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Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: only few animals were used
Objective of study:
absorption
distribution
excretion
Qualifier:
no guideline followed
Principles of method if other than guideline:
Dechlorane Plus was administered once orally to few rats at two dose levels. Excretion via urine, faeces, and expired air and residual concentrations in organs and carcass were determined.
GLP compliance:
no
Radiolabelling:
yes
Remarks:
31.5 mCi/mmol 14C
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
The rats were maintained in all-glass metabolism cages with separate collection of urine and faeces.
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
Single oral administration by gavage in corn oil, one group was fed non-labelled Dechlorane Plus at 1% in the diet for 14 days before gavage administration.
Duration and frequency of treatment / exposure:
Single administration, one group was fed non-labelled Dechlorane Plus at 1% in the diet for 14 days before gavage administration.
Dose / conc.:
1 mg/kg bw/day
Remarks:
Doses / Concentrations:
1 mg/kg bw corresponding to 4.8 µCi or 113 mg/kg bw corresponding to 3.8 µCi
No. of animals per sex per dose:
3 females and 2 males at 1 mg/kg bw, 2 females at 113 mg/kg bw, 2 females at 1 mg/kg bw with prior administration in diet.
Control animals:
no
Details on study design:
One rat was used for monitoring radioactivity in exspired air, one rat was used for monitoring the time course of blood levels for 48 hours after administration of 1 mg/kg bw, of all remaining rats, urine and faeces were collected for 4 days, then the animals were killed and radioactivity in 17 different organs and tissues and in carcass were determined.
Details on dosing and sampling:
3 females and 2 males at 1 mg/kg bw, 2 females at 113 mg/kg bw, 2 females at 1 mg/kg bw with prior administration in diet.One rat was used for monitoring radioactivity in exspired air, one rat was used for monitoring the time course of blood levels for 48 hours after administration of 1 mg/kg bw, of all remaining rats, urine and faeces were collected for 4 days, then the animals were killed and radioactivity in 17 different organs and tissues and in carcass were determined.
Statistics:
not reported
Type:
absorption
Results:
Almost no absorption after oral administration, mostly more than 90% of the dose was excreted unchanged in faeces
Type:
distribution
Results:
Almost no absorption after oral administration, mostly more than 90% of the dose was excreted unchanged in faeces
Type:
excretion
Results:
Almost no absorption after oral administration, mostly more than 90% of the dose was excreted unchanged in faeces
Details on absorption:
After single oral administration of 1 mg/kg bw, 83.5% of the dose was excreted in faeces by females and 92.7% of the dose by males indicating maximum absorption of 16.5% in females and 7.3% in males. After single oral administration of 113 mg/kg bw to females, 96.5% were excreted in faeces indicating maximum absorption of 3.5%. After single oral administration of 1 mg/kg bw to rats pretreated with the nonlabelled substance at 1% in diet for 14 days, 102% of the dose were excreted in faeces indicating almost no absorption.
Details on distribution in tissues:
The concentrations in all organs and tissues investigated, besides liver and residual carcass, were below 1 ppm. At the high dose, the liver of females contained 1.66 ppm and the residual carcass contained 1.25 ppm. All organs and tissues besides liver and residual carcass contained well below 1% of the dose. The livers of males and females at the low dose contained 1.60 and 2.29% of the dose. The residual carcass of males and females at the low dose contained 5.09 and 5.05% of the dose and of females at the high dose 0.90% of the dose. The carcass of pretreated females contained 4.44% of the dose.
Details on excretion:
Almost all of the administered dose was excreted unchanged in faeces. At 4 days after administration, low dose females had excreted 0.07% of the dose in urine and 83.5% in faeces, low dose males 0.01% in urine and 92.7% in faeces, high dose females 0.009% in urine and 96.5% in faeces, and pretreated low dose females 0.03% in urine and 102% n faeces. Excretion in expired air amounted to 0.004% of the administered dose within 4 days.
Key result
Test no.:
#1
Toxicokinetic parameters:
Cmax: about 0.27 ppm at a dose of 1 mg/kg
Key result
Test no.:
#1
Toxicokinetic parameters:
Tmax: about 12 hours at a dose of 1 mg/kg
Metabolites identified:
no
Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results almost no absorption after oral intake
Only minimal absorption after oral administration.
Executive summary:

Dechlorane Plus as radiolabeled substance was administered once orally by gavage to a small group of male and female rats at a dose level of 1 mg/kg bw, and to small groups of female rats either at a dose level of 113 mg/kg bw or at 1 mg/kg bw preceeded by administration in the diet at 1% for 14 days as nonlabeled substance. Urine and faeces were collected for 4 days, radioactivity in exspired air was determined in one rat, and the time course of blood levels was determined in one rat over 48 hours. After 4 days, the rats were killed and radioactivity in a large range of organs and tissues and in residual carcass were determined. Only small amounts around 10% of Dechlorane Plus were absorbed after oral administration and widely distributed in the body. The highest concentration was found in the liver. About 90% of the substance was excreted unchanged in faeces. Excretion in urine and exspired air was minimal. At 4 days after administration, between 1% and 8.5% of the dose administered was found in the carcass.

