Reaction mass of 3,6,9-trioxaundecane-1,11-diol and 2,2'-oxydiethanol and 2,2'-(ethylenedioxy)diethanol and 3,6,9,12-tetraoxatetrade

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

read-across based on grouping of substances (category approach)

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

Justification for type of information:

Read across based on category approach. Please see category document for further information.

Data source

Reference

Reference Type:

publication

Title:

Metabolism and disposition of diethylene glycol in rat and dog

Author:

Mathew, J.M., Parker, M.K., Matthews, H.B.

Year:

1991

Bibliographic source:

Drug Metabolism and Disposition 19(6): 1066-1070

Materials and methods

Principles of method if other than guideline:

Occuded dermal exposure to DEG was on the clipped backs of rats. Breath, urine, feces, and blood was collected and radioactivity measured. Urine was analyzed for DEG and its metabolites by HPLC.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-oxydiethanol

EC Number:

203-872-2

EC Name:

2,2'-oxydiethanol

Cas Number:

111-46-6

Molecular formula:

C4H10O3

IUPAC Name:

2,2'-oxydiethanol

Specific details on test material used for the study:

DEG was purchased from Aldrich Chemical Co, Inc. (Milwaukee, WI). [U-14C]-DEG, specific activity 14 mCi/mmol, was obstained from Amersham Laboratories (Buckinghamshire, UK) and was further purified by HPLC to a radiochemical purity of 98%.

Radiolabelling:

yes

Remarks:

[U-14C]-DEG

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

Adult male Fischer 344 rats (220-280 g) were purchased from Charles River Breeding Laboratories, Inc. (Raleigh, NC). All animals were quarantined at least 1 week before they were used. Rats were fed Certified Purina Rodent Chow #5002 and furnished tap water ad libitum. During experiments rats were housed individually in glass metabolism chambers which provide for separate collection of urine, feces, and breath.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Doses:

The dermal dose formulation contained ~25 microCi of radiolabel and 50 mg of unlabeled DEG per animal.

No. of animals per group:

3-5

Details on study design:

Dermal doses were administered onto a 12-cm2 area of skin in the intrascapular area on the backs of rats. Hair had been clipped from the area the previous day, and each rat was inspected to make sure the skin had not been nicked. After dosing, a nonocclusive protective appliance was glued over the dose area.

Determination of Radioactivity. Radiolabeled components eliminated in breath were collected separately by drawing air through a cold trap (-60°C) containing 100 ml of ethanol, and then through two traps, each containing 400 ml of 1 N NaOH. Aliquots of urine and trapping solution from the breath traps were added directly to vials containing scintillation cocktail (Scintiverse E, fisher Chemical Co.). Samples of tissue, feces, and blood (0.2-0.3 g) were digested in Soluene-350 (2 ml; Packard Instrument Co.). After digestion, samples requiring bleaching were decolorized with perchloric acid/hydrogen peroxide prior to addition of scintillation cocktail (Scintiverse E). Samples containing base and scintillate (e.g., sodium hydroxide. sodium carbonate, or Soluene-350) were kept in the dark overnight before they were assayed by liquid scintillation spectrometry.

Analysis of Biological Samples by HPLC. Urine was analyzed by HPLC for unchanged DEG and its metabolites.

Metabolites were isolated and identified by HPLC and NMR.

Results and discussion

Absorption in different matrices:

Dermally administered DEG (50 mg/12cm2) was slowly and steadily absorbed. Approximately 3% of the applied dose was absorbed per day and excreted in the urine over a 72 hour period. A total of 9.1 +/- 1.5% of the dose was recovered in the excreta, and 0.9 +/- 0.3% was recovered in tissues.

Percutaneous absorption

Time point:

72 h

Dose:

50 mg / 12 cm2

Parameter:

percentage

Remarks:

recovered in excreta

Absorption:

9.1 %

Applicant's summary and conclusion

Conclusions:

DEG slowly penetrated the skin of rats after application of 50 mg to a 12 cm2 area. Only about 10% of the dose was absorbed in 72 hr of exposure and the absorbed dose appeared to have the same fate as doses administered iv or orally.

Executive summary:

DEG slowly penetrated the skin of rats after application of 50 mg to a 12 cm2 area. Only about 10% of the dose was absorbed in 72 hr of exposure and the absorbed dose appeared to have the same fate as doses administered iv or orally.