2-[(2-nitrophenyl)amino]ethanol

Endpoint summary

Key value for chemical safety assessment

Effects on developmental toxicity

Description of key information

According to the results of the two keys studies (Dose Range Finding and Definitive Teratology Study York, 2005, OECD 414, GLP compliant), the No Observe Adverse Effect Level NOAEL for materno- and embryo-toxicity of the test item HC Yellow No. 2 in Developmental toxicity test was defined at 500 mg/kg/day. Hence the test substance was not classified for teratogenicity.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

500 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

Two key studies were availables in order to assess the potential teratogenicity effect of the test item : A first Dose Range Finding Study was performed (York, 2005, Klimisch 2, OECD 414 equivalent, GLP compliant) :

Forty presumed pregnant Crl:CD(SD) rats were randomly assigned to five dosage groups, eight rats per group. Solutions of the test substance or the vehicle, PEG 400, were administered orally (gavage) once daily to these naturally bred female rats on days 6 through 20 of presumed gestation (GD 6 - 20) at dosages of 0, 25, 75, 200 and 500 mg/kg bw/d. Viabilities, clinical observations, body weights and feed consumption values were recorded. All surviving rats were sacrificed on GD 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. Foetuses were weighed and examined for gross external alterations and sex.There were no test substance related effects on body weights, body weight gains, gravid uterine weights, corrected maternal body weights or corrected maternal body weight gains or absolute or relative feed consumption values. No Caesarean-sectioning or litter parameters were affected by dosages of the test substance as high as 500 mg/kg/day. All fetuses appeared normal at gross external examination.

Based on these data, dosages of 0 (Vehicle), 50, 200 and 500 mg/kg/day of the test item were selected for the developmental toxicity study in rats (York, 2005, Klimisch 1, OECD 414, GLP compliant). One hundred presumed pregnant Crl:CD (SD) rats (25 per group) were randomly assigned to four dosage groups. Solutions of the test substance or the vehicle, 100 % polyethylene glycol 400 (PEG 400), were administered orally once daily to rats on days 6 -20 of gestation (GD 6 - 20) at dosages of 0, 50, 200 and 500 mg/kg bw/d. Viabilities, clinical observations, body weights and feed consumption values were recorded. All surviving rats were sacrificed on GD 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. Foetuses were weighed and  examined for gross external, soft tissue and skeletal alterations and sex.

One 200 and two 500 mg/kg bw/d dosage group rats were found dead on GD 17, 19 or 20. These deaths were considered related to aspiration of the test substance. Significantly increased incidences of yellow and/or orange urine and discoloration and yellow perioral substance occurred in the 50, 200 and 500 mg/kg bw/d dosage groups. Discoloration of internal organs was also observed. All of these colour changes were not considered to be adverse. The 50, 200 or 500 mg/kg bw/d dosages of HC Yellow n° 2 were associated with significant reductions in the average number of ossified fore- and/or hind- limb phalanges that were also all within historical control range.

On the basis of these data, the maternal no-observable-adverse-effect- level (NOAEL) is 500 mg/kg bw/d. The developmental NOAEL is also 500 mg/kg bw/d. The small reduction in foetal body weights and reduced ossification site averages for phalanges were not considered adverse.

Justification for classification or non-classification

According to the results of the two keys studies (Dose Range Finding and Definitive Teratology Study (York, 2005, OECD 414, GLP compliant),the No Observe Adverse Effect Level NOAEL for materno- and embryo-toxicity of the test item HC Yellow No. 2 in Developmental toxicity test was defined at 500 mg/kg/day. Hence the test substance was not classified for teratogenicity.