Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

NOAEL was estimated to be 667.5 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt.     

Thus, as per criteria of CLP regulation, disodium [μ-[[7,7'-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) can be not classified for reproductive toxicity.     

Link to relevant study records
Reference
Endpoint:
toxicity to reproduction
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
Data is predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
other: Han Wistar
Sex:
male/female
Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
corn oil
Details on exposure:
not specified
Details on mating procedure:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
males: from 2 weeks prior to mating for at least 4 week
females: from 2 weeks prior to mating for at about 7 week
Frequency of treatment:
daily, 7/days/wk
Details on study schedule:
not specified
Dose / conc.:
667.5 mg/kg bw/day
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Details on study design:
not specified
Positive control:
not specified
Parental animals: Observations and examinations:
not specified
Oestrous cyclicity (parental animals):
not specified
Sperm parameters (parental animals):
not specified
Litter observations:
not specified
Postmortem examinations (parental animals):
not specified
Postmortem examinations (offspring):
not specified
Statistics:
not specified
Reproductive indices:
not specified
Offspring viability indices:
not specified
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
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
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified
Dose descriptor:
NOAEL
Effect level:
667.5 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reproductive performance
Remarks on result:
other: No effect observed
Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
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 examined
Other effects:
not specified
Behaviour (functional findings):
not specified
Developmental immunotoxicity:
not specified
Dose descriptor:
other: not specified
Generation:
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
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified
Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and ( not "z") )  )  and ("aa" and "ab" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anion OR Aromatic compound OR Azo compound OR Cation OR Hydroxy compound OR Phenol OR Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] OR Aliphatic Nitrogen, one aromatic attach [-N] OR Aromatic Carbon [C] OR Azo [-N=N-] OR Hydroxy, aromatic attach [-OH] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic attach [-O-] OR Suflur {v+4} or {v+6} OR Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl OR Azo OR Azoxy OR Fused carbocyclic aromatic OR Overlapping groups OR Phenol OR Sulfonic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aryl OR Azo OR Azoxy OR Fused carbocyclic aromatic OR Naphtalene OR Phenol OR Sulfonic acid by Organic Functional groups ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Organic sulphonic salts by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNS Surface Tension > 62 mN/m AND Group All Melting Point > 200 C AND Group CNS log Kow < 0.5 AND Group CNS Melting Point > 120 C AND Group CNS Melting Point > 50 C AND Group CNS Molecular Weight > 620 g/mol by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Phenols (Mucous membrane irritation) Rank C by Repeated dose (HESS)

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Aliphatic nitriles (Hepatotoxicity) Rank B by Repeated dose (HESS)

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Hydroxy, aromatic attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Suflur {v+4} or {v+6} AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Oxygen, nitrogen attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Hydroxy, aromatic attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Suflur {v+4} or {v+6} AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Phosphine oxide [O=P] OR Phosphine Type [>P-] OR Phosphite, aliphatic attach [-O-P] by Organic functional groups (US EPA)

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Hydroxy, aromatic attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Suflur {v+4} or {v+6} AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Zinc [Zn] by Organic functional groups (US EPA)

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Hydroxy, aromatic attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Suflur {v+4} or {v+6} AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Boron [B] by Organic functional groups (US EPA)

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.283

Domain logical expression index: "ab"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.17

Conclusions:
NOAEL was estimated to be 667.5 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt.
Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt. The NOAEL was estimated to be 667.5 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt.     

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
667.5 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Data is Klimisch 2 and from OECD QSAR toolbox (2018)
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:

In different studies, [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt has been investigated for reproductive toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimation in rodents, i.e. most commonly in rats for [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt along with the study available on structurally similar read across substance Black PN (CAS no 2519-30-4) and Carmoisine (CAS no 3567-69-9). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.  

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt. The NOAEL was estimated to be 667.5 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt.     

