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Administrative data

Description of key information

In a Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test, conducted according to OECD Test Guideline 422 study and in compliance with GLP, tris(2-methoxyethoxy)vinylsilane was tested in rats by oral gavage. A NOAEL for male toxicity was concluded to be 25 mg/kg bw/day based on decreased body weights, body weight gains and food consumption, effects on haematology and serum chemistry parameters as macroscopic and microscopic changes in male rats reproductive organs and tissues at 75 and 250 mg/kg bw/day. A NOAEL for females was concluded to be 75 mg/kg bw/day based on effects on haematology and serum chemistry parameters and effects on lymphoid tissues (WIL Research Laboratories, 2005).

Key value for chemical safety assessment

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
Study period:
2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
ANIMAL RECEIPT AND ACCLIMATION
100 female and 50 male, sexually mature Crl:CD®(SD)IGS BR rats were received from Charles River Laboratories, Inc., Raleigh, North Carolina on April 27, 2004. The animals were 57 days old upon receipt. Each animal was examined by a qualified technician on the day of receipt, sexed and weighed 1 day after receipt. Each rat was uniquely identified by a Monel® metal eartag displaying the animal number and housed for 15 days for acclimation purposes. During the acclimation period, the rats were observed twice daily for general changes in appearance or behavior. The animals were allowed a pretreatment week during which they did not receive the test article but their clinical conditions and body weight and food consumption data were recorded during that time.

ANIMAL HOUSING
Upon arrival and until pairing, all animals were individually housed in clean, stainless steel wire-mesh cages suspended above cage-board. The cage-board was changed three times per week. The reproductive phase females were paired for mating in the home cage of the toxicity phase male of the same treatment group. Following positive evidence of mating, the reproductive phase females were individually housed in plastic maternity cages with nesting material, ground corncob bedding (Bed-O'Cobs®; The Andersons, Industrial Products Division, Maumee, Ohio). The nesting material is periodically analyzed by the manufacturer for contaminants. No contaminants were present in the bedding at concentrations sufficient to interfere with the outcome of the study. The results of these analyses are maintained at WIL Research Laboratories, LLC. The females were housed in these cages through lactation day 4, the scheduled day of necropsy. Females for which there was no evidence of mating were placed in plastic maternity cages with nesting material upon completion of a 14-day mating period. Females that did not deliver were necropsied on post-mating day 25. Animals were housed in accordance with the Guide for the Care and Use of Laboratory Animals (National Research Council, 1996). The animal facilities at WIL Research Laboratories, LLC are accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International).

DIET, DRINKING WATER AND MAINTENANCE
The basal diet used in this study, PMI Nutrition International, LLC, Certified Rodent LabDiet® 5002, is a certified feed with appropriate analyses performed by the manufacturer and provided to WIL Research Laboratories, LLC. Feeders were changed and sanitized once per week. Municipal water supplying the facility is sampled for contaminants according to standard operating procedures. The results of the diet and water analyses are maintained at WIL Research Laboratories, LLC. No contaminants were present in animal feed or water at concentrations sufficient to interfere with the objectives of this study. The basal diet and reverse osmosis-purified (on-site) drinking water, delivered by an automatic watering system were provided ad libitum throughout the acclimation period and during the study.

