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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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Objective of study:
absorption
excretion
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The aim of the present study was to check whether the test substance is absorbed after oral administration . This was done by analyzing the urine of the animals by HPLC . The test substance was administered to 5 juvenile Wistar female rats (22 days of age at the beginning of the administration period), and to 2 adult Wistar female rats (88 days of age at the beginning of the administration period) per group for 4 consecutive days twice daily by gavage .
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Sulisobenzone
EC Number:
223-772-2
EC Name:
Sulisobenzone
Cas Number:
4065-45-6
Molecular formula:
C14H12O6S
IUPAC Name:
5-benzoyl-4-hydroxy-2-methoxybenzenesulfonic acid
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: supplied by Dr. K. Thomae GmbH, Biberach/ Riss, Germany
- Age at study initiation: 22 (juvenile animals) and 88 (adult animals) days old
- Weight at study initiation: 45.9 - 57.2 g (juvenile animals) and 249.5 - 265.2 g (adulte animals)
- Housing: animals were housed individually in metabolic glass cages (Jencons).
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 48 hours
ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24 °C
- Rel. humidity: 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
The test substance was administered at an exposure level of 1000 mg/kg bw/day, to 5 juvenile Wistar female rats/group and to 2 adult Wistar female rats/group. A dose volume of 10 mL/kg body weight (i.e. 5 mL/kg twice daily, once in the morning and once in the afternoon) was used. The calculation of the volume administered to each female was based on the individual body weight identified daily before the first of two daily doses were administered.
Duration and frequency of treatment / exposure:
The test substance was administered twice daily for 4 consecutive days
Doses / concentrations
Dose / conc.:
1 000 mg/kg bw/day (nominal)
No. of animals per sex per dose / concentration:
5 juvenile Wistar female rats/group and 2 adult Wistar female rats/group.
Control animals:
yes, concurrent vehicle
Positive control reference chemical:
not applicable
Details on study design:


- Viability was checked twice daily
- Body weights of the animals were recorded daily before the first of two daily intubations throughout the study period.
- The state of health of the animals was checked each day.
Details on dosing and sampling:
Urine of each animal was collected from day 0 to 4 and analyzed for the test item by HPLC.

The urine samples of single juvenile animals per group (n=5) were pooled, respectively. Urinary samples of the adult animals (n=2 per group) were analyzed individually.
Before HPLC-analysis, urinary samples were centrifuged for 5 min at 12000 rpm in an Eppendorf centrifuge 5414. One mL of the supernatant was diluted in 99 mL acetonitrile. This dilution was used for HPLC-analysis.
HPLC-conditions were as follows:
column eluant: Polygosil 60, 7C18, 250 x 4 mm 20 % acetonitrile + H3PO4 (1000 + 1 mL) 80 % aqua bidest. + H3PO4 (1000 + 1 mL)
detection: UV, 287 nm
Under these conditions, the retention time of the test item was about 2.5 min. Using the analytically determined concentration of the test substance in urine and the amount of urine, the total amount of the test substance in urine was calculated and set into perspectives with the total amount applied.
Statistics:
Statistical comparison between groups were carried out using the Dunnett-test (two-sided). Levels of significance were chosen as p<0.05 (*) and p<0.01 (**). All values are expressed as group means ± SD (N=10 animals per group).

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on excretion:
Juvenile animals, 1000 mg test item/kg bw/d:
- 9.4 % of the applied dose of the test itdem in urine

Adult animals, 1000 mg test item/kg bw/d:
- 23.3 and 16.6 % of the applied dose of the test item in urine

Any other information on results incl. tables

Juvenile animals, 1000 mg test item/kg bw/d:

- statistically significantly decreased mean body weight gain on study days 1 to 2 of the administration period

Adult animals, 1000 mg test item/kg bw/d:

- statistically significantly decreased mean body weight gain on study days 2 to 3 of the administration period

No clinical findings occurred in the course of the study in both test groups.

Applicant's summary and conclusion

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