Propyltriacetoxysilane

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

one-generation reproductive toxicity

Remarks:

based on generations indicated in Effect levels (migrated information)

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Propyltriacetoxysilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable. Acetic acid and citric acid are grouped together because of their close structural relationship (US EPA officially recognises acetic acid and citric acid in the same category). Therefore, citric acid has comparable values with acetic acid and the target substance propyltriacetoxysilane.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

Read-across approach from published experimental data on fertility and one-generation study on the supporting substance Citric acid.

GLP compliance:

no

Limit test:

yes

Clinical signs:

no effects observed

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:

not examined

Other effects:

no effects observed

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

not examined

Reproductive performance:

not examined

Based on the experimental results obtained with the supporting substance citric acid (NOAEL >= 2500 mg/kg bw/day (basis for effect: number of pregnancies) in rats daily treated by feed before, during, and after mating), the read-across approach was applied and the NOAEL with the substance propyltriacetoxysilane is calculated to be equal or greater than 3231.18 mg/kg bw/day.

Dose descriptor:

NOAEL

Effect level:

>= 3 231.18 mg/kg bw/day

Sex:

female

Basis for effect level:

other: (Read-across approach from citric acid effect level based on test material and basis for effect: number of pregnancies)

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

no effects observed

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings:

not specified

Based on the experimental results obtained with the analogue citric acid (NOAEL >= 2500 mg/kg bw/day in rats (basis for effect: number of young born, or survival of young animals)), the read-across approach was applied and the NOAEL with the substance propyltriacetoxysilane is calculated to be equal or greater than 3231.18 mg/kg bw/day.

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

>= 3 231.18 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: (Read-across approach from citric acid effect level based on test material and basis for effect: number of young born, or survival of young animals)

Reproductive effects observed:

not specified

As indicated in the European Chemical Agency Practical Guide 6 “How to report read –across and categories”, the structural grouping was realized using “OECD QSAR APPLICATION TOOL BOX” version 2.1.2. Presented results show that both substances have common (eco)toxicological behavior (attachment).

Table 1: Data Matrix, Analogue Approach:

