N-butyl phenyl ether

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 15, 2016 to May 24, 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Standard OECD guideline study performed in accordance with GLP with no deviations affecting reliability

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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:

N-butyl phenyl ether

EC Number:

214-426-1

EC Name:

N-butyl phenyl ether

Cas Number:

1126-79-0

Molecular formula:

C10H14O

IUPAC Name:

butoxybenzene

Details on test material:

Test Material Name: Butyl phenyl ether
Chemical Name: Butoxy benzene
Synonyms: None
Lot/Reference/Batch Number: 06027KH
Purity/Characterization (Method of Analysis and Reference): The non-GLP certificate of analysis lists the purity as 99.5% by gas liquid chromatography with structure confirmation by infrared spectroscopy (Rajzer, 2007).

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

The rats (female, nulliparous and non-pregnant) were acclimatised to the test laboratory for between 6 and 15 days. All rats were between 10 and 12 weeks of age at the study initiation.

Rats were housed individually in standard polypropylene solid bottom cages which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011). These cages have stainless steel top grills with steam sterilized corn cob bedding material and facilities for pelleted feed and drinking water (polypropylene bottle fitted with sipper tube). Rack units were rotated once in a week.
Each cage was supplied with a polypropylene water bottle with a stainless steel nozzle.
For Enrichment, Rats were provided with a wooden block in each cage
Each rat was uniquely numbered on the tail using a tattoo machine. Appropriate labels were attached to the cages indicating the study number, test item code and sex, dose, study code, cage number and animal number.
The rats were provided with feed and water, ad libitum (with the exception of overnight fasting and three hours post-dosing). The quality of feed and water is regularly monitored at Jai Research Foundation; copies of the relevant certificates of analysis are kept in the study file. There were no known contaminants in the feed and water at levels that would have interfered with the experimental results obtained.


Environmental Conditions
Temperature : 20 to 23 °C
Humidity : 49 to 58% relative humidity
Air Changes : 17 air changes/hour
Photoperiod : The photoperiod was 12 hours artificial light and 12 hours darkness, light hours being 06:00 h – 18:00 h which was maintained through an automatic timer.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

All animals were dosed on day one of the study. The animals were fasted over night on the day prior to dosing until 3 hours post dose. The test material was administered undiluted using a gavage tube attached to a 1ml syringe. Dose volume was adjusted based on the bodyweight of the rats, density of the test material and the desired dose level.
One animal was initially dosed with 2000 mg/kg bw and observed for 48 hours. in the absence of mortality at this dose, the remaining animals were given the same dose level, with one animal dosed every 48 hours.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 females

Control animals:

no

Details on study design:

The rats were observed for signs of toxicity and mortality at 0.5, 1, 2, 3, 4 and 6 hours post-administration on the day of dosing. Subsequently, the rats were observed twice a day for morbidity and mortality for a period of 14 days following oral dosing. The clinical signs were recorded once a day. Individual body weight was recorded prior to dosing on day 1, and on days 8 and 15
Necropsy
Any rats found dead during the study and all surviving rats (euthanised by carbon dioxide asphyxiation at the end of the study period) were subjected to a gross pathological examination consisting of an external examination and opening of abdominal and thoracic cavities. The stomach of each rat was opened, the contents rinsed/removed, and the mucosal surface was examined for signs of irritation, erosions, ulcers or any other findings. Gross macroscopic changes, if any, were recorded.

Statistics:

The LD50 was calculated using the Dixon’s maximum likelihood method using software (AOT 425 StatPgm)

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One animal died during the study 5 days after dosing. All other animals survided until study termination.

Clinical signs:

other: The 4 animals that survived to study termination displayed no clinical signs of toxicity. The animal that died during the study was lethargic on days 4 and 5 after dosing.

Gross pathology:

In the surviving rats the external and visceral pathology was normal.
In the rat that died during the study, the external examination did not reveal any adverse findings, however the visceral examination revealed bith liver and lung congestion.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

IN this acute oral toxicity study, 1 out of 4 female rats died after dosing with 2000 mg/kg bw. The LD50 for this substance is therefore considered to be >2000 mg/kg bw, but likely to be <5000 mg/kg bw.

Executive summary:

An acute oral toxicity study(Up-and-Down Procedure) was conducted using female Wistar rats given a single oral dose of butyl phenyl ether (Undiluted as received). A Limit Test was conducted with 2000 mg/kg body weight. The first rat survived; hence the four additional female Wistar rats each received a single dose of 2000 mg/kg body weight according to the Up-and-Down Procedure. 

No sign of toxicity was observed in the rats treated with the butyl phenyl ether at 2000 mg/Kg body weight except rat Nº 4 which showed lethargy on days 4 and 5 and was found dead on day 5.

All surviving rats were active and healthy during the study. All surviving rats gained body weight by the end of the study. 

External and visceral examination of terminally sacrificed rats and found dead rat did not reveal any lesions of pathological significance. Visceral examination of found dead rat revealed congestion of the liver and lungs. Lesions observed in found dead rat could be correlated with the test item used in the present study.

The acute oral estimated LD₅₀of the Butyl Phenyl Ether was found to be greater than 2000 mg/kg body weight in female Wistar rats.