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EC number: 225-443-9
CAS number: 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) Macrolex Grün G (CAS 4851-50-7) 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 Macrolex Grün G for systemic toxicity was considered to be 1000 mg/kg bw/day and the no-observed adverse-effect level (NOAEL) of Macrolex Grün G for reproductive/developmental toxicity was also considered to be 1000 mg/kg bw/day.
There was no effect of treatment on the circulating levels of
thyroxine (T4) in adult males or in offspring on Day 13 of age.
Adult Male at Termination
Day 13 of age Offspring (pg/mL)
Macrolex Grün G
Summary of findings in the gastrointestinal tract for animals killed
after 5 weeks of treatment
Abnormal Contents, Green
Number of tissues examined
Summary of findings in the stomach for animals killed after 5 weeks
Abnormal colour, Green
Summary of general comments for animals killed after 5 weeks of
Fur stained, Green
Tail stained, Green
The purpose of this study was to assess the potential systemic toxic
potential in Crl:CD(SD) rats, including a screen for
reproductive/developmental effects and assessment of endocrine disruptor
relevant endpoints, with administration of the test item, Macrolex Grün
G, by oral administration forat least five weeks.
Three groups of ten male and ten female rats receivedMacrolex
Grün Gat doses of 100, 300 or 1000 mg/kg/day by oral gavage
administration. Males were treated daily for two weeks before pairing,
up to necropsy after a minimum of five consecutive weeks. Females were
treated daily for two weeks before pairing, throughout pairing,
gestation and until Day 13 of lactation. Females were allowed to litter,
rear their offspring and were killed on Day 14 of lactation. The F1
generation received no direct administration of the test item; any
exposure was in utero or via the milk. A similarly constituted Control
group received the vehicle, corn oil, at the same volume dose as the
During the study, clinical condition, detailed physical
examination and arena observations, sensory reactivity, grip strength,
motor activity, body weight, food consumption, hematology (peripheral
blood), blood chemistry, thyroid hormone analysis, estrous cycles,
pre-coital interval, mating performance, fertility, gestation length,
organ weight and macroscopic pathology and histopathology investigations
The clinical condition, litter size and survival, sex ratio, body
weight, ano-genital distance and macropathology for all offspring were
also assessed. Nipple counts were performed on male offspring on Day 13
Administration with Macrolex Grün
G at doses up to and including 1000 mg/kg/day was considered to
generally be well tolerated throughout the treatment period. There were
no premature deaths, no dosing signs and no clinical signs observed in
association with dose administration.
For males receiving Macrolex Grün
G, overall mean body weight gains between Weeks 0-5 were marginally low
at all dose levels when compared with Control values. This was primarily
due to a slight dose dependent reduction in body weight gain observed in
males between Weeks 0-1, following commencement of treatment, with
statistical significance observed at 1000 mg/kg/day.
During the two-week pre-pairing treatment period, females receiving 100
mg/kg/day were unaffected by administration withMacrolex Grün
G. For females receiving 300 mg/kg/day, a reduction in body weight gain
was observed between Weeks 0-1 (50% lower than Control). Females given
G at 1000 mg/kg/day exhibited a similar decrease in body weight gain
between Weeks 1-2.Mean body weight gain wasunaffectedwhen the whole
premating period (Weeks 0-2) was considered.During the gestation period
for females receiving Macrolex Grün
G at doses up to and including 1000 mg/kg/day, a dose dependent
reduction in overall body weight gains was observed (Days 0-20),
although no statistical significance was observed. Following
parturition, body weight performance was similar to that of Controls for
females receiving 100, 300 and 1000 mg/kg/day up to Day 13 of lactation.
Estrous cyclicity, pre-coital interval, gestation length, mating
performance, fertility and gestation index were unaffected by treatment.
The hematological examination of blood and the biochemical examination
of plasma did not reveal any conclusive effect of treatment and there
was no effect upon circulating levels of thyroxine (T4) in adult males.
Macroscopic findings were limited to green content, representing
the colour of the test item, seen in the caecum, colon, ileum, jejunum,
rectum and stomach in treated animals with a dosedependent
increase in incidence and greencolour of the stomach seen in
treated animals with a dose dependent increase in
incidence.Histopathological findings in the full range of tissues
examined were considered to be unrelated to treatment. Organ weights
were considered unaffected by treatment.
The clinical condition, litter size, sex ratio, survival indices and
body weight and weight gain of offspring were unaffected by parental
There was no effect of parental treatment upon circulating levels of
thyroxine (T4) in offspring on Day 13 of age.
The ano-gential distances of offspring were unaffected by paternal
treatment and no nipples were seen on any male offspring on Day 13 of
No macroscopic findings considered to be related to paternal treatment
It was concluded that the oral administration of Macrolex Grün
G to parental Sprague-dawley rats at dose levels of 100, 300 or
1000 mg/kg/day administeredfor two weeks before pairing, during
pairing and then up to termination of the males after five weeks of
treatment and females on Day 14 of lactation, was well tolerated.
Reproductive performance, fertility, litter size and offspring
survival and growth were unaffected by parental treatment and,in the
context of this study,Macrolex Grün
Gshowed no evidence of being an endocrine disruptor.
The no-observed adverse-effect level (NOAEL) of Macrolex Grün
G for systemic toxicity was considered to be 1000 mg/kg/day and the
no-observed adverse-effect level (NOAEL) of Macrolex Grün
G for reproductive/developmental toxicity was also considered to be
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.
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.
The substance has no harmonised classification according to the Regulation (EC) No. 1272/2008 (CLP).
Based on the reproductive and developmental toxicity studies performed on Solvent Green 28 or on Category members a non-classification for fertility and development is justified.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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