CAS Number			Source chemical 77-92-9	Target chemical 17865-07-5
CHEMICAL NAME			Citric acid	Propyltriacetoxysilane
PHYSICO-CHEMICAL DATA
Melting Point			Measured data: 153 ºC	Measured data: -34.4 ºC (Freezing point)
Boiling Point			Decomposes	Measured data: 185.8 ºC at 102.1 kPa
Density			Measured data: 1.665 g/cm3 at 20 ºC	Measured data: 1.117 at 20 ºC (relative density)
Vapour Pressure			Estimated data: 5.6E-09 mm Hg	Measured data: 1.23 Pa at 20 ºC.
Partition Coefficient (log Kow)			Measured data: -1.72	Calculated (EPI-Suite, US EPA v4.1): 1.23
Water solubility			Measured data: 1330 g/L	Not applicable: Hydrolytically unstable.
ENVIRONMENTAL FATE and PATHWAY
Hydrolysis as a function of pH			No data.	Key study: Experimental results: An abiotic degradation study was performed on propyltriacetoxysilane according to OECD Guideline 111 (GLP study). The half-life at pH 1.2, 4, 7 and 9 of propyltriacetoxysilane was determined to be < 37.5 seconds since the test item was completely hydrolysed at 150 seconds after the initial contact of the test item with water and four completed half life cycles could be estimated in a reaction time of 150 seconds. The stated mechanism of hydrolysis of propyltriacetoxysilane was free acetic acid as the main hydrolysis product and the fast kinetic polycondensation reaction of the forming silanols (trihydroxypropylsilane).
Aerobic Biodegradation			Readily biodegradable	Key study: Read-across from experimental results on analogue methylsilanetriyl triacetate: Readily biodegradable.
ENVIRONMENTAL TOXICITY
Acute Toxicity to Fish			Experimental data: (96 h) LC 50 = 1516 mg/L	Weight of evidence: Read-across from experimental results with acetic acid: In the first study, Wallen et. al., 1957 (reliability 2), an acute toxicity test was performed according to OECD Guideline 302. The LC50 (based on mortality) of test material, acetic acid, inGambusia affinisfor 96h exposure period was 251 mg/L. Based on this experimental result, read-across approach was applied and LC50 (96h, based on mortality) for propyltriacetoxysilane was calculated to be 345.97 mg/L. In the study of Juhnke et. al, 1978 (reliability 2), an acute toxicity test was performed according to German Standard Method for Waste Water and Sludge of 1976 with test material acetic acid. The LC50 for 48h toxicity on the golden orfe (Leuscicus idul melanotus) was 410 mg/L (basis for effect: mortality). Based on this result, read-across approach was applied and LC50 (48h, based on mortality) for propyltriacetoxysilane was calculated to be 565.12 mg/L. In the study of Mattson et. al., 1976 (reliability 2), Fathead minnow (Pimephales promelas) were exposed under static conditions to a series of concentrations of acetic acid. The 96 h LC50 was 79-88 mg/L (basis for effect: mortality). Based on this experimental result obtained with the supporting substance acetic acid, read-across approach was applied and the LC50 (96h) for propyltriacetoxysilane was calculated to be 108.89-121.29 mg/L (basis for effect: mortality).   Supporting studies: Read-across from experimental results with sodium acetate: There are two supporting studies from DeYoung et. al., 1996 and Terhaar et. al., 1972, both with reliability 2 performed for the supporting substance sodium acetate. In the first one and based on the experimental results (120h LC50 = 13330 mg/L forPimephales promelas), read-across approach was applied and the 120h LC50 for propyltriacetoxysilane was calculated to be 13450 mg/L. In the second study and based on the experimental results (96h LC50 = 10000 mg/L forPimephales promelas), the read-across approach was applied and the 96h LC50 for propyltriacetoxysilane was calculated to be 10090 mg/L.
Acute Toxicity to Aquatic Invertebrates			Experimental data: (48 h) EC 50 = 1535 mg/L	Weight of evidence: Read-across from experimental results with acetic acid: In the first study, Janssen et. al., 1993 (reliability 2), an acute immobilisation test with acetic acid was performed according to an equivalent method to OECD Guideline 202. The EC50 inDaphnia magnafor 48h exposure period was 65 mg/L (basis for effect: mobility). Based on this experimental result, read-across approach from the supporting substance acetic acid was applied and EC50 (48h) for propyltriacetoxysilane was calculated to be 89.59 mg/L (based on mobility and with no pH adjustment). In the study by Bringmann et. al, 1982 (reliability 2), a largely standardized procedure of water toxicology for testing the potential toxic action of water pollutants measured by the immobilization ofDaphnia magnaaccording to DIN 38412, Part II guideline (Daphnia short-time test) was performed. The EC50 (48h, basis for effect: mobility) for acetic acid was 95 mg/L with no pH adjustment and 6000 mg/L with pH adjustment. Based on this result, read-across approach from supporting substance acetic acid was applied and EC50 (48h, basis for effect: mobility) for propyltriacetoxysilane was calculated to be 130.94 mg/L with no pH adjustment and 8270.11 with pH adjustment. In the study by Dowden et. al., 1965 (reliability 4), the EC50 of 86 chemicals was determined using a standardised method. The 24h EC50 of acetic acid forDaphnia magnawas determined to be 47 mg/L (basis for effect: mobility). Based on this result obtained with the supporting substance acetic acid, read-across approach was applied and the EC50 (48h, based on mobility) for propyltriacetoxysilane was calculated to be 64.78 mg/L. In the published study by Saha et. al., 2006 (reliability 4), an acute toxicity test was performed withMoina micrurain a renewal system. Based on the experimental results obtained with the supporting substance acetic acid forMoina micrura(96h LC50 = 163.72 mg/L, basis for effect: mortality), the read-across approach was applied and the 96h LC50 for propyltriacetoxysilane was calculated to be 225.66 mg/L.   Supporting studies: Read-across from experimental results with acetic acid and sodium acetate: There are two supporting studies from Anderson, 1944 (reliability 4) and Bringmann et. al., 1977, (reliability 3) performed for the supporting substances acetic acid and sodium acetate respectively. In the first one and based on the experimental results with supporting substance acetic acid (16h NOAEC = 150 mg/L forDaphnia magnaand basis for effect: mobility), read-across approach was applied and the 16h NOAEC for propyltriacetoxysilane was calculated to be 206.75 mg/L. In the second study and based on the experimental results with supporting substance sodium acetate (24h LC50 = 7170 mg/L forDaphnia magnaand basis for effect: mobility), the read-across approach was applied and the 24h LC50 for propyltriacetoxysilane was calculated to be 7234.68 mg/L.
Toxicity to Aquatic Plants			Experimental data: (72 h) EC 50 = 640 mg/L	Key study: Experimental results: An Algae Growth Inhibition Test was performed according to OECD Guideline 201 (GLP study) on test item Propyltriacetoxysilane. The EC50 value (based on growth) rate for Pseudokirchenriella subpicata at 72 hour exposure period was 24.42 mg/L without pH adjustment and > 1562.50 mg/L with pH adjustment. The NOEC (72h and based on growth rate) was determined to be 18 mg/L without pH adjustment and 40 mg/L with pH adjustment. Based on microscopic observations performed at test termination in all test concentrations no differences in size and shape of algal cells were reported as compared to the algae cells in the control.   Supporting studies: Read-across approach from experimental results on acetic acid and sodium acetate: In the study by Bringmann and Kühn 1980 (klimisch 3) performed with acetic acid, the 8 days Toxicity Threshold for Scenedermus quadricauda was determined to be 4000 mg/L based on growth rate. Based on this result, the read-across approach was applied and the 8 days Toxicity Threshold for propyltriacetoxysilane was calculated to be 5513.41 mg/L. In the study by Krebs, 1991 (klimisch 2) conducted on acetic acid, the EC50 at 24 hours of green algae exposure was 156 mg/L based on growth inhibition. The read-across was applied and EC50 (24h) for propyltriacetoxysilane was calculated to be 215 mg/L. Based on the experimental results obtained by Bringmann and Kühn 1978 (klimisch 3) with acetic acid for Microcystis aeruginosa (8d Toxicity threshold = 90 mg/L, basis for effect: cell multiplication), the read-across approach was applied and the 8 days Toxicity Threshold for propyltriacetoxysilane was calculated to be 124.05 mg/L. In the publication by Hoare et al., 1967 (klimisch 3) the EC50 at 60 hours of Anacystis nidularis (blue-green algae exposure) was determined to be 1640 mg/L based on growth inhibition. Taking into account this result, the read-across approach was applied and EC50 (60h, basis for effect: growth inhibition) for Propyltriacetoxysilane was calculated to be 1654.73 mg/L.
Toxicity to microorganisms			No data	Key study: Read-across from experimental result on analogue methylsilanetriyl triacetate: In the ready biodegradability test was performed according to OECD Guideline 301 F on analogue methyltriacetoxysilane the 28 day-NOEC was determined to be 100 mg/L since the substance degraded well and did not inhibit the degradation of the toxicity test. Based on these results, the read-across approach was applied and 28 day-NOEC for propyltriacetoxysilane was calculated to be 105.45 mg/L under test conditions.
MAMMALIAN TOXICITY
Acute Toxicity: Oral			Experimental data: LD 50 = 5790 – 7100 mg/kg bw (mice) LD 50 = 11700 mg/kg bw (rats)	Data waiving (Column 2 of REACH Annex VIII): The substance is corrosive.
Acute Toxicity: Inhalation			No data	Data waiving (Column 2 of REACH Annex VIII): The substance is corrosive.
Acute Toxicity: Dermal			Experimental data: A 4-hour skin irritation study in rabbits exposed to a solution containing 60% citric acid caused erythema and edema. This study did not assess a lethal dose value. TheLD50 was not provided.	Data waiving (Column 2 of REACH Annex VIII): The substance is corrosive.
Repeated Dose Toxicity			Repeated dose toxicity: oral: Experimental results: In a 150-day study with male New Zealand White rabbits daily treated by feed, theNOAEL was 1500 mg/kg bw/day(based on no effects observed at the only dose tested). In a 6-week study with male Sprague-Dawley rats daily treated by feed, theNOAEL was 4800 mg/kg bw/day(based on no effects observed at the highest dose tested).	Repeated dose toxicity: Oral: Weight of evidence: Read-across from experimental results with acetic acid and sodium acetate: In the first study, Alexandrov et. al., 1989 (reliability 2), an 8 month test with 60 mg/kg bw acetic acid (3 times per week, by intubation into the esophagus) in male rats was performed. The NOAEL (chronic) in male rats for acetic acid was 60 mg/kg bw. (basis for effect: mobility). Based on this experimental result, read-across approach from the supporting substance acetic acid was applied and NOAEL for propyltriacetoxysilane was calculated to be 82.70 mg/kg bw. In the study by Cory Slechta, 1986 (reliability 3), male rats were chronically treated via drinking water with sodium acetate from weaning. No effects were mentioned on survival, reinforcement behaviour or body weight gain. Based on the experimental results obtained with the supporting substance sodium acetate (NOAEL in male rats >= 0.05 mg/kg bw/day, based on no effects observed at the highest dose tested.), the read-across approach was applied and NOAEL for propyltriacetoxysilane was calculated to be >= 0.05 mg/kg bw/day. In the study by Dryden et. al., 1965 (reliability 2), male rats were daily treated by feed with sodium acetate during four weeks. No effects on growth or survival were observed at ca. 3600 mg/kg bw/day (the only dose tested). Based on the experimental results obtained with the supporting substance sodium acetate (NOAEL in male rats >= 3600 mg/kg bw/day), the read-across approach was applied and NOAEL for propyltriacetoxysilane was calculated to be >= 3632.48 mg/kg bw/day. In the study by Goldman, 1981 (reliability 3), male rats received a daily dose of sodium acetate in the diet during 3 months. Indications of altered thyroid function and decreased growth were reported at the only dose tested. However, only males were exposed to the substance, a small number of animals were used and only the body weights and several indices of thyroid function were studied. The reported effects cannot be considered as being clearly adverse. The study is considered to be of limited use in evaluating the toxicity of the substance. Based on these results from supporting substance sodium acetate (NOAEL in male rats >= 21 mg/kg bw/day, based on no evidence of clearly adverse effects at the only dose tested), read across approach was performed and NOAEL for propyltriacetoxysilane was calculated to be >= 21.19 mg/kg bw/day. In the study by Massaro et. al., 1987 (reliability 3) complex maze learning was investigated in male adult rats using a latent learning task. The adult subjects were exposed to sodium acetate in drinking water for 112 days beginning at weaning. No evidence of impairment of simple task performance was observed. The study is considered to be of limited use in evaluating the toxicity of the substance. Based on these results from supporting substance sodium acetate (NOAEL in male rats >= 0.01 mg/kg bw/day, based on no effects observed at the only dose tested), read-across approach was performed and NOAEL for propyltriacetoxysilane was calculated to be >= 0.01 mg/kg bw/day.
