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Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Read-across from analogue:

Reproductive/Developmental toxicity screening test:

Key study. Study with 12 male/ 12 female rats at doses of 100, 300, 1000 mg/kg/day, according to OECD Test Guideline 422. The result was as follows: fertility/reproductive toxicity NOAEL = 1000 mg/kg bw /day

Two-generation reproductive toxicity study:

In accordance with column 2 of REACH Annex IX, the two-generation reproductive toxicity study ( required in section 8.7.3) does not need to be conducted as the 28-day and 90-day study results do not indicate adverse effects on reproductive organs or tissues.

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The analogue with EC number 309-928-3 (Ultramarine Blue) shares the same functional group with the substance EC number 701-186-2 (Ultramarine Violet) and the results can be extrapolated to Ultramarine Violet.
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACHThe analogue approach covers the substance Ultramarine Blue (CAS 57455-37-5) and the substance Ultramarine Violet (CAS 12769-96-9).The analogue Ultramarine Blue shares the same functional group with the substance Ultramarine Violet. Therefore, they are expected to be toxicologically equivalent.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)Ultramarine blue, C.I. Pigment blue 29: CAS number: 57455-37-5, EC name: Silicic acid, aluminum sodium salt, sulfurized, EC number: 309-928-3 Ultramarine Violet, C.I. Pigment Violet 15: CAS number: 12769-96-9, EC name: sodium aluminosilicate violet, EC number: 701-186-2. No relevant impurities.
3. ANALOGUE APPROACH JUSTIFICATIONThe analogue approach covers the substance Ultramarine Blue (CAS 57455-37-5) and the substance Ultramarine Violet (CAS 12769-96-9).The analogue Ultramarine Blue shares the same functional group with the substance Ultramarine Violet. Therefore, they are expected to be toxicologically equivalent.
4. DATA MATRIX (Please, see attached document "Reporting Format for the analogue approach")
Reason / purpose:
read-across source
Principles of method if other than guideline:
Read-across approach from published data (method OECD Guideline 422) on the analogue EC number 309-928-3 (Reporting format for the analogue approach is attached). Please, see CSR appendix I.
GLP compliance:
yes
Dose descriptor:
NOAEL
Remarks:
maternal toxicity
Effect level:
>= 300 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
histopathology: non-neoplastic
Key result
Dose descriptor:
NOAEL
Remarks:
reproduction toxicity
Effect level:
>= 1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reproductive function (oestrous cycle)
reproductive function (sperm measures)
reproductive performance
Key result
Dose descriptor:
NOAEL
Remarks:
offspring development
Generation:
F1
Effect level:
>= 1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
organ weights and organ / body weight ratios
histopathology: non-neoplastic
Reproductive effects observed:
no

The analogue approach covers the substance Ultramarine Blue (CAS 57455-37-5) and the substance Ultramarine Violet (CAS 12769-96-9).

 

The analogue Ultramarine Blue shares the same functional group with the substance Ultramarine Violet. Therefore, they are expected to be toxicologically equivalent.

Based on the experimental results obtained with the analogue, the read-across approach is applied and the NOAELs for the substance Ultramarine Violet are:

-NOAEL maternal toxicity >= 300 mg/kg bw /day

-NOAEL reproductive toxicity>= 1000 mg/kg bw/day

-NOAEL offspring development >= 1000 mg/kg bw/day

Conclusions:
Based on the experimental results obtained with the analogue, the read-across approach is applied and the NOAELs for the substance Ultramarine Violet are: -NOAEL maternal toxicity >= 300 mg/kg bw /day-NOAEL reproductive toxicity>= 1000 mg/kg bw/day-NOAEL offspring development >= 1000 mg/kg bw/day
Executive summary:

Based on the experimental results obtained with the analogue, the read-across approach is applied and the NOAELs for the substance Ultramarine Violet are:

-NOAEL maternal toxicity >= 300 mg/kg bw /day

-NOAEL reproductive toxicity>= 1000 mg/kg bw/day

-NOAEL offspring development >= 1000 mg/kg bw/day

Effect on fertility: via oral route
Dose descriptor:
NOAEL
1 000 mg/kg bw/day

Effects on developmental toxicity

Description of key information

Read-across from analogue:

Reproductive/Developmental toxicity screening test:

Key study. Study with 12 female rats at doses of 100, 300, 1000 mg/kg/day, according to OECD Test Guideline 422. The result was as follows: developmental toxicity NOAEL = 1000 mg/kg bw /day

Pre-natal developmental toxicity study:

The study does not need to be conducted since based on the available data from the reproduction/developmental toxicity screening test, the test material did not cause any adverse effects.

