Registration Dossier

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Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

An OECD 422 study is planned on Solvent Violet 36. The dossier will be updated as soon as the result becomes available.


 


Key information on Category members:


- Reinblau BLW: NOAEL for systemic toxicity and reproductive / developmental toxicity = 1000 mg/kg bw/day (OECD 422, GLP, K, rel.1)

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Data waiving:
other justification
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
An OECD 422 study will be performed on Solvent Violet 36 to support the Category approach. The dossier will be updated with the new study as soon at it becomes available.
Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The study on Solvent green 28 - one of the category members - is GLP-compliant and of high quality Klimisch score =1). A new study will be conducted on Solvent Violet 36.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

There was no fertility study with Solvent Violet 36.


 


The following studies are available for category members:


 


1/ Solvent Green 28 (CAS 4851-50-7): In an OECD guideline 422 study (Combined Repeated Dose Toxicity Study and Reproductive/ Developmental Toxicity Screening Study in the Crl:CD(SD) Rat by Oral Gavage Administration) Solvent Green 28 was administered to three groups of ten male and ten female rats by oral gavage administration, for approximately 6 weeks (males) and up to eight weeks (females) (including a two week pre-pairing phase, pairing, gestation and early lactation for females), at dose levels of 100, 300 and 1000 mg/kg bw/day. A similarly constituted control group received the vehicle, corn oil, at the same volume dose as the treated groups.


The no-observed adverse-effect level (NOAEL) of Solvent Green 28 for systemic toxicity was considered to be 1000 mg/kg bw/day and the no-observed adverse-effect level (NOAEL) of Solvent green 28 for reproductive/developmental toxicity was also considered to be 1000 mg/kg bw/day.


 


2/ Solvent Blue 104 (Source : ECHA disseminated dossier) :


An OECD test guideline (OECD 421) and GLP-compliant Reproduction/Developmental Toxicity Screening Test was performed with the test item (Solvent Blue 104). Groups of 10 male and 10 female Wistar rats received doses of 0, 100, 300 and 1000 mg/kg bw by daily gavage. No toxicologically significant changes were noted in any of the parameters investigated in this study. 
An NOAEL for general toxicity of 1000 mg/kg/day was established. No test item-related effects were observed in males or females up to and including 1000 mg/kg bw/day, the highest dose level administered.
An NOAEL for reproduction and development of 1000 mg/kg/day was established. No test item-related effects on reproduction or development were observed up to and including 1000 mg/kg bw/day, the highest dose level administered.


 


 Conclusion:


The available two screening tests for reproductive toxicity and development toxicity consistently show no toxicity of the anthraquinone dye group; up to the limit dose no adverse effects are reported, and it can be concluded that “no hazard” is identified in any of these studies.

Effects on developmental toxicity

Description of key information

There was no developmental toxicity study with Solvent Violet.


 


Key information on Reinblau BLW (category member) Developmental toxicity: via oral route: NOAEL = 1000 mg/kg bw/day (OECD 414, GLP, K, Rel. 1)

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Justification for type of information:
Justification Document for the Category of Six Anthraquinone Dyes

