2-tert-butylhydroquinone

Repeated dose toxicity: dermal

Administrative data

Endpoint:

sub-chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from secondary literature

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

Repeated dose dermal toxicity study of the test chemical

Author:

EASTMAN KODAK CO

Year:

1989

Bibliographic source:

EASTMAN KODAK CO

Reference 2

Reference Type:

other: Authoritative data base

Title:

HSDB Number : 838

Author:

HSDB database

Year:

2011

Bibliographic source:

HSDB (Hazardous Substances Data Bank); US national Library of Medicine reviewed by SRC:EASTMAN KODAK CO; Potential of Mono-t-butyl Hydroquinone to Produce Skin Depigmentation with Cover Letter Dated 05/04/89; 04/25/89;

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Effect of the test chemical was studied using guinea pigs

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-tert-butylhydroquinone

EC Number:

217-752-2

EC Name:

2-tert-butylhydroquinone

Cas Number:

1948-33-0

Molecular formula:

C10-H14-O2

IUPAC Name:

2-tert-butylbenzene-1,4-diol

Details on test material:

- Name of test material: tert-Butyl hydroquinone (TBHQ)
- IUPAC name: 2-tert-Butylhydroquinone
- Molecular formula: C10H14O2
- Molecular weight: 166.219 g/mol
- Substance type: Organic

Test animals

Species:

guinea pig

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

Outbred black guinea pigs were used

Administration / exposure

Type of coverage:

not specified

Vehicle:

other: hydrophilic ointment

Details on exposure:

No data

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0.1, 1.0, and 5.0% in 1 ml
Basis:
no data

No. of animals per sex per dose:

5/sex/group

Control animals:

yes, concurrent vehicle

Details on study design:

Groups of five males and five females were dosed with 2-tert-butylhydroquinone or the vehicle (hydrophilic ointment) daily (M-F) for 13 weeks. The application site was evaluated weekly for degree of pigmentation loss and irritation. Twenty-four hours after final application, sites were evaluated for depigmentation, irritation and hyperpigmentation. Subsequently, the application site was depilated and re-evaluated for the same endpoints

Positive control:

No data

Examinations

Observations and examinations performed and frequency:

No data

Sacrifice and pathology:

No data

Other examinations:

No data

Statistics:

No data

Results and discussion

Results of examinations

Clinical signs:

not specified

Dermal irritation:

effects observed, treatment-related

Description (incidence and severity):

At 0.1% the test chemical produced weak irritant responses and did not produced depigmentation and at 1.0%, 20% of animals had spotty or uniform loss of pigment

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day

Based on:

dissolved

Sex:

male/female

Basis for effect level:

other: At 0.1%, the test substance produced weak irritant responses and did not produce depigmentation.

2

Dose descriptor:

LOAEL

Effect level:

10 000 mg/kg bw/day

Based on:

dissolved

Sex:

male/female

Basis for effect level:

other: At 1.0%, 20% of animals had spotty or uniform loss of pigment.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Based on the effects observed in the study at 0.1%, the test chemical produced weak irritant responses and did not produced depigmentation and at 1.0%, 20% of animals had spotty or uniform loss of pigment. The NOAEL and LOAEL was assessed to be 0.1% (1000 mg/kg) and 1% (10000 mg/kg) respectively.

Executive summary:

The test chemical was tested at concentrations of 0.1, 1.0 and 5.0%. Groups of five males and five females of black guinea pigs were dosed with the test chemical or the vehicle (hydrophilic ointment) daily (M-F) for 13 weeks. The application site was evaluated weekly for degree of pigmentation loss and irritation. Twenty-four hours after final application, sites were evaluated for depigmentation, irritation and hyperpigmentation. Subsequently, the application site was depilated and re-evaluated for the same endpoints. Repetitive exposure to concentrations of 1.0% and 5.0% were slightly to moderately irritating, while 0.1% produced only weak irritant response. No irritant responses to hydrophilic ointment were observed.

0.1% produced depigmentation, while 20% of animals dosed with 1.0% had spotty or uniform loss of pigment at the site of treatment. Approximately 40% of animals dosed with 5% were depigmented at the treatment site at the final evaluation.The study showed that the test chemical causes depigmentation in black guinea pigs at concentrations of 1% or greater, but that a no-effect threshold for this endpoint exists at a concentration between 0.1 and 1.0%. Hence NOAEL was assessed to be 0.1% (1000 mg/kg) and LOAEL was assessed to be 1% (10000 mg/kg).