Sodium 1-amino-9,10-dioxo-4-(2,4,6-trimethylanilino)anthracene-2-sulfonate, reaction products with acidified C10-14-tert-alkyl(linear and branched) amines

Endpoint summary

Description of key information

Based on the results of the key subacute toxicity study performed according to OECD Guideline 407, the No-Observed-Adverse-Effect-Level (NOAEL)was established at 50 mg/kg bw/day. Slight effects on liver as indicated by a slight centrilobular hypertrophy and changes in plasma enzyme activitieswere observed at 200 and 1000 mg/kg bw.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

50 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

In a subacute toxicity study according to OECD Guideline 407 the test item (described in section 1.2) was administered daily by gavage to SPF-bred Wistar rats, followed by a 14-day recovery period (RCC Notox BV, 1993). The study consisted of four groups, each comprising 5 animals per sex (main group), which were dosed at 0, 50, 200 or 1000 mg/kg bw/day. The control group and high dose group (1000 mg/kg bw/day) contained 5 additional animals per sex for the assessment of reversibility or delayed occurrence of effects (recovery group).

At 50 mg/kg bw/day: On day 27 rough coat was noted in 1/5 females and hunched posture was a transient clinical sign noted in 5/5 males and 1/5 females during days 16 and 26.

At 200 mg/kg bw/day: Hunched posture was noted in 4/5 males and 5/5 females and rough coat in 2/5 males only, between days 11 and 29. Decreased body weight and body weight gain were noted in males during the treatment period. Increased cholesterol levels were noted in the serum of females at week 4 of treatment.

At 1000 mg/kg bw/day: Alopecia was seen in males and females during the 6 week study period. Hunched posture was noted in 10/10 males and females between days 11 and 40 and rough coat was noted in 3/10 males between days 25 and 37. In addition, lethargy was noted in 5/10 males on days 20 to 24. Decreased body weight and body weight gain were noted during the treatment period in males and females and in males also during the recovery period. Decreased food consumption was noted in males and females during the treatment period. After correction for the body weight the relative food consumption was low for males and females over the first week of treatment and high for males and females over the first week of recovery and for males only also over the second week of recovery. Increased white blood cell numbers were noted at week 4 of treatment in females only. At week 4 of treatment, increased alanine aminotransferase activity and cholesterol and triglyceride levels were noted in males and females and increased aspartate aminotransferase activity in females only. After the recovery period, alanine aminotransferase activity was still high in males and cholesterol and triglyceride were still high in females. After 4 weeks, increased liver weights were noted in males and females and after the recovery period this was seen in females only. At week 4, increased liver weights were noted in males and females. After the recovery period, liver weights were high in females only. At week 4 but not after the recovery period, very slight to slight centrilobular hypertrophy of hepatocytes was noted upon microscopic examination in males and females.

Based on these results and with special regard to the transient nature of the changes in clinical appearance in animals at 50 mg/kg bw/day, the No-Observed-Adverse-Effect-Level (NOAEL) was established at 50 mg/kg bw/day.

Justification for classification or non-classification

Taking into account the provisions laid down in Council Directive 67/548/EEC and Regulation 1272/2008/EC and due to the minimal toxic effects observed in the 28-day key-study and reversible nature of these effects , the substance is not classified and labelled for repeated dose oral toxicity.