Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guidelineopen allclose all
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

Test material

Constituent 1
Chemical structure
Reference substance name:
Tris[2-[[2,4,8,10-tetra-tert-butyldibenzo[d,f][1,3,2]dioxaphosphepin-6-yl]oxy]ethyl]amine
EC Number:
279-459-6
EC Name:
Tris[2-[[2,4,8,10-tetra-tert-butyldibenzo[d,f][1,3,2]dioxaphosphepin-6-yl]oxy]ethyl]amine
Cas Number:
80410-33-9
Molecular formula:
C90H132NO9P3
IUPAC Name:
tris[2-({4,6,12,14-tetra-tert-butyl-8,10-dioxa-9-phosphatricyclo[9.4.0.0^{2,7}]pentadeca-1(11),2(7),3,5,12,14-hexaen-9-yl}oxy)ethyl]amine
Details on test material:
- Storage conditions: Room temperature
- Physical state/ color: Solid /white

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels
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).

Applicant's summary and conclusion

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.