Genetic Toxicity in vitro		Gene mutation in bacteria	Experimental data: In a bacterial reverse mutation assays usingS. typhimurium(TA97, TA98, TA100 and TA104) in the presence and absence of metabolic activation and up to 2000 μg/plate, citric acid was not mutagenic.	Weight of evidence: Read-across from experimental results with acetic acid and sodium acetate: In the study by Zeiger et. al., 1992 (reliability 1), bacterial reverse mutation assay (Ames test) according to OECD Guideline 471 and with GLP compliance was performed. A standard Ames test was carried out with acetic acid usingSalmonella typhimuriumstrains TA 98, TA 100, TA 1535, and TA 97, with and without metabolic activation. Acetic acid did not show any mutagenic effect under test conditions. Based on these experimental results, read-across approach was applied and propyltriacetoxysilane was also considered as no mutagenic under test conditions. In the study by McMahon et. al., 1979 (reliability 2), bacterial reverse mutation assay (Ames test) according to OECD Guideline 471 (with deviations) was performed. A bacterial mutagen screening technique was carried out with acetic acid usingSalmonella typhimuriumstrains TA 1535, TA 1537, TA 98 and TA 100, with and without metabolic activation. Acetic acid did not show any mutagenic effect under test conditions. Based on these experimental results, read-across approach was applied and propyltriacetoxysilane was also considered as no mutagenic under test conditions. In the study by Ishidate et. al., 1984 (reliability 2), bacterial reverse mutation assay (Ames test) according to OECD Guideline 471 (with deviations) was performed. The study was carried out with sodium acetate and usingSalmonella typhimuriumstrains TA92, TA1535, TA100, TA1537, TA94, only with metabolic activation. No significant increases in the numbers of revertant colonies were detected at the maximum dose tested. Based on these experimental results, read-across approach was applied and propyltriacetoxysilane was also considered as no mutagenic under test conditions.
		Chromosomal aberration	No data.	Weight of evidence: Read-across from experimental results with acetic acid and sodium acetate: In the study by Morita et. al., 1990 (reliability 2), a cytogenetic assay was carried out with acetic acid using Chinese hamster ovary K1 cells. Acetic acid was not clastogenic at concentrations close to those showing cytotoxicity, both with and without metabolic activation. Low pH did induce some artificial chromosome aberrations, but these were eliminated by neutralization of the test medium. Based on these experimental results and applying the read-across approach, the substance propyltriacetoxysilane is also considered as not clastogenic under test conditions. In the study by Ishidate et. al., 1983 (reliability 2), a chromosomal aberrations tests were carried out with sodium acetate using a Chinese hamster fibroblast cell line. In the studies, no metabolic activation systems were applied. The maximum dose of each sample was selected by a preliminary test in which the dose needed for 50% cell-growth inhibition was estimated using a cell densiometer. The incidence of cells with aberrations (including gaps) was 0%. Based on these experimental results, the read-across approach was applied and propyltriacetoxysilane was also considered as no mutagenic under test conditions.
		Mammalian gene mutation	No data.	Key study: Experimental results: The test item Propyl Triacetoxy Silane PTA was assessed for its potential to induce mutations at the mouse lymphoma thyamidine kinase locus using the cell line L5178Y according to OECD Guideline 476. The Experiment I was performed as a 4h short-term exposure assay up to 10.0 mM (with metabolic activation) and up to 5.5 mM (without metabolic activation). The Experiment II was performed as a 4h short-term exposure up to 8.5 mM (with metabolic activation) and a 24h long-term exposure up to 5.0 mM (without metabolic activation). No biologically relevant increase of mutants was found after treatment with the test item. Additionally, colony sizing showed no clastogenic effects induced by the test item. Therefore, Propyl Triacetoxy Silane (PTA) was considered to be non-mutagenic in the in vitro mammalian cell gene mutation assay (thymidine kinase locus) in mouse lymphoma L5178Y cells with and without metabolic activation under test conditions.
Genetic Toxicity in vivo			Experimental data: In a Dominant Lethal assay using male/female rats dosed at 3 g/kg for 5 days, citric acid did not induced germ cell genotoxicity.	Key study: Read-across from experimental results with supporting substance sodium acetate: In the study by Seiler, 1981 (reliability 2), the Testicular DNA-synthesis inhibition test (DSI test) was performed on male mice with Sodium Acetate (single oral dose by gavage). No inhibitory effect on DNA-replication was detectable in animals treated with Sodium Acetate. Based on these results, read-across approach was applied and propyltriacetoxysilane is also considered no genotoxic in animals (based on no effects on DNA-replication).
Carcinogenicity			No data.	No data.
Reproductive Toxicity	Toxicity to reproduction		Experimental data: In a one-generation oral reproductive toxicity study, female rats and mice were daily treated with citric acid before, during, and after mating. The NOAEL was equal or greater than 2500 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young). In a fertility study, female rats were exposed to citric acid in their daily diet for several months. TheNOAEL (reproductive toxicity) was 600 mg/kg bw/day(based on no effects observed at the only dose tested).	Weight of evidence: Read-across from experimental results with citric acid and citric acid, sodium salt: In the study by Bonting et. al., 1956 (reliability 2), a fertility test was carried out with citric acid on female rats (daily treated by feed for several months). No reproductive effects were observed. Based on the experimental results obtained with the supporting substance citric acid (NOAEL for reproductive effects = 600 mg/kg bw/day; LOAEL > 600 mg/kg bw/day for the same effects), the read-across approach was applied and the NOAEL for propyltriacetoxysilane was calculated to be 775.48 mg/kg bw/day, and LOAEL > 775.48 mg/kg bw/day for reproductive effects. In the study performed by Wright et. al., 1976 (reliability 2), an experiment designed to examine the effect of a 5% dietary supplement of citric acid on the reproductive capacity of the rats was carried out. Based on the experimental results obtained with the supporting substance citric acid (NOAEL P, F1 >= 2500 mg/kg bw/day in rats (basis for effect: number of pregnancies, number of young born, or survival of young animals)), the read-across approach was applied and the NOAEL for propyltriacetoxysilane was calculated to ≥ than 3231.18 mg/kg bw/day for studied effects. In the same study performed by Bonting et. al. 1956 (reliability 2), a fertility test was carried out but with citric acid, sodium salt on female rats (daily treated by feed for several months). No reproductive effects were detected. Based on the experimental results obtained with the supporting substance citric acid, sodium salt (NOAEL for reproductive effects = 50 mg/kg bw/day; LOAEL > 50 mg/kg bw/day for the same effects), the read-across approach was applied and the NOAEL for propyltriacetoxysilane was calculated to be 57.99 mg/kg bw/day, and LOAEL > than 57.99 mg/kg bw/day for reproductive effects.
	Developmental toxicity		Experimental results: In a one-generation oral reproductive toxicity study, female rats and mice were daily treated with citric acid before, during, and after mating. The NOAEL was equal or greater than 2500 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young).	Weight of evidence: Read-across from experimental results with citric acid and citric acid, sodium salt: In the study by Food and Drug Research Laboratories, 1974 (reliability 2), following mating, adult female mice, rats and rabbits were dosed daily for 17 days by oral intubation with acetic acid. No effects on nidation or on maternal or fetal survival were observed at doses up to 1600 mg/kg bw/day. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring in the controls. Based on the experimental results with supporting substance acetic acid (NOAEL >= 1600 mg/kg bw/day for maternal and developmental toxicity), the read-across approach was applied and the NOAEL of propyltriacetoxysilane for maternal and developmental toxicity was calculated to be >= 2205.36 mg/kg bw/day. In the study by Kavlock et. al., 1987 (reliability 2), pregnant mice were generally treated by oral gavage during gestation at a dose level predicted from a preliminary range finding study to induce a slight degree of maternal toxicity. No maternal toxicity and no neonatal effects (mortality and body weight) were observed at the treatment dose level of 1000 mg/kg bw/day. Based on the experimental results obtained with supporting substance sodium acetate (NOAEL >= 1000 mg/kg bw/day) for maternal and neonatal toxicity), read-across approach was applied and the NOAEL for propyltriacetoxysilane was calculated to by >= 1009.02 mg/kg bw/day. In the study by Malorny, 1969 (reliability 2) a three-generation drinking water study with calcium formate in the drinking water was performed in Wistar rats during ca. 3 years. No effects on fertility were observed. Number, weight and length of offspring did not differ in treated animals from controls. No statistical differences in organ or bone abnormalities were found. The growth of treated offspring was similar to controls. Based on experimental results on supporting substance calcium formate (NOAEL for maternal and developmental toxicity >= 200 mg/kg bw/day), the read-across approach was applied and the NOAEL for propyltriacetoxysilane was calculated to be >= 254.46 mg/kg bw/day for maternal and developmental toxicity. In the study by Wright et. al. 1976 (reliability 4), an experiment designed to examine the effect of a 5% dietary supplement of citric acid on the reproductive capacity of the mice and rats was carried out. No effects were seen on number of pregnancies, number of young born, or survival of young in treated rats, compared to controls. Based on the experimental results from supporting substance citric acid (NOAEL >= 2500 mg/kg bw/day, basis for effect: number of pregnancies, number of young born, or survival of young animals), the read-across approach was applied and the NOAEL for propyltriacetoxysilane was calculated to be >= 3231.18 mg/kg bw/day for studied effects.

