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Diss Factsheets

Administrative data

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Effects on fertility

Description of key information

The No Observed Adverse Effect level (NOAEL) for the test chemical for reproduction toxicity in test animals were  considered to be 750 mg/Kg bw/day.

Link to relevant study records
Reference
Endpoint:
one-generation reproductive toxicity
Type of information:
experimental study
Remarks:
Read across data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Data is from publication
Qualifier:
according to guideline
Guideline:
other: as below
Principles of method if other than guideline:
Chronic toxicity study of food colours TARTRAZINE, AMARANTH AND SUNSET YELLOW were observed in rats.
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Not available
- Age at study initiation: 6 and 7 weeks
- Weight at study initiation: 129 g-males and 105 g-females(appx)
- Fasting period before study: Not available
- Housing: Individual cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Not available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not available
- Humidity (%):Not available
- Air changes (per hr): Not available
- Photoperiod (hrs dark / hrs light): Not available
Route of administration:
oral: feed
Type of inhalation exposure (if applicable):
not specified
Vehicle:
other: Alphacel
Remarks:
a non-nutritive cellulose
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:Alphacel (a non-nutritive ce!lulose) was added so that the level of dye plus alphacel was 1.5 per cent. The control diet contained 1.5 per cent alphacel.

DIET PREPARATION
- Rate of preparation of diet (frequency):Not available
- Mixing appropriate amounts with (Type of food):Alphacel (a non-nutritive ce!lulose) diet
- Storage temperature of food: Not available

VEHICLE
- Justification for use and choice of vehicle (if other than water): Alphacel(a non nutritive cellulose)-No justification available.
- Concentration in vehicle: 0, appx 15,150 and 750 mg/kg
- Amount of vehicle (if gavage): Not available
- Lot/batch no. (if required): Not available
- Purity: Not available
Details on mating procedure:
Mating was not performed.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
64 weeks
Frequency of treatment:
Daily
Details on study schedule:
not specified
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
15 mg/kg bw/day (nominal)
Dose / conc.:
150 mg/kg bw/day (nominal)
Dose / conc.:
750 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Total: 120
Control - 15 males and 15 females
15 ma/kg bw - 15 males and 15 females
150 mg/kg bw - 15 males and 15 females
750 mg/kg bw- 15 males and 15 females
Control animals:
other: control diet contained 1.5 per cent alphacel.
Details on study design:
After 26 weeks on test, five rats of each group receiving 1.5 per cent colourwere killed for histological examination. Haemoglobin estimations were done using a slight modification of the
pyridine-haemochromogen method of Rimington. At the end of the experiment, electrocardiograms and electroencephalograms were recorded from six rats of each sex on the control diet and three rats of each sex on the 1.5 per cent level of each colour,
Positive control:
not specified
Parental animals: Observations and examinations:
Mortality, Body weight, food consumption and food efficiency were examined.
Oestrous cyclicity (parental animals):
No data
Sperm parameters (parental animals):
No data
Litter observations:
No data
Postmortem examinations (parental animals):
Necroscopies were performed on rats that died during the test. After 26 weeks on test, five rats of each group receiving 1.5 per cent colour were killed for histological examination. Haemoglobin estimations were done(Hb,RBC,WBC,Differential cell counts)
Gross examination-After 64 weeks all surviving rats were anaesthesized with ether on all organs and tissues gross examined .
Organ weights recorded.
Histopathological examination-Tissues with gross pathology change was studied for histopathology.
Tissues examined -Lung, liver, heart, spleen, thyroid, pancreas, stomach, small intestine, kidney, urinary bladder, adrenal, testis, prostate, coagulating gland, ovary, uterus, and thymus.
Postmortem examinations (offspring):
No data
Statistics:
Statistics –significant differences between mean values were determined by Student’s“t”test (forgrowth, food consumption and food efficiency).
Reproductive indices:
No data
Offspring viability indices:
No data
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
No effect on survival of treated male and female rats were observed at 15, 150 and 750 mg/kg bw as compared to control.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Decrease in mean body weight in females at 4, 32 and 16 weeks.
Food consumption and compound intake (if feeding study):
effects observed, non-treatment-related
Description (incidence and severity):
Decreased in food consumption of females were observed with no correlation with the concentration given in diet.
Food efficiency:
no effects observed
Description (incidence and severity):
No significant difference in male or female food efficiency was observed as compared to control.
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
effects observed, non-treatment-related
Description (incidence and severity):
The only significant difference observed was lowered white cell count for females at 750 mg/kg bw as compared to controls. No adverse effect on blood cells was observed.
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:
effects observed, non-treatment-related
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
Middle ear and respiratory infections were observed, considered to be in older rats of the colony. Chronic otitis media was observed in nearly 50 per cent of the animals. The disease was evenly distributed in the various groups.
Pathological changes in the adrenal cortex were observed in 22 animals. This particular pathology was acute in nature and was not considered to be an effect of the food colours since it was observed in two of the control animals and since there was no correlation between the incidence and the concentration of colour fed.
Histopathological findings: neoplastic:
no effects observed
Description (incidence and severity):
18 per cent tumour incidence was observed in treated rats. The differences in tumour incidence are not significant according to chi-square tests.
Other effects:
no effects observed
Description (incidence and severity):
The tracings of ECG were essentially normal. No significant deviation of electrical axis observed in treated rats.
Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified
Dose descriptor:
NOAEL
Effect level:
750 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
mortality
body weight and weight gain
food consumption and compound intake
food efficiency
haematology
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic
histopathology: neoplastic
other: No significant effect on reproductive organ weight and histopathology of sexual organs testis,ovary and uterus.
Remarks on result:
other: No toxic effect were observed.
Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
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
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified
Behaviour (functional findings):
not specified
Developmental immunotoxicity:
not specified
Dose descriptor:
other: not specified
Based on:
not specified
Sex:
not specified
Basis for effect level:
other: not specified
Remarks on result:
other: not specified
Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Reproductive effects observed:
not specified
Treatment related:
not specified
Conclusions:
NOAEL was considered to be 750 mg/kg bw when male and female rats were treated with test chemical orally in feed Alphacel (a non-nutritive cellulose) for 64 weeks.
Executive summary:

In a chronic toxicity study, male and female rats were treated with test chemical in the concentration of 0, 15, 150 and 750 mg/kg bw orally in feed Alphacel (a non-nutritive cellulose) for 64 weeks. No effect on survival of treated male and female rats were observed at 15, 150 and 750 mg/kg bw as compared to control. Decrease in mean body weight in females at 4, 32 and 16 weeks. Decreased in food consumption of females were observed with no correlation with the concentration given in diet. No significant difference in male or female food efficiency was observed as compared to control. The only significant difference observed was lowered white cell count for females at 750 mg/kg bw as compared to controls. No adverse effect on blood cells was observed. Similarly, Decrease in liver weight at 150 mg/kg bw and spleen weight at 750 mg/kg bw in female rat. These changes were not correlated with the level of food colour in the diet and are difficult to interpret. No effects on reproductive organs were observed in treated male and female rats as compared to control. Respiratory tract infections accounted for 28 deaths. Two animals died of starvation, one of meningitis, one of a ruptured right auricle and three as the result of neoplasms. In addition, Middle ear and respiratory infections were observed, considered to be in older rats of the colony. Chronic otitis media was observed in nearly 50 per cent of the animals. The disease was evenly distributed in the various groups. Pathological changes in the adrenal cortex were observed in 22 animals. This particular pathology was acute in nature and was not considered to be an effect of the food colours since it was observed in two of the control animals and since there was no correlation between the incidence and the concentration of colour fed. 18 per cent tumour incidence was observed in treated rats. The differences in tumour incidence are not significant according to chi-square tests. The tracings of ECG were essentially normal. No significant deviation of electrical axis observed in treated rats. Therefore, NOAEL was considered to be 750 mg/kg bw when male and female rats were treated with test chemical orally in feed Alphacel (a non-nutritive cellulose) for 64 weeks.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
750 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
Weight of evidence prepared from two well qualified publication.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Reproductive toxicity study:


 


1. In a chronic toxicity study, male and female rats were treated with test chemical in the concentration of 0, 15, 150 and 750 mg/kg bw orally in feed Alphacel (a non-nutritive cellulose) for 64 weeks. No effect on survival of treated male and female rats were observed at 15, 150 and 750 mg/kg bw as compared to control. Decrease in mean body weight in females at 4, 32 and 16 weeks. Decreased in food consumption of females were observed with no correlation with the concentration given in diet. No significant difference in male or female food efficiency was observed as compared to control. The only significant difference observed was lowered white cell count for females at 750 mg/kg bw as compared to controls. No adverse effect on blood cells was observed. Similarly, Decrease in liver weight at 150 mg/kg bw and spleen weight at 750 mg/kg bw in female rat. These changes were not correlated with the level of food colour in the diet and are difficult to interpret. No effects on reproductive organs were observed in treated male and female rats as compared to control. Respiratory tract infections accounted for 28 deaths. Two animals died of starvation, one of meningitis, one of a ruptured right auricle and three as the result of neoplasms. In addition, Middle ear and respiratory infections were observed, considered to be in older rats of the colony. Chronic otitis media was observed in nearly 50 per cent of the animals. The disease was evenly distributed in the various groups. Pathological changes in the adrenal cortex were observed in 22 animals. This particular pathology was acute in nature and was not considered to be an effect of the food colours since it was observed in two of the control animals and since there was no correlation between the incidence and the concentration of colour fed. 18 per cent tumour incidence was observed in treated rats. The differences in tumour incidence are not significant according to chi-square tests. The tracings of ECG were essentially normal. No significant deviation of electrical axis observed in treated rats. Therefore, NOAEL was considered to be 750 mg/kg bw when male and female rats were treated with test chemical orally in feed Alphacel (a non-nutritive cellulose) for 64 weeks.


 


2. Reproductive study was conducted for test chemical in male and female CFW mice for 80 weeks by oral feed. When Groups of 30 male and 30 female CFW mice were given diets containing 0.1, 0.25, 0.5 and 1.0% test chemical for 80 wk, with groups of 60 mice of each sex as controls. There were no dose-related effects on body-weight gain, haematology and organ weights. The incidence of histopathological findings was not altered by the feeding of test chemical. Therefore it is considered that test chemical to the diet of male and female CFW mice at levels up to 1% (equivalent to approximately 1300 mg/kg/day) for 80 wk does not induce any reprotoxic effect.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Justification for classification or non-classification

Thus based on the above annotation and CLP criteria the test chemical is not likely to exhibit reproductive toxicant substance. Hence the substance cannot be classified as reproductive toxicant.

Additional information