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 hours
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Only 3 rats per group were used, more than 100% of the substance was detected in faeces indicating that the results are not completely reliable.
Objective of study:
toxicokinetics
Qualifier:
no guideline followed
Principles of method if other than guideline:
Two groups of 3 rats each were given a single oral dose of 0.57 mg of radiolabeled Dechlorane Plus and were killed at 4 or 24 hours after administration. Dechlorane Plus was determined by liquid scintillation in blood, kidneys, liver, urine, and faeces.
GLP compliance:
no
Radiolabelling:
yes
Remarks:
14C-labeling with 27.6 µCi in 0.5 ml suspension
Species:
rat
Strain:
Sprague-Dawley
Sex:
not specified
Details on test animals and environmental conditions:
no details reported
Route of administration:
oral: unspecified
Vehicle:
other: water with 5% Tween 80 and 5% gum arabic
Duration and frequency of treatment / exposure:
Single administration
Dose / conc.:
0.57 other: mg
Remarks:
Doses / Concentrations:
0.57 mg per rat
No. of animals per sex per dose:
3 rats per group, sex unspecified, two groups given the same dose
Control animals:
no
Positive control:
none
Details on study design:
Two groups of 3 rats each were given a single oral dose of 0.57 mg of radiolabeled Dechlorane Plus and were killed at 4 or 24 hours after administration. Dechlorane Plus was determined by liquid scintillation in blood, kidneys, liver, urine, and faeces.
Details on dosing and sampling:
After a single oral dose of 0.57 mg radiolabeled Dechlorane Plus, 3 rats were killed after 4 hours and 3 rats were killed after 24 hours and samples of blood, kidneys, and liver obtained. Urine and faeces were collected during the 4 hours and 24 hours between administration and death. In the 4 hours group, urine in bladder was gained.
Statistics:
none
Type:
absorption
Results:
6% or less than 6%
Type:
distribution
Results:
maximum of 4.6% of the dose administered in liver and less than 1% in kidneys, less than 2% in total blood volume
Type:
metabolism
Results:
one metabolite was detected in liver homogenate but not identified
Type:
excretion
Results:
76.13%, 104.8%, and 103.01% of the dose were found in faeces within 24 hours, less than 1% was found in urine
Details on absorption:
The sum of total radioactivity detected in blood, kidneys, liver, and urine was at or below 6% of the total dose indicating 6% or less absorption.
Details on distribution in tissues:
Only blood, liver and kidneys were investigated. Blood (total blood volume) contained less than 2%, kidneys contained less than 1%, and liver contained less than 5% of the dose administered.
Details on excretion:
Within 4 hours after oral administration, less than 0.1% was excreted in urine, within 24 hours after oral administration, less than 1% was excreted in urine, and a mean of 94.6% (76.13%, 104.8%, 103.01%) were excreted in faeces.
Metabolites identified:
no
Details on metabolites:
One metabolite found in the liver
Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
Dechlorane Plus is only poorly absorbed after oral administration at a maximum of 6% of the dose administered. HIghest concenctrations are found in the liver. Urinary excretion is less than 1% of the dose, absorbed substance appears to be excreted in faeces.
Executive summary:

The toxicokinetics of radiolabeled Dechlorane Plus was determined in groups of 3 rats given a single oral dose of 0.57 mg per rat. 3 rats each were killed at 4 or 24 hours after administration, and the concentrations of Dechlorane Plus were determined in blood, liver, and kidneys by liquid scintillation. Urine and faeces were collected between drug administration and death and analyzed for Dechlorane Plus. Only minimal amounts were absorbed, while faecal excretion amounted to a mean of 94.6% of the dose. Urinary excretion was below 1% of the dose. The highest concentration was found in the liver followed by blood, while kidneys contained only traces of the radiolabeled substance.

Description of key information

The absorption, distribution and excretion of Dechlorane Plus was examined in two studies with oral administration to rats. Absorption from the gastrointestinal tract was between 6 and 16.5%, most of the administered substance was not absorbed and excreted unchanged in faeces. Minimal amounts by far below 1% of the dose were excreted in urine and exhaled air. Once absorbed, Dechlorane Plus was widely distributed in the body with highest concentrations in the liver. One metabolite was detected in the liver but not identified.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
10

Additional information

Dechlorane Plus was only poorly absorbed by rats after oral administration. Once absorbed, it was widely distributed throughout the body reaching highest concentrations in the liver. Excretion was almost exclusively unchanged in faeces, while only minimal amounts were excreted in urine and exhaled air. As the excretion in urine and exhaled air was much lower than the total absorption, excretion may occur via bile. Residual amounts between 1 and 8.5% of the dose were still found in the carcass at 4 days after administration. One metabolite was detected in the liver but was not identified.