IPDA-BADGE-BUMGE

Endpoint summary

Description of key information

An OECD 414 oral rat toxicity study was performed according to GLP. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

10 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

OECD 414 Study conducted

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

In the 28 -day oral repeated dose toxicity, changes were noted in body weight gain, haematology and clinical biochemistry and microscopic findings in the liver 4,4’-Isopropylidenediphenol, oligomeric reaction products with 1 - chloro-2,3-epoxypropane, reaction products with butan-1-ol and 3-aminomethyl-3,5,5 - trimethylcyclohexylamine is considered to induce toxicological changes at 500 and 1000 mg/kg.

Based on the effects observed as effects on liver were also observed in the control group, the No Observed Adverse Effect Level (NOAEL) was considered to be 500 mg/kg/day.

Increased salivation and noisy respiration were evident in animals of both sexes treated with 200 mg/ kg bw/day and to a lesser extent in animals of both sexes treated with 100 mg/kg bw/day during the treatment period. Incidences of a stained snout, labored respiration, decreased respiratory rate, hunched posture and fur loss were also evident in some females treated with 200 mg/kg bw/day, a stained snout and sneezing was also evident in some surviving males treated with 200 mg/kg bw/day and a decreased respiratory rate and hunched posture was also evident in one male treated with 100 mg/kg bw/day. Noisy respiration remained evident in one male and one female that were previously given 200 mg/kg bw/ day during the treatment-free period. The male treated with 200 mg/kg bw/day that was found dead on Day 48 had previously only shown increased salivation and noisy respiration and at necropsy, a dark

liver and dark lungs were evident. Microscopically, moderate prostatic inflammation, unilateral lymphoid aggregates and urothelial hyperplasia in the kidneys and adrenal cortical hypertrophy were evident and although the adrenal change was most likely to indicate stress and be secondary to the prostatic inflammation, the actual cause of death in this animal was undetermined.

Males treated with 200 and 100 mg/kg bw/day showed a reduction in body weight gain and food consumption throughout the treatment period and reductions in food conversion efficiency were also evident, which generally followed the fluctuations in body weight gain. Following the twenty-eight day treatment-free period, males that were previously given 200 mg/kg bw/day showed significant recovery in both body weight gain and food consumption. Females treated with 200 mg/kg bw/day showed a slight reduction in body weight gain during the first week of treatment, however, recovery was evident thereafter.

Hematological investigations at the end of the treatment period revealed increased neutrophil count in both sexes treated with 200 and 100 mg/kg bw/day and increased total leukocyte count in males treated with 200 mg/kg bw/day. The increase in neutrophil count persisted in females previously given 200 mg/kg bw/day after the treatment-free period. These findings were most likely associated with the microscopic mesenteric lymph node changes identified at 200 and 100 mg/kg bw/day. Histiocytosis with granulomas was evident in animals of both sexes from all treatment groups, varying from minimal to moderate in severity and following a dose-dependent response. At 200 and 100 mg/kg bw/day the more severe grades of histiocytosis were often accompanied by minimal abscesses. Histiocytosis in the mesenteric lymph nodes is likely to represent accumulation of material, indicating delayed clearance of an exogenous or endogenous material. At the higher grades, abscesses comprised of degenerating histiocytes with small numbers of inflammatory cells. Following the twenty-eight day recovery period, histiocytosis with granulomas and abscesses were evident in both sexes previously treated with 200 mg/kg bw/day, however, when compared with non‑recovery animals, the incidence of abscesses was lower, whereas histiocytosis persisted at much the same incidence and severity.

At the end of the dosing phase, blood chemistry investigations in treated animals identified statistically significant changes in some parameters that may indicate minor perturbations in hepatic metabolism.

in treated animals. However in the absence of any associated microscopic hepatic changes these intergroup differences were considered not to represent an adverse effect of treatment. Any other minor intergroup differences resulting from blood chemistry, hematological or organ weight investigations were also considered to be of no toxicological importance.

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: cecum; digestive: liver; digestive: stomach

Justification for classification or non-classification

Based on the above assessment on oral repeated dose toxicity, 4,4’-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with butan-1-ol and 3-aminomethyl-3,5,5-trimethylcyclohexylamine does not need to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and accordingCLP (Regulation (EC) No 1272/2008 Of The European Parliament And Of The Council) as implementation of UN-GHS in the EU.