ENVIRONMENTAL CONDITIONS
All rats were housed throughout the acclimation period and during the study in an environmentally controlled room. The room temperature and humidity controls were set to maintain daily averages of 71 ± 5°F (22 ± 3°C) and 50 ± 20% relative humidity. Room temperature and relative humidity were monitored using the Metasys DDC Electronic Environmental control system and were recorded approximately hourly. These data are summarized in Appendix B. Actual mean daily temperature ranged from 69.9°F to 75.2°F (21.1°C to 24.0°C) and mean daily relative humidity ranged from 39.0% to 48.9% during the study. Light timers were calibrated to provide a 12-hour light (6 a.m. to 6 p.m.) / 12-hour dark photoperiod. The 12-hour light / 12-hour dark photoperiod was interrupted as necessary to allow for the performance of protocol-specified activities. Air handling units were set to provide approximately 10 fresh air changes per hour.
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The vehicle and test article formulations were administered orally by gavage, via 15-gauge, polypropylene-shafted silicone-bulb-shaped-tipped dosing cannulae (Instech Solomon, Plymouth Meeting, Pennsylvania) once daily.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Prior to the initiation of dosing (May 5, 2004), representative control and test article formulations were prepared. Duplicate samples (1 mL each) for homogeneity determination were collected from the top, middle and bottom strata of the 25, 75 and 250 mg/kg/day dosing formulations and from the middle stratum of the control group preparation. The aliquots dispensed for homogeneity were representative of the size of aliquots dispensed for daily dosing procedures and included resuspension analysis over the longest period of aliquot storage. Samples from the control formulation and samples from the top and bottom strata were withdrawn from the aliquots after 6 and 12 days of refrigerated storage to confirm resuspension homogeneity and stability of the test article in the formulations. Fourteen-day refrigerated stability was assessed by comparison of the test article concentrations from samples collected from the middle stratum of each formulation on the day of preparation and following 14 days of storage. Duplicate samples (1 mL each) were collected from the middle stratum of each formulation, including the control group, for study weeks 0, 1, 2, 4 and 6 for confirmation of concentration. Using gas chromatography with flame ionization detection (GC/FID), the test article was analyzed for purity prior to the start of dosing. Characterization of the test article structure was performed by gas chromatography (GC) with mass selective detection (MSD). The determination of vinyl-tris(2-methoxyethoxy)silane in dried/deacidified corn oil formulations was performed by gas chromatography (GC) with mass selective detection (MSD).
Duration of treatment / exposure:
Four groups of male and female Crl:CD(SD)IGS BR rats (10/sex/group) were administered the test article, vinyl-tris(2-methoxyethoxy)silane, in the vehicle, dehydrated, deacidified corn oil, daily by oral gavage for 28 days; the males were treated 14 days prior to mating and continuing throughout mating. Additionally, four groups of female rats (10 per group) were mated with the treated males and were also administered the test article by oral gavage daily for a minimum of 14 days prior to mating, throughout mating and gestation and continuing through lactation day 3.
Frequency of treatment:
daily
Dose / conc.:
25 mg/kg bw/day (nominal)
Dose / conc.:
75 mg/kg bw/day (nominal)
Dose / conc.:
250 mg/kg bw/day (nominal)
No. of animals per sex per dose:
10/sex/group
Control animals:
yes, concurrent vehicle
Positive control:
no
Observations and examinations performed and frequency:
All animals were observed twice daily for appearance and behavior. Clinical observations, body weights and food consumption were recorded at appropriate intervals. In addition, detailed clinical observations (functional observational battery [FOB] conducted out of the home cage) and locomotor activity were evaluated for all adult male and toxicity phase females once prior to the start of test article administration (baseline evaluations) and again during the last week of the test article administration.
Sacrifice and pathology:
Clinical pathology assessments (hematology and serum chemistry) and macroscopic and microscopic examinations (including organ weights) were also performed on the appropriate groups of adult males and toxicity phase females. All reproductive phase females were allowed to deliver and rear their offspring to lactation day 4; surviving dams and pups were euthanized and examined on lactation day 4.
Statistics:
All statistical tests were performed using appropriate computing devices or programs. Analyses were conducted using two-tailed tests (except as noted otherwise) for minimum significance levels of 1% and 5%, comparing each test article-treated group to the control group by sex. Mean body weights and body weight changes, maternal food consumption, gestation lengths, implantation sites, unaccounted for sites, pre-coital intervals, numbers of pups born, live litter sizes, ambulatory counts measured in locomotor activity assessment, functional observational battery, clinical pathology values (excluding differential white cell counts other than lymphocytes and neutrophils) and organ weight data (absolute and relative) subjected to a parametric one-way analysis of variance (ANOVA) to determine intergroup differences (Snedecor and Cochran, 1980). If the ANOVA revealed statistically significant (p<0.05) intergroup variance, Dunnett's test (Dunnett, 1964) was used to compare the test article-treated groups to the control group. Mating, fertility, copulation and conception indices were analyzed using the Chi-square test with Yates’ correction factor (Hollander and Wolfe, 1999). Mean litter proportions (percent per litter) of pup viability and percent males at birth were subjected to the Kruskal-Wallis nonparametric ANOVA test to determine intergroup differences (Kruskal and Wallis, 1952). If the ANOVA revealed statistically significant (p<0.05) intergroup variance, the Mann-Whitney U-test (Kruskal and Wallis, 1952) was used to compare the test article-treated groups to the control group. Functional observations battery data which yielded scalar and descriptive data and qualitative histopathological findings of the control group were compared to each treated group by the Fisher’s Exact Test (Steel and Torrie, 1980).
Clinical signs:
no effects observed
Description (incidence and severity):
There were no test substance-related clinical findings in the reproductive phase females or males.
Mortality:
mortality observed, non-treatment-related
Description (incidence):
In the reproductive phase, one female in the 75 mg/kg bw/day group was euthanized in extremis on gestation day 22. The cause of moribundity for this female was considered to be dystocia. All other males and reproductive phase females survived to the scheduled necropsy. There were no test article-related clinical findings in the reproductive phase females.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Mean body weight gains were reduced in the 250 mg/kg bw/day group males during study days 14-21 and 21-28. Mean body weight in the 250 mg/kg bw/day group males was 6.7% lower than the control group value on study day 28. There were no test article-related effects on mean body weights or body weight gains in the toxicity phase females.
Food consumption and compound intake (if feeding study):
effects observed, non-treatment-related
Description (incidence and severity):
Food consumption was reduced in the 250 mg/kg/day group males during study days 0-7. There were no test substance-related effects on mean food consumption in the toxicity phase females.
Food efficiency:
not examined
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
Test substance-related decreases in the red and white blood cell parameters were observed in the 250 mg/kg bw/day male and female group. In these groups, the decreases in red blood cell indices were observed with mean red blood cell count, hemoglobin, hematocrit mean corpuscular hemoglobin concentration and percentage and absolute reticulocyte count. Additionally, there was a statistically significant decrease in the mean platelet counts and decreases in the mean white blood cell count, although not statistically significant, which were considered as test substance related. Furthermore, test substance related, statistically significant variations in white blood cell differential evaluation included decreases in basophils and eosinophils and an increase in monocytes.

