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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
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study well documented, meets generally accepted scientific principles, acceptable for assessment There are no specific ADME studies available. In a study with human volunteers, absorption of sodium perborate monohydrate from a mouthwash solution ("Bocosept") by the oral mucosa or the gastrointestinal tract was tested

Data source

Reference
Reference Type:
publication
Title:
Absorption of boron after mouthwash treatment with Bocosept
Author:
Edwall L, Karlen B & Rosen A
Year:
1979
Bibliographic source:
Europ J clin Pharmacol 15, 417 - 420

Materials and methods

Objective of study:
absorption
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Details of this study are given below
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
Sodium perborate monohydrate
IUPAC Name:
Sodium perborate monohydrate
Details on test material:
Bocosept contains 1200 mg sodium perborate and 500 mg sodium bitartrate per package. The substance is dissolved in a small volume of water, the solution is "circulated" in the mouth for about 3 min and then spat out. Treatment twice daily is recommended.
According to the manufacturer the following reactions take place in an aqueous solution of the preparation:
NaBO3 H2O + 3 H2O <--> NaBO2 + H2O2 + 3 H2O
NaBO2 + H2O <--> NaH2BO3
In the presence of sodium bitartrate different boron compounds can be formed.
Radiolabelling:
no

Test animals

Species:
human

Administration / exposure

Route of administration:
other: The substance is dissolved in a small volume of water, the solution is "circulated" in the mouth for about 3 min and then spat out
Vehicle:
water
Details on study design:
The experiments were carried out on 17 subjects with an age of 17 - 56 years. Nine were patients with severe gingivitis (no other known disease), while 8 were healthy.

One-day Studies
One package of Bocosept dissolved in water was administered according to the manufacturer's recommendation to two patients and two healthy volunteers.
The same procedure was repeated immediately after the 1st treatment with 2 patients and 2 healthy volunteers. Blood was collected before and 5, 10, 20, 40, 60, 120, 240 min and 24 hrs after the start of the 1st and 2nd mouthwash. The mouth content was spat out and was analysed for the boron content.

One-week Studies
Mouthwash:
In one series of experiments five patients rinsed their mouth with one dose every morning and evening for 7 days. Blood and urine samples were taken prior to the start of the treatment. Each morning the patient came to the hospital for blood sampling, delivery of the collected 24 hrs urine and for a mouthwash under supervision. After the 7 days of treatment, blood samples were taken and urine was delivered every morning for a further 7 days. One patient was dropped due to lack of co-operation.
Oral ingestion:
Two healthy volunteers swallowed 3 % of a dose of Bocosept (ca. 51 mg) every morning and evening for 7 days. The experimental procedure was the same as described above. Blood and urine analyses were continued for up to 2.5 days after cessation of the intake.
Details on dosing and sampling:
Assay of boron:
The assay for boron in the samples was on evaporation and ashing of the sample in a platinum crucible, formation of a complex with curcumine, and spectrophotometric measurement of UV absorption

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Single Mouthwash
Prior to the experiment, mean blood concentration of boron was 0.04 ug/mL. Two min after completion of the mouthwash the concentration was 0.96 ug/mL with reaching a maximum of 0.14 ug/mL after 2 hrs. The highest individual concentration was 0.2 ug/mL, while the mean concentration was 0.07 ug/mL after 24 hrs. There was no difference in blood boron concentration between patients and healthy volunteers. In two patients with acute ulcerative gingivitis and two healthy volunteers who were given two consecutive doses, the shape and maximal level of the blood concentration curves were similar to those in the experiments with one dose. The highest blood concentration was 0.28 ug/mL in one patient with gingivitis. The mean amount of boron that was spat out was 97 % (94 - 101) of the given dose.

Repeated treatment for 7 days
The mean blood concentration of boron prior to the treatment was 0.07 ug/mL and during the week of treatment the mean concentration was 0.15 - 0.2 ug/mL before the morning dose. Two days after completion of the treatment the mean concentration had returned to control levels. During the week of treatment the mean amount of boron excreted in the urine was 6 - 7 mg/24 hrs decreasing to 2 mg/24 hrs two days after completion of the treatment. The mean total amount of boron excreted in urine during the period from commencement of the treatment until the 4th day after discontinuation was 47.5 mg, i.e. 2.8 % of the total amount administered.
In the experiments with subjects ingesting 3 % of one dose in the morning and evening for one week, the blood concentration of boron before the morning dose was 0.09 - 0.16 ug/mL. The urine excretion of boron amounted to 3.3 - 8.6 mg/24 hrs during the first week.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
Healthy volunteers and patients with gingivitis were treated locally with an boron-containing agent. Blood levels and urinary excretion of boron were examined by a spectrophotometric method. The blood levels during a one-week course of treatment showed a low rate of boron accumulation. The highest concentration was about 0.3 ug B/mL.
It seems more likely that the uptake of boron takes place in the intestine after ingestion of residual amounts from the mouth.
Executive summary:
Healthy volunteers and patients with gingivitis were treated locally with an boron-containing agent. Blood levels and urinary excretion of boron were examined by a spectrophotometric method. The blood levels during a one-week course of treatment showed a low rate of boron accumulation. The highest concentration was about 0.3 ug B/mL. The results are indicating that only a minor amount of boron is absorbed after a mouthwash. This is based on the fact that an appreciable uptake from the oral cavity should be reflected in the blood concentration of boron within the first few minutes, where no such high concentration was observed. In the one week study (swallowing 3 % of a dose of Bocosept [ca. 51 mg]),the blood and urine concentrations were similar compared with those found after the mouthwashes. Therefore it can be concluded that most of the absorption takes part in the gastrointestinal tract. In all experiments blood boron concentrations returned to the initial level within 1 – 2 says after a single mouthwash as well as after completion of prolonged treatment. From these curves a blood half-life of 5 – 10 hrs can be derived and from the observation that the plateau level of boron in blood following long-term administration was reached after only 24 hrs.