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The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Effects on fertility

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because a pre-natal developmental toxicity study is available
Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key information

Two studíes similar to OECD TG 414 are available for the test substance:

Rat:

Based on a significant decrease in body weight gain in the high dose group the NOAEL was determined to be 50 mg/kg bw/d for the maternal animals. No adverse effects were observed in the fetuses up to the highest dose level. The developmental NOAEL was determined to be > 100 mg/kg bw/d.

Mouse:

Based on a significant decrease in body weight gain and clinical signs (skinny appearance) in the high dose group the NOAEL was determined to be 73 mg/kg bw/d for the maternal animals. No adverse effects were observed in the fetuses up to the highest dose level. The developmental NOAEL was determined to be > 146 mg/kg bw/d.

Link to relevant study records

Referenceopen allclose all

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 07, 2007 to January 07, 2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Version / remarks:
2001
Deviations:
yes
Remarks:
no determination of food consumption and fetal sex, reporting deficiencies
GLP compliance:
yes
Limit test:
no
Species:
mouse
Strain:
ICR
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Shanghai Slaccs Animal Experimental Co., Ltd., Shanghai, China
- Age at study initiation: Not reported
- Weight at study initiation: Females 23-26g, males 28-35 g
- Fasting period before study: Not reported
- Housing: Single after mating
- Diet: SuZhou Shuangshi Laboratory Animal Feed Science Co., Ltd.
- Water: Drinking water complying China national standard, ad libitum
- Acclimation period: Approx. 3 weeks

ENVIRONMENTAL CONDITIONS
- Temperature: 20-25 °C
- Humidity: 40-70%
- Air changes: Not reported
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: November 28, 2007 To: December 10, 2007
Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
VEHICLE
- Concentration in vehicle: 1.825 mg/mL, 3.65 mg/mL, 7.3 mg/mL
- Amount of vehicle: 20 mL/kg bw
Analytical verification of doses or concentrations:
no
Details on mating procedure:
One male mouse was housed with two female mice in the same cage from afternoon of the first day to the morning of the following day. Female mice were then examined for successful mating by observation of vaginal plug or sperm in female vaginal smear. The day on which a vaginal plug or sperm was observed was considered as mating success and day 0 of gestation.
Duration of treatment / exposure:
Gestation day 6-14
Frequency of treatment:
Daily
Duration of test:
18 days
Dose / conc.:
36.5 mg/kg bw/day (nominal)
Dose / conc.:
73 mg/kg bw/day (nominal)
Dose / conc.:
146 mg/kg bw/day (nominal)
No. of animals per sex per dose:
30 pregnant animals
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: Doses were selected based on acute oral toxicity data.
Doses were adjusted according to weight gain.
Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
Observations for clinical signs and mortality were made at least once daily, including changes in skin, fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behaviour pattern.

BODY WEIGHT AND BODY WEIGHT GAIN: Yes
Animals were weighed on days 0, 6, 9, 12, 14, 17 and 18.

FOOD CONSUMPTION: No

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 18
- Organs examined: Uterus

OTHER:
Necropsy was performed on all dead animals and animals with signs of abortion or premature delivery.
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 resorptions: Yes
- Other: number of dead (early and late stillbirth) litters, number of live litters, body/tail length of live litters
Fetal examinations:
- External examinations: Yes: [all per litter]
- Soft tissue examinations: Yes: [1/3 of live fetuses]
- Skeletal examinations: Yes: [2/3 of live fetuses ]
- Head examinations: Yes: [all per litter]
- Fetal body weight
Statistics:
Analysis of variance (one-way ANOVA, Dunnett's)
Chi-square and binomial distribution
Indices:
Teratogenic rate (%) = (total amount of live litters with teratogenic effects/total amount of litters) x 100
(One live litter with more than one teratogenic effect was counted as one)

