Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12-02-1990 to 21-03-1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline 402 study followed to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
2-tert.-butylphenol
IUPAC Name:
2-tert.-butylphenol
Constituent 2
Chemical structure
Reference substance name:
2-tert-butylphenol
EC Number:
201-807-2
EC Name:
2-tert-butylphenol
Cas Number:
88-18-6
Molecular formula:
C10H14O
IUPAC Name:
2-tert-butylphenol
Constituent 3
Reference substance name:
o.-tert.-butylphenol
IUPAC Name:
o.-tert.-butylphenol
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): 2-tert.-butylphenol
- Physical state: liquid
- Analytical purity: 99.97%
- Purity test date: 2014-05-07
- Lot/batch No.: 1419
- Expiration date of the lot/batch: 05/2015
- Stability under test conditions: stable
- Storage condition of test material: under N2 in tightly closed container at a cool, well ventilated place
- Colour: clear

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Charles River (U.K.) Ltd.
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 180-210 g (males); 120-140 (females).
- Fasted overnight
- Housing: In single sex groups of up to three rats in cages with stainless steel wire-mesh walls. floors and tops.
- Diet ad libitum: A pelleted diet (PRD. Special Diet Services Ltd - formerly Labsure Animal Foeds)
- Water ad libitum
- Acclimation period: 5 days prior to dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19· to 23 degrees C
- Humidity (%): 30% to 70%
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 hour day and 12 hour night

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
- Area of exposure: 6 x 8 cm
- Type of wrap if used: lint dressing (6 x 8cm) held with waterproof adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with warm dilute detergent solution and then dried.
- Time after start of exposure: 24 hours

Duration of exposure:
24 hours
Doses:
A single dose of 1020, 1420 and 2000 mg/kg (males)
A single dose of 500, 729, 1020 and 2000 mg/kg (females)
No. of animals per sex per dose:
n= 5 males; n= 5 females.
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A careful clinical examination was made at least six times on Day 1 and twice daily thereafter for the remainder
of the 14 day observation period. The initial (Day 1), Day 8 and Day 15 bodyweight9 were recorded, and changes in bodyweight calculated.

- All animals were subject to necropsy.
- Other examinations performed: clinical signs, body weight,organ weights, gross pathology.
Statistics:
No method specified

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 373 mg/kg bw
Based on:
test mat.
95% CL:
1 124
Sex:
female
Dose descriptor:
LD50
Effect level:
705 mg/kg bw
Based on:
test mat.
95% CL:
574
Mortality:
There were deaths on Days 2 to 5.
Clinical signs:
Haematuria was observed in all but 3 female rats dosed at 500 mg/kg.
At doses above 700mg/kg bw - lethargy and, prior to death, lachrymation, pale eyes, hypothermia, prostration and coma.
Isolated cases of skin pallor, periorbital encrustation, hunched posture, unkempt appearance and yellow staining of the anogenital zone were also
observed.
After removal of the occlusive dressings on Day 2, the treated skin showed either inflammation, a brown and wrinkled appearance or a
chemical burn. Scab formation followed between Days 6 and 10 and this persisted at termination on Day 15.
Body weight:
All surviving rats had gained weight relative to their Day 1 bodyweights at the end of the 14 day observation period.
Gross pathology:
Darkened appearance and petechiation of thymus, soft brain, lung congestion, pallor and exaggerated lobular pettern of the liver.
Dark spleen, pallor of the renal cortex or darkening of the renal medulla, inflammation and abnormal content of the urinary bladder,
inflammation of the stomach and abnormal gastrointestinal contents. Four rats killed on Day 15 showed exaggerated hepatic lobular pattern.
No other internal macroscopic changes were found in rats surviving the effects of treatment. Findings of inflammation, dlscolouration,
scab formation and subcutaneous congestion or inflammation at the dermal test sites were consistent with in-life observations.

Applicant's summary and conclusion

Interpretation of results:
moderately toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Adverse clinical observations and adverse gross pathology was seen in animals at all doses tested.
The LD50 in males was 1373 mg/kg bw.
the LD50 in females was 705 mg/kg bw.

Executive summary:

In an OECD guideline 402 study, Fischer 344 rats (n=5 males; n-=5 females) were treated dermally with undiluted o-tert butyl phenol at a single dose of 1020, 1420 and 2000 mg/kg (males) and 500, 729, 1020 and 2000 mg/kg (females).

The LD50 in males was 1373 mg/kg bw.

the LD50 in females was 705 mg/kg bw.

There were a range of adverse clinical signs observed and adverse gross pathology abnormalities in liver, gut and kidney.