LANXESS Deutschland GmbH has registered five mono-constituent anthraquinone dyes of similar chemical structure using a category approach: Solvent Violet 36 (CAS No 82-16-6), Solvent Green 3 (CAS No 128-80-3), Reinblau RLW (CAS No 41611-76-1), Reinblau BLW (CAS No 32724-62-2) and Solvent Green 28 (CAS No 4851-50-7). Additional data were taken from another registered anthraquinone dye, Solvent Blue 104 (CAS No 116-75-6), leading to a category consisting of six members (see attached justification in the Category dossier).
Clinical signs:
effects observed, non-treatment-related
Description (incidence and severity):
At 1000 mg/kg bw/day a total of 17 females were recorded with the clinical sign of blue staining of the tail. This was considered to be related to the blue coloured test material being excreted in the faeces. Two animals were recorded with abnormally coloured staining of the head and muzzle, where a further qualifier of colour was omitted in error, however these were recorded on Day 0 after mating, and therefore could not have been related to the test material. In addition four treated females (numbers 31,32, 33 and 34) were recorded with abnormal colouration of the tail on Day 20 after mating; however, no further qualifier of colour was recorded in error. Three out of the four of these females were confirmed as having a blue tail at necropsy on Day 20 after mating.
There were no other consistent clinical signs, nor any dosing signs, observed that were considered to be related to treatment at the limit dose of 1000 mg/kg bw/day.
Mortality:
no mortality observed
Description (incidence):
There were no premature decedents.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Mean overall bodyweight gain during gestation was similar to controls and unaffected by treatment at 1000 mg/kg/day.
There were a number of incidences of slight but statistically significant differences in mean absolute body weight at 1000 mg/kg/day when compared to the Controls (approximately 3% on Days 6, 10, 11, 12, 16, 17, 18 of gestation), however, this was principally due to slightly lower gain experienced during Days 3 to 6 of gestation, prior to the commencement of treatment, such that mean bodyweight at the start of treatment was statistically significantly lower than Controls for females receiving 1000 mg/kg/day. After the commencement of treatment, mean body weight gain during Days 6-20 of gestation for treated females was not significantly different from Controls (Controls 113g; dose group 111g).
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
Mean overall values of food consumption during Days 6-19 of gestation for females receiving 1000 mg/kg bw/day were no different from Controls and were unaffected by treatment.
Mean food consumption for treated females immediately prior to the commencement of treatment (during Days 3-5 of gestation) was marginally lower than Controls, attaining statistical significance, however, subsequent food consumption for the remainder of gestation was unaffected by treatment.
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Endocrine 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
Description (incidence and severity):
Mean gravid uterine weight was similar to Controls and unaffected by treatment and when mean values of body weight and body weight gain were adjusted for the contribution of the gravid uterus, the maternal portion of mean body weight gain during Days 6-20 of gestation was similar to Controls and unaffected by treatment at 1000 mg/kg bw/day.
Gross pathological findings:
effects observed, non-treatment-related
Description (incidence and severity):
Several females receiving 1000 mg/kg bw/day showed blue colouration of gastro-intestinal content.
Three females at 1000 mg/kg bw/day showed blue colouration of the rectal tissue, 5 females showed blue coloration of the stomach tissue and 17 females were confirmed as having blue colouration of the tail.
The blue staining observed was considered discolouration caused by the test material itself (a blue dye) and is considered not to represent toxicity.
There were no other blue coloured organs observed in any female, and no further maternal findings observed at macroscopic examination that were considered to relate to treatment.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
no effects observed
Number of abortions:
no effects observed
Description (incidence and severity):
One Control female was found to be non-pregnant. All treated females were pregnant with a live litter on Day 20 of gestation.
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:
no effects observed
Changes in number of pregnant:
no effects observed
Other effects:
no effects observed
Details on maternal toxic effects:
Embryo-fetal survival was clearly unaffected by treatment at 1000 mg/kg bw/day with mean numbers of implantations, resorptions, live young and percentages of sex ratio and pre and post-implantation loss being similar to Control values.
Key result
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
behaviour (functional findings)
body weight and weight gain
changes in number of pregnant
changes in pregnancy duration
clinical biochemistry
clinical signs
dead fetuses
early or late resorptions
effects on pregnancy duration
gross pathology
haematology
histopathology: non-neoplastic
maternal abnormalities
mortality
necropsy findings
number of abortions
organ weights and organ / body weight ratios
pre and post implantation loss
total litter losses by resorption
Key result
Abnormalities:
no effects observed
Fetal body weight changes:
effects observed, treatment-related
Description (incidence and severity):
Mean male, female and overall fetal weights in litters of females receiving 1000 mg/kg bw/day were lower than Controls, and although statistical significance was attained, the difference was marginal (approximately 0.2g or 5-6% lighter than Controls) and considered not adverse since embryo-fetal survival and development were clearly unaffected by treatment.
Mean placental weights at 1000 mg/kg/day were similar to Controls and unaffected by treatment.
Reduction in number of live offspring:
no effects observed
Changes in sex ratio:
no effects observed
Changes in litter size and weights:
no effects observed
Anogenital distance of all rodent fetuses:
not examined
Changes in postnatal survival:
not examined
External malformations:
no effects observed
Description (incidence and severity):
Fetal development was clearly unaffected by treatment at the limit dose of 1000 mg/kg bwday.
Skeletal malformations:
effects observed, non-treatment-related
Description (incidence and severity):
The incidence of major and minor abnormalities and skeletal variants showed no relationship to treatment.
At 1000 mg/kg bw/day there was a slightly increased incidence of delayed/ incomplete ossification/unossified thoracic vertebrae compared to concurrent control, however, this was within the Historical Control range.
Visceral malformations:
no effects observed
Other effects:
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:
reduction in number of live offspring
changes in sex ratio
fetal/pup body weight changes
changes in litter size and weights
changes in postnatal survival
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no
Conclusions:
Based on the results of this embryo-fetal developmental toxicity study in rats, it was concluded that the No-Observed--Adverse-Effect-Level (NOAEL) of Macrolex Blau 3R for maternal toxicity was the limit dose of 1000 mg/kg bw/day.
For embryo-fetal development, the limit dose of 1000 mg/kg bw/day was considered to be the No-Observed-Adverse-Effect-Level (NOAEL), when administered during the organogenesis and fetal growth phases of gestation in the rat, as there was a marginal reduction in fetal weight which was considered not adverse due to there being no effect of treatment upon embryo-fetal survival or development.
Executive summary:

The objective of this study was to assess the influence of Macrolex Blau 3R, a blue powder, on embryo-fetal survival and development when administered during the organogenesis and fetal growth phases of pregnancy in the Sprague Dawley CD rat. The study was conducted according to the OECD TG 414 and in compliance with GLP.


