Tris[2-[[2,4,8,10-tetra-tert-butyldibenzo[d,f][1,3,2]dioxaphosphepin-6-yl]oxy]ethyl]amine

Endpoint summary

Description of key information

The oral LD50 in rats was greater than 5000 mg/kg body weight.

The dermal LD50 in rats was greater than 2000 mg/kg body weight.

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:

March - April 1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

usage of 5 male and 5 females animals

GLP compliance:

yes

Limit test:

yes

Specific details on test material used for the study:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test substance was suspended to achieve a concentration suitable for the selected dose levels.

FORM AS APPLIED IN THE TEST (if different from that of starting material): suspended in Polyethylene glycol 400 (PEG 400)

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY limited
- Age at study initiation: 7 - 8 weeks old
- Weight at study initiation: males: 191 g (mean); females: 185 g (mean)
- Fasting period before study: yes, overnight
- Housing: 5 animals/cage
- Diet: NAFAG No. 890 , NAFAG, Gossau SG; ad libitum
- Water: ad libitum
- Acclimation period: a minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 400

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg bw

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 1/2/3/4/5/24 hours after applikation of the test substance and daily thereafter until day 14
- Frequency of weighing: on the day of applikation of the test substance (day 1), day 7 and day 14
- Necropsy of survivors performed: yes

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

no mortality observed

Clinical signs:

- sedation (from 1 h until 24 h after treatment)
- slight dyspnoea (from 1 h until day 6 after treatment)
- slight exophthalmos (from 1 h until day 5 after treatment)
- ruffled fur (moderate from 1 h until 24 h after treatment and slight until day 6 after treatment)
- slight diarrhoea (from 5 h until 24 h after treatment)
- slightly curved body position (from 1 h until day 5 after treatment)

Body weight:

no effects observed

Gross pathology:

no effects observed

The animals recovered within 7 days.

Interpretation of results:

GHS criteria not met

Executive summary:

The acute oral LD50 of the test substance in rats of both sexes observed over a period of 14 days is greater than 5000 mg/kg. The test material is therefore practically non toxic to the rat by this route of administration.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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:

20.6.2017 - 12.7.2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

other: Acute Toxicity (Dermal); Official Journal of the European Union, No. L 142

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nousan No. 8147, November 24, 2000 as this in line with OECD 402.

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: Charles River Wiga GmbH, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation: mean weight males: 230 g, females: 206.4g
- Fasting period before study: not specified
- Housing: Single housing in Makrolon cage, type III
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

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

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal and dorsolateral parts of the trunk
- % coverage: 10%
- Type of wrap if used: The test item was covered with an air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Removal of the semi-occlusive dressing, rinsing of the application site with warm water
- Time after start of exposure: 24 h

VEHICLE
- Amount(s) applied (volume or weight with unit): 4ml/kg body weight
- Concentration (if solution): 50g/100 ml

Duration of exposure:

24 h

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before application (day 0), weekly thereafter and on the last day of observation. Clinical signs for each animal were recorded several times on the day of application and at least once during each workday thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, scoring of skin findings

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No mortality occurred

Clinical signs:

No systemic clinical signs were observed during clinical examination. No local effects were observed.

Body weight:

The body weights of the male animals increased within the normal range throughout the study period. The body weights of the female animals increased in two animals within the normal range throughout the study period. During the first week, one female showed loss of body weight but this female gained weight normally during the second week. In two female animals the body weights increased in a normal range during the first week but slightly decreased or stagnated during the second week. Due to the fact that stagnation or slight loss of body weight is commonly known for females after dermal applications, this effect is not considered to be treatment-related.

Gross pathology:

No macroscopic pathologic abnormalities were noted in any animal examined on the last day of observation (5 males and 5 females).

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose (LD50) of the test item after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.

Executive summary:

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the test item (as suspension in corn oil Ph.Eur.). The clipped application site (dorsal and dorso-lateral parts of the trunk, comprising at least 10% of the total body surface) was covered by semi-occlusive dressing during the 24-hour exposure period. The animals were observed for 14 days. No mortality occurred. Neither signs of systemic toxicity nor local skin effects were observed. The body weights of the male animals increased within the normal range throughout the study period. The body weights of the female animals increased in two animals within the normal range throughout the study period. During the first week, one female showed loss of body weight but this female gained weight during the second week. In two female animals, the body weights increased in a normal range during the first week but slightly decreased or stagnated during the second week. Due to the fact that stagnation or slight loss of body weight is commonly known for females after dermal applications, this effect is not considered to be treatment-related. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study (5 males and 5 females). Accordingly, the acute dermal median lethal dose (LD50) was determined to be greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity

In a GLP-compliant acute oral toxicity study (limit test) similar to OECD guideline 423, the test substance (as suspension in polyethylene glycol PEG 400) was applied per gavage to 5 male and 5 female young rats (Tif: RAIf) at a single dose of 5000 mg/kg body weight. The animals were fasted overnight before the application of the test substance. Physical condition and rate of deaths were monitored throughout an observation period of 14 days.

No mortality occurred. Except of some slight to moderate signs and symptoms on the day of test substance application, which disappeared completely within one week, no signs of severe toxicity were observed.

Therefore, the acute oral LD50 of the test substance was determined to be greater than 5000 mg/kg body weight.

Acute dermal toxicity

In a GLP-compliant acute dermal toxicity study (Limit Test) following OECD guideline 402, young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the test item (as suspension in corn oil Ph.Eur.). The clipped application site (dorsal and dorso-lateral parts of the trunk, comprising at least 10% of the total body surface) was covered by semi-occlusive dressing during the 24-hour exposure period. The animals were observed for 14 days. No mortality occurred. Neither signs of systemic toxicity nor local skin effects were observed. The body weights of the male animals increased within the normal range throughout the study period. The body weights of the female animals increased in two animals within the normal range throughout the study period. One female showed loss of body weight during the first week but weight gain was noted in week two. In two female animals, the body weights slightly decreased or stagnated during the second week. Since stagnation or slight loss of body weight is commonly known for females after dermal applications, this effect is not considered to be treatment-related. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study (5 males and 5 females). Accordingly, the acute dermal median lethal dose (LD50) was determined to be greater than 2000 mg/kg body weight.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute toxicity under Regulation (EC) No. 1272/2008.