4-tert-butyl-3-hydroxy-2,6-xylylacetonitrile

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant guideline study, available as unpublished report

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing guideline of 12 Nosan No. 8147

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-tert-butyl-3-hydroxy-2,6-xylylacetonitrile

EC Number:

259-766-1

EC Name:

4-tert-butyl-3-hydroxy-2,6-xylylacetonitrile

Cas Number:

55699-10-0

Molecular formula:

C14H19NO

IUPAC Name:

2-(4-tert-butyl-3-hydroxy-2,6-dimethylphenyl)acetonitrile

Details on test material:

- Name of the test substance used in the study report: 4-tert-Butyl-3-hydroxy-2,6-xylylacetonitrile
- Physical state: white powder
- Storage: ambient temperature, and away from light

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier supplier, 53940 Le Genest-St-Isle, France
- Age at study initiation: about 7 weeks
- Weight at study initiation: 210.1 - 230.5 kg
- Fasting period before study: overnight
- Housing: 3 animals per cage, 31 x 46 x 19 cm polypropylene cages with stainless steel lid; bedding composed of wood shavings delivered dust-free and sterilized (gamma-radiation) supplied by SICSA (94142 Alfortville France)
- Diet: pelleted from (A04-10) deliverd sterilezed to gamma-radiations by SAFE (89290 Augy, France)
- Water: tap water in polypropylene bottles
- Acclimation period: at least 5 days
- Nulliparous and non-pregnant females were used

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): about 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: The test substance (powder), was administered suspended in corn oil, vehicle chosen after performing previous tests of solubility.

DOSE PREPARATION
The preparation (at 150 mg/mL concentration) was homogenized manually with a spatula. The preparation obtained was looking like a pale yellow homogenous thick liquid. The preparation (at 200 mg/mL concentration) was homogenized using a pestle in a mortar. The preparation obtained was looking like a pale yellow homogenous suspension. Both preparations were put under magnetic stirring during treatments. The preparations of the test substance were performed few minutes before treatment the day of the study D1 in sufficient quantity for the necessities of the study.

MAXIMUM DOSE VOLUME APPLIED: 2 mL/kg for the 300 mg/kg dosage and to 10 mL/kg for the 2000 mg/kg dosage

Doses:

300 and 2000 mg/kg

No. of animals per sex per dose:

6 females per dose

Control animals:

no

Details on study design:

- Experimental chronology: According to the test substance nature, the experiment started (1st step) on 3 female animals receiving a pre-defined dosage (300 mg/kg) of test substance. After this 1st step, according to the methodology described in the OECD guideline 423, the study was performed using a stepwise procedure, on 3 other animals receiving the test substance at the dose level of 300 mg/kg of body weight, under the same conditions as the animals from the step 1 and on 6 other animals receiving the test substance at the dose level of 2000 mg/kg of body weight (steps 3 and 4).
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were regularly observed the day of administration (immediately, during the 30 minutes following gavage, 1h, 2h, 3h and 4h after administration) then at least once a day for 14 days at least. The animals were regularly weighed on D-1 the day before administration then on D1 just before administration of the test substance and on D4, D8 and D15 i.e. 3, 7 and 14 days after administration.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed in animals exposed to 300 or 2000 mg/kg.

Clinical signs:

other: - No clinical signs were observed in all animals exposed to 300 mg/kg. - Some clinical signs were observed during the first 4 hours following the treatment (first a piloerection and a reduced motor activity were observed in all the animals receiving 2000

Gross pathology:

No organ or tissue lesion macroscopically visible was found during the post mortem examination performed in all the animals 14 days after treatment with the 300 mg/kg and 2000 mg/kg dose levels.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Conclusions:

Under the conditions of this study the oral LD50 in Sprague-Dawley rats is above 2000 mg/kg bw.

Executive summary:

In an OECD 423 guideline study performed in compliance with GLP, the test substance was administered to six female Sprague-Dawley rats per dose by oral gavage. Rats were exposed to 300 or 2000 mg/kg bw After an observation period of 14 days surviving animals were necropsied. No mortality was observed in all exposed animals. No significant toxicity signs were observed in the animals receiving the 300 mg/kg dosage. Some toxicity signs were observed during the first 4 hours in rats treated with 2000 mg/kg bw (first piloerection and a reduced motor activity were observed in all animals; these symptoms were then associated to porphyrin deposits around the muzzle and hollow flanks). These signs totally disappeared after two days. No organ or macroscopically visible tissue lesion were found during the post mortem examination. The LD50 was determined to be above 2000 mg/kg bw.