6H-dibenz[c,e][1,2]oxaphosphorin 6-oxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The experimental work was carried out between 13/06/1994 and 30/06/1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Performed according to GLP and OECD Guidelines and no deviations reported

Justification for data waiving:

other:

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ukanol DOP 95 (HCA)

IUPAC Name:

Ukanol DOP 95 (HCA)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Ukanol DOP 95
- Physical state: a white powder
- Other: Test article characterisation, purity, stability etc. is the responsibility of Sponsor.

Test animals

Species:

rat

Strain:

other: SPF Wistar rats of the stock Mol:WIST

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Stock Mol:WIST from the MØIIegaard Breeding Centre Ltd., Ejby, DK-4623 Lille Skensved
- Age at study initiation: At the beginning of the study the male rats were 8 to 9 weeks old and the female rats were 7 to 8 weeks.
- Weight at study initiation: Male rats weighed 138 to 160 g and female rats weighed 134 to 146 g.
- Housing: The rats were individually ear-marked and kept in Macrolone cages Type III (42 x 26 x 15 cm) 2 or 3 to a cage, males and females separated. The bedding was pinewood sawdust ''Linocel Granulat'' from Company Altromin, 32791 Lage, Lippe. Regular analyses of bedding, diet, and drinking water are performed. Certificates of analysis are retained. The room temperature was 21 ± 3°C, and the relative humidity at 55 ± 15%. Air change 10 times per hour, and light from 06 to 18 h. The rats were kept in animal room No. 2.
- Diet (e.g. ad libitum): The rats were fed a complete rodent diet “Altromin 1326 from Company Altromin, 32791 Lage, Lippe ad libitum.
- Water (e.g. ad libitum): The rats had free access to drinking water acidified with hydrochloric acid to pH 2.5.
- Acclimation period: 5 days

The experiment was made on 10 (5 males and 5 females) SPF Wistar rats of the stock Mol:WIST from the MØIIegaard Breeding Centre Ltd., Ejby, DK-4623 Lille Skensved.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): light from 06 to 18 h

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Natriumcarboxymethylcellulose 1% and 0.1 ml Tween 80.

Doses:

The volume administered was 10 ml/kg body weight. The test article was administered orally by gavage to rats fasted for approximately 18 hours prior to dosing. After dosing the feed was withheld for a further 3 hours. The dosing took place between 09 and 10 h.

No. of animals per sex per dose:

5 (5 males and 5 females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Each rat was observed 1, 3 and 6 hours after administration and thereafter daily for a period of 14 consecutive days
- Necropsy of survivors performed: yes (all rats were killed with CO2 on day 14 and subjected to a gross autopsy examination).
- Other examinations performed: Body weights were recorded on day 0, 7 and 14

Statistics:

No details provided in report

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No male and no female rats died during the whole study

Clinical signs:

See Table 2 and Table 3 of the attached report for the pharmacotoxic clinical signs of the rats observed daily throughout the study.

Body weight:

Male: mean 149–247 g
Female: mean 141–186 g

The male and female rats had a normal body weight gain throughout the study. See Table 1 in attached report for body weights.

Gross pathology:

Autopsy of the males showed in two animals a slight swelling of the liver and the edge of the liver was pale. Autopsy of the other male and female rats after two weeks observation period revealed no gross pathological finding.

Other findings:

Male: One hour after the application sedation and pinched abdomen were observed in two animals. The other 3 animals showed piloerection and pinched abdomen. Three hours after the application two animals were normal. Three and six hours after the application piloerection with or without pinched abdomen were observed in the other animals. From day 1 and throughout the rest of the 14 day observation period all animals showed a normal behaviour and appearance.

Female: One and three hours after the application all animals showed piloerection and pinched abdomen. After 6 hours only piloerection was observed. One animal showed piloerection on day 1. The other animals were normal. From day 2 and throughout the rest of the 14 day observation period all animals showed a normal behaviour and appearance.

Applicant's summary and conclusion

Conclusions:

No male and female rats died during the test period. The oral LD50 value for UKANOL DOP 95 in rats must be above 2000 mg/kg body weight.

Executive summary:

The acute oral toxicity to rats was determined according to the method recommended in the OECD Guideline, ''Acute Oral Toxicity”, No. 401, Feb. 1987.

 

Under the experimental conditions described in this report, the oral LD₅₀value for rats was found to be above 2000 mg UKANOL DOP 95/kg b.wt.