3-(2-hydroxyethyl)-p-phenylenediammonium sulphate

Basic toxicokinetics

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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The aim of the study was to investigate the percutaneous absorption under approximately realistic conditions using two different formulations and a test substance solution, the distribution into the organs 72 hours after application, the mode and rate of elimination. 14C labelled test substance was used in order to simplify the analysis.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-(2-hydroxyethyl)-p-phenylenediammonium sulphate

EC Number:

298-995-1

EC Name:

3-(2-hydroxyethyl)-p-phenylenediammonium sulphate

Cas Number:

93841-25-9

Molecular formula:

C8H12N2O.H2O4S

IUPAC Name:

2-(2,5-Diaminophenyl)ethanol sulfate (1:1)

Specific details on test material used for the study:

Test substance : 2-(2,5-Diaminophenyl)ethanol sulphate
Other name : Betoxol
Radioactive test substance : Ring-14C (synthesis by Amersham, England)
Radiochemical purity : 97%

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

other: dermal (3 experiments), oral (2 experiments)

Vehicle:

other: two different hair dyeing formulations (dermal), water (oral)

Details on exposure:

Cutaneous application (experiment A, B, C) : Application occurred once for 30 minutes to the dorsal, median thoracic to lumbar area. The dorsal skin of the animals was clipped one day before application of the test substance using an electric hair clipper (1mm cutterhead). Anaesthesia : 40mg thiopental i.p. per kg bw before administration of the formulations and the solution. Application of the formulations : Spreading evenly until the skin was wetted with a spatula to an area of 3cm x 3cm. Determination of the actual mass applied was by weighing. Application of the solution : The solution was applied and spread evenly until the skin was wetted using a plastic syringe. Rinsing : The formulation or the solution was left for 30 min then scraped off using a spatula followed by rinsing until the rinsing water and the absorbent tissue which was used to dab the skin dry were free of colour. The treated area was covered with 4 layers of gauze fixed by adhesive tape.

Oral application : Sixteen hours before application the rats were deprived of feed and the test substance solution applied by gavage. The actual mass administered was determined by weighing.

Duration and frequency of treatment / exposure:

Seventy two hours

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

1.63 other: mg/cm2

Remarks:

experiment A

Doses / concentrations 2

Dose / conc.:

1.63 other: mg/cm2

Remarks:

experiment B

Doses / concentrations 3

Dose / conc.:

1.67 other: mg/cm2

Remarks:

experiment C

Doses / concentrations 4

Dose / conc.:

15.1 other: mg/kg bw

Remarks:

experiment D

Doses / concentrations 5

Dose / conc.:

15.9 other: mg/kg bw

Remarks:

experiment E

No. of animals per sex per dose / concentration:

Three females and three males were used in each of the five experiments (A-E).

Control animals:

other: oral application of the test substance was used as a reference

Details on study design:

The test substance is a constituent of hair dyeing products. The aim of the study was to investigate the percutaneous absorption under approximately realistic conditions using two different formulations and a test substance solution, the distribution into the organs 72 hours after application, the mode and rate of elimination.

Details on dosing and sampling:

Six samples of each formulation and solutions of the test substance were taken to check the homogeneity and also to determine the specific radioactivity.
Application site washings (rinsings) ie combined samples of scraped off formulations dissolved in methanol/water, solution of shampoo, rinsing water, methanol/water extracts of the absorbent tissue used for drying skin.
Blood samples.
Urine and faeces : Daily collection from the metabolism cages.
The animals were killed after 72 hours (experiments A, B, C, D) and 24 hours (experiment E).
Post mortem organs taken : Adrenals, blood, brain, fat, femur, heart, kidneys, liver, lungs, muscle, ovaries, skin (untreated).

Results and discussion

Any other information on results incl. tables

The mean percutaneous absorptions of the test substance were very low in each of the three experiments. (0.063% for hair dyeing formulation I, 0.077% for hair dyeing formulation II plus hydrogen peroxide, 0.124% for the test substance solution). The 14C labelled compound was excreted to a larger extent via urine (75-86% of the eliminated 14C) and to a lesser extent via faeces (14-25%). The mean excretion within the first 24 hours was fast (87-95% of the eliminated 14C in experiments A to C). Mean 14C concentrations of blood and the 14 analysed organs in experiments A to C were all near or below the detection limit after 72 hours. After oral administration of the test substance the 14C labelled compound was excreted to a larger extent via urine (86% of the eliminated 14C) and to a lesser extent via faeces (14%). The 14C compound excreted within the first 24 hours equated to 99%. Highest 14C cncentrations were detected in the thyroid, liver and adrenals. Lowest detected in testes, fat, femur. The blood level was highest after 35 minutes post administration and declined with an initial half-life of ~50 minutes.

Applicant's summary and conclusion

Conclusions:

The mean percutaneous absorptions of the test substance were low in each of three experiments (0.063% for hair dyeing formulation I, 0.077% for hair dyeing formulation II plus hydrogen peroxide, 0.124% for the test substance solution). The 14C labelled compound was excreted to a larger extent via urine (75-86% of the eliminated 14C) and to a lesser extent via faeces (14-25%). The mean excretion within the first 24 hours was fast (87-95% of the eliminated 14C in experiments A to C). After oral administration of the test substance the 14C labelled compound was excreted to a larger extent via urine (86% of the eliminated 14C) and to a lesser extent via faeces (14%). The 14C compound excreted within the first 24 hours equated to 99%.

Executive summary:

14C labelled 2,5 -diaminophenylethanol sulphate was applied to the dorsal skin of rats for 30 minutes then washed off. The test substance was integrated into two different hair dyeing formulations (I and II) or was evaluated as a solution in water. Hair dyeing formulation II was mixed with Welloxon (containing 9% hydrogen peroxide) before application. Oral application of the test substance was used as a reference. An additional experiment was performed to determine the blood level after peroral application.

Experiment	Characteristics	Samples drawn	Duration
A	cutaneous application formulation I	rinsing water, treated skin, urine, faeces, organs, carcass	72 hours
B	cutaneous application formulation II + Welloxon	rinsing water, treated skin, urine, faeces, organs, carcass	72 hours
C	cutaneous application solution of test item	rinsing water, treated skin, urine, faeces, organs, carcass	72 hours
D	oral application solution of test item	urine, faeces, organs, carcass without GIT	72 hours
E	oral application solution of test substance	blood	24 hours

The mean percutaneous absorptions of the test substance were very low in each of the three experiments. (0.063% for hair dyeing formulation I, 0.077% for hair dyeing formulation II plus hydrogen peroxide, 0.124% for the test substance solution). The 14C labelled compound was excreted to a larger extent via urine (75-86% of the eliminated 14C) and to a lesser extent via faeces (14-25%). The mean excretion within the first 24 hours was fast (87-95% of the eliminated 14C in experiments A to C). Mean 14C concentrations of blood and the 14 analysed organs in experiments A to C were all near or below the detection limit after 72 hours. After oral administration of the test substance the 14C labelled compound was excreted to a larger extent via urine (86% of the eliminated 14C) and to a lesser extent via faeces (14%). The 14C compound excreted within the first 24 hours equated to 99%. Highest 14C cncentrations were detected in the thyroid, liver and adrenals. Lowest detected in testes, fat, femur. The blood level was highest after 35 minutes post administration and declined with an initial half-life of ~50 minutes.