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Toxicological information

Basic toxicokinetics

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Objective of study:
absorption
distribution
excretion
Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
Radiolabeled Dechlorane Plus was synthetized from 14C-hexachlorocyclopentadiene and 1,4-cyclooctadiene and purified after TLC separation with hexane by LC purification in tetrahydrofuran. The ratio of isomers was 5.4 : 1.
(14C) Dechlorane Plus: purity: 99,2%
Radiolabelling:
yes
Remarks:
31.5 mCi/mmol 14C

Test animals

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.

Administration / exposure

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.
Doses / concentrations
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

Results and discussion

Main ADME resultsopen allclose all
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

Toxicokinetic / pharmacokinetic studies

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.
Toxicokinetic parametersopen allclose all
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

Metabolite characterisation studies

Metabolites identified:
no

Applicant's summary and conclusion

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.