4-sec-butyl-2,6-di-tert-butylphenol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 Oct 1999 - 10 Jan 2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-sec-butyl-2,6-di-tert-butylphenol

EC Number:

241-533-0

EC Name:

4-sec-butyl-2,6-di-tert-butylphenol

Cas Number:

17540-75-9

Molecular formula:

C18H30O

IUPAC Name:

4-(butan-2-yl)-2,6-di-tert-butylphenol

Test material form:

liquid

Details on test material:

Appearance: Colorless to yellow liquid.
Storage: At room temperature under a nitrogen blanket.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Harlan Sprague Dawley, Inc.
- Age at study initiation: Young adult animals
- Weight at study initiation: males 245-268 g; females 175-203 g
- Fasting period before study: Yes
- Housing: Housed individually in suspended stainless steel cages
- Diet: Available ad libtum (PMI Certified Rodent Chow #5002 (Purina Mills, Inc.))
- Water: Free acces to municipal tap water.

- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 – 23
- Humidity (%): 34 - 74
- Air changes (per hr): approx 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 10 November 1999 to 10 Januari 2000

Administration / exposure

Route of administration:

oral: gavage

Details on oral exposure:

GAVAGE METHOD: A ball tipped stainless steel gavage needle attached to a syringe

Frequency: single dosage, on day 0.


MAXIMUM DOSE VOLUME APPLIED:
6.67 mL/kg body weight.
Density of substance (0.90 g/mL)

DOSAGE PREPARATION:
Test substance was administered as received from the sponsor and dispensed fresh on the day of dosing.

Doses:

6000 mg/kg body weight
5000 mg/kg body weight
2000 mg/kg body weight

No. of animals per sex per dose:

6000 mg/kg body weight - 5 females
5000 mg/kg body weight - 5 males and 5 females
2000 mg/kg body weight - 5 females

Control animals:

no

Details on study design:

Individual doses were calculated based on the animal's fasted (day 0) body weight.

- Duration of observation period following administration: 14 days
- Frequency of observations: twice on day 0 (post dose) and thereafter daily
Mortality/Viability: twice daily
Body weights: Individual body weights were obtained for the LD50 study animals prior to fasting (day -1), prior to dosing on day 0 and for all surviving animals on days 7 and 14. Animals found dead after day 0 were also weighed.
Clinical signs: At periodic intervals on the day of dosing (Day 0) and once daily thereafter, until Day 14.
- Necropsy of survivors performed: All LD50 study animals which died spontaneously during the study or were euthanized by carbon dioxide inhalation at study termination (day 14) were necropsied.

Statistics:

The LD50 and 95% confidence intervals were calculated for females using a computer adaption of the method Litchfield and Wilcoxon.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

6 662 mg/kg bw

Based on:

test mat.

95% CL:

>= 3 920.1 - <= 11 320.4

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

6000 mg/kg body weight - 2/5 females
5000 mg/kg body weight - 0/5 males and 2/5 females
2000 mg/kg body weight - 0/5 females

All mortality occured by study day 5

Clinical signs:

other: The most notable clinical abnormalities observed during the study included decreased activity, wobbly gait, breathing abnormalities, soft/mucoid stools, decreased defecation,decreased food consumption, fecal/urine stain, rough haircoat, hunched posture, o

Gross pathology:

Gross internal findings observed in the animals that died included two incidences of abnormal content in the small intestine. No significant gross internal findings were observed at necropsy on study day 14.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

An acute oral toxicity study with ISONOX-132 in rats was performed similar to OECD 401. The acute oral LD50 of ISONOX-132 in the male rat was estimated to be > 5000 mg/kg body weight . In the female rat, the oral LD50 was determined to be 6662 mg/kg body weight. Therefore the substance does not need to classified according to GHS and CLP criteria.

Executive summary:

An acute oral toxicity study with ISONOX-132 in rats was performed according to OECD 401 . The doses applied were 6000 mg/kg body weight in 5 females, 5000 mg/kg body weight in 5 males and 5 females and 2000 mg/kg body weight in 5 females. Mortallity occurred on day 5 for 2 females that were dosed 5000 mg/kg body weight and 2 females that were dosed 6000 mg/kg body weight. The most notable clinical abnormalities observed during the study were decreased activity, wobbly gait, breathing abnormalities, soft/mucoid stools, decreased defecation,decreased food consumption, fecal/urine stain, rough haircoat, hunched posture, ocular discharge, dark material around the facial area and most of the time a gain in weight. Gross internal findings observed in the animals that died included two incidences of abnormal content in the small intestine. No significant gross internal findings were observed at necropsy at the end of the study. Based on this the acute oral LD50 of ISONOX-132 in the male rat was estimated to be > 5000 mg/kg body weight. and in the female rat, the oral LD50 was determined with method litchfield and wilcoxon to be 6662 mg/kg body weight. ISONOX-132 does not need to be classified according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and according toRegulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).