In the 250 mg/kg bw/day male and female groups, changes in the granulocyte and erythrocoid series were observed. The myeloid:erythoid (M/E) ratio was decreased in males and females. Additionally, the percentages of myelocyte neutrophil, metamylocute neutrophil, band neutrophil, segmented neutrophil, eosinophil and total granulocytes were decreased in the 250 mg/kg bw/day male and groups. The relative percentages of rubriblasts, prorubriblasts, rubicytes, erythroid mitotic figures and total erythrocytes were increased in theses males and females. The increased percent erythrocytes in the bone marrow consisted of an increase in the erythroid proliferation pool (immature erythrocytes). This correlated with the decreases observed in red blood cell count, hemoglobin and hematocrit. No evidence of a reticulocytosis was evidenced supportive of a non-regenerative response at the peripheral level. However, review of bone marrow histopathology showed minimal to mild hypoplasia in some of the animals in the 250 mg/kg bw/day. Therefore, the relevance or mechanism for the cytologic changes cannot be determined.

Statistically significant decreases in mean hematocrit and hemoglobin were observed in the 250 mg/kg bw/day male group and in hemoglobin in the 75 mg/kg bw/day male group. Furthermore, decreased mean activated partial thromboplastin time was observed as well as an increase in the percent prorubricytes in the bone marrow in the 75 mg/kg bw/day male group. However, there was no dose response and/or only small variations from the control values occurred and consequently, these changes were considered as not test substance related.

