Trichloroisobutylsilane

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

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

Adequacy of study:

key study

Study period:

from 14 Nov 1991 to 26 Mar 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted in accordance with an appropriate OECD test guideline and in compliance with GLP, using a closely related test substance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

17980-47-1

EC Number:

605-871-6

Cas Number:

17980-47-1

IUPAC Name:

17980-47-1

Constituent 2

Reference substance name:

Triethoxyisobutylsilane

EC Number:

402-810-3

EC Name:

Triethoxyisobutylsilane

IUPAC Name:

Triethoxyisobutylsilane

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Ltd, Manston Kent, UK
- Age at study initiation: (P) 3-4 wk
- Weight at study initiation: (P) Males: treatment wk 1, approx 194-195 g; Females: treatment wk 1, approx 154-156 g;
- Housing: 1 mated female/polypropylene cage with soft wood bedding
- Use of restrainers for preventing ingestion (if dermal): yes/no
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: 16 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 40-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 1991-11-14 To: 1992-03-26

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
Test substance filtered to remove sediment then dissolved in dried arachis oil by shaking to achieve a homogenous mixuture. From wk 12 two batches were prepared and analysed separately for each dose, then pooled prior to administration. Control vehicle was prepared weekly.

Details on mating procedure:

- M/F ratio per cage: 1:1
- Length of cohabitation: up to 3 wk
- Proof of pregnancy: vaginal smear

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

GC

Duration of treatment / exposure:

74 days prior to mating (m,f); 3 wk mating (m,f): up to PND 21 (m,f)

Frequency of treatment:

daily

Details on study schedule:

P males and females 3-4 wk old at start of study; presumably 16-17 wk at mating.
Fi not mated.

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 50, 250, 1000 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

32

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: 14-day range finding study
- Rationale for animal assignment: random based on stratified body weights

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: Yes / No / No data
- Time schedule: daily (before and 1 h after dosing)

BODY WEIGHT: Yes / No / No data
- Time schedule for examinations: days 1, 4, 7, 14, 21

FOOD CONSUMPTION
- Food consumption: days 1, 4, 7, 14, 21

WATER CONSUMPTION No

Oestrous cyclicity (parental animals):

Not examined

Sperm parameters (parental animals):

Not examined

Litter observations:

STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: yes
- If yes, maximum of 8 pups/litter (4/sex/litter as nearly as possible); excess pups were killed and discarded.

PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical abnormalities, reflexological observations.

GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities

Postmortem examinations (parental animals):

SACRIFICE
- Male animals: All surviving animals
- Maternal animals: All surviving animals PND21

GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations

HISTOPATHOLOGY
The tissues indicated in OECD 415 from all parental animals were prepared for microscopic examination

Postmortem examinations (offspring):

GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations

HISTOPATHOLOGY / ORGAN WEIGTHS
None

Statistics:

Adult body weight and food consumption, litter size and weight, group mean pre-coital length, individual offspring bodyweight: F-max test with one way analysis of variance. For significant differences, pair wise comparison of control with treated groups using Students t test.
Gestation length, offspring sex rations, landmarks of offspring physical development, reflexological responses: Kruskall Wallis non-parametric rank sum test. There were no significant differences between control and treated groups so no pair wise evaluations were performed.
Mating, pregnancy, parturition indices: Fischer Exact Probability Test.
Offspring Viability Indices: Chi-squared analysis.

Reproductive indices:

food conversion index; precoital interval; mating index; pregnancy index; gestation length; parturition index, live birth index

Offspring viability indices:

live birth index; viability index (days 1, 4, 7 14, 21); sex ratio; offspring physical development

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, treatment-related

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

not examined

Reproductive performance:

effects observed, treatment-related

Details on results (P0)

At 1000 mg/kg bw/day four adults died and all adult animals showed evidence of salivation immediately post dosing and in some cases pre-dosing. The salivation was considered in the report to be a reflex reaction rather than evidence of systemic toxicity and to have contributed to the deaths.
Salivation was seen in 3 males at 250 mg/kg bw/day.

At 1000 mg/kg bw/day a reduction in the total number of pregnancies was seen but without statistically significant differences in the mating and pregnancy indices. Therefore, this was considered not to be a treatment-related effect on fertility.

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Sex:

male/female

Results: F1 generation

General toxicity (F1)

Clinical signs:

not examined

Mortality / viability:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Histopathological findings:

not examined

Details on results (F1)

Live birth index and live litter size, before and after litter standardization were comparable for all groups throughout lactation up to weaning. There were no effects on litter sex ratios.

At 1000 mg/kg bw/day there was a slight but statistically significant difference in group mean litter weights and individual offspring body weight on day 7 post partum, that continued through day 14 and 21. But the increase in weight gain, relative to the group starting weight for each period of measurement, was comparable for each group. At 1000 mg/kg bw/day the reduction in offspring body weight from day 7 post partum was not considered in the report to be evidence of an effect on offspring development. Measures of offspring development gave no indication of a treatment-related effect. There were no significant findings at 250 and 50 mg/kg bw/day.

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

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

Based on:

test mat.

Sex:

male/female

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

A well reported one generation toxicity study conducted according to the current guideline (OECD 415) and GLP found that gavage administration of up to 1000 mg/kg bw/day to parental rats for 10 wk prior to mating and throughout gestation and lactation gave no clear evidence of adverse reproductive effects in the parents or offspring.