Conclusions:

Based on the experimental results obtained with the analogue citric acid (NOAEL >= 2500 mg/kg bw/day in rats (basis for effect: number of pregnancies, number of young born, or survival of young animals)), the read-across approach was applied and the NOAEL with the substance propyltriacetoxysilane is calculated to be equal or greater than 3231.18 mg/kg bw/day for studied effects.

Executive summary:

Based on the experimental results obtained with the analogue citric acid (NOAEL >= 2500 mg/kg bw/day in rats (basis for effect: number of pregnancies, number of young born, or survival of young animals)), the read-across approach was applied and the NOAEL with the substance propyltriacetoxysilane is calculated to be equal or greater than 3231.18 mg/kg bw/day for studied effects.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

3 231.18 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Three fertily studies, one of them including a one-generation study, are available with Klimisch score =2 in a weight of evidence approach. The overall quality of the database was determined as appropriate for assessment.

Additional information

Weight of evidence:

 

Read-across from experimental results with citric acid and citric acid, sodium salt:

 

In the study by Bonting et. al., 1956 (reliability 2), a fertility test was carried out with citric acid on female rats (daily treated by feed for several months). No reproductive effects were observed. Based on the experimental results obtained with the supporting substance citric acid (NOAEL for reproductive effects = 600 mg/kg bw/day; LOAEL > 600 mg/kg bw/day for the same effects), the read-across approach was applied and the NOAEL for propyltriacetoxysilane was calculated to be 775.48 mg/kg bw/day, and LOAEL > 775.48 mg/kg bw/day for reproductive effects.

 

In the study performed by Wright et. al., 1976 (reliability 2), an experiment designed to examine the effect of a 5% dietary supplement of citric acid on the reproductive capacity of the rats was carried out. Based on the experimental results obtained with the supporting substance citric acid (NOAEL P, F1 >= 2500 mg/kg bw/day in rats (basis for effect: number of pregnancies, number of young born, or survival of young animals)), the read-across approach was applied and the NOAEL for propyltriacetoxysilane was calculated to ≥ than 3231.18 mg/kg bw/day for studied effects.

 

In the same study performed by Bonting et. al. 1956 (reliability 2), a fertility test was carried out but with citric acid, sodium salt on female rats (daily treated by feed for several months). No reproductive effects were detected. Based on the experimental results obtained with the supporting substance citric acid, sodium salt (NOAEL for reproductive effects = 50 mg/kg bw/day; LOAEL > 50 mg/kg bw/day for the same effects), the read-across approach was applied and the NOAEL for propyltriacetoxysilane was calculated to be 57.99 mg/kg bw/day, and LOAEL > than 57.99 mg/kg bw/day for reproductive effects.

Key value for chemical safety assessment:

According to the experimental results with supporting substances citric acid and citric acid, sodium salt, no toxicity to reproduction was observed in any case. Therefore and based on read-across approaches, the NOAEL for propyltriacetoxysilane was calculated to be >= 3231.18 mg/kg bw/day, based on no effects observed at the highest dose tested.

Short description of key information:
Effects on fertility: Weight of evidence: Based on the experimental results on rats and mice treated with supporting substances citric acid and citric acid, sodium salt, read-across approach was applied and no toxicity to reproduction was observed in any case. The NOAEL for propyltriacetoxysilane was calculated to >= 775.48 mg/kg bw/day (based on no effects observed at the highest dose).

Justification for selection of Effect on fertility via oral route:
According to the experimental results with supporting substances acetic acid and sodium acetate and the read-across approaches, No Observed Adverse Effect Level NOAEL (subacute) for propyltriacetoxysilane taken into account for chemical safety assessment is >= 3632.48 mg/kg bw/day (based on no effects observed at the highest dose tested).

Effects on developmental toxicity

Description of key information

Developmental toxicity/Teratogenicity: Weight of evidence: Based on the experimental results on rats, mice, and rabbits treated with supporting substances acetic acid, sodium acetate, citric acid and calcium formate, read-across approach was applied and no maternal nor developmental toxicity was observed in treated animals exposed to high doses of these substances.  The NOAEL for propyltriacetoxysilane was calculated to >= 2205.36 mg/kg bw/day (based on no effects observed at the highest dose). 

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Propyltriacetoxysilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

Read-across approach from published experimental on Acetic acid.

