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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:
12-02-1990 to 28-03-1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline 401 (1981) protocol followed. Study performed 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 401 (Acute Oral Toxicity)
Deviations:
no
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:
TEST ANIMALS
- 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

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: not specified
- Amount of vehicle (if gavage): 10 ml/kg
- Rationale for the selection of the starting dose: A range finding study with one female and one male animal indicated the LD50 was in the range 500-1500 mg/kg
Doses:
Single dose of 474, 664, 930, 2551 and 5000 mg/kg
No. of animals per sex per dose:
n= 5 males
n=5 females
Control animals:
no
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 end
twice daily thereafter for the remainder of the 14 dey observation period. The initial (Day 1), Day 8 and Day 15 bodyweights were recorded and
changes in bodyweight calculated.

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

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
789 mg/kg bw
Based on:
test mat.
95% CL:
695
Mortality:
There were deaths among rats dosed at 664 mg/kg and above and no rat
survived oral administration of o-tert.buty1 phenol at 2551 or 5000 mg/kg.
The majority of deaths occurred during Day 1 (5000 mg/kg) or Day 2 (930 and
2551 mg/kg) but single animals dosed at 664 and 930 mg/kg were found dead on
Day 3 and a single male (664 mg/kg) was killed on humane grounds on Day 10.
Clinical signs:
Common effects and signs of reaction to treatment observed at all dose levels were lachrymation, abasia/ataxia and prostration.
Hunched posture and lethargy were common at the lower and intermediate dose levels, particularly 664 mg/kg.
An unkempt appearance and/or yellow staining of the anogenital zone developed in the majority of rats surviving to Day 2.
Among the animals dosed at 5000 mgjkg there were incidences of pallor or a derkened appearance of the eye, cyanosis and Wheezing.
Coma was observed at dose levels of 664 mg/kg and was always followed by death. There were isolated cases of dierrhoea, tachypnoea,
hypothermia, tremor, salivation, piloerection, epistaxis, periorbital encrustation and swelling or opacity of the eye.
Body weight:
All surviving rats had gained weight relative to their Day 1 bodyweights by the end of the 14 day observation period.
Gross pathology:
Internal macroscopic abnormalities revealed during necropsy were: exaggerated hepatic lobular pattern, darkened liver, darkened spleen,
renal pallor and/or a granular appearance of the kidneys and inflammation with abnormal contents of the gastrointestinal tract.
No significant lesions were found among the rats terminated on Day 15.

Applicant's summary and conclusion

Interpretation of results:
moderately toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 in both males and females is 789 mg/kg bw.
Executive summary:

In an OECD guideline 401 study, Fischer 344 rats (n=5 males; n-=5 females) were treated by oral gavage with o-tert butyl phenol in corn oil at doses of 474, 664, 930, 2551 and 5000 mg/kg. The LD50 was 789 mg/kg bw. There were a range of adverse clinical signs at doses from 664 mg/kg upwards.