In another experimental study conducted by Fordet al(Food Chem. Toxic. Vol. 25, No. 12, pp. 919-925, 1987) on structurally similar read across substance Carmoisine (CAS no 3567-69-9), Wistar male and female rats were treated with Carmoisine in the concentration of  0 (control), 100, 400 or 1200 mg /kg body weight/day orally in feed for 115 weeks. No significant change of carmoisine on the condition or behaviour of the animals, apart from coloration of the fur, urine and faeces with an intensity increasing with dose. No effect on survival of treated rats was observed. No effect on mating, pregnancy, lactation and weaning of P treated rats as compared to control. In addition, Effect like coloration of the fur, urine and faeces with an intensity increasing with dose in F1 pups. But no significant change was observed in animals behaviour and condition in treated group compare to control. No significant change was observed in the survival of F1 treated group compare to control. Significant change was observed in the body weights of F1 males receiving 400 and 1200 mg/kg/day were lower than those of the controls throughout the study. Females receiving 1200 mg/kg/day weighed significantly less than the controls from week 32 onwards. In both sexes the magnitude of the observed differences increased with time. Significant change was observed in the food intakes of the1200 mg /kg/day males was observed compare to control. Even in female 1200 mg/kg/day were greater than those of the controls, but the differences in females was unrelated to dose. Water intakes of treated animals showed some inconsistency during the study. For the first 12 months there was a dose-related higher intake in both sexes receiving 400 or 1200 mg /kg/day. During the second year the water intake of males receiving 1200mg/kg/day or of females receiving 400 mg/ kg/day was no longer different from that of the controls. No significant change was observed at all dose level 100, 400 or 1200 mg /kg body weight/day of treated group compare to control. Lower glucose concentrations were observed in males at dose level of 1200 mg/kg/day compare to control. While a Lower glucose concentration was observed in females at dose level of 400 and 1200 mg/kg/day compare to control. Semi-quantitative analyses of urine were hindered in treated animals, particularly at the 1200 mg/kg/day, by the colour of the urine which obscured the colour reaction of the reagent test strips. Despite these limitations, which meant that some samples obtained from 1200 mg/kg/day animals were not usable, a higher proportion of samples from the 1200 mg/kg/day females showed a high level of protein at both 18 and 24 months. No significant change was observed in any organ except caecum weight. The caecum was the only organ whose weight and relative weight (g/100 g body weight) showed changes associated with treatment. At 1200 and 400 mg/kg/day dose level in males both weight and relative weight of the caecum, with and without contents, were greater than the control values, although the increases were only statistically significant at the1200 mg /kg body weight/day. In females at the dose level of 1200 mg /kg body weight/day only the relative weight of the empty caecum was significantly greater than that of the controls. The changes in caecum weight were accompanied by observations at autopsy that the caecum wall was thicker in the treated animals. Similarly, significant thickness was observed in caecum wall at 1200 mg /kg body weight/day group of treated animals compare to control. Age-related changes to be expected in rats of the strain used. Some of the changes recorded showed a positive dose-related trend together with a significantly higher incidence when individual groups were compared with the controls. These were pupillary hyperplasia of the bladder in males and blood/fibrin cysts of the adrenal gland and internal hyperplasia / medial hypertrophy of the pancreatic blood vessels in females. The total incidences of benign or malignant tumours showed no treatment-related differences. There were no differences between the treated and control groups in the incidences of individual types of tumour apart from adrenal phaeochromocytoma which showed a statistically significant treatment-related difference in males based on four tumours in the 1200 mg/kg/day group compare to controls. A similar difference was not observed in females. Therefore, NOAEL was considered to be 1200 mg/kg bw for P generation and 400 mg/kg bw for F1 generation when Wistar male and female rats were treated with Carmoisine orally in feed for 115 weeks.

Further supported by experimental study conducted by Holmeset al(Toxicology, 10 (1978) 169-183) on structurally similar read across substance Carmoisine (CAS no 3567-69-9), Sprague-Dawley male and female rats were treated with Carmoisine in the concentration of 0,175, 400 and 1000 mg/kg bw orally in feed for 480 days. No significant changes in body weight and food consumption of P rats were observed as compared to control. Similarly, no effect on viability of F1a, F1b, F2a, F2b, F3a and F3b pups as compared to control. In addition, No effect on reproductive parameters such as Fertility index, Copulation index, Number of pups/litter at birth, Stillbirth incidence, Viability index of pups and Lactation index were observed in P, F1b and F2b rats as compared to control. Therefore, NOAEL was considered to be 1000 mg/kg bw for P, F1b and F2b generation when Sprague-Dawley male and female rats were treated with Carmoisine orally in feed for 480 days.

Again supported by experimental study conducted by Carsonet al(J. Toxicol.-Cut. & Ocular Toxicol. 3(3), 309-331 (1984)) on structurally similar read across substance FD&C Red 4 (CAS no 4548-53-2), Swiss-Webstermale and female mice were treated with FD &C Red 4in the concentration of 1500 mg/kg bw/day in distilled water applied twice weekly on 6 cm2 dorsal area of skin. No effect was observed on survival, clinical sign and body weight of treated male and female mice as compared to control. Similarly, lesion in Mammary Gland and Subcutaneous papillary were observed gross pathologically in treated mice, but the observed effect were similar to control. In addition, All grades Malignant lymphoma and Variation in nuclear morphology in Liver, Infarction, Malignant and Myeloid metaplasia, Leukocytic aggregations in Spleen, all grades Malignant lymphoma , Leukemic and round cell infiltration and Leukocytic aggregation in Kidneys , Malignant lymphoma in Lymph Nodes, Malignant lymphoma, Inflammation, pneumonitis, bronchitis and Necrotic changes in Lungs and all grades Malignant lymphoma in Thymus were observed in male and female treated mice. No significant difference in the incidence of this lesion were observed as compared to control and considered to be not treatment related. Therefore, NOAEL was considered to be 1500 mg/kg bw/day when Swiss-Webster male and female mice were treated with FD&C Red 4.