GLP compliance:

no

Limit test:

no

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
Based on the experimental results obtained with acetic acid in rat (NOAEL >= 1600 mg/kg bw/day for maternal toxicity), the read-across approach is applied and the NOAEL for maternal toxicity of propyltriacetoxysilane is calculated to be equal or greater than 2205.36 mg/kg bw/day.

Dose descriptor:

NOAEL

Effect level:

>= 2 205.36 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Dose descriptor:

NOAEL

Effect level:

>= 2 205.36 mg/kg bw/day

Basis for effect level:

other: developmental toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Based on the experimental results obtained with acetic acid in rat (NOAEL >= 1600 mg/kg bw/day for developmental toxicity), the read-across approach is applied and the NOAEL for developmental toxicity of propyltriacetoxysilane is calculated to be equal or greater than 2205.36 mg/kg bw/day.

Abnormalities:

not specified

Developmental effects observed:

not specified

As indicated in the European Chemical Agency Practical Guide 6 “How to report read –across and categories”, the structural grouping was realized using “OECD QSAR APPLICATION TOOL BOX” version 2.1.2. Presented results show that both substances have common (eco)toxicological behavior (attachment).

Table 1: Data Matrix, Analogue Approach:

CAS Number			Source chemical 64-19-7	Target chemical 17865-07-5
CHEMICAL NAME			Acetic acid	Propyltriacetoxysilane
PHYSICO-CHEMICAL DATA
Melting Point			Measured data: 16.7 ºC	Measured data: -34.4 ºC (Freezing point)
Boiling Point			Measured data: 118.1 ºC	Measured data: 185.8 ºC at 102.1 kPa
Density			Measured data: 1.0446 g/cm3 at 25 ºC	Measured data: 1.117 at 20 ºC (relative density)
Vapour Pressure			Measured data: 11.4 mm Hg at 20 °C	Measured data: 1.23 Pa at 20 ºC.
Partition Coefficient (log Kow)			Measured data: -0.17	Calculated (EPI-Suite, US EPA v4.1): 1.23
Water solubility			Measured data: 50 g/L	Not applicable: Hydrolytically unstable.
ENVIRONMENTAL FATE and PATHWAY
Hydrolysis as a function of pH				Key study: Experimental results: An abiotic degradation study was performed on propyltriacetoxysilane according to OECD Guideline 111 (GLP study). The half-life at pH 1.2, 4, 7 and 9 of propyltriacetoxysilane was determined to be < 37.5 seconds since the test item was completely hydrolysed at 150 seconds after the initial contact of the test item with water and four completed half life cycles could be estimated in a reaction time of 150 seconds. The stated mechanism of hydrolysis of propyltriacetoxysilane was free acetic acid as the main hydrolysis product and the fast kinetic polycondensation reaction of the forming silanols (trihydroxypropylsilane).
Aerobic Biodegradation			Experimental results: Readily biodegradable	Key study: Read-across from experimental results on analogue methylsilanetriyl triacetate: Readily biodegradable.
ENVIRONMENTAL TOXICITY
Acute Toxicity to Fish			Experimental data: (96 h) LC 50 = 251 mg/L (Gambusia affinis) (48 h) LC 50 = 410 mg/L (Golden orfe) (96 h) LC 50 = 79-88 mg/L (Fathead minnow)	Weight of evidence: Read-across from experimental results with acetic acid: In the first study, Wallen et. al., 1957 (reliability 2), an acute toxicity test was performed according to OECD Guideline 302. The LC50 (based on mortality) of test material, acetic acid, inGambusia affinisfor 96h exposure period was 251 mg/L. Based on this experimental result, read-across approach was applied and LC50 (96h, based on mortality) for propyltriacetoxysilane was calculated to be 345.97 mg/L. In the study of Juhnke et. al, 1978 (reliability 2), an acute toxicity test was performed according to German Standard Method for Waste Water and Sludge of 1976 with test material acetic acid. The LC50 for 48h toxicity on the golden orfe (Leuscicus idul melanotus) was 410 mg/L (basis for effect: mortality). Based on this result, read-across approach was applied and LC50 (48h, based on mortality) for propyltriacetoxysilane was calculated to be 565.12 mg/L. In the study of Mattson et. al., 1976 (reliability 2), Fathead minnow (Pimephales promelas) were exposed under static conditions to a series of concentrations of acetic acid. The 96 h LC50 was 79-88 mg/L (basis for effect: mortality). Based on this experimental result obtained with the supporting substance acetic acid, read-across approach was applied and the LC50 (96h) for propyltriacetoxysilane was calculated to be 108.89-121.29 mg/L (basis for effect: mortality).   Supporting studies: Read-across from experimental results with sodium acetate: There are two supporting studies from DeYoung et. al., 1996 and Terhaar et. al., 1972, both with reliability 2 performed for the supporting substance sodium acetate. In the first one and based on the experimental results (120h LC50 = 13330 mg/L forPimephales promelas), read-across approach was applied and the 120h LC50 for propyltriacetoxysilane was calculated to be 13450 mg/L. In the second study and based on the experimental results (96h LC50 = 10000 mg/L forPimephales promelas), the read-across approach was applied and the 96h LC50 for propyltriacetoxysilane was calculated to be 10090 mg/L.
Acute Toxicity to Aquatic Invertebrates			Experimental data: (48 h) EC 50 = 65 mg/L (Daphnia magna) (48 h) EC 50 = 95 mg/L (no pH adjustment), 6000 mgl/L (with pH adjustment) (Daphnia magna) (24 h) EC 50 = 47 mg/L (Daphnia magna)	Weight of evidence: Read-across from experimental results with acetic acid: In the first study, Janssen et. al., 1993 (reliability 2), an acute immobilisation test with acetic acid was performed according to an equivalent method to OECD Guideline 202. The EC50 inDaphnia magnafor 48h exposure period was 65 mg/L (basis for effect: mobility). Based on this experimental result, read-across approach from the supporting substance acetic acid was applied and EC50 (48h) for propyltriacetoxysilane was calculated to be 89.59 mg/L (based on mobility and with no pH adjustment). In the study by Bringmann et. al, 1982 (reliability 2), a largely standardized procedure of water toxicology for testing the potential toxic action of water pollutants measured by the immobilization ofDaphnia magnaaccording to DIN 38412, Part II guideline (Daphnia short-time test) was performed. The EC50 (48h, basis for effect: mobilitly) for acetic acid was 95 mg/L with no pH adjustment and 6000 mg/L with pH adjustment. Based on this result, read-across approach from supporting substance acetic acid was applied and EC50 (48h, basis for effect: mobility) for propyltriacetoxysilane was calculated to be 130.94 mg/L with no pH adjustment and 8270.11 with pH adjustment. In the study by Dowden et. al., 1965 (reliability 4), the EC50 of 86 chemicals was determined using a standardised method. The 24h EC50 of acetic acid forDaphnia magnawas determined to be 47 mg/L (basis for effect: mobility). Based on this result obtained with the supporting substance acetic acid, read-across approach was applied and the EC50 (48h, based on mobility) for propyltriacetoxysilane was calculated to be 64.78 mg/L. In the published study by Saha et. al., 2006 (reliability 4), an acute toxicity test was performed withMoina micrurain a renewal system. Based on the experimental results obtained with the supporting substance acetic acid forMoina micrura(96h LC50 = 163.72 mg/L, basis for effect: mortality), the read-across approach was applied and the 96h LC50 for propyltriacetoxysilane was calculated to be 225.66 mg/L.   Supporting studies: Read-across from experimental results with acetic acid and sodium acetate: There are two supporting studies from Anderson, 1944 (reliability 4) and Bringmann et. al., 1977, (reliability 3) performed for the supporting substances acetic acid and sodium acetate respectively. In the first one and based on the experimental results with supporting substance acetic acid (16h NOAEC = 150 mg/L forDaphnia magnaand basis for effect: mobility), read-across approach was applied and the 16h NOAEC for propyltriacetoxysilane was calculated to be 206.75 mg/L. In the second study and based on the experimental results with supporting substance sodium acetate (24h LC50 = 7170 mg/L forDaphnia magnaand basis for effect: mobility), the read-across approach was applied and the 24h LC50 for propyltriacetoxysilane was calculated to be 7234.68 mg/L.
