Diiron titanium pentaoxide

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Description of key information

According to REGULATION 1907/2006, Annex XI, testing on reproductive toxicity was omitted since there is sufficient weight of evidence from several sources of information including structural similar substances leading to the conclusion that the substance has no dangerous properties. Diiron titanium pentaoxide is an insoluble and non-reactive compound and is part of mixtures in pigments in various concentrations. The substance is a mixed oxide of titanium dioxide and iron oxide. No toxic effects on reproductive organs have been reported for the pigment after repeated exposure. Due to the lack of systemic availability, effects on reproductive organs are not expected. No oncogenic potential after long-term administration of the pigment up to two years was detected. From the OECD 421 study performed with the read-across substance TiO2, no reproductive toxicity was observed. Therefore, and because of animal welfare reasons an additional screening reproductive/developmental toxicity study for Diiron titanium pentaoxide is not required since same results are expected.

Link to relevant study records

Reference

Reference 1

Endpoint:

screening for reproductive / developmental toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
Diiron titanium pentaoxide is an insoluble and non-reactive compound and is part of mixtures in pigments in various concentrations. The substance is a mixed oxide of titanium dioxide and iron oxide. Diiron titanium pentaoxide as a single component has not been tested for reproductive toxicity. However, data from pigments which contain diiron titanium pentaoxide and data from the oxides titanium dioxide (TiO2) and iron oxide (Fe2O3) are available and considered sufficient for evaluation.
Titanium dioxide has been investigated in a reproductive and developmental toxicity screening test in rats [OECD TG 421]. Titanium dioxide was administered by oral gavage to 10 animals/sex at 0 or 1,000 mg/kg bw/day (limit test), to male rats from two weeks prior to mating, during the mating period and, approximately, two weeks post mating, and to female rats from two weeks prior to mating, during the mating period, gestation period and 3 days after lactation. During the observation period, there were no dose related effects on clinical signs, body weights, food consumption, mating, gestation, delivery, organ weights, necropsy and histopathology in parents. No dose-related changes in clinical signs, body weights, viability index, external malformations and sex ratios were noted in pups. This study found no indication of any reproductive toxicity in parent animals or developmental toxicity in pups. Therefore, the NOAEL for reproductive and developmental toxicity was >1000 mg/kg bw/day (OECD SIDS, April 2013).
Furthermore, a sub-chronic feeding toxicity study equal to OECD TG 408 was performed to investigate the toxicity of different mica-based pearlescent pigments (13.5% diiron titanium pentaoxide). Groups of 40 rats (20 males and 20 females) received the pigments incorporated into feed pellets at the highest internationally recommended concentration of 50000 ppm, for the males and females, respectively. One placebo group (20 males and 20 females) received feed pellets containing mica only at 50,000 ppm. In addition, a control group consisting of 80 rats (40 males and 40 females) were fed exclusively with standard commercial feed pellets. Treatment was for 3 months followed by a 2-months recovery period. No treatment related mortalities occurred during the study. A slight increase of body weights was observed in females receiving the second pigment compared to the feed control group 1. Food intake was temporarily or permanently increased in males and females of all groups treated with mica or mica-based pigments due to the 5% mineralic content in the diet. No treatment-related effects were observed in haematology or clinical chemistry. Gross pathology revealed a discoloration of the gut content in the animals of the treatment groups which was not observed in the recovery animals and which is not considered to be an adverse effect. All histopathological findings encountered were considered to have arisen spontaneously. No histopathological changes could be detected in uterus, testes or epididymides. The organs weights of uterus, ovaries, testes and prostate were not changed compared to the untreated control. In conclusion, no adverse effects were observed in rats treated with mica pigments at 50000 ppm.
In a further study the possible toxicity of Titanium Dioxide Coated Mica (contained 2-7% Diiron titanium pentraoxide) and its oncogenic potential was evaluated using a standardized and accepted test regimen by administration in the diet of Fischer 344 rats at levels of 0, 10000, 20000 and 50000 ppm for 104 weeks. No adverse effects have been reported which could be attributed to the test item. Based on these findings, administration of Titanium Dioxide coated mica in the diet of rats at concentrations up to 50000 ppm did not significantly alter survival nor demonstrate toxic effects. Additionally, no indication of oncogenic potential was elicited by the test material at the designated concentration levels. Based on the concentration of diiron titanium pentaoxide in this pigment (up to 7%) and the food consumption during this chronic toxicity study a NOAEL of 180 mg/kg bw/day and 230 mg/kg bw/day for male and female rats was calculated.
In conclusion, no toxic effects on reproductive organs have been reported for the pigment after repeated exposure. Due to the lack of systemic availability, effects on reproductive organs are not expected. No oncogenic potential after long-term administration of the pigment up to two years was detected. From the OECD 421 study performed with TiO2, no reproductive toxicity was observed. Therefore, and because of animal welfare reasons an additional screening reproductive/developmental toxicity study for Diiron titanium pentaoxide was not performed since same results are expected.