Teratogenic index = LD50 of females/minimum teratogenic dose
Description (incidence and severity):
In the high dose group 6/30 animals showed a skinny appearance whereas this was not apparent in the mid and low dose groups and the vehicle control group.
Mortality:
no mortality observed
Description (incidence):
There were no dead animals observed during the course of the study.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
There was no significant change in body weight in all dose groups. The body weight gain was significantly decreased in the high dose group when compared to the vehicle control.
Food consumption and compound intake (if feeding study):
not examined
Pre- and post-implantation loss:
no effects observed
Description (incidence and severity):
No significant differences in implantations were observed when compared to the vehicle control.
Total litter losses by resorption:
no effects observed
Description (incidence and severity):
No significant difference in the number of pregnant rats with resorptions was observed when compared to the vehicle control.
Early or late resorptions:
no effects observed
Description (incidence and severity):
The number of resorptions was not significantly increased when compared to the vehicle control.
Dead fetuses:
no effects observed
Description (incidence and severity):
No significant difference in the number of pregnant rats with dead litters was observed when compared to the vehicle control.
Changes in number of pregnant:
no effects observed
Description (incidence and severity):
The number of pregnant rats in the treatment groups was comparable to the vehicle control group.
Other effects:
no effects observed
Description (incidence and severity):
There was no significant effect in the number of corpora lutea and the number of dead litters between the treated groups and the vehicle control.
Key result
Dose descriptor:
NOAEL
Effect level:
73 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
body weight and weight gain
clinical signs
Key result
Abnormalities:
no effects observed
Localisation:
other: no adverse effects observed up to maximum dose level
Reduction in number of live offspring:
no effects observed
Description (incidence and severity):
No significant differences were observed between the treatment groups and the vehicle control group.
Changes in sex ratio:
not examined
Changes in litter size and weights:
no effects observed
Description (incidence and severity):
No significant differences were observed in the number of live fetuses and fetal body weight between the treatment groups and the vehicle control group.
External malformations:
effects observed, non-treatment-related
Description (incidence and severity):
The incidence (%) of fetuses with external malformations/variations was 0 (vehicle control), 0.5 (36.5 mg/kg bw/d), 0.7 (73 mg/kg bw/d) and 0.7 (146 mg/kg bw/d). No significant differences were observed between the treatment groups and the vehicle control group.
Skeletal malformations:
effects observed, non-treatment-related
Description (incidence and severity):
The incidence (%) of fetuses with skeletal malformations/variations was 2.5 (vehicle control), 4.1 (36.5 mg/kg bw/d), 3.9 (73 mg/kg bw/d) and 6.5 (146 mg/kg bw/d). No significant differences were observed between the treatment groups and the vehicle control group.
Visceral malformations:
no effects observed
Description (incidence and severity):
No visceral malformations/variations were observed in the treatment groups and the vehicle control group.
Other effects:
no effects observed
Description (incidence and severity):
Placental weight, fetus body and tail length: No significant differences were observed between the treatment groups and the vehicle control group.
Key result
Dose descriptor:
NOAEL
Effect level:
> 146 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: no adverse effects observed up to maximum dose
Key result
Abnormalities:
effects observed, non-treatment-related
Localisation:
other: external/skeletal: not specified
Key result
Developmental effects observed:
no
Conclusions:
The NOAEL for maternal toxicity was determined to be 73 mg/kg bw/d based on reduced body weight gain. The developmental NOEAL was determined to be > 146 mg/kg bw/d.
Executive summary:

The teratogenicity test of Blue MGI 1037-Na on mice was performed according to the Guidelines for the Testing of Chemicals (2004)414 which is referred to OECD 414.

Three different dose-level test groups of low, middle and high dosage, a negative control group and a Vitamin A positive control group were set up in this test. The dosage of each test group was 36.5mg/kg, 73mg/kg and 146mg/kg respectively. 30 pregnant female mice were assigned to each group. The day on which a vaginal plug or sperm were observed was counted as day 0 of gestation.
From day 6 to day 14 of gestation. 0.2 mL/10g bw of test substance was administered daily by garage to mice in 3 different dose-level test groups as well as control groups. Clinical observations
were recorded every day. From day 6 of gestation, mice were weighed every other 3 days dining the dosing period. All of female mice were sacrificed one day prior to the day of delivery (the 18th day since the gestation). Immediately after caesarean the uteri were removed and gravid uteri were weighed. Implantation status were record: the number of implantations, of dead litters (early stillbirth, late stillbirth), of resorptions, of live litters, of corpora luteas. The development of fetuses was recorded one by one: body weight, body length, tail length. And the examination of teratogenicity of fetuses: appearance, skeletal and organ alternatives. SPSS13.0 statistical software was applied to analyze all data and results. The maximum no observed adverse effect level (NOAEL) of teratogenicity test was obtained through statistical analysis.

