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Description of key information

The NOAEL was established on the basis of reduced weight gain in femal rats during a subchronic repeadted dose study. No observation of any specific mode of action was made.

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004 - 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
.
Qualifier:
according to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
GLP compliance:
yes
Limit test:
no
Specific details on test material used for the study:
Scansmoke R909 Raw pyroligneous acid (Acids 9-12 % , carbonyls 6.2 - 7.1 %, phenols 7.1 %)
Batch no.: 03/2004
Species:
rat
Strain:
Wistar
Remarks:
CRL:(WI)BR
Sex:
male/female
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Remarks:
Test article was admixed with diet.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Samples of each dose level were analyzed for exact concentrations and homogeneity of test item in the pelleted diet.
Duration of treatment / exposure:
up to 90 days
Frequency of treatment:
daily with the diet
Dose / conc.:
0 ppm
Dose / conc.:
5 000 ppm
Remarks:
Corresponding to 5000 mg/kg diet or 5 g/kg diet, and to 1253 mg/kg bw/day in male rats and 498 mg/kg bw/day in female rats
Dose / conc.:
12 000 ppm
Remarks:
Corresponding to 12000 mg/kg diet or 12 g/kg diet female rats corresponding to 1129 mg/kg bw/day
Dose / conc.:
20 000 ppm
Remarks:
Corresponding to 20000 mg/kg diet or 20 g/kg diet, in male rats corresponding to 1253 mg/kg bw/day
No. of animals per sex per dose:
10
Control animals:
yes, concurrent no treatment
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes, all animals were observed for general appearance, behaviour, signs of toxicity and mortality.
- Time schedule: Once daily

DETAILED CLINICAL OBSERVATIONS: Yes, neurobehavioural examination, see below
- Time schedule: Before the first treatment, then on week 13 outside the home cage

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly

FOOD CONSUMPTION AND COMPOUND INTAKE:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes, body weight and food consumption were measured weekly.

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / Not specified

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes / No / Not specified
- Time schedule for examinations:

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Before treatment and and on week 12
- Dose groups that were examined: Conducted on all animals before treatment and in the control and high dose groups on week 12

HAEMATOLOGY: Yes, performed on all animals
- Time schedule for collection of blood: At termination of study
- Anaesthetic used for blood collection: Yes (identity) / No / Not specified
- Animals fasted: Yes / No / Not specified
- How many animals:
- Parameters checked in table [No.?] were examined.

CLINICAL CHEMISTRY: Yes, performed on all animals
- Time schedule for collection of blood: At termination of study
- Animals fasted: Yes / No / Not specified
- How many animals:
- Parameters checked in table [No.?] were examined.

URINALYSIS: Yes, performed on all animals
- Time schedule for collection of urine: At termination of study
- Metabolism cages used for collection of urine: Yes / No / Not specified
- Animals fasted: Yes / No / Not specified
- Parameters checked in table [No.?] were examined.

NEUROBEHAVIOURAL EXAMINATION: Yes, functional observation battery (modified Irwin test)
- Time schedule for examinations: Before the first treatment, then on week 13 outside the home cage
- Dose groups that were examined:
- Battery of functions tested: sensory activity / grip strength / motor activity / reactivity to stimuli of different types

IMMUNOLOGY: No

OTHER: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
Gross pathological examination was performed on all animals at study termination. Organ weights were taken and tissues were preserved for histopathological examination. Histopathological examination of tissues/organs was performed on tissues/organs collected from all animals in high dose group and control animals.