Toxicity to Aquatic Plants			Experimental data: (8 d) Toxicity threshold (TT) = 4000 mg/L (Scenedesmus quadricauda)	Key study: Experimental results: An Algae Growth Inhibition Test was performed according to OECD Guideline 201 (GLP study) on test item Propyltriacetoxysilane. The EC50 value (based on growth) rate for Pseudokirchenriella subpicata at 72 hour exposure period was 24.42 mg/L without pH adjustment and > 1562.50 mg/L with pH adjustment. The NOEC (72h and based on growth rate) was determined to be 18 mg/L without pH adjustment and 40 mg/L with pH adjustment. Based on microscopic observations performed at test termination in all test concentrations no differences in size and shape of algal cells were reported as compared to the algae cells in the control.   Supporting studies: Read-across approach from experimental results on acetic acid and sodium acetate: In the study by Bringmann and Kühn 1980 (klimisch 3) performed with acetic acid, the 8 days Toxicity Threshold for Scenedermus quadricauda was determined to be 4000 mg/L based on growth rate. Based on this result, the read-across approach was applied and the 8 days Toxicity Threshold for propyltriacetoxysilane was calculated to be 5513.41 mg/L. In the study by Krebs, 1991 (klimisch 2) conducted on acetic acid, the EC50 at 24 hours of green algae exposure was 156 mg/L based on growth inhibition. The read-across was applied and EC50 (24h) for propyltriacetoxysilane was calculated to be 215 mg/L. Based on the experimental results obtained by Bringmann and Kühn 1978 (klimisch 3) with acetic acid for Microcystis aeruginosa (8d Toxicity threshold = 90 mg/L, basis for effect: cell multiplication), the read-across approach was applied and the 8 days Toxicity Threshold for propyltriacetoxysilane was calculated to be 124.05 mg/L. In the publication by Hoare et al., 1967 (klimisch 3) the EC50 at 60 hours of Anacystis nidularis (blue-green algae exposure) was determined to be 1640 mg/L based on growth inhibition. Taking into account this result, the read-across approach was applied and EC50 (60h, basis for effect: growth inhibition) for Propyltriacetoxysilane was calculated to be 1654.73 mg/L.
Toxicity to microorganisms			No data	Key study: Read-across from experimental result on analogue methylsilanetriyl triacetate: In the ready biodegradability test was performed according to OECD Guideline 301 F on analogue methyltriacetoxysilane the 28 day-NOEC was determined to be 100 mg/L since the substance degraded well and did not inhibit the degradation of the toxicity test. Based on these results, the read-across approach was applied and 28 day-NOEC for propyltriacetoxysilane was calculated to be 105.45 mg/L under test conditions.
MAMMALIAN TOXICITY
Acute Toxicity: Oral			Experimental data: LD 50 = 3250-8610 mg/kg bw (rats) LD 50 = 4960 mg/kg bw (mice)	Data waiving (Column 2 of REACH Annex VIII): The substance is corrosive.
Acute Toxicity: Inhalation			Experimental results: (4 h) LC50 = 11.4 mg/L	Data waiving (Column 2 of REACH Annex VIII): The substance is corrosive.
Acute Toxicity: Dermal			Experimental results: LD 50 = 1060 mg/kg bw (rabbits)	Data waiving (Column 2 of REACH Annex VIII): The substance is corrosive.
Repeated Dose Toxicity			Repeated dose toxicity: oral: 8-month study with male rats treated by gavage 3 times per week. TheLOAEL = 60 mg/kg bw/day(based on hyperplasia of the esophagus and forestomach, indicative of irritation at point of contact, only one dose tested). The NOAEL = Not established(only one dose tested). Repeated dose toxicity: inhalation: 35-day study with rats and mice. TheNOAEL was ca. 0.09 mg/L/day(based on no evidence of adverse effects at any dose tested).	Repeated dose toxicity: Oral: Weight of evidence: Read-across from experimental results with acetic acid and sodium acetate: In the first study, Alexandrov et. al., 1989 (reliability 2), an 8 month test with 60 mg/kg bw acetic acid (3 times per week, by intubation into the esophagus) in male rats was performed. The NOAEL (chronic) in male rats for acetic acid was 60 mg/kg bw. (basis for effect: mobility). Based on this experimental result, read-across approach from the supporting substance acetic acid was applied and NOAEL for propyltriacetoxysilane was calculated to be 82.70 mg/kg bw. In the study by Cory Slechta, 1986 (reliability 3), male rats were chronically treated via drinking water with sodium acetate from weaning. No effects were mentioned on survival, reinforcement behaviour or body weight gain. Based on the experimental results obtained with the supporting substance sodium acetate (NOAEL in male rats >= 0.05 mg/kg bw/day, based on no effects observed at the highest dose tested.), the read-across approach was applied and NOAEL for propyltriacetoxysilane was calculated to be >= 0.05 mg/kg bw/day. In the study by Dryden et. al., 1965 (reliability 2), male rats were daily treated by feed with sodium acetate during four weeks. No effects on growth or survival were observed at ca. 3600 mg/kg bw/day (the only dose tested). Based on the experimental results obtained with the supporting substance sodium acetate (NOAEL in male rats >= 3600 mg/kg bw/day), the read-across approach was applied and NOAEL for propyltriacetoxysilane was calculated to be >= 3632.48 mg/kg bw/day. In the study by Goldman, 1981 (reliability 3), male rats received a daily dose of sodium acetate in the diet during 3 months. Indications of altered thyroid function and decreased growth were reported at the only dose tested. However, only males were exposed to the substance, a small number of animals were used and only the body weights and several indices of thyroid function were studied. The reported effects cannot be considered as being clearly adverse. The study is considered to be of limited use in evaluating the toxicity of the substance. Based on these results from supporting substance sodium acetate (NOAEL in male rats >= 21 mg/kg bw/day, based on no evidence of clearly adverse effects at the only dose tested), read across approach was performed and NOAEL for propyltriacetoxysilane was calculated to be >= 21.19 mg/kg bw/day. In the study by Massaro et. al., 1987 (reliability 3) complex maze learning was investigated in male adult rats using a latent learning task. The adult subjects were exposed to sodium acetate in drinking water for 112 days beginning at weaning. No evidence of impairment of simple task performance was observed. The study is considered to be of limited use in evaluating the toxicity of the substance. Based on these results from supporting substance sodium acetate (NOAEL in male rats >= 0.01 mg/kg bw/day, based on no effects observed at the only dose tested), read-across approach was performed and NOAEL for propyltriacetoxysilane was calculated to be >= 0.01 mg/kg bw/day.
Genetic Toxicity in vitro		Gene mutation in bacteria	Experimental results: In a bacterial reverse mutation assay usingSalmonella typhimurium(TA98, TA100, TA1535, TA97 and TA1537) in the presence and absence of metabolic activation and up to 10000 μg/plate, acetic acid was not mutagenic.	Weight of evidence: Read-across from experimental results with acetic acid and sodium acetate: In the study by Zeiger et. al., 1992 (reliability 1), bacterial reverse mutation assay (Ames test) according to OECD Guideline 471 and with GLP compliance was performed. A standard Ames test was carried out with acetic acid usingSalmonella typhimuriumstrains TA 98, TA 100, TA 1535, and TA 97, with and without metabolic activation. Acetic acid did not show any mutagenic effect under test conditions. Based on these experimental results, read-across approach was applied and propyltriacetoxysilane was also considered as no mutagenic under test conditions. In the study by McMahon et. al., 1979 (reliability 2), bacterial reverse mutation assay (Ames test) according to OECD Guideline 471 (with deviations) was performed. A bacterial mutagen screening technique was carried out with acetic acid usingSalmonella typhimuriumstrains TA 1535, TA 1537, TA 98 and TA 100, with and without metabolic activation. Acetic acid did not show any mutagenic effect under test conditions. Based on these experimental results, read-across approach was applied and propyltriacetoxysilane was also considered as no mutagenic under test conditions. In the study by Ishidate et. al., 1984 (reliability 2), bacterial reverse mutation assay (Ames test) according to OECD Guideline 471 (with deviations) was performed. The study was carried out with sodium acetate and usingSalmonella typhimuriumstrains TA92, TA1535, TA100, TA1537, TA94, only with metabolic activation. No significant increases in the numbers of revertant colonies were detected at the maximum dose tested. Based on these experimental results, read-across approach was applied and propyltriacetoxysilane was also considered as no mutagenic under test conditions.
