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Diss Factsheets

Toxicological information

Endpoint summary

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Administrative data

Description of key information

Subacute NOAEL (rat, male/female): 200 mg/kg bw/day (Directive 92/69 EEC, B.7/GLP)

Subacute NOEL (rat, male/female): 200 mg/kg bw/day (Directive 92/69 EEC, B.7/GLP)

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP Compliance, not OECD guideline
Qualifier:
according to guideline
Guideline:
other: Directive 92/69 EEC, B. 7
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Route of administration:
oral: unspecified
Vehicle:
corn oil
Details on oral exposure:
Method of administration: gavage
Duration of treatment / exposure:
Test duration: 28 days
Frequency of treatment:
Dosing regime: 7 days/week
No. of animals per sex per dose:
Male: 10 animals at 0 mg/kg bw/day
Male: 5 animals at 50 mg/kg bw/day
Male: 5 animals at 200 mg/kg bw/day
Male: 10 animals at 500 mg/kg bw/day
Female: 10 animals at 0 mg/kg bw/day
Female: 5 animals at 50 mg/kg bw/day
Female: 5 animals at 200 mg/kg bw/day
Female: 10 animals at 500 mg/kg bw/day
Clinical signs:
no effects observed
Description (incidence and severity):
There were no test article-related clinical signs noted in any dose group.
Mortality:
no mortality observed
Description (incidence):
All animals survived the scheduled treatment period.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
There was no effect on body weights.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
Food consumption was uneffected by treatment with test article.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
effects observed, non-treatment-related
Description (incidence and severity):
Ophthalmologic findings were noted in a small proportion of animals from all groups. They included corneal opacity and degeneration of the eyes. These findings occured at similar incidences in the control and treated groups at the end of the treatment period. Therefore, they are considered to be unrelated to treatment with test article.
Haematological findings:
effects observed, non-treatment-related
Description (incidence and severity):
There were no treatment related effects on hematology, clinical biochemistry and urinalysis data at termination of the treatment nor at the end of the treatment free recovery period which could be considered of toxicological significance.
However a few minor findings with statistical significance were recorded between the control and treated rats of group 4 at termination of the treatment and/or recovery period. The toxicological relevance of these statistical findings is considered to be doubtful.
Clinical biochemistry findings:
effects observed, non-treatment-related
Description (incidence and severity):
There were no treatment related effects on hematology, clinical biochemistry and urinalysis data at termination of the treatment nor at the end of the treatment free recovery period which could be considered of toxicological significance.
However a few minor findings with statistical significance were recorded between the control and treated rats of group 4 at termination of the treatment and/or recovery period. The toxicological relevance of these statistical findings is considered to be doubtful.
Urinalysis findings:
effects observed, non-treatment-related
Description (incidence and severity):
There were no treatment related effects on hematology, clinical biochemistry and urinalysis data at termination of the treatment nor at the end of the treatment free recovery period which could be considered of toxicological significance.
However a few minor findings with statistical significance were recorded between the control and treated rats of group 4 at termination of the treatment and/or recovery period. The toxicological relevance of these statistical findings is considered to be doubtful.
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
Organ weights were uneffected by treatment with test article.
Gross pathological findings:
effects observed, non-treatment-related
Description (incidence and severity):
Most macroscopic findings recorded were unremarkable and within the range of spontaneous alterations which may be seen in rats of this age and strain.
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, non-treatment-related
Description (incidence and severity):
Chiefly minor degrees of hepatocellular vacuolization representing slight hepatic lipidosis, were noted in the liver of both control and treated rats at both sacrifices. This was considered to be due to the vehicle, corn oil.
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Dose descriptor:
NOAEL
Effect level:
200 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.
Dose descriptor:
NOEL
Effect level:
200 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
200 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Information from migrated NONS file, as per inquiry number 06-2120077351-60-0000, permission to refer granted by ECHA.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated dose toxicity (oral)

There is one 28 day repeated dose toxicity study in rats available.

In a sub-acute toxicity study (Directive 92/69 EEC, B.7/GLP), 3,9-bis[2,4-bis(1-methyl-1-phenylethyl)phenoxy]-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane was administered by oral gavage to Sprague Dawley rats (5/sex/group) in corn oil at 0, 62.5, 200 or 500 mg/kg bw/day for 28 days, 7 days per week.

After 28 days test duration, all animals survived the scheduled treatment period. There were no effect on body weights or food consumption. There were no test article-related clinical signs noted in any dose group.

Ophthalmologic findings were noted in a small proportion of animals from all groups. They included corneal opacity and degeneration of the eyes. These findings occured at similar incidences in the control and treated groups at the end of the treatment period. Therefore, they are considered to be unrelated to treatment with test article. There were no treatment related effects on hematology, clinical biochemistry and urinalysis data at termination of the treatment nor at the end of the treatment-free recovery period which could be considered of toxicological significance.  However a few minor findings with statistical significance were recorded between the control and treated rats of group 4 at termination of the treatment and/or recovery  period. The toxicological relevance of these statistical findings is considered to be doubtful.

Organ weights were unaffected by treatment with test article. Most macroscopic findings recorded were unremarkable and within the range of spontaneous alterations which may be seen in rats of this age and strain. Chiefly minor degrees of hepatocellular vacuolization representing slight hepatic lipidosis, were noted in the liver of both control and treated rats at both sacrifices. This was considered to be due to the vehicle, corn oil. The NOAEL for repeated dose toxicity in males and females was established as 200 mg/kg bw/day (nominal). The NOEL for repeated dose toxcity in males and females was established as 200 mg/kg bw/day (nominal).

Justification for classification or non-classification

Based on available information in the dossier, the substance 3,9-bis[2,4-bis(1-methyl-1-phenylethyl)phenoxy]-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane (CAS No. 154862-43-8) does not need to be classified for specific target organ toxicity (repeated) when considering the criteria outlined in Annex I of 1272/2008/EC.