Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
Aug. 26, 1985 to Sep. 9, 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to a method comparable to OECD guideline 401 and conducted according to GLP. It is a read across study, hence maximum reliability rating of 2 assigned according to ECHA guidance.
Qualifier:
equivalent or similar 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:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories Inc.
- Age at study initiation: young adult
- Housing: individually housed in wire mesh bottom cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
All animals were housed in environment controlled rooms as per "Guide for the Care and Use of Laboratory Animals". A 12 h light-dark cycle was maintained.

Route of administration:
oral: gavage
Vehicle:
other: Not applicable
Doses:
5.0 g/kg bw
No. of animals per sex per dose:
5/sex
Details on study design:
All animals were observed frequently on the day of dosing and twice daily for the remainder of the study. All external signs of toxicity or pharmacological effects were noted. Body weights were recorded initially, on Day 8 and 15 or at death. All animals that died and those sacrificed at termination of the study were subjected to a gross necropsy and all abnormalities were noted. Cage side observations included, but not limited to changes in the fur and skin, eyes and mucous membranes, respiratory system, circulatory system, autonomic and central nervous systems, somatomotor activity, and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, lethargy, sleep and coma.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
No deaths occured
Clinical signs:
Diarrhea, salivation, decreased activity, wet abdomen, sore-rectal area, hair loss at abdomen were observed in both males and females. Nasal discharge was observed in one mail. Swollen hind legs and sore hind legs were observed in one female.
Body weight:
Mean body weight increased as compared to initial.
Gross pathology:
No noteworthy findings
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of the test substance was found to be >5,000 mg/kg bw in rats (Reagan, 1985).
Executive summary:

A study was conducted to determine the acute oral toxicity of the read across substance ‘A mixture of: hexyldioctylphosphineoxide; dihexyloctylphosphineoxide; trioctylphosphineoxide’ in male and female Sprague-Dawley rats. The substance was administered by gavage to each of ten rats at a level of 5,000 m/kg bw. Animals were observed for external signs of toxicity, body weights and mortality. All animals that died prematurely and those sacrificed at termination of the study were subjected to a gross necropsy and all abnormalities were noted. All animals survived the 15 d post-administration observation period. Diarrhea, salivation, decreased activity, wet abdomen, sore-rectal area, hair loss at abdomen was observed in both males and females. Nasal discharge was observed in one mail. Swollen and sore hind legs were observed in one female. Mean body weight increased as compared to initial. No noteworthy findings were observed in gross pathology. Under the study conditions, the acute oral LD50 was found to be >5,000 mg/kg bw (Reagan EL, 1985).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The information requirements for this tonnage band is sufficiently met with the available data.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
Apr. 21, 1986 to May 5, 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to a method comparable to OECD guideline 402 and conducted according to GLP. It is a read across study, hence maximum reliability rating of 2 assigned according to ECHA guidance.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: an FDRL-and USDA approved supplier.
- Age at Initiation: young adult.
- Identification: ear tag, color coded cage tag.
- Housing: individually housed in wire-mesh bottom cages
- Feed: NIH 09 Rabbit Ration, ad libitum, supplied fresh daily
- Water: tap water, ad libitum. Monitored for contaminants at periodic intervals according to FDRL Standard Operating Procedures.
- Photoperiod: 12 h light/dark cycle
- Weight before the beginning of the test: 2-3 kg
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The back of each rabbit was clipped with an electric clipper on the day prior to dosing. The test substance was topically applied to the non-abraded dorsal skin at a dose level of 2,000 mg/kg bw. The test sites were wrapped with an occlusive binder consisting of a layer of plastic wrap and stockinette sleeve held in place with tape. The binders were removed 24 h post-dose administration and the exposure sites gently wiped with gauze to remove as much non-absorbed test substance as possible.
Duration of exposure:
24 h
Doses:
2,000 mg/kg bw
No. of animals per sex per dose:
5/sex
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: mortality and toxicity signs were recorded three times on the day of dosing and twice daily thereafter. Individual body weight data were recorded on Day 1, (prior to dose-administration) 8 and 15.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the whole study.
Clinical signs:
All animals exhibited well-defined erythema and edema at study Day 2. Eschar formation was noted in all animals by study Day 4. Diarrhea, soft stools and nasal discharge were sporadically noted from study Day 2. These findings are common among laboratory stock animals. One male exhibited anorexia and respiratory irregularity on study Day 4 and 5.
Body weight:
Weight loss was noted at Day 8 in four males and five females. This effect was transient as weight gain was noted in all animals at study termination.
Gross pathology:
No internal lesions or abnormalities were noted in any animal at study termination. The test site of all animals exhibited prominent subcutaneous vascularization.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 of the test substance was found to be >2,000 mg/kg bw in New Zealand White rabbits (Busch BA, 1986).
Executive summary:

A study was conducted in rabbits to evaluate the acute dermal toxicity of the read across substance ‘A mixture of: hexyldioctylphosphineoxide; dihexyloctylphosphineoxide; trioctylphosphineoxide’ in a method equivalent to the OECD Guideline 402, in compliance with GLP. The back of each rabbit was clipped with an electric clipper on the day prior to dosing. The test substance was topically applied to the non-abraded dorsal skin at a dose level of 2,000 mg/kg bw. The test sites were wrapped with an occlusive binder consisting of a layer of plastic wrap and stockinette sleeve held in place with tape. The binders were removed 24 h post-dose administration and the exposure sites gently wiped with gauze to remove as much non-absorbed test substance as possible. The observation period after the dermal administration lasted for 14 d. Mortality and toxicity signs were recorded three times on the day of dosing and twice daily thereafter. Individual body weight data were recorded on Days 1 (prior to dose-administration), 8 and 15. All animals killed at the termination of the study were subjected to gross necropsy. Under the study conditions, the acute dermal LD50 of the test substance was found to be >2,000 mg/kg bw in New Zealand White rabbits (Busch BA, 1986).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The information requirements for this tonnage band is sufficiently met with the available data.

