Benzo[rst]phenanthro[10,1,2-cde]pentaphene-9,18-dione, reaction products with 1-chlorododecane

Endpoint summary

Description of key information

Dose range finding study in rats - Oral, gavage

OECD 422 in rats - Oral, gavage

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

good

System:

hepatobiliary

Organ:

liver

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The purpose of this study was to evaluate the potential effects of C.I. Solvent Red 175 Solid (solvent stripped) on general toxicity, neurological and reproductive function, and prenatal/early neonatal growth and survival of offspring in rats following repeated gavage administration. Groups of 12 male and 12 female Crl:CD(SD) rats were administered C.I. Solvent Red 175 Solid (solvent stripped) daily by gavage at dose levels of 0 (control), 100, 300, or 1000 mg/kg/day. Males were dosed for at least four weeks prior to breeding and continuing throughout breeding for a minimum of 48 days. The females were dosed for four weeks prior to breeding, continuing through breeding (up to two weeks), gestation (three weeks), and lactation (thirteen days). Effects on general systemic toxicity, neurobehavioral activity, clinical chemistry, hematology, coagulation, thyroid hormone levels, urine parameters, gonadal function, estrous cyclicity, mating behavior, conception, development of the conceptus, parturition and early postnatal growth and survival of pps were evaluated. In addition, a gross necropsy of the adults was conducted with extensive histopathologic examination of tissues. Litter size, pup survival, sex, body weight, anogenital distance, nipple retention, and gross external morphological alterations were assessed.

Treatment-related clinical observations consisted of red feces in all treated animals and red discolored fur in several treated animals which were attributed to the dye nature of the test material and considered a biomarker of exposure.

There were no treatment-related effects on body weight, body weight gain, feed consumption, neurological or reproductive function, or prenatal neonatal survival, growth, or development of the offspring in any treated groups compared to controls.

Males given 1000 mg/kg/day had a treatment-related increase in mean prothrombin time and mean urea nitrogen concentration that were interpreted to be non-adverse. 

Males and females given 1000 mg/kg/day had treatment-related higher mean absolute and relative liver weights (11.1% and 11.9% higher for males, respectively, and 10.7% and 7.5% higher for females, respectively). No treatment-related change in liver weight was observed in males or females at 100 or 300 mg/kg/day. 

Males given 1000 mg/kg/day had treatment-related slight hypertrophy of periportal hepatocytes and slight necrosis (with or without inflammation) of individual hepatocytes. Females given 1000 mg/kg/day had treatment-related very slight hypertrophy of periportal hepatocytes, very slight vacuolization (consistent with fatty change) of periportal hepatocytes, and very slight necrosis (with or without inflammation) of individual hepatocytes. Males given 300 mg/kg/day had treatment-related very slight hypertrophy of periportal hepatocytes and treatment-related slight necrosis, (with or without inflammation), of individual hepatocytes. No treatment-related liver histopathology was observed at 300 mg/kg/day in females or at 100 mg/kg/day in either sex. 

Based on the presence of treatment-related very slight or slight necrosis of individual hepatocytes in males given 300 or 1000 mg/kg/day and in females given 1000 mg/kg/day, the no-observed adverse effect level (NOAEL) for general toxicity was 100 mg/kg/day for males and 300 mg/kg/day for females. The NOEL for neurological and reproductive toxicity or for effects on prenatal/neonatal growth, survival, and development was 1000 mg/kg/day, the highest dose tested.

Justification for classification or non-classification

The toxicological effects (hyertrophy of hepatocytes and necrosis of individual hepatocytes) observed in the liver in male and female rats dosed at 1000 mg/kg and in males dose at 300 mg/kg we rated as slight to very slight. They did not appear to impact the functioning of the organ nor the overal wellbeing of the animals. All effects observed at doses greater than 100 mg/kg bw.

It is therefore concluded that classification for repeated dose toxicity is not required.