Reference 2

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Study summary available only from OECD SIDS Document.

Qualifier:

according to guideline

Guideline:

OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

yes

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

other: 1% methylcellulose (MC) solution

Analytical verification of doses or concentrations:

not specified

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

During the observation period, there were no dose related effects on clinical signs, body weights, food consumption, mating, gestation, delivery, organ weights, necropsy and histopathology in parents.

Key result

Dose descriptor:

NOAEL

Remarks:

systemic

Effect level:

1 000 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: highest dose tested

Key result

Critical effects observed:

no

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Description (incidence and severity):

No dose-related changes in clinical signs, body weights, viability index, external malformations and sex ratios were noted in pups.

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

1 000 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: highest dose tested

Key result

Critical effects observed:

no

Key result

Reproductive effects observed:

no

Conclusions:

No reproductive or developmental toxicity was reported after oral administration to rats.

Executive summary:

Titanium dioxide has been investigated in a reproductive and developmental toxicity screening test in rats (OECD TG 421). Titanium dioxide was administered by oral gavage to 10 animals/sex at 0 or 1000 mg/kg bw/day (limit test), to male rats from two weeks prior to mating, during the mating period and, approximately, two weeks post mating, and to female rats from two weeks prior to mating, during the mating period, gestation period and 3 days after lactation. During the observation period, there were no dose related effects on clinical signs, body weights, food consumption, mating, gestation, delivery, organ weights, necropsy and histopathology in parents. No dose-related changes in clinical signs, body weights, viability index, external malformations and sex ratios were noted in pups. This study found no indication of any reproductive toxicity in parent animals or developmental toxicity in pups. Therefore, the NOAEL for reproductive and developmental toxicity was 1000 mg/kg bw/day.

Reference 3

Endpoint:

extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the extended one-generation reproductive toxicity study does not need to be conducted because there are no results from available repeated dose toxicity studies that indicate adverse effects on reproductive organs or tissues, or reveal other concerns in relation with reproductive toxicity

