2-(4-amino-2-nitroanilino)ethanol

Endpoint summary

Key value for chemical safety assessment

Effects on developmental toxicity

Description of key information

On the basis of these data from the key studies, the maternal no- observable-adverse-effect-level (NOAEL) for HC Red No. 3 was 200 mg/kg/day and the developmental NOAEL was 1000 mg/kg/day. The test substance was not classified for Teratogenicity according to the CLP criteria.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

Two key studies were available to assess the potential teratogenic effect of the HC Red No.3 :

-A first Dose Range Finding study was performed in order to select appropriate dose for a Definitive Teratogenicity test (York, 2005, Klimisch 2, OECD 414, GLP compliant). Forty presumed pregnant Crl:CD rats, eight per group, were randomly assigned to five dosage groups. Formulations of the test substance, HC Red 3, and/or the vehicle, 100% polyethylene glycol 400 (PEG 400), were administered orally once daily to rats on days 6 through 20 of gestation (DGs 6 through 20) at dosages of 0, 50, 200, 500 and 1000 mg/kg/day. The dosage volume was 5 mL/kg. Viabilities, clinical observations, body weights and feed consumption values were recorded. All rats were sacrificed on DG 21. The gravid uterus was weighed and examined for the number and distribution of corpora lutea, implantation sites and uterine contents. Fetuses were weighed and examined for gross external alterations and sex. Caesarean-sectioning and subsequent fetal observations were conducted without knowledge of dosage group. the Test Article HC Red No. 3 induced no significant differences in body weight  between treated and control animals. No significant differences the litter sizes were observed between treated and control animals. No significant differences in the number of live or resorbed foetuses were observed between treated and control animals. No differences in foetal abnormalities were observed between treated and control groups. The NOAEL for materno and embryo-toxicity was considered to be 1000 mg/kg/day.

- Based on the results of the previous Dose Range Finding study, the selected doses for the main study were 0, 50, 200 and 1000 mg/kg bw/d (York, 2005, Klimisch 1, OECD 414, GLP compliant). Solutions of the test substance HC Red 3 and/or the vehicle, 100% polyethylene glycol 400 (PEG 400), were administered orally once daily to rats (6 rats per dose group) on days 6 through 20 of gestation (DGs 6 through 20). The dosage volume was 5 mL/kg. Viabilities, clinical observations, body weights and feed consumption values were recorded. All surviving rats were sacrificed on DG 21. The gravid uterus was excised, weighed and subsequently examined for the number and distribution of corpora lutea, implantation sites and uterine contents. A gross necropsy was performed. Fetuses were weighed and examined for gross external alterations, sex and either soft tissue or skeletal alterations. The treatment by oral gavage of the test article HC Red No.3 induced Significant increases in the incidences of discolored skin, fur and/or urine, as well as perioral substance  in rats assigned to the 50 mg/kg/day and higher dosage levels and were considered to be related to the color of the test substance. The 1000 mg/kg/day dosage produced additional increased clinical signs of perivaginal substance, as well as decreases in body weight gains, corrected maternal body weights and body weight gains and feed consumption values. The 1000 mg/kg/day dosage caused reversible delays in ossification (reductions in the numbers of ossified hindlimb metatarsals and phalanges). On the basis of these data, the maternal no- observable-adverse-effect-level (NOAEL) for HC Red No. 3 was 200 mg/kg/day and the developmental NOAEL was 1000 mg/kg/day.

Justification for classification or non-classification

On the basis of these data from the key studies, the maternal no- observable-adverse-effect-level (NOAEL) for HC Red No. 3 was 200 mg/kg/day and the developmental NOAEL was 1000 mg/kg/day. The test substance was not classified for Teratogenicity according to the CLP criteria.