mixture of two components: 1. N-(1,3- dimethylbutyl)-N´- phenyl-p-phenylenediamine 2. N1-(1,3-dimethylbutyl)- N4-(4-(1-methyl-1- phenylethyl)phenyl)ben zene-1,4-diamine

Endpoint summary

Description of key information

In a GLP and OECD 407 6 males and 6 females rats Wistar were exposed to Dusantox L by gavage in three doses ( 40 -80 -120 mg/kg bw) during 28 days (7days/week).
The oral administration of Dusantox L to rats by gavage for period of 90 days consecutive days at the dose levels 10,30,60mg/kg/day did not cause any mortality. The study was carried out by GLP and OECD 408.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

LOAEL

10 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

In a GLP and OECD 407 6 males and 6 females rats Wistar were exposed to Dusantox L by gavage in three doses ( 40 -80 -120 mg/kg bw) during 28 days (7days/week). The control a two satelite groups were observed for futher 14 days after termination of exposure.Data of mortality, body weight, organ weight, haematology, clinical chemistry and urinalyses are available.

Clinical observations: At the assessment of the clinical symptoms the range and the frequency of the findings were the greatest in the highest dose level for the both sexes. These findings were assessed as the reactions to the present substance. There were the next findings: dirty fell in the area of the nostrils, diarea, lethargy, apathy, breathing defect and denutrition. On the 27th day after application one animal-male died because of stomach inflammation.

Laboratory findings: The hematologic examination was carried out by the laboratory examinations. The differences in the highest dose were found out. At the urine examinations no great different values were found out. The biometry of apparatuses was also carried out.

No great differences of the absolute weights were found out.

Effects in organs: At the assessment of the weight of the particular body apparatuses the mild loss of the weight at the heighest doses was registered for both sexes. Reduced absolute weight of other apparatuses - heart, spleen and thymus at the males and heart at the females - was only related to the reduction of the total animal weight at the highest dose.

At the application of the dose of 120mg/kg the toxic effects of the substance were registered but these were stopped after finishing the dosing. The dose of 40mg/kg can be considered as the dose without harmful effects - NOAEL in
regard to odd findings.

The oral administration of Dusantox L to rats by gavage for period of 90 days consecutive days at the dose levels 10,30,60mg/kg/day did not cause any mortality. The study was carried out by GLP and OECD 408.

Administration of the test substance Dusantox L had negative effect especially on growth, clinical status, red and white bloodliver andcomponent, haemocoagulation, metabolism of ions of animals, affected the structure and function of irritatedstomach. Reversible changes of growth(lower body weight) and clinical status (symptoms of stress, irritation and decreased activity), partly irreversible changes of haematological parameters (decreased value of red blood component and PT, increased white cells count), reversible changes of biochemical parameters (hypercholesterolaemia, hypoglycaemia, increased activity of ALP, changed value of phosphorzs, sodium, potassium and chloride ions), reversible macroscopic findings (mucosal haemorrhages in stomach and light colour of liver) and partly irreversible histological affections in liver (vacuolar dystrophy) and reversible histological affections in stomach mucosa (erosions) and spleen (pigmentation) were observed in treated animals. High incidence of biologically and/or statistically significant differences was recorded at the middle and especially at the highest dose level. But also at the lowest dose level some serious and statistically significant changes were recorded (especially in the values of red blood component, haemocoagulation, and in biometry and structure of liver). Some sex differences in the reaction of animals to the treatment by the test substance have been detected - more marked differences in growth, blood parameters and microscopic structure of liver were determined in females.

The value of LOAEL for Males and Females was established as 10 mg/kg/day.

The value of NOAEL for males and Females is less than 10 mg/kg/day.

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

Justification for classification or non-classification

Based on the findings of the above mentioned GLP and OECD guideline studies the test substance Dusantox L is meet the criteria for classification both according to Directive 67/548/EEC (DSD) as harmful, R48 and according to regulation 1272/2008/EC (GHS, CLP) classification for specific targe organ toxicity category 1, H 372.