Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Method equivalent to guideline study (except for skin abrasion) performed under GLP standards

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guideline
equivalent or similar to
OECD Guideline 402 (Acute Dermal Toxicity)
stratum corneum penetrated by abrasion immediatelty prior to treatment
Principles of method if other than guideline:
Treatment sites abraded to penetrate straum corneum, but not dermis (and so as not to cause bleeding)
GLP compliance:
Test type:
other: standard acute method but with skin abrasion
Limit test:

Test material

Details on test material:
Aqueous TBHP 70, 70 % tertiary butyl hydroperoxide
Lot number: A209413

Test animals

New Zealand White
Details on test animals and environmental conditions:
- Source: Langshaw farms, Augusta Michigan
- Weight at study initiation: 2.15 - 2.89 kg
- Housing: suspended stainless steel wire-bottomed cages
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow, 5322 ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7-32 days

Administration / exposure

Type of coverage:
unchanged (no vehicle)
Details on dermal exposure:
- Area of exposure: 240 sq. cm
- % coverage: 10%
- Type of wrap if used: Rubber latex dental dam secured with surgical porous tape.

- Washing (if done): no

Duration of exposure:
24 hours
0.5 mL/kg (480 mg/kg), 0.6 mL/kg (576 mg/kg), 0.75 mL/kg (720 mg/kg), 0.90 mL/kg (864 mg/kg), 1.30 mL/kg (1248 mg/kg), 2.08 mL/kg (1997 mg/kg).
No. of animals per sex per dose:
10 rabbits per dose (5 male and 5 female).
For the 0.6 mL/kg dose level, only 9 rabbits (4 males; 5 females) were available.
For the 0.75 mL/kg and 0.90 mL/kg dose levels, only 6 rabbits (3 males; 3 females) were used.
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed closely for gross signs of systemic toxicity and mortality at frequent intervals during the day of dosing and at least twice daily thereafter for a total of 14 days. Body weights were weighed at 0, 6 and 13 days.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Dose descriptor:
Effect level:
440 mg/kg bw
Remarks on result:
other: Adjusted for 70% TBHP content
Dosages expressed in terms of Aq. TBHP-70 test material.
At the 720 mg/kg dose level - 2 deaths occurred on day 0 and the rest died on day 1.
At 864 mg/kg and 1248 mg/kg dose levels - all animals died on day 1.
At the 1997 mg/kg dose level - 2 deaths at 2 hours post exposure, 2 deaths at 3 hours post exposure, 1 death at 4 hours post exposure, 3 deaths at 5 hours post exposure, 1 death at 6 hours post exposure.
Clinical signs:
Dosages expressed in terms of Aq. TBHP-70 test material.
No systemic toxicity observed at 480 mg/kg, 576 mg/kg, 864 mg/kg dose levels. At 720 mg/kg dose level, one animal appeared not to have use of its hindlimbs. At the 1248 mg/kg dose level, systemic signs were first observed 20 mintues after dosing and consisted of cyanosis, lethargy and bodies cool to touch. At the 1997 mg/kg dose level, systemic signs were first observed 30 minutes after dosing and consisted of eyes and gums appearing darkened. At 1 hour after dosing, additional signs observed consisted of ataxia, lethargy, slow and laboured respiration and nasal discharge. At 2 hours additional signs observed consisted of congestion, prostration, nystagmus and red discharge from nares; systemic signs increased in severity with time until death of the animals.
Body weight:
There was little change to the body weight means throughout the test.
Gross pathology:
Dosages expressed in terms of Aq. TBHP-70 test material.
480 mg/kg dose: Lungs pale in colour, but exuded foamy red material when sectioned. Liver surface appeared grained much like leather, bulged when sectioned and bled profusely and showed definite areas of pale yellow white and dark red, appeared to be acute congestion of the liver. In one rabbit, the spleen appeared to have dark red black areas that bulged on the surface of the upper half and flowed dark material when sectioned. In another rabbit, the spleen had multiple focal irregular pale areas. In one rat, the intestines was distended with gas.
576 mg/kg dose: no significant gross pathological findings.
720 mg/kg dose: In two animals the lungs were dark rose grey in colour. In another 3 animals, there was haemorrhage around the brain stem, red pink fluid in abdominal cavity, the urinary bladder contained dark red material, the peritoneal cavity was yellow gold in colour and lungs red tan in colour. In one rat, there was haemorrhage around the eyes, peritoneal cavity yellow gold in colour, liver chocolate in colour, lungs pinkish in colour.
864 mg/kg dose: In one rat, the intestines were pale and slight yellow in colour, the conjunctiva appeared slightly reddened and lungs were dark rose grey in colour.
1248 mg/kg dose: All animals displayed dark red brown lungs with marked autolysis.
1997 mg/kg dose: In five animals, the blood appears chocolate colour, body fat, tan to light brown in colour, lungs tan to chocolate in colour, spleen chocolate in colour and congested, liver chocolate in colour, leather grained surface and congested, kidneys chocolate and congested, spleen chocolate and congested, urinary bladder contracted to an almond size. In four animals, they displayed small urinary bladders which contained dark brown material.

Any other information on results incl. tables

An LD50 value of 628 mg/kg (95% confidence limits 559 to 705) is reported in this study.

Applicant's summary and conclusion

Interpretation of results:
Migrated information Criteria used for interpretation of results: EU
This study shows that TBHP is harmful to rabbits via dermal exposure: LD50 value 440 mg/kg.
Executive summary:

The study shows that TBHP is harmful to rabbits when given via the dermal route, with an acute LD50 value of 440 mg/kg. The results presented here corresponds to a classification of acute dermal toxicity category 3 under Regulation 1272/2008, CLP GHS.