2-tert-butylphenol

Endpoint summary

Description of key information

Two key oral acute toxicity studies:  Gardner 1990 study (OECD guideline 401 study performed to GLP) and  Taupin 1981 study (US 1981 guideline method).
Two supporting studies for the oral route:  Tufnell 1991 and Yamashita 2000 (both OECD guideline 401 studies).
One dermal acute toxicity study: Gardner 1990.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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

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

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:

other: 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 appearan

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

789 mg/kg bw

Quality of whole database:

Three standard acute studies rated Klimisch 1 (Gardner 1990, Taupin 1981 and Tufnell 1991)
One standard acute study rated Klimisch 2 (Yamashita 2000)

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

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

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

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

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:

other: 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

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

705 mg/kg bw

Quality of whole database:

Klimisch 1; OECD guideline 402 study performed to GLP.

Additional information

ORAL: o-tert butyl phenol is acutely toxic by the oral route and a range of adverse findings in liver, kidney and the gastrointestinal tract, aswell as a range of clinical signs are present in all studies at single acute oral gavage doses greater than 500 mg/kg.

LD50 (oral) Gardner 1990 = 789 mg/kg

LD50 (oral) Taupin 1981 = male and female combined = 868 mg/kg bw (756 - 995 mg/kg bw)

LD50 (oral) Tufnell 1991 = >200 - <2000 mg/kg (males and females)

LD50 (oral) Yamashita 2000 = 1231 mg/kg (males); 1414 mg/kg (females)

There were no deaths and no signs of systemic toxicity at an oral dose of 200 mg/kg in the Tufnell 1991 study.

DERMAL: In a single acute dermal study ( Gardner 1990), there was a significant difference in LD50 observed between males and females. The dermal LD50 for females is 705 mg/kg; for males the dermal LD50 is 1373 mg/kg.

INHALATION: there are no specific data for the inhalation.

Justification for selection of acute toxicity – oral endpoint
The best available OECD 401 guideline study, performed to GLP, with the lowest derived LD50.

Justification for selection of acute toxicity – dermal endpoint
The only available acute toxicity study by the dermal route

Justification for classification or non-classification

Based upon the evidence from four acute oral toxicity studies, o-tert butyl phenol should be classified as an acute oral toxicant, harmful if swallowed. The oral LD50 from the best available study is 789 mg/kg.

Based upon the evidence in one acute dermal toxicity study, o-tert butyl phenol should be classified as an acute dermal toxicant, toxic if in contact with the skin. The dermal LD50 for females is 705 mg/kg; for males the dermal LD50 is 1373 mg/kg.

As there are no data for the inhalation route.