Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

no data

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key information

According to the result of the key study and to CLP criteria, the registered substance 2 -amino-6 -chloro-4 -nitrophenol was not classified for toxicity to reproduction and teratogenicity.

The NOAEL for developmental toxicity was established at ≥ 90 mg/kg bw.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
90 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
reliability 2
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

The developmental toxicity study of Chlororange (2-amino-6-chloro-4-nitrophenol) was conducted following methods comparable to the OECD Guideline 414 (Prenatal Developmental Toxicity Study).

Male and female rats were placed together for mating during the cohabitation period. The presence of spermatozoa in a vaginal smear was considered as Day 0 of gestation. Mated females were assigned randomly to the following treatment groups of 20 females each:

Group 1: Vehicle control (0.5% sodium carboxymethylcellulose)

Group2: 10 mg/kg bw/day

Group 3: 30 mg/kg bw/day

Group 4: 90 mg/kg bw/day

Aqueous 0.5% sodium carboxymethylcellulose served as the vehicle. The test substance was administered to mated female rats by oral gavage once daily from Days 5 through 15 of gestation.

The female rats were observed daily for clinical signs, abortions, premature deliveries and deaths. Body weights were recorded on Day 0 and at Days 5, 10, 15 and 20. Food consumption values were measured for day-intervals 0-5, 5-15, and 15-20 and for the entire study period (0-20).

All rats were sacrificed by CO2 asphyxiation on Day 20, and a macroscopic examination was performed. The number of corpora lutea in each ovary was recorded. The uterus of each rat was examined for pregnancy, number and distribution of implantations, live and dead foetuses, early and late resorptions, birth position (anterior/posterior), and placentae.

Each fetus was identified, weighed and examined for sex and gross external alterations. Approximately one-third of the fetuses in each litter were examined for soft tissue alterations and the remaining fetuses in each litter examined for skeletal alterations.

All females showed normal habits and behaviours throughout the study, and no animaldiedprior to scheduled sacrifice. Females of all dose groups had orange discolored urine throughout the application period at dose related intensity. Mean maternal bodyweight gain and mean food consumption was significantly reduced during the treatment phase in the females of the high dose group (90 mg/kg bw).

Gross necropsy did not reveal any organ alterations attributable to treatment.

No significant differences in the mean number of viable fetuses, the male to female fetal sex ratio, total bodyweights, birth position, number of runts, post-implantation losses, implantations, resorptions, uteri weights, placenta weights and corpora lutea between dosage groups and the control group were observed.

External, skeletal and visceral examinations of fetuses revealed minor variations (wavy ribs) at comparable intergroup frequencies with incidence within the spontaneous variation range of this strain of animals. 5 mid dose group fetuses and one high dose group fetus were found with head-neck edemas or whole-body edemas (anomalies) but since the incidence of this finding revealed no dose relation, it is considered to be coincidental.

Based on the above, administration of Chlororange (2-amino-6-chloro-4-nitrophenol) to female Crl:Wi/Br strain Wistar rats by oral gavage during gestation Days 5 to 15 at dose levels of 0, 10, 30 and 90 mg/kg bw resulted in a NOAEL of 30 mg/kg bw for maternal toxicity (significant reduction in body weight gain and mean food consumption).

The NOAEL for developmental toxicity was established at ≥ 90 mg/kg bw, the highest dose administered.

Justification for classification or non-classification

According to the result of the key study and to CLP criteria, the registered substance 2 -amino-6 -chloro-4 -nitrophenol was not classified for toxicity to reproduction and teratogenicity.

The NOAEL for developmental toxicity was established at ≥ 90 mg/kg bw.