Calcium bis[2-[(2-hydroxynaphthyl)azo]naphthalenesulphonate]

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

32 mg/kg bw/day

Study duration:

chronic

Species:

rat

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Read across justification

Toxicity to reproduction of the test substance was not examined. The test item shares structural similarity to an analogue substance. Both are Ba-salts and include 1 -amino-2 -naphthol which is connected via azo bond with an aromatic sulfonic acid. Enzymatic azo reduction of the substances may lead to release of 1-amino-2 -naphthol. The salts are poor soluble in water and octanol and dissolve most likely in an acidic environment (e.g. stomach). Therefore, it is acceptable to derive information on reproductive-toxicity from experimental data of the analogue substance.

Procedure and observations

The test material, D&C Red No. 9, was administered to rats in the diet at concentrations of 100, 200 and 500 ppm (equ. to 8, 14 and 42 mg/kg bw/day) for 8 weeks prior to mating (CFTA 1982). The treatment was continued during gestation and lactation. The test material was judged not to have an effect on body weight, food consumption, or fertility of the F0 generation rats. Similarly, no effect was evident on the viability or growth of F1 pups from birth to weaning. Rats from parents treated with graded dietary concentrations of D&C Red No. 9 (0, 100, 200 and 500 ppm) have been continued on treatment for 30 months after weaning. The only difference between the treated groups and the control (0 ppm) groups now judged to be related to the test material is the increase in the spleen weight in the high dose females at the 12 month interval. The apparent decreased values of red cell parameters seen at 12 months were not evident at 18 or 24 months. The gross and histopathologic evaluation and the tumor incidence analyses of the animals did not reveal any compound related effect.

In a multi-generation reproduction study in Charles River CD rats, D & C Red #9 was fed in the diet at dosage levels of 0. 05, 0.5, 1. 5 and 5.0 mg/kg/day. Ten male and 20 female rats were used in each treated group and also as a control group. No changes considered to be related to compound were seen for parental rats or pups with respect to general behavior or appearance, body weight or survival. The fertility, gestation, viability and lactation indices of all litters were comparable for the control and treated groups. An examination of the ovaries and uteri of all dams sacrificed on day 19 of gestation in the F2c litter failed to reveal any abnormal gross anatomical changes. No unusual changes were observed in the examination of pups stillborn or dying during the study. No compound related gross or microscopic pathologic lesions were observed in any F1 or F3a rats from this study which were sacrificed and necropsied. No compound related organ weight variations were observed at sacrifice in F 1 parental rats.

Short description of key information:
Toxicity to reproduction of the test substance was not examined. Reliable experimental data on a structural analogue are available. The test material, D&C Red No. 9, was administered to rats in the diet at concentrations of 100, 200 and 500 ppm (equ. to 8, 14 and 42 mg/kg bw/day) for 8 weeks prior to mating (CFTA 1982). The treatment was continued during gestation and lactation. Rats from parents treated with graded dietary concentrations of D&C Red No. 9 (0, 100, 200 and 500 ppm) have been continued on treatment for 30 months after weaning. The test material was judged not to have an effect on body weight, food consumption, or fertility of the F0 generation rats. Similarly, no effect was evident on the viability or growth of F1 pups from birth to weaning. In a multi-generation reproduction study the test item was fed in the diet at dosage levels of 0. 05, 0.5, 1. 5 and 5.0 mg/kg/day to male and female rats. No changes seen for parental rats or pups with respect to general behavior or appearance, body weight or survival. The fertility, gestation, viability and lactation indices of all litters were comparable to control. Abnormal gross anatomical changes or microscopic pathologic lesions were not observed.

Effects on developmental toxicity

Description of key information

Developmental toxicity of the test substance was not examined. Reliable experimental data on a structural analogue are available. In two teratology studies in female rats and female rabbits, respectively, the test item was administered by gavage at dosage levels of 1.5, 5.0 and 15.0 mg/kg/ day. Positive control groups received retinoic acid or Thalidomide. No changes in behavior and appearance or effects on body weight were observed. No effect upon any maternal (body weight, corpora lutea, empty implantation sites, early resorptions, late resorptions, and live or dead term fetuses) or fetal (mean body weight, sex, external, internal and skeletal abnormalities) parameters evaluated was seen at any dose level.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

15 mg/kg bw/day

Species:

other: rats and rabbits

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

Read across justification

Toxicity to reproduction of the test substance was not examined.The test item sharesstructural similarity to an analogue substance. Both are Ba-salts and include 1 -amino-2 -naphthol which is connected via azo bond with an aromatic sulfonic acid. Enzymatic azo reduction of the substances may lead to release of 1-amino-2 -naphthol. The saltsare poor soluble in water and octanol and dissolve most likely in an acidic environment (e.g. stomach). Therefore, it is acceptable to derive information on reproductive-toxicity from experimental data of the analogue substance.

Procedure and observation

In a teratology study in female Charles River CD rats, the test item was administered by gavage at dosage levels of 1.5, 5.0 and 15.0 mg/kg/ day. Three negative control groups of rats received the vehicle, 0.5% Methocel, and a positive control group of rats received 7. 5 mg/kg/day of retinoic acid. All rats received the compounds or vehicle on days 6 through 15 of gestation. Twenty pregnant rats were used in each control and treated group. No changes in behavior or appearance considered to be related to the material were observed. Increases in body weight were similar for control and treated rats. Cesarean sections were done on the 20th day of gestation. No compound related effect upon any maternal (body weight, corpora lutea, empty implantation sites, early resorptions, late resorptions, and live or dead term fetuses) or fetal (mean body weight, sex, external, interaal and skeletal abnormalities) parameters evaluated was seen in any dose group.

In a teratology study in female Dutch Belted rabbits, the test item was administered by gavage at dosage levels of 1.5, 5.0 and 15.0 mg/kg/ day. Three negative control groups of rabbits received the vehicle, 0.5% Methocel, and a posit:ive control group of rabbits received 150 mg/kg/day of Thalidomide. All rabbits received the compounds or vehicle on days 6 through 18 of gestation. Ten pregnant rabbits were used in each control and treated group. No changes in behavior and appearance were observed. Changes in body weight were similar for control and treated rabbits. Cesarean sections were done on t.he 29th day of gestation. No effect upon any maternal (body weight, corpora lutea, empty implantation sites, early resorptions, late resorptions, and live or dead term fetuses) or fetal (mean body weight, sex, external, internal and skeletal abnormalities) parameters evaluated was seen at any dose level. Several abnormalities occurred in single fetuses without an indication of a dosage relationship. These conditions were considered spontaneaus in origin.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for reproductive toxicity under Directive 67 / 548 / EEC.

 

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for reproductive toxicity under Regulation (EC) No. 1272/2008.