HISTOPATHOLOGY: Yes
Histological examination was foreseen on organs showing abnormalities in the low and middle dose groups as well.
Statistics:
One-way analysis of variance on homogenous data. If positive results, significance of the inter-group differences was tested with Duncan's Multiple Range test. Where significant heterogeneity was found, Kolmogorov-Smirnov test was used on normal distribution data. In the case of not-normal distribution the non-parametric method of Kruskal-Wallis one-way analysis of variance was applied. If positive results were found, the inter-group comparisons were performed using Mann-Whitney U-test.
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
The summarised body weight gain was below the control in all dosed female groups: -17%, -10% and -26%, respectively. In the absence of clear dose dependency, the alteration was considered toxicologically relevant in the 20000 ppm group.
Food consumption and compound intake (if feeding study):
effects observed, non-treatment-related
Description (incidence and severity):
The daily mean food consumption was similar in the male and female experimental groups. However, if the food consumption of the female dosed animals is compared with the female control, it is apparent that food consumption does not increase over time in the same manner as in the control group. In the female highest dose group food consumption in g/animal/day is about the same in the last weeks of the study as it was in the beginning.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
no effects observed
Description (incidence and severity):
No eye alterations were found.
Haematological findings:
no effects observed
Description (incidence and severity):
Haematological parameters changed within the historical control ranges specific for this species and strain without clear dose dependency and these were not considered to be of toxicological relevance.
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
Clinical chemistry parameters changed within the historical control ranges specific for this species and strain without clear dose dependency and these were not considered to be of toxicological relevance.
Urinalysis findings:
no effects observed
Description (incidence and severity):
Clinical chemistry parameters changed within the historical control ranges specific for this species and strain without clear dose dependency and these were not considered to be of toxicological relevance.
Behaviour (functional findings):
no effects observed
Description (incidence and severity):
No difference was found between the experimental groups in the sensory reactivity to stimuli of different types, grip strength and motor activity.
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
Description (incidence and severity):
Test item related alterations were not found in the weighed organs. The alterations were without any toxicological relevance since they were within the historical control ranges and occurred independently from dose administered.
Gross pathological findings:
effects observed, non-treatment-related
Description (incidence and severity):
Macroscopic alterations of organs were related to the sacrificing procedure (emphysema and pinprick-sized haemorrhages in the lungs) or were common findings in experimental rats (hydrometra in uterus and bi lateral pyelectasia).
Neuropathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
Test item related histopathological alterations were not detected in the organs subjected to microscopic examination.
Histopathological findings: neoplastic:
no effects observed
Description (incidence and severity):
Test item related histopathological alterations were not detected in the organs subjected to microscopic examination.
Other effects:
not examined
Details on results:
No mortality occurred during the study. General physical condition and behavior of animals were normal in all experimental groups. No difference was found between the experimental groups in the sensory reactivity to stimuli of different types, grip strength and motor activity. The summarised body weight gain was below the control in all dosed female groups: -17 %, -10 % and -26 %, respectively. In the absence of clear dose dependency, the alteration was considered toxicologically relevant in the 20000 ppm group. The daily mean food consumption was similar in the male and female experimental groups. However, if the food consumption of the female dosed animals is compared with the female control, it is apparent that food consumption does not increase over time in the same manner as in the control group. In the female highest dose group food consumption in g/animal/day is about the same in the last weeks of the study as it was in the beginning.
Hematological, clinical chemistry and urine parameters changed within the historical control ranges specific for this species and strain without clear dose dependency and these were not considered to be of toxicological relevance. No eye alterations were found after the 90-day oral administration of Scansmoke R 909. Test item related alterations were not found in the weighed organs. The alterations were without any toxicological relevance since they were within the historical control ranges and occurred independently from dose administered. Macroscopic alterations of organs were related to the sacrificing procedure (emphysema and pinprick-sized haemorrhages in the lungs) or were common findings in experimental rats (hydrometra in uterus and bi lateral pyelectasia). Test item related histopathological alterations were not detected in the organs subjected to microscopic examination.
Key result
Dose descriptor:
NOAEL
Effect level:
1 129 mg/kg bw/day (nominal)
Based on:
test mat.
Remarks:
calculated from 12000 ppm ( = mg/kg diet)
Sex:
female
Basis for effect level:
body weight and weight gain
Dose descriptor:
NOAEL
Effect level:
>= 20 000 ppm
Based on:
test mat.
Sex:
male
Remarks on result:
not determinable due to absence of adverse toxic effects
Dose descriptor:
NOEL
Effect level:
< 500 ppm
Based on:
test mat.
Sex:
female
Basis for effect level:
body weight and weight gain
Remarks on result:
not determinable
Remarks:
Below the control in all dosed female groups
Dose descriptor:
NOEL
Effect level:
>= 20 000 ppm
Based on:
test mat.
Sex:
male
Basis for effect level:
other: No detectable difference to the control animals in all evaluations made.
Remarks on result:
not determinable
Key result
Critical effects observed:
no
Executive summary:

This repeated dose 90-day oral study in rats of the sub-chronic toxicity of Scansmoke R909 fo llowing dietary administration was conducted according to GLP and to OECD guidelines, and is thus acceptable to cover this end-point.

A moderate body weight depression was observed in female rats at all dose levels. However, taking into account the lack of a clear dose response relationship and the lack of alterations in the males, the body weight depression was considered by the laboratory to be of toxicological relevance at the 20000 ppm level.

The no observed effect level (NOEL) was 20000 ppm in male rats and lower than 5000 ppm in the females. It corresponds to 1253 mg/kg bw/day in male rats and 498 mg/kg bw/day in female rats. The no observed adverse effect level (NOAEL) was 20000 ppm in male rats and 12000 ppm in female rats, corresponding to 1253 mg/kg bw/day and 1129 mg/kg bw/day, respectively.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
1 129 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Sole study available for this endpoint

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

Justification for classification or non-classification