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

Endpoint summary

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:

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:

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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

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

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 16 2012 - January 4 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Modern, guideline, GLP study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

control animal included

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal breeding facility, JRF
- Age at study initiation: 8 to 14 weeks
- Weight at study initiation: males 268-300; females 203-221
- Fasting period before study: no
- Housing: individually in polypropylene cages with stainless steel grid tops.
- Diet: Teklad Certified Global High Fiber Rat/Mice Feed manufactured by Harlan, USA ad libitum
- Water: UV sterilised and reverse osmosis filtered water ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 65-66
- Air changes (per hr): min 15
- Photoperiod: 12 hrs dark /12 hrs light (light 06:00 - 18:00)

IN-LIFE DATES: From: 19 Nov 2012 To: 11 Dec 2012

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Remarks:

moistened with water

Details on dermal exposure:

TEST SITE
- Area of exposure: dorso lumbar area of trunk
- % coverage: ~ 10
- Type of wrap if used: porous gauze dressing (not more than 8-ply) and a non-irritating tape (Medi tape 330 hypo-allergenic surgical tape)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): cotton wool soaked in distilled water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 406-600 mg (2000 mg/kg)
- For solids, paste formed: pulverised and moistened with 0.2 mL distilled water

Duration of exposure:

24 hours

Doses:

single

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at least twice per day for morbidity and mortality. Clinical signs once daily, body weights on day 0, 7 and 14.
- Necropsy of survivors performed: yes

Statistics:

body weight was statistically analysed by Student's "t" test.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality, no signs of systemic toxicity and no abnormalities at necropsy at only dose tested

Mortality:

There were no mortalities

Clinical signs:

No signs of toxicity were observed

Body weight:

Mean body weight of treated group was comparable to controls

Gross pathology:

There were no lesions of pathological significance

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

In an OECD guideline acute dermal toxicity study using groups of 5 males and 5 females the acute dermal median lethal dose of HCA was > 2000 mg/kg.

Executive summary:

Two groups of 5 male and 5 female rats were clipped and 0.2mL of distilled water or 2000 mg/kg HCA applied to an area of skin equal to approximately 10% of the body surface. The test site was covered with a semi-occlusive dressing for 24 hours, when it was removed and test site washed with distilled water. The animals were observed daily for signs of systemic toxicity and weighed at intervals during a 14 day observation period. At the end of the study the animals were killed and examined post mortem.

There were no mortalities, no signs of systemic toxicity, no treatment related effects on body weight and no abnomalities at necropsy.

The acute dermal median lethal dose of HCA was > 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Oral toxicity:

- Assessment of Acute Oral Toxicity in Rats: 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.

- Subacute Toxicity Experiment of HCA (Synthetic Resin Stabilizer): A subacute toxicity test of HCA was performed by administering the feed added with 0, 0.24, 0.6 and 1.5% of HCA to rats for 16 weeks.

 

As a result, it was concluded that the limit dose of HCA in the feed was between 0.6% and 1.5%. In tens of 1 kg of body weight, this maximum dose comes to 0.399 ~ 1.023 g/day for males and 0.445 ~ 1.094 g/day for males, or 0.419 ~ 1.052 g/day on average.