol
was in accordance with OECD TG 428 (2000).
A TLC check for test substance stability of the formulated material revealed that [U- 14 C triazine]
cyromazine represented more than 98% of the radioactivity. The permeability check of the membranes
revealed mean permeability constants (Kp) of tritiated water in the range of 0.54–0.98 × 10 -3 cm/h
and 0.53–0.96 × 10 -3 cm/h for rat and human epidermis, respectively. At the end of the experiment,
the skin rinse was analysed. In both groups, unchanged cyromazine amounted to more than 97% of
the radioactivity present in the skin rinse. It was concluded that cyromazine remained unchanged for
24 h on the epidermis.
Within 24 h, 16.9% of the lowest dose, 19.1% of the intermediate dose, and 0.25% of the
highest dose penetrated the rat epidermis membrane (Table 20), corresponding to penetration of
0.19 μg·cm -2 , 4.21 μg·cm -2 , and 2.07 μg·cm -2 , respectively. The flux, which reflects the penetration
CYROMAZINE X-X JMPR 2006