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Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
9.2. 2000 - 17.8.2000
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
other: Body responsible for the test
Title:
Unnamed
Year:
2000

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: B.7 subacute toxicity -28/90 day test - oral repetitive application. OECD NR.407
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of test material:Dusantox L - liquid viscous substance
Chemical name: N-1,3-dimethylbutyl-N'-phenyl-p-phenylenediamine, reaction products with 2-phenylpropene

Composition:
1. N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine
58,9 % area
CAS No.: 793-24-8
Molecular formula:C18H24N2
Molecular weight: 268,4
Smiles Code:N(c(ccc(Nc(cccc1)c1)c2)c2)C(CC(C)C)C

2.N-[4-(alpha,alpha'dimethylbenzyl)phenyl]-N'-(1,3-
dimethylbutyl)-p-phenylenediamine (i.e. p-cumyl-6PPD)
41,0 % area
CAS No.: 194478-84-7
Molecular formula:C27H34N2
Molecular weight: 386,6
Smiles Code:CC(C)CC(C)(Nc1ccc(Nc2ccc(C(C)(C)c3ccccc3)cc2)cc1)


3. Impurities
alpha-methylstyrene 0,1 % area
CAS No.: 98-83-9


Test batch: No.: 7/99

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: TOP VELAZ, s.r.o. závod Koleč CZ
- Age at study initiation: 6 weeks
- Weight at study initiation: males: 193-195 g, females: 175-176g
- Housing: 2 rats in one cage
- Diet (e.g. ad libitum): standard food, ad libidum
- Water (e.g. ad libitum): ad libidum
- Acclimation period:6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
Method of administration:
gavage
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
Test duration: 28 days
Frequency of treatment:
Dosing regime: 7 days/week- 28 days
No. of animals per sex per dose:
Male: 6 animals at 40 mg/kg bw/day
Male: 6 animals at 80 mg/kg bw/day
Male: 6 animals at 120 mg/kg bw/day
Female: 6 animals at 40 mg/kg bw/day
Female: 6 animals at 80 mg/kg bw/day
Female: 6 animals at 120 mg/kg bw/day

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Food efficiency:
effects observed, treatment-related
Water consumption and compound intake (if drinking water study):
effects observed, treatment-related
Ophthalmological findings:
effects observed, treatment-related
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
no effects observed
Behaviour (functional findings):
effects observed, treatment-related
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
effects observed, treatment-related
Details on results:
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.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
ca. 40 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.
Dose descriptor:
NOEL
Effect level:
<= 40 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Classified as: Not classified