Registration Dossier

Administrative data

Description of key information

The repeated dose oral toxicity study of Chlororange (2-amino-6-chloro-4-nitrophenol) was performed by following methods similar to the OECD Guideline 408 (Repeated Dose 90 -Day Oral Toxicity in Rodents).

Male and female rats were assigned to 4 groups (15 animals/sex/group;for control and 90 mg/kg dose groups an additional 10 animals/sex formed recovery groups) and were treated for 90 days as follows:

Group 1: Control (0.5% Carboxymethylcellulose)

Group 2: 10 mg/kg bw/day

Group 3: 30 mg/kg bw/day

Group 4: 90 mg/kg bw/day

No animals died during the study. No adverse clinical signs, except for an orange-red discoloration of urines in the mid and high dose animals, were observed. Body weight gain rates were significantly reduced in high-dose males during the second half of the study. The reduced male body weight was nearly compensated by significantly increased weight gain rates during the recovery period. No significant differences were seen in food consumption andfood conversion ratios.

Hematological investigation revealed intergroup differences in prothrombin time, leukocyte and reticulocyte count, which occurred sporadically within the limits of the normal range. Clinical chemistry values indicated several statistical significant intergroup differences. These changes, however, were not persistent, not dose-related and randomly sex-related and were therefore considered to be coincidental.

No test substance-related findings were seen at terminal autopsy. Organ weight changes of the liver, lung and thymus of males and females in the high dose and recovery groups were not consistent. However, increases in kidney weight were found in males and females both of the high dose and recovery groups. The histomorphological examinations revealed no treatment related organ alterations in high-dose group animals.

Based on above, treatment related adverse effects were observed at the highest tested dose level i.e.90 mg/kg bw/day (reduced body weight and increased kidney weights).

In conclusion, Chlororange (2-amino-6-chloro-4-nitrophenol) when administered by oral gavage daily for 13 weeks to male and female Crl: Wi/Br strain Wistar rats at dose levels of 0, 10, 30 and 90 mg/kg bw/day, revealed a no observed adverse effect level (NOAEL) at 30 mg/kg bw/day for male and female rats.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
30 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
reliability 1

Additional information

Justification for classification or non-classification

The repeated dose oral toxicity study of Chlororange (2-amino-6-chloro-4-nitrophenol) was performed by following methods similar to the OECD Guideline 408 (Repeated Dose 90 -Day Oral Toxicity in Rodents): No animals died during the study. No adverse clinical signs, except for an orange-red discoloration of urines in the mid and high dose animals, were observed. Body weight gain rates were significantly reduced in high-dose males during the second half of the study. The reduced male body weight was nearly compensated by significantly increased weight gain rates during the recovery period. No significant differences were seen in food consumption andfood conversion ratios.

Hematological investigation revealed intergroup differences in prothrombin time, leukocyte and reticulocyte count, which occurred sporadically within the limits of the normal range. Clinical chemistry values indicated several statistical significant intergroup differences. These changes, however, were not persistent, not dose-related and randomly sex-related and were therefore considered to be coincidental.

No test substance-related findings were seen at terminal autopsy. Organ weight changes of the liver, lung and thymus of males and females in the high dose and recovery groups were not consistent. However, increases in kidney weight were found in males and females both of the high dose and recovery groups. The histomorphological examinations revealed no treatment related organ alterations in high-dose group animals.

Based on above, treatment related adverse effects were observed at the highest tested dose level i.e.90 mg/kg bw/day (reduced body weight and increased kidney weights).

In conclusion, Chlororange (2-amino-6-chloro-4-nitrophenol) when administered by oral gavage daily for 13 weeks to male and female Crl: Wi/Br strain Wistar rats at dose levels of 0, 10, 30 and 90 mg/kg bw/day, revealed a no observed adverse effect level (NOAEL) at 30 mg/kg bw/day for male and female rats. According to CLP criteria, there was no sufficient adverse effect to determined a STOT effect.