4,4-bis(methoxymethyl)biphenyl

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 19 January 1998 and 12 February 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

UK GLP standards (Schedule 1, Good Laboratory Practice Regulations 1997 (SI 1997/654)). Date of signature: 31/03/98

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-bis(methoxymethyl)-1,1'-biphenyl

EC Number:

700-008-0

Cas Number:

3753-18-2

Molecular formula:

C16 H18 O2

IUPAC Name:

4,4'-bis(methoxymethyl)-1,1'-biphenyl

Constituent 2

Reference substance name:

4,4-bis(methoxymethyl)-biphenyl

IUPAC Name:

4,4-bis(methoxymethyl)-biphenyl

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent, UK
- Age at study initiation: Eight to 12 weeks
- Weight at study initiation: Males: 224 - 249 g, Females: 200 - 230 g.
- Fasting period before study: Overnight fast immediately before dosing, and three to four hours after dosing
- Housing: solid floor polypropylene cages furnished with woodflakes
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 22°C
- Humidity (%): 46 to 64%
- Air changes (per hr): Fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light followed by 12 hours continuous darkness


IN-LIFE DATES: From: Day of dosing (Day 0) To: Day of sacrifice (Day 14)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: not stated in report
- Amount of vehicle (if gavage): The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
- Justification for choice of vehicle: not stated in report
- Lot/batch no. (if required): not stated in report
- Purity: not stated in report

MAXIMUM DOSE VOLUME APPLIED: The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable) - not applicable
- Rationale for the selection of the starting dose:

Doses:

Range finding study: 500, 1000 and 2000 mg/kg

Main study: 1000, 1414 and 2000 mg/kg

No. of animals per sex per dose:

Range finding study: 1 male and 1 female per dose level

Main study: 5 females per dose level, 5 males at the 1000 mg/kg dose level only.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14.

- Necropsy of survivors performed: yes

- Other examinations performed:macroscopic observations

Statistics:

Using the mortality data obtained, the acute median lethal dose (LD50) and 95% confidence limits of the test material were calculated using the method of Thompson, w.R. Bact. Reviews, 11, 115-145 (1947). The LD50 and 95% confidence limits were calculated for males only.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

1 366 mg/kg bw

95% CL:

> 1 153 - 1 619

Mortality:

Three animals treated with 1414 mg/kg and all animals treated with 2000 mg/kg were found dead one to six days after dosing.

Clinical signs:

Clinical observations noted at dose levels of 1414 or 2000 mg/kg were ataxia, dehydration, emaciation, hunched posture, lethargy, pilo-erection, ptosis, decreased respiratory rate, laboured respiration, staining around the eyes and snout, occasional body tremors and splayed or tiptoe gait. Incidents of diarrhoea and pallor of the extremities were noted in two animals treated with 1414 mg/kg. Surviving animals treated with 1414 mg/kg recovered five days after dosing. All animals treated with 1000 mg/kg appeared normal throughout the study.

Body weight:

Surviving animals showed expected gain in bodyweight during the study.

Gross pathology:

Common abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs' dark liver, dark kidneys and slight haemorrhage of the gastric mucosa. Additional abnormalities in animals treated with 2000 mg/kg were sloughing of the non-glandular epithelium of the stomach, pale gastric mucosa and haemmorhage of the small and large intestines. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Other findings:

- Organ weights: Not recorded.
- Histopathology: Not recorded
- Potential target organs: Not recorded
- Other observations: none

Any other information on results incl. tables

Range-finding study

Animals treated with 2000 mg/kg were found dead two days after dosing. clinical observations noted at this dose level were ataxia, pallor of the extremities, hunched posture, lethargy, pilo-erection, ptosis, decreased respiratory rate, laboured respiration, red/brown staining around the mouth, body tremors and splayed gait. There were no deaths or clinical observations noted at dose levels of 1000 or 500 mg/kg.

Based on this information, dose levels of 1000, 1414 and 2000 mg/kg bodyweight were selected for the main study.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 of Females only: 1366 (1153 - 1619) mg/kg bodyweight

Male animals were considered not to be markedly more sensitive to the test material than female animals.

Executive summary:

The method used was based on the recommendations of the OECD Guidelines for Testing of Chemicals No. 401 "Acute Oral Toxicity" (adopted 24 February 1987) and Method B1 of commission directive 92/69/EC (which constitutes Annex V of Council Directive 64/548/EEC).

LD50 of Females only: 1366 (1153 - 1619) mg/kg bodyweight Male animals were considered not to be markedly more sensitive to the test material than female animals.