2,6-di-tert-butyl-α-dimethylamino-p-cresol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study performed according to OECD guideline 401 (1981) under GLP-like quality surveillance (QAU statement included)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,6-di-tert-butyl-α-dimethylamino-p-cresol

EC Number:

201-816-1

EC Name:

2,6-di-tert-butyl-α-dimethylamino-p-cresol

Cas Number:

88-27-7

Molecular formula:

C17H29NO

IUPAC Name:

2,6-di-tert-butyl-4-[(dimethylamino)methyl]phenol

Details on test material:

- Physical state: solid
- purity: commercial grade

Test animals

Species:

rat

Strain:

other: Tif:RAIf(SPF), F3-crosses of RII 1/Tif x RII 2/Tif

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 166-221 g
- Fasting period before study: overnight
- Housing: in groups of 5 in Macrolon cages type 4 with standardized soft wood bedding (Societe Parisienne des sciures, Pantin).
- Diet: Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland), ad libitum
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 15
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: January 7, 1985 - January 29, 1985

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Distilled water containing 0.5% carboxymethylcellulose and 0.1% polysorbate 80

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:

100, 500, and 1000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality: daily; a.m. and p.m. on working days, a.m. on weekend days; Signs and Symptoms: daily; Body weight: on days 1, 7, 14 and at death
- Necropsy: Spontaneously dying animals were submitted to a gross necropsy as soon as possible; survivors at the end of the observation period.

Statistics:

- From the body weights, the group means and their standard deviations were calculated.
- The LD50 values (including their 95% confidence limits) were computed by the logit model (J. Berkson, J. Am. Stat. Ass. iS (1944), 357-365).

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

515 mg/kg bw

Based on:

test mat.

95% CL:

236 - 2 577

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

365 mg/kg bw

Based on:

test mat.

95% CL:

149 - 765

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

461 mg/kg bw

Based on:

test mat.

95% CL:

296 - 779

Mortality:

1000 mg/kg: all animal died within 3 hours after treatment
500 mg/kg: 1 male died 1/5 day after treatment and 3/5 females died within 3 hours after treatment.
100 mg/kg: all animals survived the treatment.

Clinical signs:

other: Dyspnea, exophthalmos, ruffled fur, and abnormal body positions were seen, being common symptoms in acute tests. Tremor was seen in all dose groups within 24 hours after application. The animals of the two higher dose groups showed sedation on the applica

Gross pathology:

Enlargement of the liver was observed in one male of the 100 mg/kg bw dose group. Hemorrhagic lungs were seen in one male of the 500 mg/kg bw dose group. In one male of the 1000 mg/kg bw dose group, dilatation of the small intestine was observed.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Upon an acute oral administration and 14 day post-treatment observation period, the following LD50 were determined: 515 mg/kg bodyweight (males), 365 mg/kg bodyweight (female), 461 mg/kg bodyweight (both sexes).