This teratogenicity test in mice indicated that Blue MGI 1037-Na had maternal toxicity to a certain extent: however, no embryonic toxicity and teratogenicity were observed. The maximum teratogenic NOAEL was 146 mg/kg in this test.

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 06, 2007 to December 28, 2007
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Version / remarks:
2001
Deviations:
yes
Remarks:
no determination of food consumption and fetal sex, reporting deficiencies
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Shanghai Slaccs Animal Experimental Co., Ltd., Shanghai, China
- Age at study initiation: Not reported
- Weight at study initiation: Females 200-300g, males 300-400 g
- Fasting period before study: Not reported
- Housing: Single after mating
- Diet: SuZhou Shuangshi Laboratory Animal Feed Science Co., Ltd.
- Water: Drinking water complying China national standard, ad libitum
- Acclimation period: Approx. one week

ENVIRONMENTAL CONDITIONS
- Temperature: 20-25 °C
- Humidity: 40-70%
- Air changes: Not reported
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: November 14, 2007 To: November 28, 2007
Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
VEHICLE
- Concentration in vehicle: 2.5 mg/mL, 5 mg/mL, 10 mg/mL
- Amount of vehicle: 10 mL/kg bw
Analytical verification of doses or concentrations:
no
Details on mating procedure:
One male rat was housed with two female rats in the same cage from afternoon of the first day to the morning of the following day. Female rats were then examined for successful mating by observation of vaginal plug or sperm in female vaginal smear. The day on which a vaginal plug or sperm was observed was considered as mating success and day 0 of gestation.

Duration of treatment / exposure:
Gestation day 6-15
Frequency of treatment:
Daily
Duration of test:
20 days
Dose / conc.:
25 mg/kg bw/day (nominal)
Dose / conc.:
50 mg/kg bw/day (nominal)
Dose / conc.:
100 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Vehicle and positive control group: 25 pregnant animals
Test item groups: 30 pregnant animals/dose
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: Doses were selected based on acute oral toxicity and 28 day repeated dose toxicity data.
Doses were adjusted according to weight gain.
Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
Observations for clinical signs and mortality were made at least once daily, including changes in skin, fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behaviour pattern.

BODY WEIGHT AND BODY WEIGHT GAIN: Yes
Animals were weighed on days 0, 6, 9, 12, 15, 18 and 20.

FOOD CONSUMPTION: No

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: Uterus

OTHER:
Necropsy was performed on all dead animals and animals with signs of abortion or premature delivery.
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 resorptions: Yes
- Other: number of dead (early and late stillbirth) litters, number of live litters, body/tail length of live litters
Fetal examinations:
- External examinations: Yes: [all per litter]
- Soft tissue examinations: Yes: [1/3 of live fetuses]
- Skeletal examinations: Yes: [2/3 of live fetuses ]
- Head examinations: Yes: [all per litter]
- Fetal body weight
Statistics:
Analysis of variance (one-way ANOVA, Dunnett's)
Chi-square and binomial distribution
Indices:
Teratogenic rate (%) = (total amount of live litters with teratogenic effects/total amount of litters) x 100
(One live litter with more than one teratogenic effect was counted as one)

