2-ethylhexyl mercaptoacetate

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:

other: Study according to generally accepted scientific standards but no information on test substance purity was reported..

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1971

Materials and methods

Objective of study:

absorption

distribution

excretion

metabolism

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The metabolism of 2-ethylhexyl thioglycolate was studied in rats. 3 young male received by gavage 80 mg of 35S marked 2-ethylhexyl thioglycolate. Faeces and urine were analysed every 24 hours. After 3 days observation, liver, kidney, spleen, brain, musculature, heart, lungs, serum, adrenals, hypophyse and thymus were sampled. The radioactivity of the extracts, solutions and residues was quantitatively measured. The qualitative measure of individual samples was done with thin layer chromatography. There was no data whether control test was performed.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylhexyl mercaptoacetate

EC Number:

231-626-4

EC Name:

2-ethylhexyl mercaptoacetate

Cas Number:

7659-86-1

Molecular formula:

C10H20O2S

IUPAC Name:

2-ethylhexyl 2-sulfanylacetate

Radiolabelling:

yes

Remarks:

35S

Test animals

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: young
- Weight at study initiation: mean bodyweight: 200g
- Individual metabolism cage: yes
- Diet (e.g. ad libitum): Pellet food ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sunflower oil

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
VEHICLE
- Justification for use and choice of vehicle (if other than water): no data
- Concentration in vehicle: 160 g/L
- Amount of vehicle (if gavage): 0.5 mL
- Lot/batch no. (if required): no data
- Purity: no data

HOMOGENEITY AND STABILITY OF TEST MATERIAL: no data

Duration and frequency of treatment / exposure:

1 treatment

Doses / concentrations

Dose / conc.:

80 other: mg

No. of animals per sex per dose / concentration:

3

Control animals:

not specified

Positive control reference chemical:

not needed

Details on study design:

- Dose selection rationale: literature data

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled : liver, kidney, spleen, brain, muscle, heart, lungs, serum, adrenals, hypophyse and thymus were observed, and feces and urine
- Time and frequency of sampling: Liver, kidney, splenn, brain, musculature, heart, lungs, serum, adrenals, hypophyse and thymus after 3 days, feces and urine: every 24 hours

METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled : Liver, kidney, splenn, brain, musculature, heart, lungs, serum, adrenals, hypophyse and thymus were observed as well as faeces and urine
- Time and frequency of sampling: liver, kidney, splenn, brain, musculature, heart, lungs, serum, adrenals, hypophyse and thymus after 3 days, faeces and urine: every 24 hours
- From how many animals: 3
- Method type(s) for identification : Liquid scintillation counting, TLC
- Limits of detection and quantification: no data

TREATMENT FOR CLEAVAGE OF CONJUGATES (if applicable):

Statistics:

no data

Results and discussion

Preliminary studies:

Not conducted.

Main ADME results

Main ADME results 1

Type:

excretion

Results:

After 3 days, faeces excretion reaches 7.3 % of used activity and urine excretion reaches 73.0 %

Main ADME results 2

Type:

absorption

Results:

The substance is well absorbed but remains not in the organs

Main ADME results 3

Type:

distribution

Results:

No major site of accumulation (regarding concentration per g tissue) could be defined

Main ADME results 4

Type:

metabolism

Results:

The intact substance was neither found in excrements nor in organs

Toxicokinetic / pharmacokinetic studies

Details on excretion:

After 3 days, faeces excretion reaches 7.3 % of used activity and urine excretion reaches 73.0 % . Total amount of secreted radioactivity after 3 days is 80.3%. (See table 1 for further details).
It was assumed that a part of the glycol acid was metabolised to CO2 and expired.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Sulphur containing and ninhydrin positive metabolism products were found in all organs and excrements.

