14H-benz[4,5]isoquino[2,1-a]perimidin-14-one

Endpoint summary

Description of key information

Physicochemical data as well as toxicological studies indicate a low bioaccumulation potential of 14H-benz[4,5]isoquino[2,1-a]perimidin-14-one (CAS no 6829-22-7).

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

Macrolex Rot E2G (14H-benz[4,5]isoquino[2,1-a]perimidin-14-one) is an organic odourless red powder (melting point 257 °C). The QSAR determination of the vapour pressure of the substance using the model MPBPWIN included in the Estimation Program Interface (EPI) Suite v4.11 revealed a value of 1.36E-9 Pa at 25 °C. Due to the low vapour pressure and high melting point human exposure via vapour is assumed to be limited.

The water solubility of 14H-benz[4,5]isoquino[2,1-a]perimidin-14-one determined by the column elution method at 20 °C and was 11µg/L. The partition coefficient (Pow) of Macrolex Rot E2G was determined by the Shake Flask Method according to the guideline OECD 107 at room temperature (22 °C). Result: Partition coefficient: log Pow = 5.5 (at 22 °C).

Based on these values there is no evidence of absorption due the insolubility of the substance in water and the high octanol-water partition coefficient.

14H-benz[4,5]isoquino[2,1-a]perimidin-14-one has very low acute toxicity (discriminating dose oral > 5000 mg/kg bw and discriminating dose inhalation > 1817 mg/m³ (technically maximum attainable concentration). 14H-benz[4,5]isoquino[2,1-a]perimidin-14-one is not irritating to skin and eyes and weak sensitizing according a modified LLNA.

In a subacute toxicity the test item 14H-benz[4,5]isoquino[2,1-a]perimidin-14-one was applied daily per gavage for 4 consecutive weeks in doses of 0 (control), 100, 300 or 1000 mg/kg bw to male and female rats. Morbidity/mortality checks were performed at least twice daily. Clinical observations were performed daily. A full clinical examination was performed weekly. Individual body weights were recorded weekly. Food consumption was measured weekly for each cage of animals. Modified Irwin test (Neurological Function Assessment) was performed pretest and in week 4. Clinical laboratory determinations were performed in week 4.

All animals were killed at the end of the treatment period and necropsied. Selected organs were weighed. Organ/tissue samples were fixed and preserved at necropsy for all animals. Selected organs/tissues from group 1 (0 mg/kg bw/day) and 4 (1000 mg/kg bw/day) animals killed at the end of the treatment period were examined histopathologically.

No test item-related in vivo effects and no test item-related histopathological changes were observed.

Based on the results of this study, the dose level of 1000 mg/kg bw/day (highest applied dose) was considered as a No Observed Adverse Effect Level (NOAEL).

The toxicity of the test item 14H-benz[4,5]isoquino[2,1-a]perimidin-14-one (CAS-No. 6829-22-7) on reproduction and/or development of the male and female rat was investigated in a reproduction/ developmental toxicity screening test according to OECD guideline 421.

Three groups of 10 male and 10 female Wistar Han rats were given the test item, Macrolex Rot E2G, by daily oral (gavage) administration at dose levels of 100, 300 and 1000 mg/kg/day from 14 days before mating then for up to 4 weeks for males and throughout mating, gestation and through day 3 of lactation for females. A control group of 10 male and 10 female rats received a similar volume (l0 mL/kg) of the vehicle [1 % (w/v) Carboxymethylcellulose], Clinical condition, body weight and food consumption of the animals were monitored throughout the study. After two weeks of treatment, one male and one female of the same group were paired for a maximum of 14 days. The females were retained throughout gestation, allowed to litter and rear their young through to postnatal day (PND) 4 and then necropsied. Vaginal smears were taken daily for each female from the first day of pairing to verify positive copulation. Litter parameters, including the number of pups born, pup survival, sex and pup weights were recorded up to PND 4.

The dams with their pups were necropsied on day 4 of lactation, where applicable. All animals, including PND 4 pups, were submitted to a macroscopic examination. The numbers of uterine implantations were determined and the ovaries were weighed for each female. The males were necropsied after completion of the mating period and the testes and epididymides were weighed.

Selected tissue samples were fixed and preserved from all animals. Selected organs/tissues from group 1 and 4 animals were examined histopathologically.

There were no unscheduled deaths or systemic clinical signs associated with the test item.

There was no effect of the test item on mean body weight change or food consumption for either sex throughout the study.

There was no adverse effect of the test item on mating performance or fertility. The mean duration of gestation was normal (approximately 22 days) in all groups. There was no influence of treatment with the test item on pre- or postnatal pup survival of either sex.

Mean pup weight at birth and postnatal day 4 was comparable with that in the experimental control.

No organ weight, macroscopic or microscopic changes were noted to suggest a toxicological effect of Macrolex Rot E2G on the ovaries, testes and epididymides of treated animals.

Taken together, there were no adverse effects of 14H-benz[4,5]isoquino[2,1-a]perimidin-14-one on the reproduction and/or development of the male and female rat up to the limit dose of 1000 mg/kg/day inclusive.

Overall, based on the physicochemical date, very low water solubility and high octanol-water partition coefficient and based on the acute and subacute toxicological studies, limited absorption and a low bioaccumulation potential can be expected of 14H-benz[4,5]isoquino[2,1-a]perimidin-14-one .