2-methoxy-4-(methoxymethyl)phenol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted between 14 November and 18 December 2007.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-methoxy-4-(methoxymethyl)phenol

EC Number:

226-882-9

EC Name:

2-methoxy-4-(methoxymethyl)phenol

Cas Number:

5533-03-9

Molecular formula:

C9H12O3

IUPAC Name:

2-methoxy-4-(methoxymethyl)phenol

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

CD

Sex:

female

Details on test animals or test system and environmental conditions:

Rats were supplied by Charles River (UK) Ltd, Margate, Kent, UK. They were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatisation period of at least 5 days, the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study, the animals were eight to twelve weeks of age. The bodyweight variation did not exceed ± 20% of the initial/mean bodyweight of any previously dosed animals.
The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes. With the exception of the overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (Certified Rat and Mouse Diet) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70%, respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

Vaniwhite was administered by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose level to confirm the survival of the previously dosed animals.
For the dose of 2000 mg/kg bw, the test material was used as supplied, undiluted. For the dose of 300 mg/kg bw, the test material was prepared as a solution in arachis oil BP.

Doses:

Two doses were used in the study: 300 and 2000 mg/kg bw.
Using the available information on the toxicity of the test material, 2000 mg/kg bw was chosen as the starting dose. A single animal was treated and in the absence of mortality at this dose, an additional group of animals was treated with the same dose. Due to mortality, an additional animal was treated with the dose of 300 mg/kg bw and in the absence of mortality at this dose, an additional group of animals was treated with the same dose.

No. of animals per sex per dose:

5 rats per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: The animals were observed 1/2, 1, 2 and 4 hours after application and thereafter daily for up to 14 days, morbidity and mortality checks were made twice daily
- Necropsy of survivors performed: yes, at the end of the observation period the animals were killed by cervical dislocation, necropsied and subjected to external examination and opening of the abdominal and thoracic cavities
- Body weights: Individual body weights were recorded on the day of treatment and on days 7 and 14 or at death.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Three animals treated at a dose level of 2000 mg/kg were found dead during the day of dosing. There were no deaths in animals treated at the dose level of 300 mg/kg.

Clinical signs:

Signs of systemic toxicity noted during the study included: piloerection, hunched posture, lethargy, ataxia, decreased respiratory rate, laboured respiration, loss of righting reflex, increased lachrymation, prostration and coma. Surviving animals appeared normal one day after dosing.

Body weight:

The surviving animals in the group dosed with 2000 mg/kg and all animals in the group dosed with 300 mg/kg showed expected gains in bodyweight over the observation period.

Gross pathology:

Terminal necropsy of animals that died during the observation period revealed the following abnormalities: haemorrhagic lungs, dark liver, dark kidneys and haemorrhage of the gastric mucosa. No abnormalities were noted in animals that were killed at the end of the observation period, at both of the doses, 2000 and 300 mg/kg.

Applicant's summary and conclusion

Interpretation of results:

other: Classified as Category 4 for acute oral toxicity.

Remarks:

According to EU CLP 1272/2008 and its amendments.

Conclusions:

The acute oral LD50 for the substance in rats was determined to be between 300 and 2000 mg/kg. In accordance with GHS criteria, the substance needs to be classified as Category 4 for acute toxicity by the oral route.

Executive summary:

Acute oral toxicity was performed according to the guideline OECD TG 420. Five female rats were administered the substance at dose level of 2000 mg/kg. Because three rats died, a dose of 300 mg/kg was administered to the next five rats. None of these rats died. Observed signs of systemic toxicity were hunched posture, lethargy, ataxia, decreased respiratory rate, laboured respiration, loss of righting reflex, increased lachrymation, prostration and coma. The necropsy of the animals that died after dosing 2000 mg/kg bw revealed: haemorrhagic lungs, dark liver, dark kidneys and haemorrhage of the gastric mucosa. The acute oral LD50 for the substance in rats was determined to be between 300 and 2000 mg/kg, therefore the substance needs to be classified as Category 4 for acute toxicity by the oral route when applying the EU CLP and GHS criteria.