		Chromosomal aberration	Experimental results: Acetic acid was not clastogenic in anin vitroassay using Chinese hamster ovary K1 cells at concentrations < 16 mM; however, insufficient information was provided in the robust summary of this study to adequately evaluate the results.	Weight of evidence: Read-across from experimental results with acetic acid and sodium acetate: In the study by Morita et. al., 1990 (reliability 2), a cytogenetic assay was carried out with acetic acid using Chinese hamster ovary K1 cells. Acetic acid was not clastogenic at concentrations close to those showing cytotoxicity, both with and without metabolic activation. Low pH did induce some artificial chromosome aberrations, but these were eliminated by neutralization of the test medium. Based on these experimental results and applying the read-across approach, the substance propyltriacetoxysilane is also considered as not clastogenic under test conditions. In the study by Ishidate et. al., 1983 (reliability 2), a chromosomal aberrations tests were carried out with sodium acetate using a Chinese hamster fibroblast cell line. In the studies, no metabolic activation systems were applied. The maximum dose of each sample was selected by a preliminary test in which the dose needed for 50% cell-growth inhibition was estimated using a cell densiometer. The incidence of cells with aberrations (including gaps) was 0%. Based on these experimental results, the read-across approach was applied and propyltriacetoxysilane was also considered as no mutagenic under test conditions.
		Mammalian gene mutation	No data.	Key study: Experimental results: The test item Propyl Triacetoxy Silane PTA was assessed for its potential to induce mutations at the mouse lymphoma thyamidine kinase locus using the cell line L5178Y according to OECD Guideline 476. The Experiment I was performed as a 4h short-term exposure assay up to 10.0 mM (with metabolic activation) and up to 5.5 mM (without metabolic activation). The Experiment II was performed as a 4h short-term exposure up to 8.5 mM (with metabolic activation) and a 24h long-term exposure up to 5.0 mM (without metabolic activation). No biologically relevant increase of mutants was found after treatment with the test item. Additionally, colony sizing showed no clastogenic effects induced by the test item. Therefore, Propyl Triacetoxy Silane (PTA) was considered to be non-mutagenic in the in vitro mammalian cell gene mutation assay (thymidine kinase locus) in mouse lymphoma L5178Y cells with and without metabolic activation under test conditions.
Genetic Toxicity in vivo			No data.	Key study: Read-across from experimental results with supporting substance sodium acetate: In the study by Seiler, 1981 (reliability 2), the Testicular DNA-synthesis inhibition test (DSI test) was performed on male mice with Sodium Acetate (single oral dose by gavage). No inhibitory effect on DNA-replication was detectable in animals treated with Sodium Acetate. Based on these results, read-across approach was applied and propyltriacetoxysilane is also considered no genotoxic in animals (based on no effects on DNA-replication).
Carcinogenicity			No data.	No data.
Reproductive Toxicity	Toxicity to reproduction		No data.	Weight of evidence: Read-across from experimental results with citric acid and citric acid, sodium salt: In the study by Bonting et. al., 1956 (reliability 2), a fertility test was carried out with citric acid on female rats (daily treated by feed for several months). No reproductive effects were observed. Based on the experimental results obtained with the supporting substance citric acid (NOAEL for reproductive effects = 600 mg/kg bw/day; LOAEL > 600 mg/kg bw/day for the same effects), the read-across approach was applied and the NOAEL for propyltriacetoxysilane was calculated to be 775.48 mg/kg bw/day, and LOAEL > 775.48 mg/kg bw/day for reproductive effects. In the study performed by Wright et. al., 1976 (reliability 2), an experiment designed to examine the effect of a 5% dietary supplement of citric acid on the reproductive capacity of the rats was carried out. Based on the experimental results obtained with the supporting substance citric acid (NOAEL P, F1 >= 2500 mg/kg bw/day in rats (basis for effect: number of pregnancies, number of young born, or survival of young animals)), the read-across approach was applied and the NOAEL for propyltriacetoxysilane was calculated to ≥ than 3231.18 mg/kg bw/day for studied effects. In the same study performed by Bonting et. al. 1956 (reliability 2), a fertility test was carried out but with citric acid, sodium salt on female rats (daily treated by feed for several months). No reproductive effects were detected. Based on the experimental results obtained with the supporting substance citric acid, sodium salt (NOAEL for reproductive effects = 50 mg/kg bw/day; LOAEL > 50 mg/kg bw/day for the same effects), the read-across approach was applied and the NOAEL for propyltriacetoxysilane was calculated to be 57.99 mg/kg bw/day, and LOAEL > than 57.99 mg/kg bw/day for reproductive effects.
	Developmental toxicity		Experimental results: A series of developmental toxicity studies were conducted in CD-1 mice, Wistar rats, and Dutch-belted rabbits. Pregnant females were daily administered acetic acid by gavage on gestation day 6 – 16 for rats and mice, and 6 – 19 for rabbits. The NOAEL (maternal and developmental toxicity) (rats, mice, and rabbits) = 1600 mg/kg bw/day (based on no effects observed at the highest dose tested).	Weight of evidence: Read-across from experimental results with citric acid and citric acid, sodium salt: In the study by Food and Drug Research Laboratories, 1974 (reliability 2), following mating, adult female mice, rats and rabbits were dosed daily for 17 days by oral intubation with acetic acid. No effects on nidation or on maternal or fetal survival were observed at doses up to 1600 mg/kg bw/day. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring in the controls. Based on the experimental results with supporting substance acetic acid (NOAEL >= 1600 mg/kg bw/day for maternal and developmental toxicity), the read-across approach was applied and the NOAEL of propyltriacetoxysilane for maternal and developmental toxicity was calculated to be >= 2205.36 mg/kg bw/day. In the study by Kavlock et. al., 1987 (reliability 2), pregnant mice were generally treated by oral gavage during gestation at a dose level predicted from a preliminary range finding study to induce a slight degree of maternal toxicity. No maternal toxicity and no neonatal effects (mortality and body weight) were observed at the treatment dose level of 1000 mg/kg bw/day. Based on the experimental results obtained with supporting substance sodium acetate (NOAEL >= 1000 mg/kg bw/day) for maternal and neonatal toxicity), read-across approach was applied and the NOAEL for propyltriacetoxysilane was calculated to by >= 1009.02 mg/kg bw/day. In the study by Malorny, 1969 (reliability 2) a three-generation drinking water study with calcium formate in the drinking water was performed in Wistar rats during ca. 3 years. No effects on fertility were observed. Number, weight and length of offspring did not differ in treated animals from controls. No statistical differences in organ or bone abnormalities were found. The growth of treated offspring was similar to controls. Based on experimental results on supporting substance calcium formate (NOAEL for maternal and developmental toxicity >= 200 mg/kg bw/day), the read-across approach was applied and the NOAEL for propyltriacetoxysilane was calculated to be >= 254.46 mg/kg bw/day for maternal and developmental toxicity. In the study by Wright et. al. 1976 (reliability 4), an experiment designed to examine the effect of a 5% dietary supplement of citric acid on the reproductive capacity of the mice and rats was carried out. No effects were seen on number of pregnancies, number of young born, or survival of young in treated rats, compared to controls. Based on the experimental results from supporting substance citric acid (NOAEL >= 2500 mg/kg bw/day, basis for effect: number of pregnancies, number of young born, or survival of young animals), the read-across approach was applied and the NOAEL for propyltriacetoxysilane was calculated to be >= 3231.18 mg/kg bw/day for studied effects.

