cis-4-[3-(p-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine

Endpoint summary

Description of key information

After single oral administration,¹⁴C-Fenpropimorph was rapidly absorbed from the gastrointestinal tract. Absorption was nearly complete at the high dose level and was calculated to about 90 and about 70 % at the low dose for males and females, respectively. After absorption, radioactive material was distributed in all organs and tissues. The excretion of radioactivity was rapid and occurred mainly via urine and faeces, and in the case of the morpholine-labelled-¹⁴C-Fenpropimorph, also in exhaled CO₂.

 

The parent compound was metabolized by several hydroxylation, oxidation, sulfoxylation and demethylation process, combined with cleavage of the morpholine-ring. The decomposition product dimethylmorpholine originates from cleavage of the C-N-bondage of the parent compound. Besides, biotransformation reactions, conjugation with glucoronic acid combined with further degradations and derivative process occured.

The main biotransformation route was hydroxylation of the hydrocarbon chain, followed by a further oxidation step, associated with hydroxylation of the morpholine ring system and cleavage of the morpholine-ring-system.

Dermal absorption:

The dermal absorption of fenpropimorph was studied with concentrations of 0.04, 0.4 and 1.2 mg/cm². For each dose level and sampling point 4 male rats were used. The exposure duration was 8 hours, after which the test substance was washed off. After 8 hours of exposure, 64 - 76% of the administered material could be washed off. The absorbed amount after 8 hours ranged between 6 - 10%, regardless of the concentration, and between 10 - 17% at 24 to 72 hours. Thus, an increase of 30 fold in the concentration resulted in no significant change of the relative absorption, indicating that the process of absorption was not saturated.

The decrease of radioactivity at the application site (from 8 to 72 hours) from 34.13 - 13.64% at 1.2 mg/cm², from 31.10 - 8.04% at 0.40 mg/cm²and from 29.15 - 2.27 % at 0.04 mg/cm², was not associated with a comparable increase in absorbed material. This indicates that the test substance at the site of application, after the wash, is not readily, if at all, available for dermal absorption. The report concludes that the loss was due to exfoliation. Based on the results of the in vitro study, dermal penetration through rat skin is approximately 15 times faster than through human skin, regardless of the dose level.

Based on the results available, a dermal penetration of about 10% can be assumed; which was also confirmed by EFSA in 2008 (see chapter 13).

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

100