Reaction mass of 1,1,1,5,5,5-hexamethyl-3-phenyl-3-((trimethylsilyl)oxy)trisiloxane and 1,1,1,7,7,7-hexamethyl-3,5-diphenyl-3,5-bis[(trimethylsilyl)oxy]tetrasiloxane and 1,1,1,9,9,9-hexamethyl-3,5,7-triphenyl-3,5,7-tris((trimethylsilyl)oxy)pentasiloxane

Endpoint summary

Description of key information

In the key 90-day repeated dose oral (gavage) study conducted to OECD Test Guideline 408 and to GLP (Dow Corning Corporation, 1995), no adverse systemic effects attributable to treatment with phenyl silsesquioxanes were observed at doses up to 1000 mg/kg bw/day (the highest dose tested).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

no neurobehavioural tests included

GLP compliance:

yes (incl. QA statement)

Limit test:

yes

Species:

rat

Strain:

other: Fischer 344N

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Raleigh, NC
- Age at study initiation: approx. 7 weeks
- Weight at study initiation: Males 77-93 g Females 75-103 g on arrival
- Fasting period before study: no
- Housing: individually in stainless steel wire mesh cages
- Diet: Purina Rodent Chow 5002 Meal ad libitum except prior to necropsy
- Water: Reverse osmosis purified from local supply ad libitum
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 23-61
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 07 December 1993 to 09 March 1994

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
Twice weekly

VEHICLE
- Concentration in vehicle: 0, 5, 30, 90, 200 mg/mL
- Amount of vehicle: 5mL/kg
- Lot/batch no.: Sigma Chemical Co. 42H0864 and 43H0315

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Samples of the dosing formulations (approximately 20 or 40 ml each), including undiluted vehicle, used during treatment weeks l-2, 2-3, 6-7 and
l0-l I were taken for concentration analysis

Duration of treatment / exposure:

91 or 92 days

Frequency of treatment:

Once daily

Dose / conc.:

25 mg/kg bw/day (actual dose received)

Dose / conc.:

150 mg/kg bw/day (actual dose received)

Dose / conc.:

450 mg/kg bw/day (actual dose received)

Dose / conc.:

1 000 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

yes, sham-exposed

Details on study design:

Not stated

Positive control:

No

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once or twice daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION: Yes
- Time schedule: weekly
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/animal/week: Yes

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: pre-treatment and Week 12
- Dose groups that were examined: All

HAEMATOLOGY: Yes
- Time schedule for collection of blood: day 92 or 93
- Anaesthetic used for blood collection: Yes (sodium pentobarbital)
- Animals fasted: Yes / No / No data
- How many animals: All
- Parameters in table 1 were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: day 92 or 93
- Animals fasted: Yes
- How many animals: All
- Parameters in table 2 were examined.

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

ORGAN WEIGHTS: Yes (see table 3)
GROSS PATHOLOGY: Yes (see table 4)
HISTOPATHOLOGY: Yes (see table 4)

Statistics:

Data was analysed by analysis of variance (ANOVA) followed by Duncan's multiple range comparison test.

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

Absolute and relative liver weights showed statistically significant increase in all treated groups, however, no underlying histopathology noted to support the organ weight change.

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: No effects attributable to treatment at doses up to 1000 mg/kg/day

Critical effects observed:

no

Conclusions:

In a 90-day repeated oral gavage study conducted to OECD Test Guideline 408 and to GLP (reliability score 1), no changes attributable to treatment at doses up to 1000 mg/kg bw/day (the highest dose tested) silsesquioxanes, phenyl, were observed in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subchronic

Species:

rat

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

The key study is the only repeated dose toxicity study available for phenyl silsesquioxanes (Dow Corning Corporation, 1995). In the study F344 rats were given the test substance by oral gavage at doses of 25, 150, 450 or 1000 mg/kg bw/day (controls received corn oil only) for 91 or 92 consecutive days. Absolute and relative liver weights showed statistically significant increase in all treated groups; however, no underlying histopathology was observed to support the organ weight change. Therefore the NOAEL for this study was ≥1000 mg/kg bw/day.

Justification for classification or non-classification

Based on the 90-day oral repeated dose toxicity study, phenyl silsesquioxanes does not require classification for adverse effects following repeated exposures according to Regulation (EC) No 1272/2008.