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Key value for chemical safety assessment

Effects on developmental toxicity

Description of key information

Based on the result of the key study (Gaouna, 2005, GLP, Klimisch 1, OECD 414 method), the No Observed Adverse Effect Level NOAEL for the test article 4 -amino-3 -nitrophenol was defined at 400 mg/kg/day.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
400 mg/kg bw/day
Study duration:
Additional information

One key study is available to assess the potential developmental prenatal toxicity of the test substance. A developmental toxicity/teratogenicity study was performed (Gaouna, 2005, GLP, Klimisch 1, OECD 414 method).

Three groups of 24 mated female rats of the Sprague-Dawley strain received the test item, 4-amino-3-nitrophenol, by daily oral administration at 5, 20 or 400 mg/kg/day from day 6 to day 19 (p.c.). Another group of 24 females, acting as a control group, received only the vehicle under the same experimental conditions at a dosage volume of 5 mL/kg/day. Clinical signs and mortality were checked daily. Body weight and food consumption were recorded at designated intervals. On day 20 p.c., the dams were sacrificed and subjected to a macroscopic examination. The gravid uterus was weighed. The fetuses were removed by hysterectomy. The following litter parameters were recorded: number of corpora lutea, implantation sites, early and late resorptions, dead and live fetuses. The fetuses were weighed, sexed and subjected to external, and visceral or skeletal examinations. No deaths were reported and clinical signs were limited to orange coloured urine. An increase of short supernumerary rib was reported at 400 mg/kg/day in foetuses of some of the litters which was however, not statistically significant. There was no maternal toxicity or effects on embryo-foetal development in any of the exposure levels used. The NOAEL for maternal and developmental toxicity was 400 mg/kg/day.

Additionnaly another study is available (Springhall, 1991, GLP, Klimisch 2, similar methodwith OECD 414 guideline)

The test substance was administered, by gavage, to 4 groups of 24 pregnant Sprague-Dawley rats . The test substance was daily administered at dosage levels of 100, 250 or 600 mg/kg bw. All mated females were sacrificed at day 20 of gestation. The animals were observed daily for clinical signs. Individual body weights were recorded at days 0, 6-15 and 20. Immediately following sacrifice, the uterus was removed, weighed and the number of (non)viable foetuses, early and late resorptions and the number of total implantations and corpora lutea was recorded. A macroscopic examination of the organs was carried out. All foetuses were individually weighed and the sex of the foetuses was determined. Two third of the foetuses was examined for skeletal defects and variations of the ossification and one third was evaluated for visceral imperfections (organic defects). Two females of the high dose group died during the study. Most females of all treated groups had yellow/orange fur staining and yellow/orange stained urine. The high dose females showed significantly reduced body weights. A dose related increase in the number of foetuses exhibiting the skeletal variant of uni- or bilateral vestigial (rudimentary) 14th rib; significant from 250 mg/kg bw onwards, was observed. No irreversible structural changes were observed. Based on this result, the NOAEL for maternal toxicity was defined as 250 mg/kg bw/day and the NOEL for embrytoxicity was defined at 100 mg/kg bw/day.

The rats were administered from the day 6 to the day 15 of gestation instead of until the sceduled caesarian section required in the OECD guideline. However, the study was considered to be relevant but is not up to modern standard. The first key study (Gaoua, 2005) is performed according to current OECD guideline, hence it was considered as more relanvant for assessment.

Justification for classification or non-classification

Based on the result of the key study (Gaouna, 2005, GLP, Klimisch 1, OECD 414 method), the No Observed Adverse Effect Level NOAEL for the test article 4 -amino-3 -nitrophenol was defined at 400 mg/kg/day. The test item was not considered as a reprotoxic/teratogenic substance.

Additional information