Above studies are supported by experimental study conducted by Burnettet al(Toxicology And Applied Pharmacology, 29,75-l 55 (1974)) on structurally similar read across substance FD&C Red 4 (CAS no 4548-53-2), male and female rats pups were treated with Red No. 4. In the concentration based on multiples ( 1 x, 10x, 30x, and 100x) of the A.D.T., no doses in excess of 1000 mg/kg/day were used. No indications of adverse effects on reproductive performance were observed in treated pups. Therefore, NOAEL was considered to be 1000 mg/kg/day for F2b generation, when male and female rats pups were treated with Red No. 4.

Again supported by experimental study conducted by Borzelleca et al (Food Chem. Toxic. Vol. 23, No. 6, pp. 551-558, 1985) on structurally similar read across substance FD & C Blue No. 2 (CAS no 860-22-0), CD male and female rats were treated with FD & C Blue No. 2 in the concentration of 0, 304, 632 and 1282 mg/kg/day for male and 0, 363, 775 and 1592 mg/kg/day for female in basal diet. No effect on survival, body weight and food consumption of treated rats were observed as compared to control in F0 generation. No effect on numbers of pregnant females per group and pup viability at birth were observed in treated rats as compared to control. No effect on pup viability at birth were observed although pup mortality were increased at 1282 for male and 1592 mg/kg/day for female during lactation and weaning period and at 632 mg/kg/day for male and 1592 mg/kg day for female during weaning period as compared to control. Sufficient pups were available in F1 generation. Hair loss (apparently due to friction against the cage), nasal and ocular discharge, staining of the hair in the anogenital region and soft stools were observed in treated pups but these random observations are not uncommon in the CD rat and therefore were not considered to be related to compound administration. Slightly decreased body weight were observed at 1282 mg/kg/day for male and 1592 mg/kg/day for female and 632 mg/kg/day for male and 1592 mg/kg/day for female as compared to control. This was due to low number of pups prior to the random selection of pups for the F1 generation. Dose-related increase in food consumption was observed in treated rats as compared to control. The increased food consumption was probably due to the influence of the non-nutritive character of the test compound at these high concentrations in F1 generation. Similarly, Focal and diffuse retinopathy, conjunctivitis, uveitis and cataracts were observed in treated rats but observed changes were not related to compound administration. No significant effect on hematology, Clinical chemistry and urine-analysis of treated rats were observed as compared to control in F1 generation. At 1592 mg/kg/day decrease in relative thyroid and kidney weight at 12 month and increased mean relative spleen and liver weights at 30 month and at 363 mg/kg/day decrease in relative thyroid at 12 month in female were observed as compared to control. Blue discoloration of the gastro-intestinal tract was noted in the treated groups. In addition, Increase in grossly visible abnormalities in urinary bladders of treated male rats at 1282 mg/kg/day were observed as compared to control in F1 generation. The observed findings were consistent with those reported in the literature for aged rats of this strain. Non-neoplastic mycoplasma pulmonis, infection by Corynebacterium kutcheri, Periarteritis nodosa, characterized by fibrinoid necrosis of the arterial walls, occurred most commonly in the arteries of the pancreas, mesentery and testes and atrophy of the seminiferous tubules, accompanied by oligospermia or aspermia. All non-neoplastic lesions were randomly distributed in treated and control animals and were not dose related. In male rats at 1282 mg/kg/day Neoplastic Pituitary-gland neoplasms, carcinomas/adenocarcinomas of mammary-gland and transitional-cell neoplasms of the urinary bladder were observed in treated rats as compared to control. The observed effect were not statistically significant as compared to control. Statistically significant increase in carcinomas/adenocarcinomas of mammary-gland and gliomas were observed in treated rats as compared to control. In female rats, Pituitary-gland neoplasms and malignant mammary-gland neoplasms (carcinoma, adenocarcinoma) observed in treated rats as compared to control. The observed effect were not statistically significant as compared to control. Therefore, NOAEL for F0 and F1 generation was considered to be 1282 mg/kg/day for male and 1592 mg/kg/day for female rats when CD male and female rats were treated with FD & C Blue No. 2 orally for 30 months.

Thus, based on the above study and predictions on disodium [μ-[[7,7'-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) and its read across substances, it can be concluded that NOAEL value is 667.5 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, disodium [μ-[[7,7'-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) can be not classified for reproductive toxicity.     

 

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

Based on the above study and predictions on disodium [μ-[[7,7'-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) and its read across substances, it can be concluded that NOAEL value is 667.5 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, disodium [μ-[[7,7'-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) can be not classified for reproductive toxicity.