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
According to REGULATION (EC) No 1907/2006, an Extended-One Generation Reproductive study shall be initially performed if there are results available from repeated dose toxicity studies that indicate adverse effects on reproductive organs or tissues, or reveal other concerns in relation with reproductive toxicity.
Diiron titanium pentaoxide is an insoluble and non-reactive compound and is part of mixtures in pigments in various concentrations. The substance is a mixed oxide of titanium dioxide and iron oxide. Diiron titanium pentaoxide as a single component has not been tested for reproductive toxicity. However, data from pigments which contain diiron titanium pentaoxide and data from the oxides titanium dioxide (TiO2) and iron oxide (Fe2O3) are available and considered sufficient for evaluation.
Titanium dioxide has been investigated in a reproductive and developmental toxicity screening test in rats [OECD TG 421]. Titanium dioxide was administered by oral gavage to 10 animals/sex at 0 or 1,000 mg/kg bw/day (limit test), to male rats from two weeks prior to mating, during the mating period and, approximately, two weeks post mating, and to female rats from two weeks prior to mating, during the mating period, gestation period and 3 days after lactation. During the observation period, there were no dose related effects on clinical signs, body weights, food consumption, mating, gestation, delivery, organ weights, necropsy and histopathology in parents. No dose-related changes in clinical signs, body weights, viability index, external malformations and sex ratios were noted in pups. This study found no indication of any reproductive toxicity in parent animals or developmental toxicity in pups. Therefore, the NOAEL for reproductive and developmental toxicity was >1000 mg/kg bw/day (OECD SIDS, April 2013).
Furthermore, a sub-chronic feeding toxicity study equal to OECD TG 408 was performed to investigate the toxicity of different mica-based pearlescent pigments (13.5% diiron titanium pentaoxide). Groups of 40 rats (20 males and 20 females) received the pigments incorporated into feed pellets at the highest internationally recommended concentration of 50,000 ppm, for the males and females, respectively. One placebo group (20 males and 20 females) received feed pellets containing mica only at 50,000 ppm. In addition, a control group consisting of 80 rats (40 males and 40 females) were fed exclusively with standard commercial feed pellets. Treatment was for 3 months followed by a 2-months recovery period. No treatment related mortalities occurred during the study. A slight increase of body weights was observed in females receiving the second pigment compared to the feed control group 1. Food intake was temporarily or permanently increased in males and females of all groups treated with mica or mica-based pigments due to the 5% mineralic content in the diet. No treatment-related effects were observed in haematology or clinical chemistry. Gross pathology revealed a discoloration of the gut content in the animals of the treatment groups which was not observed in the recovery animals and which is not considered to be an adverse effect. All histopathological findings encountered were considered to have arisen spontaneously. No histopathological changes could be detected in uterus, testes or epididymides. The organs weights of uterus, ovaries, testes and prostate were not changed compared to the untreated control. In conclusion, no adverse effects were observed in rats treated with mica pigments at 50000 ppm.
In a further study the possible toxicity of Titanium Dioxide Coated Mica (contained 2-7% Diiron titanium pentraoxide) and its oncogenic potential was evaluated using a standardized and accepted test regimen by administration in the diet of Fischer 344 rats at levels of 0, 10000, 20000 and 50000 ppm for 104 weeks. No adverse effects have been reported which could be attributed to the test item. Based on these findings, administration of Titanium Dioxide coated mica in the diet of rats at concentrations up to 50000 ppm did not significantly alter survival nor demonstrate toxic effects. Additionally, no indication of oncogenic potential was elicited by the test material at the designated concentration levels. Based on the concentration of diiron titanium pentaoxide in this pigment (up to 7%) and the food consumption during this chronic toxicity study a NOAEL of 180 mg/kg bw/day and 230 mg/kg bw/day for male and female rats was calculated.
In the REACH disseminated dossier for iron oxide (CAS 1309-37-1) it was concluded that due to the lack of systemic availability, effects on reproductive organs are not expected for this substance.
In conclusion, no toxic effects on reproductive organs have been reported for the pigment after repeated exposure. Due to the lack of systemic availability, effects on reproductive organs are not expected. No oncogenic potential after long-term administration of the pigment up to two years was detected. From the OECD 421 study performed with TiO2, no reproductive toxicity was observed. Therefore, and because of animal welfare reasons an Extended-one Generation Reproductive study for Diiron titanium pentaoxide is not required.

Reference 4

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

For Read-Across Justification please refer to Section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: highest dose tested

Key result

Critical effects observed:

no

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

1 000 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: highest dose tested

Critical effects observed:

no

Key result

Critical effects observed:

no

Key result

Reproductive effects observed:

no

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Effects on developmental toxicity

Description of key information

According to REGULATION 1907/2006, Annex XI, testing was omitted since there is sufficient weight of evidence from several sources of information including structural similar substances leading to conclusion that the substance has no dangerous properties. Diiron titanium pentaoxide is a mixed oxide of titanium dioxide and iron oxide. Diiron titanium pentaoxide as a single component has not been tested for developmental toxicity / teratogenicity. However, based on the available long-term toxicity studies in rodents and the physico-chemical properties of the substance, it is concluded that diiron titanium pentaoxide is a non-reactive and non-toxic compound. Therefore, no developmental toxicity hazard for Diiron titanium pentaoxide is expected. In a study according to OECD TG 414 performed with the read-across substance TiO2, no developmental toxicity was observed up to the highest dose of 1000 mg/kg bw/day. Therefore, and because of animal welfare reasons additional developmental toxicity studies for Diiron titanium pentaoxide are not required.