Statistically significant increased prothrombin time in the 250 mg/kg bw/day female group and increased mean corpuscular volume the 25 and 75 mg/kg bw/day female groups were observed. However, these changes were not considered as test substance-related.
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
A statistically significant decreased mean albumin, total protein and globulin levels and increased mean albumin/globulin ratio was noted in the 250 mg/kg bw/day male and female groups. These changes were considered as test substance related effects. Furthermore, statistically significant increased mean bilirubin level in the 250 mg/kg bw/day and mean chloride levels in the 25 and 75 mg/kg bw/day male groups occurred. Decreased mean blood urea nitrogen levels were observed in the 25 and 75 mg/kg bw/day female groups. These changes were not considered as adverse effects since there was not a dose response and similar trend in the opposite sex or small variations compared to control occurred.
Urinalysis findings:
not examined
Behaviour (functional findings):
no effects observed
Description (incidence and severity):
There were no test article-related effects observed at the FOB or locomotor activity evaluations in the males or toxicity phase females at any dose level.
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Mean absolute and relative (to final body and brain weight) thymus and adrenal gland weights were observed in the 75 and 250 mg/kg bw/day male groups and in 250 mg/kg bw/day female group. These were reduced in a dose-related manner compared to the control group values. The differences were statistically significant in the 250 mg/kg bw/day group and correlated with the microscopic finding of lymphoid depletion. There were no microscopic correlates in the 25 and 75 mg/kg bw/day dose groups why the changes were not considered as adverse in these dose groups.

Mean absolute and relative thymus weights were decreased in the 75 and 250 mg/kg bw/day in females. However, since the decrease at 250 mg/kg bw/day was statistically significant only and correlated with lymphoid depletion. Therefore, the decrease at 250 mg/kg bw/day was considered as test substance-related only.

Statistically significant mean absolute and relative (to final body and brain weight) prostate weight in the 75 and 250 mg/kg bw/day groups were reduced in a dose-related manner compared to the control group values. Mean absolute and relative (to final body and brain weights) adrenal gland, right and left testis, right and left epididymis and seminal vesicle weighs were reduced in the 250 mg/kg bw/day. With the exception of the mean absolute and relative seminal vesicle weights, the differences from the control group were statistically significant. The reductions in male reproductive organ weights correlated with reduced fertility and microscopic findings in the 250 mg/kg bw/day group. A histological correlation for decreases in mean adrenal gland weight was not observed. No other test-substance related changes were observed.

In the 250 mg/kg bw/day dose male group, mean absolute or relative (to final body weight) brain, liver, kidney and thyroid/parathyroid weights were reduced compared to the control group values. Although not statistically significant, the 8 % decrease in mean final body weight in this group compared to the control group appears to be most likely explanation for these decreased organ weights. However, in the absence of a dose response, similar changes in the females or histopathological alterations to correlate with the weight decreases, the changes were not considered to be test substance related.
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
Test substance-related changes were observed in the testes, epididymides and thymus in the 250 mg/kg bw/day and changes in the spleen was noted in the 75 and 250 mg/kg bw/day groups. Small and soft epididymides and/or testes were observed in all the 250 mg/kg bw/day male group. Small thymus was observed in 9 of 10 animals in the 250 mg/kg bw/day group. These changes correlated with decreased reproductive organ and thymus weight noted for males in this group. In the spleen, adhesions or white areas were observed in 2 of 10 males in the 75 mg/kg bw/day and 5 of 10 males in the 250 mg/kg bw/day group.

Test substance-related changes were observed in the thymus and spleen were observed in the 250 mg/kg bw/day female group. Small thymus was observed in 3 of 10 animals in the 250 mg/kg bw/day. Additionally, adhesions or white areas in the spleen were observed in the 3 of 10 animals in the 250 mg/kg bw/day.

