Reaction product of phosphorus trichloride with reaction mass of 4-tert-butylphenol and phenol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19-JUL 2001 - 13-AUG-2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

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:

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

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,4-di-tert-butylphenyl diphenyl phosphite; 2-tert-butylphenyl diphenyl phosphite; 4-tert-butylphenyl diphenyl phosphite; triphenyl phosphite

EC Number:

941-802-9

Molecular formula:

Unspecified

IUPAC Name:

2,4-di-tert-butylphenyl diphenyl phosphite; 2-tert-butylphenyl diphenyl phosphite; 4-tert-butylphenyl diphenyl phosphite; triphenyl phosphite

Details on test material:

- Physical state: yellowish liquid
- Storage condition of test material: at room temperature (range of 17-23°C), away from direct sunlight

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Biotechnology and Animal Breeding Division, CH-4414 Fullinsdorf / Switzerland
- Age at study initiation: Males 8 weeks, females 10 weeks
- Weight at study initiation: m: 180.5 - 196.2 g; f: 166.5 - 183.4 g
- Fasting period before study: 16 to 20 hours
- Housing: In groups of three per sex in Makrolon type-4 cages with wire mesh tops and standardized softwood bedding
- Diet: Pelleted standard Provimi Kliba 3433 rat maintenance diet, batch no. 72/01 (Provimi Kliba AG, CH-4303 Kaiseraugst/ Switzeriand) ad libitum.
- Water: Community tap-water ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 300

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/ml
- Amount of vehicle (if gavage): 10 ml/kg body weight
- Justification for choice of vehicle: chosen after a non-GLP solubility trial performed before experimental starting date.
- Lot/batch no. (if required): 412565/1 50501

MAXIMUM DOSE VOLUME APPLIED:
10 ml/kg body weight

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

3 males or 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Mortality / Viability: Daily during acclimatization and twice daily during days 1-15.
- Body weights: On test days 1 (pre-administration), 8 and 15.
- Clinical signs: Daily during acclimatization and at least four times on test day 1 after the test item administration. Once daily during days 2-15. All abnormalifies were recorded.

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

No death occurred during the study.

Clinical signs:

other: Ruffled fur, hunched posture, slight or marked emaciation was noted in two females and in on male between test day 7 and 10. All other animals were without clinical signs.

Gross pathology:

No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

the median lethal dose of the test item after single oral administrafion to rats of both sexes, observed over a period of 14 days is: LD50 (rat): > 2000 mg/kg body weight.

Executive summary:

One group of three male or three female HanBri: WIST (SPF) rats was treated by oral gavage with the test article at 2000 mg/kg body weight. The test item was suspended in vehicle (PEG 300) at a concentration of 0.2 g/ml and administered at a volume of 10 ml/kg. The animals were examined for clinical signs daily during the acclimatization period, four times during test day 1 and once daily during test days 2-15. Mortality/viability was recorded daily during the acclimatization period and together with clinical signs at the same fime intervals on test day 1 and twice daily on test days 2-15. Body weights were recorded on day 1 (prior to administrafion) and on days 8 and 15. All animals were necropsied and examined macroscopically. All animals survived until the end of the study period. Ruffled fur, hunched posture, slight or moderate emaciation was noted in two females and on male between test day 7 and 10. All other animals were without clinical signs. Two females (nos. 2 and 3) lost weight between test day 1 and test day 8, male no. 6 did not gain weight in this period. The body weight of all other animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy. In conclusion, the median lethal dose of the test item after single oral administrafion to rats of both sexes, observed over a period of 14 days is: LD50 (rat): > 2000 mg/kg body weight.