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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 13 - December 18, 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Cross-reference
Reason / purpose:
reference to same study

Data source

Referenceopen allclose all

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 Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): hydroquinone
- Analytical purity: at least 99%
- Batch: TSO1661000
- Stability under test conditions: yes, as this is an acute study

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Wilmington, MA, USA
- Age at study initiation: range finding study 10-13 w, main study 9 w for males, 14-15 w for females
- Weight at study initiation: males 258-298 g, females 228-292 g
- Fasting period before study: 17 h
- Housing: single
- Diet: PMI #5002, pelleted ad libitum
- Water: tap water ad libitum
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.3-23.6
- Humidity (%): 39.2-61.1
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: degassed water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2.85%, 3.15%, 3.45%, 3.75% in the main study; dosing solutions freshly prepared
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 1 mL
Doses:
285, 315, 345, 375 mg/kg bw
No. of animals per sex per dose:
7 males, 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs three times on day of dosing and once daily thereafter, body weights on day 0, 7, and 14
- Necropsy of survivors performed: yes, also for animals found dead
- 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.
Statistics:
LD 50 values and confidence intervals determined by using the Trimmed Spearman-Karber (TSK) Computer Program, US Environmental Protection Agency

Results and discussion

Preliminary study:
400 and 500 mg/kg bw: convulsions followed by death
100 to 375 mg/kg-dose groups: tremor immediately after dosing; brown discoloration of urine between day 0 and 3 after dosing indicating excretion of hydroquinone
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 375 mg/kg bw
Remarks on result:
other: mortality 1/5 at 375 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
367.3 mg/kg bw
95% CL:
> 342.1 - < 394.3
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 375 mg/kg bw
Remarks on result:
other: mortality: 1/5 male and 3/5 females at 375 mg/kg bw
Mortality:
males: 1/5 at 375 mg/kg
females: 1/5 at 285 mg/kg, 0/5 at 315 mg/kg, 1/5 at 345 mg/kg, 3/5 at 375 mg/kg
all deaths within 1 h after administration
Clinical signs:
- Immediately after dosing:
minor to moderate tremors observed in all dose groups;
minor convulsions characterized by spasmodic jumping immediately after dosing noted for 2/5 f at 285 mg/kg, for 1/5 m and 1/5 f at 345 mg/kg, and for 1/5 m and 3/5 f at 375 mg/kg; convulsions mostly in animals found dead within 1 h

- 1h p.a.: minor tremors in 1/5 f at 315 mg/kg, and 1/5 m and 1/4 f at 345 mg/kg

- 4 h p.a.: no signs of tremors or convulsions

- Day 0 - 2: brown discoloration of urine indicating excretion of hydroquinone
Body weight:
No effect
Gross pathology:
Minor to moderate thymus hemorrhage for some of the animals that died on the day of dosing;
Minor hydronephrosis in a single male surviving rat at 345 mg/kg not considered to be treatment-related

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on LD50 values of 367 mg/kg bw in female rats and >375 mg/kg bw in male rats hydroquinone was classified as harmful according to the criteria of EC Directive 67/548/CEE. Central nervous system stimulation was indicated immediately after dosing by the observation of tremors in all animals as well as by the induction of convulsions in single animals over the whole dose range.
Executive summary:

In an acute oral toxicity study according to OECD Guideline 401, hydroquinone was administered to groups of 5 male and 5 female Sprague-Dawley rats at doses of 285, 315, 345 and 375 mg/kg bw (2.85% to 3.75% solutions in degassed water) by gavage. Selection of dose groups was based on a range-finding toxicity study. During a 14 day post-observation period abnormal clinical signs, mortalities, and body weight gain was recorded. Gross necropsy was performed on all dead and surving rats.

Mortality was observed in males at 375 mg/kg (1/5), and in females at 285 mg/kg, at 345 mg/kg, at 375 mg/kg (1/5, 1/5, 3/5). All deaths occurred within 1 h after administration and were mostly preceeded by convulsions. Central nervous system stimulation was indicated immediately after dosing by the observation of tremors in all animals as well as by the induction of convulsions in single animals over the whole dose range. The LD50 values were 367 mg/kg bw in female rats and >375 mg/kg bw in male rats.