All other changes were considered to be spontaneous and/or incidental and therefore, unrelated to the test substance. Although pale pancreas was observed in the 250 mg/kg bw/day male group only, the finding was not considered as test substance related due to the absence of histologic correlation.
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
In the 250 mg/kg bw/day dose male group, minimal to mild hypocellularity of the sternal bone marrow was observed in 5 of 10 males and in 2 of 10 females; aggregates of mature granulocytes were absent from histologic sections of the affected marrow; in the thymus, minimal to moderate lymphoid depletion was observed in 7 of 10 males and 3 of 10 females which correlated to reduced thymus gland weights; mild lymphoid depletion of the mandibular (3 of 9 males and 5 of 10 females) and/or mesenteric lymph nodes (5 of 10 males and 3 of 10 females). These changes were considered as test substance-related. In the 250 mg/kg bw/day female group, 2 animals had lymphoid depletion in the mesenteric lymph node although this was not considered as test substance related since the thymus and mandibular lymph nodes were unaffected.

In the 250 mg/kg bw/day dose female group, minimal to mild hypocellularity of the sternal bone marrow was observed in 2 of 10 animals. Aggregates of mature granulocytes were absent from histologic sections of the affected marrow. Hypocellularity of the bone marrow was considered a consistent finding with the hematology alterations.

In the spleen, capsular fibrosis was observed in 4 of 10 males and 3 of 10 females in the 250 mg/kg bw/day male group. This change was noted as adhesions to various abdominal structures or as white areas on the spleen. In contrast to the changes in hematopoietic cell numbers in the bone marrow and lymphoid depletion in the 250 mg/kg bw/day group in various tissues, red and white pulp components of the spleen appeared within normal limits. 2 males in the 75 mg/kg bw/day group had adhesions observed macroscopically although neither had capsular fibrosis.

In the testes, moderate to severe and bilateral seminiferous tubule degeneration was observed in 10 of 10 males in the 250 mg/kg bw/day male group. This correlated with decreased testicular organ weights, macroscopic findings (small and/or soft testes) and reduced fertility. Degeneration was characterised by a marked reduction or absence of spermatogeni epithelium. Minimal seminiferous tubule degeneration was observed in one control male and this was considered as incidental or background changes unrelated to treatment. Similarly, mild degeneration was observed in one male in the 25 mg/kg bw/day group and was associated with the absence of one epididymis which was considered as a spontaneous condition unrelated to the test substance.
Secondary to the extensive loss of spermatogenesis in the 250 mg/kg bw/day male group, all animals had mild to moderate hypospermia in the epididymides and 9 of 10 animals had luminal cellular debris. Hypospermia correlated to the decreased epididymal weigths and macroscopic findings why it was considered as treatment related.

