Hydroquinone

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 26 - August 10, 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Hydroquinone: Acute and subchronic toxicity studies with emphasis on neurobehavioral and nephrotoxic effects.

Author:

Topping DC, Bernard LG, O'Donoghue JL, English JC

Year:

2007

Bibliographic source:

Food Chem Toxicol 45, 70 - 78

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

(occlusive wrapping)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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
- Analytical purity: at least 99%
- Stability under test conditions: yes, assumed as this is an acute study
- Batch: TSO1661000

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Covance Reseaerch Products, Denver, PA, USA
- Age at study initiation: at least 3 mo
- Body weight at study initiation: males 2.329-2.492 kg, females 2.040-2.592 kg
- Fasting period before study: no
- Housing: single
- Diet: PMI #5325 ad libitum
- Water: ad libitum
- Acclimation period: 5 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8-22.9
- Humidity (%): 47.8-70
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: moistened with water

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal skin
- % coverage: 10% of total body surface
- Type of wrap if used: not specified


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations at least once during exposure period on day 0 and once daily on days 1-14, weighing on day 0, 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross findings; clinical observations included, but were not limited to, examination of the hair, skin, eyes, mucous membranes, motor activity, feces, urine, respiratory system, circulatory system, autonomic nervous system, central nervous system, and behaviour patterns.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male/female

Dose descriptor:

LDLo

Effect level:

> 2 000 mL/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: other: No adverse neurobehavioral effects Brown discoloration of urine on day 2 after dosing indicating dermal absorption and excretion of hydroquinone

Gross pathology:

No changes

Other findings:

Application sites appeared normal from termination of exposure up to the end of the observation period

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

With a dermal LD50 value of more than 2000 mg/kg bw in rabbits no classification for acute dermal toxicity according to criteria of the GHS and EC Directive 1272/2008 is warranted.

Executive summary:

Hydroquinone was administered to groups of 5 male and 5 female New Zealand White rabbits at a dose of 2000 mg/kg bw under an occlusive wrapping (limit test according to OECD Guideline 402). During a 14 day post-observation period no abnormal clinical signs, mortalities or necropsy findings occurred, and body weight gain was not affected. Dermal absorption of hydroquinone was indicated by brown discoloration of urine due to excretion of hydroquinone and its metabolites. The dermal LD50 value in rabbits is more than 2000 mg/kg bw.