Additional information

Oral

A study was conducted to determine the acute oral toxicity of the read across substance ‘A mixture of: hexyldioctylphosphineoxide; dihexyloctylphosphineoxide; trioctylphosphineoxide’ in male and female Sprague-Dawley rats. The substance was administered by gavage to each of ten rats at a level of 5,000 m/kg bw. Animals were observed for external signs of toxicity, body weights and mortality. All animals that died prematurely and those sacrificed at termination of the study were subjected to a gross necropsy and all abnormalities were noted. All animals survived the 15 d post-administration observation period. Diarrhea, salivation, decreased activity, wet abdomen, sore-rectal area, hair loss at abdomen was observed in both males and females. Nasal discharge was observed in one mail. Swollen and sore hind legs were observed in one female. Mean body weight increased as compared to initial. No noteworthy findings were observed in gross pathology. Under the study conditions, the acute oral LD50 was found to be >5,000 mg/kg bw (Reagan EL, 1985).

A study was conducted to determine the acute oral toxicity of test substance in male Wistar rats. Doses of 5,000 and 10,000 mg/kg bw were administered to non-fasted animals, which were then observed for mortality and signs of toxicity. Gross autopsy was performed on all. The observation period was 14 d. Mortality was 1/10 and 0/2 for the 10,000 and 5,000 mg/kg bw groups, respectively. No signs of toxicity were observed. In the autopsy, the liver of the animal that died before end of the study was found to be mottled tan and red, the stomach was distended, transparent and gas filled, the kidneys were light tan and kidney medullae was red, the intestines were distended, injected, liquid and blood filled, yellow, red and black in area. In the survivors, no remarkable effects were observed. Under the study conditions, the acute oral LD50 of the test substance was found to be >10,000 mg/kg bw in rats (Brown DR, 1979). Full study details were not available, so that the reliability of this study was considered to be low.

Dermal

A study was conducted in rabbits to evaluate the acute dermal toxicity of the read across substance ‘A mixture of: hexyldioctylphosphineoxide; dihexyloctylphosphineoxide; trioctylphosphineoxide’ in a method equivalent to the OECD Guideline 402, in compliance with GLP. The back of each rabbit was clipped with an electric clipper on the day prior to dosing. The test substance was topically applied to the non-abraded dorsal skin at a dose level of 2,000 mg/kg bw. The test sites were wrapped with an occlusive binder consisting of a layer of plastic wrap and stockinette sleeve held in place with tape. The binders were removed 24 h post-dose administration and the exposure sites gently wiped with gauze to remove as much non-absorbed test substance as possible. The observation period after the dermal administration lasted for 14 d. Mortality and toxicity signs were recorded three times on the day of dosing and twice daily thereafter. Individual body weight data were recorded on Days 1 (prior to dose-administration), 8 and 15. All animals killed at the termination of the study were subjected to gross necropsy. Under the study conditions, the acute dermal LD50 of the test substance was found to be >2,000 mg/kg bw in New Zealand White rabbits (Busch BA, 1986).

A study was conducted to determine the acute dermal toxicity of test substance in male New Zealand White rabbit. Doses of 2,000 and 4,000 mg/kg bw of the test substance were applied to clipped, unabraded skin of the test animals. Animals were observed for mortality, signs of toxicity and skin irritation. Gross autopsy was performed on all. The observation period was 14 d. Number of mortalities were 4/4 and 0/4 for the 4,000 and 2,000 mg/kg bw groups, respectively. Erythema, edema and ecchymosis, and scabs on skin of survivors were observed at 14 d. In the autopsy, livers of animals dying before study end were found to be red and the stomachs were opaque and injected. In the survivors, no remarkable effects were observed. Under the study conditions, the acute dermal LD50 of the test substance was found to be 2,830 mg/kg bw (1,730 to 4,620 mg/kg bw) in rabbits (Brown DR, 1979). Full study details were not available, so that the reliabilty of this study was considered to be low.

Justification for selection of acute toxicity – oral endpoint
The study was conducted according to a method comparable to OECD Guideline 401 and conducted according to GLP.

Justification for selection of acute toxicity – dermal endpoint
Reliable study with a method comparable to OECD Guideline 402 and conducted according to GLP.

Justification for classification or non-classification

Oral

Based on the oral LD50value of >5,000 mg/kg bw for the read-across substance, no classification is warranted for acute oral toxicity according to CLP (EC 1272/2008).

Dermal

Based on the dermal LD50value of >2,000 mg/kg bw for the read-across substance, no classification is warranted for acute dermal toxicity according to CLP (EC 1272/2008).