Link to relevant study records

Reference

Reference 1

Endpoint:

developmental toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
Diiron titanium pentaoxide is an insoluble and non-reactive compound and is part of mixtures in pigments in various concentrations. The substance is a mixed oxide of titanium dioxide and iron oxide. Diiron titanium pentaoxide as a single component has not been tested for developmental toxicity / teratogenicity. However, data from data from the oxide titanium dioxide (TiO2) are available and considered sufficient for evaluation.
Studies according OECD TG 414 have been performed to determine the potential maternal and developmental toxicity of six different commercial forms and sizes of titanium dioxide particles (pigment-grade or ultrafine grade). The test substances were formulated in sterile water and the formulations were administered by oral gavage to time-mated Sprague–Dawley daily beginning on gestation day (GD) 6 through GD 20. In additional studies, formulations were administered to Wistar rats beginning on GD 5 through 19. The dose levels used in all studies were 0, 100, 300, or 1000 mg/kg bw/day; control group animals were administered the vehicle. During the in-life portions of the studies, body weights, food consumption, and clinical observations before and after dosing were collected on a daily basis. All dams were euthanized just prior to expected parturition. The gross necropsies included an examination and description of uterine contents including counts of corpora lutea, implantation sites, resorptions, and live and dead fetuses. All live fetuses were sexed, weighed, and examined externally and euthanized. Following euthanasia, fresh visceral and head examinations were performed on selected fetuses. The fetal carcasses were then processed and examined for skeletal alterations. There was no evidence of maternal or developmental toxicity at any dose level tested in any of the six studies. Based on these results, the NOAEL for titanium dioxide was 1000 mg/kg bw/day, the highest administered dose, in both the rat strains.
Furthermore, based on the available long-term toxicity studies in rodents and the physico-chemical properties of the substance, it is concluded that diiron titanium pentaoxide does is a non-reactive and non-toxic compound.
In the REACH disseminated dossier for iron oxide (CAS 1309-37-1) it was concluded that due to the lack of systemic availability, effects on developmental toxicity/teratogenicity are not expected for this substance.
Therefore, no developmental toxicity hazard for Diiron titanium pentaoxide is expected. In the study according to OECD TG 414 performed with TiO2, no developmental toxicity was observed up to the highest dose of 1000 mg/kg bw/day. Therefore, and because of animal welfare reasons an additional developmental toxicity study for Diiron titanium pentaoxide was not performed since same results are expected.

Reference 2

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.3700 (Prenatal Developmental Toxicity Study)

Qualifier:

according to guideline

Guideline:

EU Method B.31 (Prenatal Developmental Toxicity Study)

GLP compliance:

not specified

Remarks:

no information provided

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Crl:CD(SD)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 9 weeks

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
The dose volume was 5 mL/kg for all groups.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Samples of the dosing formulations were collected and analyzed near the beginning and end of the dosing periods. The results of these analyses confirmed that the formulations were at targeted concentrations, uniformly mixed, and stable under the experimental conditions used during the study.

Details on mating procedure:

- Impregnation procedure: purchased timed pregnant

Duration of treatment / exposure:

Formulations were administered beginning on gestation day (GD) 6 through GD 20.