Teratogenic index = LD50 of females/minimum teratogenic dose
Clinical signs:
effects observed, non-treatment-related
Description (incidence and severity):
Single animals in all treatment groups and the vehicle control showed a skinny appearance.
Mortality:
no mortality observed
Description (incidence):
There were no dead animals observed during the course of the study.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
There was no significant change in body weight in all dose groups. The body weight gain was significantly decreased in the high dose group when compared to the vehicle control.
Food consumption and compound intake (if feeding study):
not examined
Pre- and post-implantation loss:
no effects observed
Description (incidence and severity):
No significant differences in implantations were observed when compared to the vehicle control.
Total litter losses by resorption:
no effects observed
Description (incidence and severity):
No significant difference in the number of pregnant rats with resorptions was observed when compared to the vehicle control.
Early or late resorptions:
no effects observed
Description (incidence and severity):
The number of resorptions was not significantly increased when compared to the vehicle control.
Dead fetuses:
no effects observed
Description (incidence and severity):
No significant difference in the number of pregnant rats with dead litters was observed when compared to the vehicle control.
Changes in number of pregnant:
no effects observed
Description (incidence and severity):
The number of pregnant rats in the treatment groups was comparable to the vehicle control group.
Other effects:
no effects observed
Description (incidence and severity):
There was no significant effect in the number of corpora lutea and the number of dead litters between the treated groups and the vehicle control.
Key result
Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
body weight and weight gain
Key result
Abnormalities:
no effects observed
Localisation:
other: no adverse effects observed up to maximum dose level
Reduction in number of live offspring:
no effects observed
Description (incidence and severity):
No significant differences were observed between the treatment groups and the vehicle control group.
Changes in sex ratio:
not examined
Changes in litter size and weights:
no effects observed
Description (incidence and severity):
No significant differences were observed in the number of live fetuses and fetal body weight between the treatment groups and the vehicle control group.
External malformations:
effects observed, non-treatment-related
Description (incidence and severity):
The incidence (%) of fetuses with external malformations/variations was 0.5 (vehicle control), 1.0 (25 mg/kg bw/d), 0.8 (50 mg/kg bw/d) and 1.3 (100 mg/kg bw/d). No significant differences were observed between the treatment groups and the vehicle control group.
Skeletal malformations:
effects observed, non-treatment-related
Description (incidence and severity):
The incidence (%) of fetuses with skeletal malformations/variations was 0.8 (vehicle control), 1.5 (25 mg/kg bw/d), 2.9 (50 mg/kg bw/d) and 2.9 (100 mg/kg bw/d). No significant differences were observed between the treatment groups and the vehicle control group.
Visceral malformations:
no effects observed
Description (incidence and severity):
No visceral malformations/variations were observed in the treatment groups and the vehicle control group.
Other effects:
no effects observed
Description (incidence and severity):
Placental weight, fetus body and tail length: No significant differences were observed between the treatment groups and the vehicle control group.
Key result
Dose descriptor:
NOAEL
Effect level:
> 100 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: no adverse effects observed up to maximum dose level
Key result
Abnormalities:
no effects observed
Localisation:
other: no adverse effects observed up to maximum dose level
Key result
Developmental effects observed:
no
Conclusions:
The NOAEL for maternal toxicity was determined to be 50 mg/kg bw/d based on reduced body weight gain. The developmental NOEAL was determined to be > 100 mg/kg bw/d.
Executive summary:

The teratogenicity test of Blue MGI 1037-Na on rats was performed according to Guidelines for the Testing of Chemical (2004) 414 which is referred to OECD 414. Three different dose-level test groups of low, middle and high dosage, a negative control group and a Vitamin A positive control group were set up in this test. The dosage of each test group was 25 mg/kg, 50 mg/kg and 100 mg/kg respectively. 20-30 pregnant female rats were assigned to each group. The day on which a vaginal plug or sperm were observed was counted as day 0 of gestation. From day 6 to day 15 of gestation. 1 mL/100g BW of test substance was administered daily by garage to rats in 3 different dose-level test groups as well as control groups. Clinical observations were recorded every day. From day 6 of gestation, rats were weighed every other 3 days during the dosing period. All of female rates were sacrificed one day prior to the day of delivery (the 20th day since the gestation). Immediately after caesarean. The uteri were removed and gravid uteri were weighed. Implantation status were record: the number of implantations, of dead litters (early stillbirth, late stillbirth), of resorptions, of live litters, of corpora luteas. The development of fetuses was recorded one by one: body weight, body length, tail length. And the examination of teratogenicity of fetuses: appearance, skeletal and organ alternatives. SPSS13.0 statistical software was applied to analyze all data and results. The maximum no observed adverse effect level (NOAEL) of teratogenicity test was obstained through statistical analysis. The NOAEL for maternal toxicity was determined to be 50 mg/kg bw/d based on reduced body weight gain. The developmental NOEAL was determined to be > 100 mg/kg bw/d.

