Chlorodimethylvinylsilane

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to an appropriate OECD test guideline, with acceptable restrictions. The restrictions were limited observations regarding the FOB.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

limited observations regarding the FOB

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hydroxytrimethylsilane

EC Number:

213-914-1

EC Name:

Hydroxytrimethylsilane

Cas Number:

1066-40-6

IUPAC Name:

trimethylsilanol

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): Trimethylsilanol- Substance type: organosilane - Physical state: liquid- Analytical purity: Not clear from German report

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

castor oil

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

Four weeks

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:0, 80, 250 and 750 mg/kg bw/dayBasis:actual ingested

No. of animals per sex per dose:

Five

Control animals:

yes, concurrent vehicle

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Apathy and short-lived staggering.

Mortality:

mortality observed, treatment-related

Description (incidence):

Apathy and short-lived staggering.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Body weight gain was reduced in males and females of the 750 mg/kg bw/day group by about 10 and 14%, respectively.

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

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

no effects observed

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Dose dependent increase in relative liver weights in females.

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Deposits of brown pigment in the bile ducts of 4/5 males at the highest dose level. Minimal bile duct proliferation in one animal at this dose level.

Histopathological findings: neoplastic:

not examined

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

histopathology: non-neoplastic

organ weights and organ / body weight ratios

Target system / organ toxicity

Key result

Critical effects observed:

yes

Lowest effective dose / conc.:

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

System:

hepatobiliary

Organ:

bile duct

liver

Treatment related:

yes

Dose response relationship:

yes

Relevant for humans:

not specified

Any other information on results incl. tables

Clinical signs: There were no deaths. Short lived staggering in highest dose male and female rats shortly after dosing. Apathy on the day of termination was also observed in this group. No effects on food and water consumption. Body weight gain was reduced in males and females of the 750 mg/kg bw/day group by about 10 and 14%, respectively. There were statistically significant differences in some haematology parameters in the 250 mg/kg bw/day dose group, but these were not considered toxicologically significant as there was no effect at the highest dose (no dose dependency) and individual values were all within the normal range. In males and females of the 750 mg/kg bw/day group alkaline phosphatase was significantly lower than the controls. Statistically significant reduction in glucose levels of males in the 80 and 750 mg/kg bw/day group, statistically significant reduction in urea and increased GOT in females of the 250 mg/kg bw/day group. These changes were not considered to be toxicologically significant as there was no dose-dependency and the values were all within the normal range of the historical controls. At 80 mg/kg bw/day there was a statistically significant decrease in male rat serum phosphate levels, which was not thought to be toxicologically significant as there were no changes at the two higher doses. Relative liver weights of female animals increased in a dose-dependent manner in the 250 and 750 mg/kg bw/day groups. There were statistically significant increases in adrenal weights in males of the 80 and 750 mg/kg bw/day groups, and kidney weights in females of the 80 mg/kg bw/day group. However, these effects were not considered to be toxicologically significant as there was no dose-dependency. Four of five male rats in the highest dose group had small deposits of brown pigment in the bile ducts. One of these animals also had minimal bile duct proliferation.

Applicant's summary and conclusion

Conclusions:

In an oral gavage study conducted to OECD test guideline 407, groups of Wistar rats (5/sex/dose) were given daily doses of either 0 (castor oil vehicle only), 80, 250 and 750 mg/kg bw/day for 28 days. Clinical observations, food and water intake, body weights, organ weights, clinical chemistry, haematology, and histopathology were all recorded. Toxicologically relevant adverse effects (reduced body weight gain, reduced alkaline phosphatase, reduced glucose (males), increased liver weights (females), and increased adrenal weights (males), and minor deposits in the bile ducts) were observed at the highest dose of 750 mg/kg bw/day. The NOAEL was 250 mg/kg bw/day, as effects observed at this or the lower dose of 80 mg/kg bw/day, were not dose-dependent and often values were within the normal range for historical controls.