Frequency of treatment:

daily

Duration of test:

20 days

Dose / conc.:

100 mg/kg bw/day (nominal)

Dose / conc.:

300 mg/kg bw/day (nominal)

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

22

Control animals:

yes, concurrent vehicle

Maternal examinations:

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: daily

FOOD CONSUMPTION AND COMPOUND INTAKE : Yes

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 21
- Organs examined: uterine contents including counts of corpora lutea, implantation sites, resorptions, and live and dead fetuses

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes

Fetal examinations:

- External examinations: Yes: [all per litter]
- Soft tissue examinations: Yes: [half per litter]
- Skeletal examinations: Yes: [all per litter]
- Head examinations: Yes: [half per litter]
- Body weight of each live foetus was recorded.

Statistics:

Levene's test for homogeneity and Shapiro and Wilk test for normality; One-way analysis; Dunnett's test, Exact ManneWhitney with a Bonferroni-Holm adjustment

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Number of abortions:

no effects observed

Pre- and post-implantation loss:

no effects observed

Total litter losses by resorption:

no effects observed

Early or late resorptions:

no effects observed

Dead fetuses:

no effects observed

Changes in pregnancy duration:

not examined

Changes in number of pregnant:

no effects observed

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: highest dose tested

Key result

Abnormalities:

no effects observed

Fetal body weight changes:

effects observed, non-treatment-related

Description (incidence and severity):

At 100 mg/kg/day, mean fetal weight was significantly increased relative to the control group mean. This increase was considered to be spurious and unrelated to the test substance because it was minimal in magnitude and not dose dependent.

Reduction in number of live offspring:

no effects observed

Changes in sex ratio:

no effects observed

Changes in litter size and weights:

effects observed, non-treatment-related

Changes in postnatal survival:

not examined

External malformations:

no effects observed

Skeletal malformations:

no effects observed

Visceral malformations:

no effects observed

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: highest dose tested

Key result

Abnormalities:

no effects observed

Key result

Developmental effects observed:

no

Conclusions:

Under the conditions of this study, there was no evidence of either maternal or developmental toxicity at doses up to 1000 mg/kg bw/day.

Executive summary:

Studies according OECD TG 414 have been performed to determine the potential maternal and developmental toxicity of six different commercial forms and sizes of titanium dioxide particles (pigment-grade or ultrafine grade). The test substances were formulated in sterile water and the formulations were administered by oral gavage to time-mated Sprague–Dawley daily beginning on gestation day (GD) 6 through GD 20. In additional studies, formulations were administered to Wistar rats beginning on GD 5 through 19. The dose levels used in all studies were 0, 100, 300, or 1000 mg/kg bw/day; control group animals were administered the vehicle. During the in-life portions of the studies, body weights, food consumption, and clinical observations before and after dosing were collected on a daily basis. All dams were euthanized just prior to expected parturition. The gross necropsies included an examination and description of uterine contents including counts of corpora lutea, implantation sites,resorptions, and live and deadfetuses. All live fetuses were sexed, weighed, and examined externally and euthanized. Following euthanasia, fresh visceral and head examinations were performed on selected fetuses. The fetal carcasses were then processed and examined for skeletal alterations. There was no evidence of maternal or developmental toxicity at any dose level tested in any of the six studies. Based on these results, the NOAEL for titanium dioxide was 1000 mg/kg bw/day, the highest administered dose, in both the rat strains.

Reference 3

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

For Read-Across Justification please refer to Section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: highest dose tested

Key result

Abnormalities:

no effects observed

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: highest dose tested

Key result

Abnormalities:

no effects observed

Key result

Developmental effects observed:

no

Reference 4

Endpoint:

developmental toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
According to REGULATION 1907/2006, Annex IX, column 2, the study shall be initially performed on one species. A decision on the need to perform a study at this tonnage level or the next on a second species should be based on the outcome of the first test and all other relevant available data. Since all available data for the pigment and the read across substances TiO2 and Fe2O3 reveal no adverse effects on reproductive organs or development in rats a further study on developmental toxicity for a 2nd species is not required.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

adverse effect observed

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available information is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available information, the test substance is not classified for toxicity to reproduction or developmental toxicity according to Regulation (EC) No 1272/2008 (CLP), as amended for the twelfth time in Regulation (EU) No 2019/521.