diuron (ISO); 3-(3,4-dichlorophenyl)-1,1-dimethylurea

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
In rats Diuron is rapidly absorbed, metabolised and excreted after single and repeated oral and inhalation exposure.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Refer to basic toxicokinetics.

Discussion on bioaccumulation potential result:

Radio-labelled Diuron was used to investigate its biokinetic behaviour in the Wistar rat (Weber and Abbink, 1988). The substance was administered to male and female rats in a single oral dose of 5 or 200 mg/kg bw, or a single intravenous dose of 5 mg/kg body weight. Animals of both sexes were also given fifteen daily oral doses of 5 or 200 mg/kg body weight. A bile cannula was inserted prior to treatment of the male rats given the single 5 mg/kg bw oral dose. The radioactivity in the excreta, blood and bile was measured at various times. The radioactivity in the tissues and the carcass was determined at the time of sacrifice. The recovery rate ranged from 92 to 107% of the radioactivity administered.

The radioactivity was almost completely absorbed following oral administration of Diuron. A total of more than 95% of the recovered radioactivity was thus found in the urine (57.4%), bile (37.7%) and in the residual body (0.5%) in animals with bile fistulas. The levels of radioactivity in the blood reached a peak 1.7 to 6.8 hours after treatment. Thus, the absorption is relatively quick and almost complete.

The radioactivity was rapidly eliminated from the animal body. More than 97% of the balanced radioactivity was eliminated from the body via urine and faeces within 72 hours after treatment in all the animal groups. Elimination was mainly via the urine (68 – 87% of total dose), 50% of the total being eliminated within eight hours after treatment and 90% within 12 hours in nearly all cases. Male rats with bile cannulae eliminated about 38% of the recovered amount in the bile within 48 hours, about 57% in the urine, and only about 4% in the faeces indicating entero-hepatic circulation.

Only a very small amount of radioactivity (0.01%) could be detected in the expired air within three days after oral administration of a single 200 mg/kg bw dose.

Only low levels of radioactive residues were found in the animal excluding the gastrointestinal tract three days after treatment (0.5 - 0.8% of the balanced radioactivity following a single dose, and 1.1 - 2.5% after multiple doses). The dose-normalised concentrations in the animal excluding the gastrointestinal tract after a single dose were P = 0.0054 - 0.0067. The relative concentrations rose by a factor of 3 - 5 after multiple doses. This indicates that the tissues were not saturated by the 15 multiple doses indicating accumulation to be unlikely. The overall tissue concentration was very low due to the fast excretion of the radioactivity.

Absorption, distribution and elimination of Diuron were independent from dose levels and administration.

 

In addition, the metabolism of Diuron in the Wistar rat following inhalation was investigated (Pauluhn and Eben, 1986). Animals were exposed to Diuron concentrations of 4.1, 37.4 or 268.1 mg/m³over periods of four and eight weeks. The urine of the individual animals was collected over a period of 18 hours following the exposure and extracted. Aliquots were acid-hydrolysed. The percentages of the metabolites were based on the molecular weight of Diuron, and on the amount of Diuron inhaled over a period of one day.

The major metabolite formed after inhalation of Diuron was 3,4-dichlorophenyl-urea, which was exclusively eliminated in the form of the free compound (3.6 - 13.3%). Other metabolites, e. g. 3,4-dichlorobenzenamine and N-(3,4-dichlorophenyl)-N’-methyl-urea, were excreted as conjugates only. The unchanged substance (0.1 - 0.2%) was only detected in the urine of animals from the two highest dose groups. A total of 6.1 - 18.6% of the daily inhaled quantity of Diuron was excreted in the form of the compounds mentioned.