In the prostate, decreased section and/or atrophy was observed in 4 of 10; 6 of 10; 6 of 10 and 10 of 10 animals in the 0, 25, 75 and 250 mg/kg bw/day respectively. However, the number of animals within these groups having both decreased secretion and atrophy was 0 of 10; 1 of 10; 1 of 10 and 6 of 10 animals. The combination of these changes correlated with the decreased prostate weights in the 250 mg/kg bw/day group. Decreased secretion was characterised by extensive regions of acini devoid of eosinophilic secretory material (in the absence of free secretory material suggestive of post mortem/artefactual leakage) or small acini due to reduced amounts of secretory material often with a convoluted epithelial surface composed of enlarged cells. Atrophy was characterised by a similar reduction in secretory material, however, also by a marked thinning of the epithelium. Decreased secretion and atrophy were both considered as test substance related in the 250 mg/kg bw/day. it was unclear which change, atrophy or decreased secretion that was the largest contributor to the decreased prostate weights observed in the 250 mg/kg bw/day group. A histological correlation for the significantly reduced prostate weights in the 75 mg/kg bw/day group was unclear. However, the slightly increased incidence of atrophy in this group compared to the control group and finding mildly severe (compared to minimal) atrophy only in the 75 and 250 mg/kg bw/day groups, suggesting that prostatic atrophy may be the greater influence on the prostate weight decreased and may a test substance related change in the 75 mg/kg bw/day. No other test substance-related findings were observed.
Histopathological findings: neoplastic:
not examined
Other effects:
not examined
Dose descriptor:
NOAEL
Effect level:
25 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
body weight and weight gain
clinical biochemistry
food consumption and compound intake
gross pathology
haematology
histopathology: non-neoplastic
organ weights and organ / body weight ratios
Dose descriptor:
NOAEL
Effect level:
75 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
clinical biochemistry
haematology
histopathology: non-neoplastic
organ weights and organ / body weight ratios
Critical effects observed:
yes
Lowest effective dose / conc.:
75 mg/kg bw/day (nominal)
System:
haematopoietic
Organ:
bone marrow
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
not specified
Conclusions:
In a repeated dose oral toxicity study, conducted according to OECD test guideline 422 and in compliance with GLP, a NOAEL for male systemic toxicity was concluded to be 25 mg/kg/day based on decreased body weights, body weight gains and food consumption, effects on hematology parameters (decreased blood cell counts and changes in the granulocyte and erythroid series) and serum chemistry parameters (decreased albumin, protein and globulin) at 250 mg/kg bw/day and effects on lymphoid tissues (macroscopic and microscopic findings and/or decreased organ weights) at 75 and/or 250 mg/kg bw/day. For female systemic toxicity was 75 mg/kg/day based on effects on hematology and serum chemistry parameters and effects on lymphoid tissues for females at 250 mg/kg/day which were similar to the effects noted for males.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
25 mg/kg bw/day
Study duration:
subacute
Species:
rat
System:
cardiovascular
Organ:
bone marrow

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 for repeated dose toxicity via the oral route, conducted according to OECD Test Guideline 422 and in compliance with GLP, concluded a NOAEL of 25 mg/kg bw/day for male toxicity. This was based on decreased body weights, body weight gains and food consumption, effects on haematology parameters (decreased blood cell counts and changes in the granulocyte and erythroid series) and serum chemistry parameters (decreased albumin, protein and globulin) at 250 mg/kg bw/day and effects on lymphoid tissues (macroscopic and microscopic findings and/or decreased organ weights) at 75 and/or 250 mg/kg/day as macroscopic and microscopic changes in male rats reproductive organs and tissues at 75 and 250 mg/kg bw/day. A NOAEL for females was concluded to be 75 mg/kg bw/day (nominal) based on effects on haematology and serum chemistry parameters and effects on lymphoid tissues at 250 mg/kg/day which were similar to the effects noted for males. The effects on haematology parameters included decreased blood cell counts and changes in the granulocyte and erythroid series. Serum chemistry showed decreased albumin, protein and globulin (WIL Research Laboratories, 2005).

No data are available for the registration substance for sub-chronic (90-day) repeated dose toxicity. The most appropriate route of exposure for studies on this substances is oral because its low vapour pressure (0.43 Pa at 25°C) means that suitable concentrations could not be obtained in an inhalation study (saturation concentration 4 ppm at 25°C).

Good quality 90-day repeated dose toxicity data are available to allow the toxicity of the non-silicon hydrolysis product to be assessed for the exposure of human via the environment.

The study reports treatment related histopathological changes observed in the testes, thymus, haematopoietic tissues (spleen , bone marrow, liver). A dose dependent degeneration of the germinal epithelium of the seminiferous tubules was also reported, with only partial recovery observed in the days of recovery from treatment (Dieter, 1993). A NOAEL could not be determined since testicular degeneration in males and decreased thymus weights in males and females occurred at the lowest concentration administered, 750 ppm. Therefore, the LOAEL was concluded to be 750 ppm (estimated to be equivalent to 70 mg actual ingested/kg bw/day).  

Justification for classification or non-classification

Based on the available Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test (OECD Test Guideline 422) study on the registered substance the registrants self-classify tris(2-methoxyethoxy)vinylsilane for specific target organ toxicity based on repeated exposure as STOT Category 2 based on effects on bone marrow.