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EC number: 236-675-5
CAS number: 13463-67-7
Results of several studies of the toxicity to early life-stages of
different fish species indicate that dispersed microsized TiO2 is not
chronically toxic to freshwater fish up to at least 160 mg/L (NOEC ≥ 160
- 1000 mg/L) whereas dispersed nanosized TiO2 is not chronically toxic
up to 80 mg/L (NOEC ≥ 80 - < 1000 mg/L). Considering the low solubility
of microsized TiO2, it is further concluded that microsized TiO2 is not
chronically toxic up to its solubility limit.
One reliable study demonstrates that microsized TiO2 materials are
not chronically toxic to freshwater fish: In a study by Shaw et al.
(2016), the titanium dioxide bulk material NM-100 (148.3 ± 109.7 nm) did
not affect embryo survival, hatching rate and the time to hatch of Danio
rerio embryos at the highest test concentration of 160 mg/L (as
dispersion) in a fish early-life stage toxicity test (OECD TG 210) after
4 d and 6 d of exposure. Further, an effect on larvae length, muscle
block width and yolk sac volume could not be observed after 6 d of
exposure (NOEC ≥ 160 mg/L (nominal)). Due to the shorter exposure period
of 6 d instead of 30 d as recommended in OECD 210, this study cannot be
considered a key study and is instead applied in a weight-of evidence
Further studies (rated Klimisch 3 due to individual shortcomings)
investigating the toxicity of microsized TiO2 to early life-stages and
adults of freshwater fish including Danio rerio, Phoxinus phoxinus, and
Coregonus atumnalis migratorius demonstrate that microsized TiO2 is not
chronically toxic to freshwater fish up to its solubility limit and
dispersed TiO2 concentration of 500 mg/L. In a 115 d early-life stage
toxicity test with embryos and in a 30 d juvenile fish growth test by
Beim et al (1982) with Coregonus autumnalis migratorius, dispersed
microsized TiO2 concentrations up to 3 mg/L did not negatively affect
survival and growth of exposed fish (115 d NOEC and 30 d NOEC: ≥ 3 mg/L
(nominal)). To the contrary, a stimulation of growth, weight and length,
was observed (Beim et al. 1982). In a 28 d fish growth test by Beim et
al (1982) with adult Phoxinus phoxinus, dispersed microsized TiO2
concentrations up to 1000 mg/L (nominal) did not affect survival and
growth of exposed fish (28 d NOEC: ≥ 1000 mg/L (nominal)). Faria et al.
(2014) also observed that dispersed microsized TiO2 did not
significantly affect the survival and length of zebrafish embryos in an
early life-stage toxicity test following OECD TG 212. Morphological
effects were also not observed up to the highest test concentration and
the determined 8 d NOEC amounts to ≥ 1000 mg TiO2/L (dispersed, nominal).
Beim et al. (1982) performed a 30 d fish growth test with juvenile
Phoxinus phoxinus and microsized TiO2 concentrations of up to 1000 mg/L
(dispersed, nominal) did not affect survival and growth (length) of
Phoxinus phoxinus whereas the weight of fish exposed to microsized TiO2
concentrations of 1000 mg/L were significantly lower than the weight of
control fish, resulting in a 30 d NOEC of ≥ 500- < 1000 mg/L (nominal).
However, all chronic fish experiments were performed at
concentrations several magnitudes above the solubility limit of
microsized TiO2. Transformation/dissolution data of different microsized
TiO2 materials indicate a low solubility in environmental media as
dissolved Ti concentrations after 28 d were below the respective LOD/LOQ
(< 0.11 / < 0.34 µg Ti/L). In sum, it
is concluded that microsized TiO2 is not chronically toxic to fish up to
concentrations of ≥ 160 mg/L dispersed TiO2 and its solubility limit in
Marine data do not exist.
