6,6'-di-tert-butyl-4,4'-thiodi-m-cresol

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The data concern a literature study; GLP conditions or Guidelines for testing are not mentioned, but the study is well performed and documented.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Radiolabelled 4,4'-Thiobis(6-tert-butyl-3-cresol) was administered to rats or mice by means of oral gavage, i.v. injection, or dermal application. After 72 hours, all animals were killed and the amount of radiolabel in the carcass, faeces and urine was determined.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): TBBC
- Analytical purity: > 96%

Radiolabelling:

yes

Remarks:

14C

Test animals

Species:

other: rat and mice

Strain:

other: femal sencar mice and male fischer rats

Administration / exposure

Type of coverage:

other: metal perforated tissue capsule

Vehicle:

other: ethanol/aceton mixture

Duration of exposure:

72 hours

Doses:

See results section table 1.

Details on study design:

TEST SITE
- Preparation of test site: clipped
- Area of exposure: 4.2 cm2
- % coverage:
- Type of cover / wrap if used:
- Time intervals for shavings or clipplings:

SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: yes

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

not examined

Absorption in different matrices:

-See Table 1 below

Total recovery:

- Total recovery: averaged 93% of applied dose

Any other information on results incl. tables

Table 1 Effect of route of exposure on faecal elimination and skin retention of 6,6’-di-tert-butyl-4,4’-thiodi-m-cresol-derived radioactivity in Sencar mice and Fischer rats.

species	exposure route (dose in mg/kg bw)	% IBB^ain daily faecal excretions day 1           day 2              day 3	% IBB in total faecal excretions	% IBB on treated skin site
mouse     rat	intravenous (5) oral (5) dermal (5) intravenous (5) oral (5) dermal (5) dermal (50) dermal (200)	59                18                    17 89*              6.5                   2* 5**              9                      8 -                    -                       - -                    -                       - -                    -                       - -                    -                       - -                    -                       -	94 96 22** 77^b 103^b 1.7*** 0.3 0.4	76     98 100 100

* p<0.05 vs. intravenous treatment; ** p<0.01 vs. oral or intravenous treatment; *** p<0.05 vs. doses of 50 or 200 mg/kg bw.

^a    IBB = internal body burden, i.e., the total accountable radioactivity representing the sum of the radioactivity in the excreta, skin site, and carcass. It averaged 93% of the applied dose.

^b    Data from Birnbaum 1983

Applicant's summary and conclusion

Conclusions:

The dermal absorption of 14C-labelled 4,4'-thiobis(6-tert-butyl-m-cresol) (TBBC) was studied in female Sencar mice and male Fischer rats. Dermal application resulted in about 20% absorption in mice with more than 70% of the initial body burden (IBB) remaining on the treated skin site 3 days after treatment.
In rats, less than 20% of a dermal dose was absorbed. Absorption did not increase linearly as the dose increased. Oral and i.v. exposures were conducted in the Sencar mice and compared to previously published rat oral and i.v. data. The disposition was similar between rats and mice after these routes of exposures, and the major route of elimination of absorbed TBBC was the feces in both species.