Conclusions:

Based on the experimental results obtained with acetic acid in rat (NOAEL >= 1600 mg/kg bw/day for both maternal and developmental toxicity), the read-across approach is applied and the NOAEL for maternal and developmental toxicity of propyltriacetoxysilane is calculated to be equal or greater than 2205.36 mg/kg bw/day.

Executive summary:

Based on the experimental results obtained with acetic acid in rat (NOAEL >= 1600 mg/kg bw/day for both maternal and developmental toxicity), the read-across approach is applied and the NOAEL for maternal and developmental toxicity of propyltriacetoxysilane is calculated to be equal or greater than 2205.36 mg/kg bw/day.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

2 205.36 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Four teratology studies, one of them performed on rats, mice and rabbits, and another one in rats and mice, are available. Three studies have a Klimisch score = 2 and one has a Klimisch score = 4 in a weight of evidence approach. The overall quality of the database was determined as appropriate for assessment.

Additional information

Weight of evidence:

 

Read-across from experimental results with acetic acid, sodium acetate, calcium formate and citric acid:

 

In the study by Food and Drug Research Laboratories, 1974 (reliability 2), following mating, adult female mice, rats and rabbits were dosed daily for 17 days by oral intubation with acetic acid. No effects on nidation or on maternal or fetal survival were observed at doses up to 1600 mg/kg bw/day. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring in the controls. Based on the experimental results with supporting substance acetic acid (NOAEL >= 1600 mg/kg bw/day for maternal and developmental toxicity), the read-across approach was applied and the NOAEL of propyltriacetoxysilane for maternal and developmental toxicity was calculated to be >= 2205.36 mg/kg bw/day.

 

In the study by Kavlock et. al., 1987 (reliability 2), pregnant mice were generally treated by oral gavage during gestation at a dose level predicted from a preliminary range finding study to induce a slight degree of maternal toxicity. No maternal toxicity and no neonatal effects (mortality and body weight) were observed at the treatment dose level of 1000 mg/kg bw/day. Based on the experimental results obtained with supporting substance sodium acetate (NOAEL >= 1000 mg/kg bw/day) for maternal and neonatal toxicity), read-across approach was applied and the NOAEL for propyltriacetoxysilane was calculated to by >= 1009.02 mg/kg bw/day.

 

In the study by Malorny, 1969 (reliability 2) a three-generation drinking water study with calcium formate in the drinking water was performed in Wistar rats during ca. 3 years. No effects on fertility were observed. Number, weight and length of offspring did not differ in treated animals from controls. No statistical differences in organ or bone abnormalities were found. The growth of treated offspring was similar to controls. Based on experimental results on supporting substance calcium formate (NOAEL for maternal and developmental toxicity >= 200 mg/kg bw/day), the read-across approach was applied and the NOAEL for propyltriacetoxysilane was calculated to be >= 254.46 mg/kg bw/day for maternal and developmental toxicity.

 

In the study by Wright et. al. 1976 (reliability 4), an experiment designed to examine the effect of a 5% dietary supplement of citric acid on the reproductive capacity of the mice and rats was carried out. No effects were seen on number of pregnancies, number of young born, or survival of young in treated rats, compared to controls. Based on the experimental results from supporting substance citric acid (NOAEL >= 2500 mg/kg bw/day, basis for effect: number of pregnancies, number of young born, or survival of young animals), the read-across approach was applied and the NOAEL for propyltriacetoxysilane was calculated to be >= 3231.18 for studied effects.

Key value for chemical safety assessment:

 

According to the experimental results with supporting substances acetic acid, sodium acetate, sodium formate and citric acid on mice, rats and rabbits, no maternal or developmental toxicity was seen in treated animals exposed to high doses of these substances. Therefore and based on read-across approaches, the NOAEL for propyltriacetoxysilane was calculated to be >= 2205.36 mg/kg bw/day, based on no effects observed at the highest dose tested in a reliable study (the NOAEL >= 3231.18 mg/kg bw/day was obtained in the read-across approach from a not assignable study, Klimisch 4, and was excluded as a key value for chemical safety assessment).

Justification for selection of Effect on developmental toxicity: via oral route:
According to the experimental results with supporting substances acetic acid, sodium acetate, sodium formate and citric acid on mice, rats and rabbits, no maternal or developmental toxicity was seen in treated animals exposed to high doses of these substances. Therefore and based on read-across approaches, the NOAEL for propyltriacetoxysilane was calculated to be >= 2205.36 mg/kg bw/day, based on no effects observed at the highest dose tested in a reliable study (the NOAEL >= 3231.18 mg/kg bw/day was obtained in the read-across approach from a not assignable study, Klimisch 4, and was excluded as a key value for chemical safety assessment).

Justification for classification or non-classification

Based on available data and according to the CLP Regulation, propyltriacetoxysilane is not classified as dangerous for reproduction.