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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

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Diss Factsheets

Administrative data

Link to relevant study record(s)

Description of key information

Rapid dermal absorption 19.5 to 21.5%, after 72 hours where the urine was the main route of elimination, Dunsire & Paul (1991).

Rapid dermal absorption 23 to 27% after 72 hours, urine the main route of elimination, Api (2004).

Key value for chemical safety assessment

Additional information

Dunsire & Paul (1991) and Api (2004) have been provided as a weight of evidence, providing information on the dermal absorption, desorption and elimination of the test material. The methodology followed for both studies were in most parts the same. The radiolabelled test material was applied to rats at concentrations of 1000, 100 and 10 mg/kg, formulated in diethyl phthalate. The test material was applied on gauze to a sight clipped free of hair and secured with a semi-occlusive dressing for 6 hours. After which the site was washed with diethyl phthalate and animals were monitored in metabolism cages until 72 hours post exposure. Urine, faeces and expired air were collected for 72 hours after dosing and at 72 hours post dose blood, selected tissues and the remaining carcasses were analysed for radioactivity.

Under the conditions of the Dunsire & Paul (1991) test, radioactivity was steadily absorbed through the skin and eliminated almost exclusively in urine; 3, 2 and 1% of the dose 6 h after dosing at the high, medium and low dose levels respectively and 19, 19 and 18%, respectively, at 72 h. Less than 1% of the dose was eliminated in faeces over the 72 h period at all dose levels, and in general less than 1% of the dose was retained in the carcass at 72 h post dose. Varying amounts of dose were still associated with the dose site at 72 h post dose (approximately 2-7%) and of this material some was bound to the skin - the amount bound also varied considerably (approximately 18-37% of observed radioactivity). Small amounts of radioactivity (generally <0.5% dose) were associated with non dosed skin at this time - as the bulk of this material could be removed with solvent it would seem likely to be due to contamination from the dose site. Investigation of concentrations of radioactivity in tissues at 72 h post dose revealed a linear relationship between dose levels. In all cases, highest concentrations were observed in the kidney and concentrations in all tissues examined were generally higher than plasma concentrations. All animals were observed grooming extensively after the removal of dose patches and cleaning of the site, at 6 hours post application. Therefore there is a possibility that some oral ingestion occurred. The average rate of dermal absorption over the 72 hour observation period was determined to be between 19.5 and 21.5%.

Under the conditions of the Api (2004) test, the results clearly indicate that the 14C-label from the test material was about 30% absorbed. Additionally the study indicated that the 14C-label had steady dermal penetration over 72 h that totalled 23–27% of the administered dose. This range was calculated from the amount of radioactivity found in urine, faeces, tissues, carcass and washed, treated skin. Most of the absorbed radiolabel was eliminated in the urine (approximately18–19% of administered dose) with a small amount being excreted in faeces (approximately 0.3–0.8%). The faecal excretion may be due to dermal absorption followed by biliary excretion into the gastrointestinal tract. The absorbed dose that was retained in the animal body 72 h after dosing was approximately 0.4–0.7%, with low levels of radioactivity also measured in the liver, kidney and gastrointestinal tract (approximately 0.01–0.03%). Larger amounts of radioactivity (ca. 2–7% dose) were still present on the dosed area of the skin at study termination. Even after the dosed area was washed to remove any ‘free’ 14C-labeled material, 18–37% of the 14C-label remained. This residual label appeared to be bound to the skin.

Both studies were performed to a good standard with a sufficient level of reporting to assess the quality of the information provided. The studies were assigned a reliability score of 2 in line with the principles for assessing data quality as defined in Klimisch (1997).

The conclusion that the test material is rapidly absorbed through the skin and the main route of elimination is the urine was taken forward for risk assessment.