Hydroquinone

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 1 August to 14 August 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

Study meets basic scientific principles as a range-finding toxicity study, sufficient documentation; study acceptable as key study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Principles of method if other than guideline:

14-day range-finding toxicity study investigating mortality, clinical signs and body weights, as well as gross necropsy

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hydroquinone

EC Number:

204-617-8

EC Name:

Hydroquinone

Cas Number:

123-31-9

Molecular formula:

C6H6O2

IUPAC Name:

hydroquinone

Details on test material:

- Name of test material (as cited in study report): hydroquinone
- Physical state: colourless, crystalline solid
- Analytical purity: > 99%
- Purity test date:
- Lot/batch No.: 56978
- Stability under test conditions: 7 days both in the dark and under normal lighting conditions
- Storage condition of test material: bulk material was stored at room temperature in tin-foil wrapped flasks in a closed box

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Portage, MI, USA
- Age at study initiation: 6-8 w
- Fasting period before study: no
- Housing: 5 per cage
- Diet: Purina Rodent Laboratory Chow Pellets ad libitum
- Water: tap water ad libitum
- Acclimation period: 13 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 27 °C (64 - 80 °F)
- Humidity (%): 50 - 65
- Air changes (per hr): 12 - 15 room air changes per hr
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

open

Vehicle:

ethanol

Details on exposure:

TEST SITE
- Area of exposure: clipped scapular area
- % coverage: no data
- Time intervals for shavings or clipplings: no data

REMOVAL OF TEST SUBSTANCE: no

TEST MATERIAL
- Amount(s) applied per mouse (volume or weight with unit): ca. 0.1 mL at 300 to 2400 mg/kg bw; two applications of 0.1 mL/mouse at 4800 mg/kg bw with a 15- to 30-min interval to allow the applied material to dry
- Concentration (if solution): up to 480 mg/mL
- Constant volume or concentration used: yes
- For solids: the dosing solution of the 480 mg/kg dose group was rather a suspension than a true solution and was homogenized in a Warring Blender and continuously stirred during dosing

VEHICLE
- Justification for use and choice of vehicle (if other than water): solubility

USE OF RESTRAINERS FOR PREVENTING INGESTION: no data

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

12 treatments in 14 d

Frequency of treatment:

5 d/w

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 300, 600, 1200, 2400 and 4800 mg/kg bw/d
Basis:
nominal per unit body weight

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once per day

BODY WEIGHT: Yes
- Time schedule for examinations: day 0, 7 and 14

GROSS PATHOLOGY: Yes, all animals

Other examinations:

Preliminary qualitative skin absorption study:
groups of 6 mice were treated with doses of 0, 4 oder 40 mg/animal (ca. 40 or 400 mg/kg bw applied as 0.2 mL of 2% or 20% HQ solutions in 95% ethanol) on the clipped interscapular region for three days. Rats were housed in individual metabolism cages and urine was collected at 2, 8, 24, 48 and 72 hrs after the initial dose. Hydroquinone was detected in ether extracts of original urine samples and urine treated with ß-glucuronidase and aryl sulfatase by thin layer chromatography (Uv detection after iodine treatment).

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Dermal irritation:

not specified

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY: no signs of intoxication; crystals of the test substance were seen on the skin and fur of the 4800 mg/kg group

BODY WEIGHT AND WEIGHT GAIN
Final body weights were lower than initial weights in all groups including controls, but were comparable among all test groups.

DERMAL ABSORPTION STUDY:
HQ was detected qualitatively in urine as early as 2 hrs after application and during the whole observation period of 72 hrs (up to 24 hr after last treatment). The intensity of the spot on the TLC was higher after enzymatic cleavage of glucuronide and sulfate conjugates. However, contamination of the urine by HQ released from the skin or the fur could not be ruled out.

Effect levels

Dose descriptor:

NOEL

Effect level:

4 800 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no effects observed

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

In a 14 day range finding dermal toxicity study with male and female B6C3F1 mice, no signs of intoxication were observed up to 4800 mg/kg bw/d. A preliminary qualitative dermal absorption study indicated systemic availability of unknown amounts of HQ as glucuronide and sulfate conjugates were excreted in urine.

Executive summary:

In a 14 day range finding dermal toxicity study with groups of 5 male and 5 female B6C3F1 mice (12 open applications on 5 d/w of 300 to 4800 mg/kg bw/d in 95% ethanol as vehicle), there was no indication of toxicity from survival, clinical signs, body weights and gross necropsy up to 4800 mg/kg bw/application. So the NOEL in B6C3F1 mice is 4800 mg/kg bw/d. Crystals of the test substance were seen on the skin and fur of the 4800 mg/kg group. A preliminary qualitative dermal absorption study indicated systemic availability of unknown amounts of HQ as glucuronide and sulfate conjugates were excreted in urine.