Registration Dossier

Toxicological information

Exposure related observations in humans: other data

Currently viewing:

Administrative data

exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study weel documented, meets generally accepted scientific principles, acceptable for assessment.

Data source

Reference Type:
Urinary excretion of ethylenethiourea in five volunteers on a controlled diet (multicentric study).
Aprea C, Betha A, Catenacci G, Lotti A, Minoia C, Passini V, Pavan I, Roggi C, Ruggieri R, Soave C, Sciarra G, Vannini P and Vitalone V.
Bibliographic source:
Sci.Tot.Environ. 203 : 167-179.

Materials and methods

Type of study / information:
Exposure of the general population to ETU
Endpoint addressed:
not applicable
Test guideline
no guideline followed
Principles of method if other than guideline:
Measure of ETU in food.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Details on test material:
Other name : Ethylenethiourea (ETU)


Ethical approval:
confirmed, but no further information available
Details on study design:
A group of five male non smoker volunteers consuming food and wine assayed for ETU. The study covered a period of 8 days.
The subjects were in good health and had normal liver and kidney function. They were not occupationally exposed to ETU.

Analysis :
On Days 1 and 2 of the experiment, ail the urine passed in 24 h was collected in a single container: from 08.00 h on Day 1 to 08.00 h on Day 2 and then from the latter time to 08.00 h on Day 3. On the days that followed, urine passed in the 24 h was collected in three separate containers, one for each 8-h period, namely from 08.00 h to 16.00 h, from 16.00 h to 24.00 h and from 24.00 h to 08.00 h. The analytical procedure involved extraction from urine with dichloromethane and inverse phase HPLC analysis with spectrophotometric detection at 232 nm. The detection limit was 1µg/1; the recovery and coefficient of variation were 90% and 10%, respectively.
Exposure assessment:
Details on exposure:
The volunteers took meals (breakfast, lunch and dinner) together during the 8 days of the study, and ate the same quantities of each food. The food was analysed day by day, divided into the three categories: wine, fruit and vegetables, other foods. During the experiment, none of the subjects consumed any foods or drinks other than what they were given. The three meals were balanced in relation to the nutritional requirements of the volunteers.
In the first 2 days (Days 1 and 2), no wine, fruit or vegetables were served. On Days 3, 4 and 5, wine, fruit and vegetables were included in the diet. On Days 6 and 7, wine, fruit and vegetables were again eliminated from the menu. On Day 8, these two categories were again included.

Results and discussion

The concentration of ETU measured in the red wine consumed by the volunteers throughout the experiment was 8.8 µg/l. Since 600 ml of wine was consumed on the days in which wine was part of the diet, the daily intake of ETU was 5.28 µg for each volunteer. This corresponds to a dose (mean ± S.D.) of 0.070 ± 0.004 µg/kg body wt (range 0.068-0.221 µg/kg body wt). Since the concentration of ETU was below the detection limit in most food sample, it was not possible to evaluate dietary intake of ETU. Assuming ETU concentrations equal to the detection limit for the 8 days of the study, the daily intake of ETU would be 0.128 ± 0.042 µg/kg body wt (mean ± S.D.) (range 0.068-0.221 µg/kg body weight).

Applicant's summary and conclusion

In the general population not occupationally exposed to pesticides, the main route of exposure to ETU is through the food chain.
In the present study, assay of urinary ETU in subjects not occupationally exposed to pesticides was associated with assay of ETU in food and wine in the daily diet. Urinary excretion of ethylenethiourea was monitored in non-smoking male volunteers given a diet with no detectable ethylenethiourea except in wine (8.8 µg/L) for 8 days. An average of 48.3% of the ethylenethiourea ingested from wine was excreted unmodified in the urine.
Executive summary:

Urinary excretion of ethylenethiourea (ETU) was monitored for 8 days in a group of five male non-smoker volunteers on a diet, the items of which were assayed for ETU and carbon sulphide. Urinary excretion of ETU reflected the consumption of wine, fruit and vegetables. Urinary ETU concentrations ranged from 0.6 to 6.7 µg/g creatinine. ETU concentrations in the food eaten by the volunteers were generally below the detection limit whereas in wine 8.8gg/1ETU was detected. Evolution of carbon sulphide by food samples ranged from 0.03 to 0.17 mg/kg. Mean (±S.D.) daily intake of ETU in wine was 3.5 ± 0.2% of the acceptable daily intake (ADI): 0.070 ± 0.004 µg/kg body wt. During the 8 days of the study, an average of 48.3% of the ETU ingested in wine was excreted unmodified by the kidneys. Twenty-four-hour urinary excretion of ETU was significantly correlated with daily intake of ETU (r = 0.768) and CS2evolved by the daily food items (r = 0.414).