One reliable study demonstrates that nanosized TiO2 materials are
not chronically toxic to freshwater fish: The titanium dioxide
nanomaterial NM-105 (20.6 ± 3.9 nm) did not affect embryo survival and
hatching rate of Danio rerio at the highest test concentration of 160
mg/L (as dispersion) in an early-life stage fish toxicity test (OECD TG
210) after 4 d and 6 d of exposure. No effect on larvae length, muscle
block width and yolk sac volume could be observed after 6 d of exposure
(NOEC ≥ 160 mg/L (nominal)). Although a delay of hatching could be
observed at the highest tested nano-TiO2 concentration (6 d LOEC: 160
mg/L; 6 d NOEC: 80 mg/L (nominal)), effects occurred at nano-TiO2
concentrations exceeding the recommended limit test concentration of 10
mg/L according to OECD 210. Hence, nano-TiO2 is considered to be not
chronically toxic to Danio rerio embryos. Due to the shorter exposure
period of 6 d instead of 30 d, as recommended in OECD TG 210, this study
cannot be considered key study and is instead applied in a
Additionally, in a standard fish, juvenile growth test performed
according to OECD TG 215 to evaluate chronic effects of wastewater-borne
TiO2 NPs on rainbow trout (Oncorhynchus mykiss), no effects on growth
rate, behavior and mortality were observed after exposure for 28 d at
the highest test concentrations of wastewater-borne TiO2 NPs,
effluent-supplemented TiO2 NPs and water-dispersed TiO2 NPs (Zeumer et
al. 2020). Derived NOECs for effluent-supplemented NPs and
water-dispersed TiO2 NPs were ≥ 0.08 mg TiO2/L and ≥ 0.07 mg TiO2/L,
respectively, based on measured concentrations (time-weighted average).
Since tested concentrations were selected based on environmental
relevance, and testing was not performed at the limit concentration of
10 mg/L (as specified in OECD TG 210), results of this study cannot be
considered as key results and are thus applied in a weight-of evidence
In further studies (rated Klimisch 3 due to individual
shortcomings), three different titanium dioxide nanomaterials P25,
NM-103, and NM-104 did not significantly affect the survival of
zebrafish embryos in an early life-stage toxicity test (OECD TG 212) and
8 d NOEC values of ≥ 1000 mg n-TiO2/L (dispersed, nominal) were derived
by Faria et al (2014). Furthermore, morphological effects were not
observed with the exception of marginal effects on body length at the
highest test concentration of 1000 mg n-TiO2/L but not at 100 mg
n-TiO2/L (dispersed). A NOEC should nevertheless not be derived from the
study by Faria et al (2014) since the separation factor should not
exceed 3.2 according to OECD TG 212. Further, according to OECD TG 212,
concentrations higher than 100 mg/L should not to be tested. Three
supporting studies, including one fish early-life stage toxicity test
(Bar-Ilan et al. 2013), one short-term toxicity test on fish embryo and
sac fry stages (Bar-Ilan et al. 2012), and one prolonged fish toxicity
test (Clemente et al. 2015), additionally indicate that nanosized TiO2
is not chronically toxic to embryos and juveniles of Danio rerio and
Piaracus mesopotamicus since unbounded NOEC values ranged from ≥ 100 to
≥ 10,000 mg/L dispersed n-TiO2. The latter studies are considered as
supporting studies since validity criteria were not provided (Bar-Ilan
et al. 2013, Clemente et al. 2015), validity criteria were not met
(Bar-Ilan et al. 2013), and/or tests were performed with too much
biomass (Clemente et al. 2015).
Finally, based on reliable chronic toxicity studies it is
concluded that nanosized TiO2 dispersions are not chronically toxic to
freshwater fish up to ≥ 80 mg/L.
Based on a weight of evidence approach, dispersed microsized TiO2
is not chronically toxic to freshwater fish up to ≥ 160 mg/L.
Considering the low solubility of microsized TiO2, it is further
concluded that microsized TiO2 is not toxic up to its solubility limit.
Dispersions of nanosized TiO2 are not chronically toxic to freshwater
fish up to ≥ 80 mg/L.
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