 

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
100 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Guideline study with acceptable restrictions and reporting deficiencies
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Toxicity to reproduction: other studies

Additional information

The teratogenicity test of Blue MGI 1037-Na on rats was tested according to Guidelines for the Testing of Chemical (2004) 414 which is referred to OECD 414.Three different dose-level test groups of low, middle and high dosage, a negative control group and a Vitamin A positive control group were set up in this test. The dosage of each test group was 25 mg/kg, 50 mg/kg and 100 mg/kg respectively. 20-30 pregnant female rats were assigned to each group. The day on which a vaginal plug or sperm were observed was counted as day 0 of gestation. From day 6 to day 15 of gestation. 1 mL/100g BW of test substance was administered daily by garage to rats in 3 different dose-level test groups as well as control groups. Clinical observations were recorded every day. From day 6 of gestation, rats were weighed every other 3 days during the dosing period. All of female rates were sacrificed one day prior to the day of delivery (the 20th day since the gestation). Immediately after caesarean. The uteri were removed and gravid uteri were weighed. Implantation status were record: the number of implantations, of dead litters (early stillbirth, late stillbirth), of resorptions, of live litters, of corpora luteas. The development of fetuses was recorded one by one: body weight, body length, tail length. And the examination of teratogenicity of fetuses: appearance, skeletal and organ alternatives. SPSS13.0 statistical software was applied to analyze all data and results. The maximum no observed adverse effect level (NOAEL) of teratogenicity test was obstained through statistical analysis.The teratogenicity test in SD rats indicated that Blue MGI 1037-Na had maternal toxicity to a certain extent. However, no embryonic toxicity and teratogenicity were observed. The maximum teratogenic NOAEL was 100 mg/kg in this test.

Furthermore, a teratogenicity test of Blue MGI 1037-Na on mice was performed according to the Guidelines for the Testing of Chemicals (2004) 414 which is referred to OECD 414.

Three different dose-level test groups of low, middle and high dosage, a negative control group and a Vitamin A positive control group were set up in this test. The dosage of each test group was 36.5 mg/kg, 73 mg/kg and 146 mg/kg respectively. 30 pregnant female mice were assigned to each group. The day on which a vaginal plug or sperm were observed was counted as day 0 of gestation.
From day 6 to day 14 of gestation. 0.2 mL/10g BW of test substance was administered daily by garage to mice in 3 different dose-level test groups as well as control groups. Clinical observations were recorded every day. From day 6 of gestation, mice were weighed every other 3 days dining the dosing period. All of female mice were sacrificed one day prior to the day of delivery (the 18th day since the gestation). Immediately after caesarean the uteri were removed and gravid uteri were weighed. Implantation status were record: the number of implantations, of dead litters (early stillbirth, late stillbirth), of resorptions, of live litters, of corpora luteas. The development of fetuses was recorded one by one: body weight, body length, tail length. And the examination of teratogenicity of fetuses: appearance, skeletal and organ alternatives. SPSS13.0 statistical software was applied to analyze all data and results. The maximum no observed adverse effect level (NOAEL) of teratogenicity test was obtained through statistical analysis.This teratogenicity test in mice indicated that Blue MGI 1037-Na had maternal toxicity to a certain extent: however, no embryonic toxicity and teratogenicity were observed. The maximum teratogenic NOAEL was 146 mg/kg in this test.

 

 

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
Based on available experimental information, the test substance is not classified for developmental toxicity according to Regulation (EC) No 1272/2008 (CLP), as amended for the twelfth time in Regulation (EU) 2019/521.

Additional information