Any other information on results incl. tables

Table 1: Mean values of excretion of 35S activity throughout the study period

	% activity
Faeces 1^stday	3.9 +/- 0.02
Faeces 2^ndday	2.8+/- 0.02
Faeces 3^rdday	0.6+/- 0.01
Total accumulated in faeces	7.3
Urine 1^stday	67.8+/- 0.01
Urine 2^ndday	2.2+/- 0.01
Urine 3^rdday	3.0+/- 0.01
Total accumulated in urines	73.0
Total excredet for 3 days	80.3

Table 2: Proportion of 35S activity to the chloroform exctract (=1) of water phase and solid residue

	Chloroform extract	Water phase	Solid residue
Faeces 1^stday	1	0.2	3.9
Faeces 2^ndday	1	0.1	0.8
Faeces 3^rdday	1	0.7	0.7
Urine 1^stday	1	725	-
Urine 2^ndday	1	113	-
Urine 3^rdday	1	2000	-
Liver	1	9.7	0.0
Kidney	1	7.0	47
Spleen	1	41.5	0.0
Brain	1	3.3	45
Musculature	1	3.0	0.0
Heart	1	8.5	1.0
Lungs	1	4.5	19.0
Serum	1	112	0.0
Thymus	1	4.8	0.0

Table 3 : Summary of the TLC separation products and 35S-wearing metabolism product revealed by autoradiography after incorporation of TGE+.

	Hexane Acetic Acid		Propanol water
	TGE	Sulphur positive	Amino acid positive	Amino acid negative
Liver
CHCl3- extract	-	1	n.a.	n.a.
Water phase	-	1	2	-
Residue	-	2	-	-
Kidney
CHCl3- extract	-	1	n.a.	n.a.
Water phase	-	1	2	-
Residue	-	1	2	-
Spleen
CHCl3- extract	-	1	n.a.	n.a.
Water phase	-	1	1	-
Residue	-	2	1	-
Lungs
CHCl3- extract	-	1	n.a.	n.a.
Water phase	-	1	2	-
Residue	-	1	1	-
Faces
CHCl3- extract	-	-	n.a.	n.a.
Water phase	-	1	3	2
Residue	-	1	-	1
Urine
CHCl3- extract	-	2	n.a.	n.a.
Water phase	-	1	1	5

Applicant's summary and conclusion

Conclusions:

No bioaccumulation potential based on study results
The substance is well absorbed. No major site of accumulation (regarding concentration per g tissue) could be defined.
The intact substance was neither found in excrements nor in organs.
After 3 days, faeces excretion reaches 7.3 % of used radioactivity and urine excretion reaches 73.0 % .
Sulphur containing and ninhydrin positive metabolism products (linked to amino acids and peptides products) were found in all organs and excrements.

Executive summary:

In a metabolism study, 3 male rats (weight 200 g, strain unspecified) were given a single oral dose of 80 mg³⁵S-thioglycolic acid 2-ethylhexyl ester (70 µCi)/rat (Seidler et al., 1971). They were then housed singly in metabolism cages for 3 days and their faeces and urine were collected over 24-hour periods in each case. Faeces and urine were analyzed every 24 hours. After 3 days observation, liver, kidney, spleen, brain, musculature, heart, lungs, serum, adrenals, hypophyse and thymus were sampled. The radioactivity of the extracts, solutions and residues was quantitatively measured. The qualitative measure of individual samples was done with thin layer chromatography. 2-EHTG is well absorbed by oral administration. On the first day, 67.8% of the administered radioactivity was eliminated in the urine and 3.9% in the faeces. A total of 80.3% of the administered radioactivity was excreted in the urine and faeces within 3 days. Only small amounts of radioactivity accumulated in the organs (adrenals, pituitary < 0.0001%, thymus 0.0002%, values for other organs not specified). The intact substance was neither found in excrements nor in organs. Thioglycolic acid 2-ethylhexyl ester was almost completely metabolized and excreted in the form of sulfur-containing and/or ninhydrin-positive (linked to amino acids and peptides products) metabolites, which were detectable by thin layer chromatography. 2-EHTG is expected to be initially hydrolysed in several tissues by carboxylesterases to thioglycolic acid and the corresponding alcohol (2-ethylhexanol).