2,3,4-trihydroxybenzophenone

Endpoint summary

Description of key information

The acute oral LD50 for male rats was determined to be greater than 5000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted 24 Feb 1987

Deviations:

yes

Remarks:

(environmental conditions missing, test was only conducted in male rats, non-GLP)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Simonsen Laboratories, Int., Gilroy, CA, USA
- Weight at study initiation: 92 - 125 g (preliminary study); 93 - 108 g (main study)
- Fasting period before study: All animals were fasted overnight.
- Housing: 5 animals per cage were housed in hanging polycarbonate shoebox cages containing hardwood chip bedding.
- Diet: Commercial rodent diet (Ourina Cwertified Laboratory Chow, 5002), ad libitum.
- Water: UV-purified drinking water, ad libitum.
- Acclimation period: 7 days

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 40 mL/kg bw, administered in volumes of 20 mL/kg bw twice about 3 h apart.

DOSAGE PREPARATION: Volumes exceeded the usual 10 mL/kg bw because it was not possible to prepare suspensions of sufficient concentraiton that were suitable for gavage.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

20 (test substance group) and 10 (controls)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed closely immediately after treatment and several times later at the day of treatment. Thereafter, animals were observed for physiologic and behavioral responses and for mortality once daily. Body weights were recorded initially and then weekly during the 14 days observation period.
- Necropsy of survivors performed: yes

Preliminary study:

A preliminary study was performed to establish doses to be given in the main test. Groups of 5 male rats each were treated with doses of 100, 500, 1000, 1500, 2500, 3500 and 5000 mg/kg bw. No deaths occured following treatment up to 3500 mg/kg bw with the test substance. One rat given 3500 mg/kg bw had difficulty breathing and appeared to have been dosed improperly. This animal was killed and found to have froth in the trachea. One rat in the 5000 mg/kg bw group died within 16 h. A suspected misdose (indicated by labored breathing after the second dose) could not be confirmed because of cannibalism of the thoracic area by cage-mates. Survivors in all dose groups gained weight throughout the 14 days observation period. Therefore a dose of 5000 mg/kg bw was chosen for the main study.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

5000 mg/kg bw: 1/20 animals died within 2 h of the administration of the second dose.

Clinical signs:

diarrhoea

lethargy (hypoactivity)

other: 5000 mg/kg bw: One rat had a humped appearance throughout the study.The urine and occasionally the stools were discolored for up to several days in the survivors.

Body weight:

other body weight observations

Remarks:

No effect on body weight and body weight gain was noted.

Gross pathology:

5000 mg/kg bw: The male rat that died within 2 hours showed dark reddish fluid in the bladder and gastrointestinal tract but no other gross abnormalities were seen. Enlarged spleen, raised, pinpoint-size spots and hemorrhaged lungs were noted each in 1/20 rats.
Control: Pale liver and brown fluid in the pleural and abdominal cavities were observed in 1/10 rats.

Table 1: Group body weight averages (g)

	Day 0	Day 7	Day 14	Body Weight Gain
Control	99.6	155.0	206.1	106.5
5000 mg/kg bw	99.2	141.2	195.7	96.5

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 for male rats was determined to be greater than 5000 mg/kg bw.

Executive summary:

An acute oral toxicity study was conducted using young male rats. 20 rats were treated with 5000 mg/kg bw of the test item in corn oil. The dose was split into two portions that were administered ca. 3 h apart. 10 control animals received corn oil using the same amounts and treatment scheme. Animals were observed for 14 days after treatment. 1 animal treated with the test item died within 2 h of the administration of the second dose. The survivors were lethargic shortly after treatment and during the first day of the study. Diarrhea occurred in a few rats. One rat had a humped appearance throughout the study. The urine and occasionally the stools were discolored for up to several days in the survivors. No effect on body weight and body weight gain was noted. Gross pathological examination showed that the male rat treated with test item that died within 2 hours showed dark reddish fluid in the bladder and gastrointestinal tract but no other gross abnormalities were seen. Enlarged spleen, raised, pinpoint-size spots and hemorrhaged lungs were noted each in 1/20 treated rats. One animal of the control group had pale liver and brown fluid in the pleural and abdominal cavities. The acute oral LD50 for male rats was determined to be greater than 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 5 000 mg/kg bw

Quality of whole database:

The study is considered to be of sufficient quality to address the endpoint.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

An acute oral toxicity study was conducted using young male rats. 20 rats were treated with 5000 mg/kg bw of the test item in corn oil. The dose was split into two portions that were administered ca. 3 h apart. 10 control animals received corn oil using the same amounts and treatment scheme. Animals were observed for 14 days after treatment. 1 animal treated with the test item died within 2 h of the administration of the second dose. The survivors were lethargic shortly after treatment and during the first day of the study. Diarrhea occurred in a few rats. One rat had a humped appearance throughout the study. The urine and occasionally the stools were discolored for up to several days in the survivors. No effect on body weight and body weight gain was noted. Gross pathological examination showed that the male rat treated with test item that died within 2 hours showed dark reddish fluid in the bladder and gastrointestinal tract but no other gross abnormalities were seen. Enlarged spleen, raised, pinpoint-size spots and hemorrhaged lungs were noted each in 1/20 treated rats. One animal of the control group had pale liver and brown fluid in the pleural and abdominal cavities. The acute oral LD50 for male rats was determined to be greater than 5000 mg/kg bw.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute toxicity, the test item does not require classification for acute toxicity via the oral route according to Regulation (EC) No 1272/2008 (CLP).