2-methyl-4-phenylbutan-2-ol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 June 2017 to 27 October 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-methyl-4-phenylbutan-2-ol

EC Number:

203-074-4

EC Name:

2-methyl-4-phenylbutan-2-ol

Cas Number:

103-05-9

Molecular formula:

C11H16O

IUPAC Name:

2-methyl-4-phenylbutan-2-ol

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Yinghai (Cangzhou) Aroma Chemical Company Ltd.;CP008-170101
- Expiration date of the lot/batch: 30-06-2018
- Purity: 99.7%

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: INTOX PVT. LTD.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9 to 11 weeks
- Weight at study initiation: 181 g to 194 g
- Fasting period before study:
- Housing: Animals were housed in room number AR-06, in the experimental animal facility of INTOX PVT. LTD., maintained under appropriate barriers.
Animals were housed in sterilised solid bottom polypropylene cages [size: 42 cm (L) x 29 cm (W) x 19 cm (H)] with stainless steel grill tops, facilities for food and water bottle, and with bedding of clean and sterilised paddy husk. Cages were suspended on movable stainless steel racks.
- Diet: Altromin' brand extruded pelleted rat feed manufactured by M/s Altromin Spezialfutter GmbH & Co. KG, Germany, and supplied by ATNT Laboratories, Mumbai was provided ad libitum.
- Water: Potable water passed through 'Aquaguard' water filter was provided ad libitum in sterilized bottles with stainless steel sipper tubes.
- Acclimation period: six to twenty days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark.


IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test item at the concentrations of 2000 mg/kg bw, was administered to each rat by a single oral gavage. The test item was administered by oral gavage to each rat as a single dose using a suitably graduated syringe and a stainless steel intubation needle (size: 16G). The dosage volume administered to individual rat is as tabulated above and was adjusted according to its most recently recorded body weight

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 females

Control animals:

no

Details on study design:

On the day of dosing, all animals were observed for signs of toxicity and death, periodically during the first 24 hours with special attention given during the first 4 hours (i.e. at 10 minutes, 30 minutes, 1 hour, 2 and 4 hours following dosing) and thereafter they were observed once a day for 14 days post dosing. The appearance, progress and disappearance of these signs were recorded.

The body weights of rats were individually recorded at one day prior to dosing (day -1), on the day of dosing (day 0, fasting body weight), on day 7 and at termination on day 14. Weight gain and group mean values were computed over day -1 body weights

At end of the study, all surviving animals were weighed and humanely sacrificed by carbon dioxide asphyxiation. All animals in the study were subjected to a complete necropsy and the gross pathological changes were recorded. Histological examination was not carried out in the absence of gross pathological changes.

Statistics:

The LD50 and the confidence intervals were calculated using the software program (AOT425StatPgm) available on EPA’s Internet Web site at http:// www.epa.gov/oppfead1/harmonized

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Dimethyl phenyl ethyl carbinol (DMPEC) did not cause any mortality in the treated female rats at the dose level of 2000 mg/kg body weight.

Clinical signs:

other: Abnormal clinical signs were observed in treated rats at the dose level of 2000 mg/kg body weight. Test Item induced abdominal breathing and hypoactivity in the treated rats. The animals became free of these signs on day 1 after treatment

Gross pathology:

No gross pathological alterations were encountered in any of the female rats in this study at necropsy conducted at termination of the study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study in rats, the LD50 (female) for DMPEC was >2000 mg/kg bw.

Executive summary:

In an acute oral toxicity study (R/16936/AOR/17), Wistar female rats (5/dose) were given DMPEC (99.7%) at doses of 2000 mg/kg bw and observed for 14 days.

LD50 (female): was >2000 mg/kg bw.

DMPEC did not cause any mortality in the treated female rats at the dose level of 2000 mg/kg body weight. Abnormal clinical signs were observed in treated rats at the dose level of 2000 mg/kg body weight. Test Item induced abdominal breathing and hypoactivity in the treated rats. The animals became free of these signs on day 1 after treatment. The body weight gain by rats treated at 2000 mg/kg was not affected during the 14 days observation period post dosing . No gross pathological alterations were encountered in any of the female rats in this study at necropsy conducted at termination of the study.

This acute oral study is classified as acceptable. It does satisfy the guideline requirement for an acute oral study (OECD 425) in the rat.