One group of 22 females received Macrolex Blau 3R suspended in 0.5% CMC-Na solution at the limit dose of 1000 mg/kg bw/day by daily oral gavage administration at a dose volume of 10 mL/kg/day from Day 6 to 19 after mating. A similarly constituted Control group received the vehicle, according to the same dose volume and regimen. Animals were killed on Day 20 after mating for reproductive assessment and fetal examination.


Clinical observations, body weight and food consumption were recorded. Adult females were examined macroscopically at necropsy on Day 20 after mating with the weight of the gravid uterus recorded. All fetuses were weighed, subjected to an external macroscopic examination and then subsequently to detailed internal visceral or skeletal examination.


 


Treatment of pregnant female Sprague Dawley rats with Macrolex Blau 3R daily from Day 6 to Day 19 after mating, inclusive, at the limit dose of 1000 mg/kg bw/day was well tolerated and elicited no deaths and no toxicity related changes in clinical condition of the adult females.


At 1000 mg/kg bw/day a total of 17 females were recorded with the clinical sign of blue staining of the tail. At necropsy several females receiving 1000 mg/kg/day showed blue colouration of gastro-intestinal contents, three females showed blue colouration of rectal tissue, 5 females were recorded with blue coloration of stomach tissue and 17 females were confirmed as having blue colouration of the tail. The blue staining observed was considered discolouration caused by the test material itself (a blue dye) and is considered not to represent toxicity.


Body weight gain and food consumption during gestation were unaffected by treatment and there were no other maternal findings observed at macroscopic examination that were considered to relate to treatment.


There was no effect of treatment at 1000 mg/kg bw/day upon embryo-fetal survival or placental weights, and fetal development was also unaffected by treatment at this limit dose, with the incidence of major and minor abnormalities and skeletal variants showing no relationship to treatment.


Mean male, female and overall fetal weights at 1000 mg/kg bw/day were lower than Controls, but the difference was considered marginal (approx. 5-6%) and was clearly not adverse since embryo fetal survival and development were unaffected by treatment.


 


Based on the results of this embryo-fetal developmental toxicity study in rats, it was concluded that the No-Observed-Adverse- Effect-Level (NOAEL) of Macrolex Blau 3R for maternal toxicity and embryo-fetal development was the limit dose of 1000 mg/kg bw/day.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The available study on Reinblau RLW - one of the category member - is GLP-compliant and of high quality (Klimisch score = 1)
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

no data

Toxicity to reproduction: other studies

Additional information

A developmental toxicity study according to OECD TG 414 was conducted with Reinblau RLW (one of the category members) in rats. Test stubstance was administered during the organogenesis and fetal growth phases of pregnancy in the Sprague Dawley CD rat. One group of 22 females received Reinblau RLW suspended in 0.5% CMC-Na solution at the limit dose of 1000 mg/kg bw/day by daily oral gavage administration at a dose volume of 10 mL/kg bw/day from Day 6 to 19 after mating. A similarly constituted Control group received the vehicle alone. Animals were killed on Day 20 after mating for reproductive assessment and fetal examination. Clinical observations, body weight and food consumption were recorded. Adult females were examined macroscopically at necropsy on Day 20 after mating with the weight of the gravid uterus recorded. All fetuses were weighed, subjected to an external macroscopic examination and then subsequently to detailed internal visceral or skeletal examination.


Based on the results of this embryo-fetal developmental toxicity study in rats, it was concluded that the No-Observed-Adverse- Effect-Level (NOAEL) of Reinblau RLW for maternal toxicity and embryo-fetal development was the limit dose of 1000 mg/kg bw/day.

Justification for classification or non-classification

Harmonised classification:


The substance has no harmonised classification according to the Regulation (EC) No. 1272/2008 (CLP). 


 


Self-classification:


None of the category members is classifed for reproductive or developmental toxicity. An OECD 422 study is planned on Solvent Violet 36. The dossier will be updated as soon as the new study becomes available.

Additional information