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
November 1966
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
The study is not well documented. No GLP study.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
Number of animals per group 12 instead of 16 minimum; duration of treatment is not clear.
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
not specified
Details on test animals and environmental conditions:
-Age at study initiation: Female rats of approximately the same age.-Weight at study initiation: between 300 and 350g- Diet (e.g. ad libitum): oxoid breeding diet
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
no
Details on mating procedure:
Males were placed with respective females overnight and mating was confirmed by the presence of spermatozoo in vaginal smears, and this was designated the first day of pregnancy.
Duration of treatment / exposure:
7 days prior to mating
Frequency of treatment:
Every day
Duration of test:
The mothers were killed on the 22nd day of pregnancy
Dose / conc.:
10 mg/kg bw/day (nominal)
Remarks:
100 ppm in the diet
Dose / conc.:
100 mg/kg bw/day (nominal)
Remarks:
1000 ppm in the diet
Dose / conc.:
1 000 mg/kg bw/day (nominal)
Remarks:
10000 ppm in the diet
Dose / conc.:
10 000 mg/kg bw/day (nominal)
Remarks:
100000 ppm in the diet
No. of animals per sex per dose:
5 groups of 12 animals in eachGroup 1: no test material in dietGroup 2: 100 ppm in dietGroup 3: 1000 ppm in dietGroup 4: 10000 ppm in dietGroup 5: 100000 ppm in diet
Control animals:
yes
Fetal examinations:
-Litter size-Weight of live young-Resorptions-MalformationsIn addition, foetuses from ten of the twelve animals of each group were cleared and stained with alizarin and examined for defects of the skeleton. The foetuses from the remaining two mothers were sent for histopathological examination. The following tissues were specially observed: eye, heart, liver, ossification centres.
Mortality:
no mortality observed
Description (incidence):
There were no maternal deaths.
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
At higher concentrations 1000 mg/kg bw and 10000 mg/kg bw, there were pathological effects in the kidneys, stomach, intestine and bladder which one would associate with a high and prolonged intake of a siliceous earth.
Details on maternal toxic effects:
Maternal toxic effects:yesDetails on maternal toxic effects:There were no maternal deaths.When fed in the diet of rats in a concentration up to 10000 ppm (1000 mg/kg/day), the test substance had no effects on the growth, blood cellular constituents and haemoglobin or on the main biochemical constituents of the blood and urine. No significant effect on the organ weights.At higher concentrations 1000 mg/kg bw and 10000 mg/kg bw, there were pathological effects in the kidneys, stomach, intestine and bladder which one would associate with a high and prolonged intake of a siliceous earth.
Dose descriptor:
NOAEL
Effect level:
> 100 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
gross pathology
Fetal body weight changes:
no effects observed
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed
Reduction in number of live offspring:
no effects observed
Changes in litter size and weights:
no effects observed
External malformations:
effects observed, non-treatment-related
Description (incidence and severity):
No malformations were observed in the control and the top dose level. At 10 mg/kg bw /day dose level one foetus had its hind limbs flexed inwards and another was slightly oedematous. Both these foetuses were from the same mother. At 100 mg/kg bw/day dose level two foetuses from the same mother had all their limbs twisted. At 1000 mg/kg bw/day dose level one foetus had a hernia and another had its limbs slightly twisted.
Visceral malformations:
effects observed, non-treatment-related
Description (incidence and severity):
An increase in the pericardial space was observed in one foetus from the controls, two foetuses from one animal from the 1000 mg/kg bw/day dose level and three from one animal from the 10000 mg/kg bw/day dose level. No other abnormalities were detected.
Details on embryotoxic / teratogenic effects:
The test material has no teratogenic effects at the dose levels from 10 mg/kg bw/day to 1000 mg/kg bw/day.
Key result
Dose descriptor:
NOAEL
Effect level:
> 10 000 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: teratogenicity
Abnormalities:
no effects observed
Developmental effects observed:
no
Conclusions:
The NOAEL maternal toxicity is > 100 mg/kg bw per day, the NOAEL teratogenicity is > 10000 mg/kg bw per day.
Executive summary:

The study was performed to assess the teratogenic activity of the test material according to a method similar to OECD guideline 414). It was given an oral administration of the test material mixed in their diet at four different dose levels (10, 100, 1000, 10000 mg/kg bw) to 5 different groups of 12 female rats in each (a total of 60) during 7 days prior to mating. No maternal deaths and no teratogenical effects were observed. Results of the investigations confirm that the test material has not teratogenic activity.

The NOAEL maternal toxicity is > 100 mg/kg bw per day

The NOAEL teratogenicity is > 10000 mg/kg bw per day

Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
1 000 mg/kg bw/day

Justification for classification or non-classification

Based on the available information:

fertility/reproductive toxicity NOAEL = 1000 mg/kg bw /day

developmental toxicity NOAEL = 1000 mg/kg bw /day

the substance is not classified.