Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restriction;

Data source

Reference
Reference Type:
publication
Title:
Acute, Subacute and Subchronic Inhalation Toxicity of Cyclopentene
Author:
Kimmerle G., Thyssen J.
Year:
1975
Bibliographic source:
Int. Arch. Arbeitsmed. 34, 177-184

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
4 groups of rats (10/sex/dose) were exposed to cyclopentene for 12 weeks.
Laboratroy examinations of blood and urine were carried out. At the end of the exposure period all animals were sacrificed and the internal organs were macroscopically and histologically examined.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Cyclopentene
EC Number:
205-532-9
EC Name:
Cyclopentene
Cas Number:
142-29-0
Molecular formula:
C5H8
IUPAC Name:
cyclopentene
Details on test material:
Analytical purity: 99.8 % (technical)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Weight at study initiation: 140-150 g
- Housing: housed in groups of 5 in cages
- Diet (e.g. ad libitum): ad libitum (Altromin standard diet)
- Water (e.g. ad libitum): ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 2°C
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
not specified
Remarks:
presumably whole body application
Duration of treatment / exposure:
12 weeks
Frequency of treatment:
6 hours/day for 5 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 0.3, 0.9, 3.2 mg/l (vapour)
Basis:

No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
Post-exposure period: no

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
HAEMATOLOGY: Yes
- Time schedule for collection of blood: one day before the end of the inhaltation test
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: one day before the end of the inhalation test
- How many animals: all
- Parameters checked: SGPT, SGOT, AP, bilirubin, urea, creatinine, glucose
URINALYSIS: Yes
- Time schedule for collection of urine: one day before the end of the inhalation test





Sacrifice and pathology:
GROSS PATHOLOGY: Yes
heart, lungs, liver, spleen, kidneys, adrenals, thyroid, thymus and gonads
HISTOPATHOLOGY: Yes
heart, lungs, liver, spleen, kidneys, adrenals, thyroid, thymus and gonads ,prostata, lymph nodes, brain, eyes aorta, thigh-muscle and sternal bone

Results and discussion

Results of examinations

Details on results:
CLINICAL SIGNS AND MORTALITY
no noticeable changes in appearance and behaviour.

BODY WEIGHT AND WEIGHT GAIN
no noticeable changes in body weight
(Body weight gain (in g) at 12 weeks: males - 106 (0.3 mg/ml), 93 (0.9 mg/ml), 93 (3.2 mg/ml) vs. 97 in the control group; females - 26 (0.3 mg/ml), 27 (0.9 mg/ml), 23 (3.2 mg/ml) vs. 25 in the control group)

HAEMATOLOGY/CLINICAL CHEMISTRY
The haematological values and serum-enzyme activities (SGOT, SGPT, P .P) as well as the serum concentrations of urea, creatinine ,
bilirubin and glucose were within the physiological range and

URINANALYSIS
There was no significant change in the composition of the urine .

ORGAN WEIGHTS
None of the organ weights showed statistically significant differences among groups

GROSS PATHOLOGY / HISTOPATHOLOGY: NON-NEOPLASTIC
No histopathological changes were seen which could be attributed to the inhalation of cyclopentene .

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
> 3.2 other: mg/l
Sex:
male/female
Dose descriptor:
LOAEL
Effect level:
> 3.2 other: mg/l
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Results of haemotological examinations

 concentrationmg/l  haemoglobing/100ml  RBC10^6/mm³  Thrombocytes 10^3/mm³ PVC %   Leucocytes              
           Total 10^3/mm³  Neutro-phils % Baso-phils%   Eosino-phils%  Lympho-cytes% Mono-cytes% 
 Males                    
 0  14.6 8.43  995  49  7.6  17   0
 0.3  14.4 8.45  1016  48  8.2  14  84 
 0.9  14.9 8.30  1003  50  5.8  18  81 
 3.2 14.4  34  980  48  79  16  83 
                     
 Females                    
 0  14.0 7.78  1063  60  5.5  17  82 
 0.3 14.3  7.93  1095  61  5.1  16  82 
 0.9  14.1 8.02  1066  58  5.8  15  83 
 3.2 15.0  8.51  1118  58  6.1  19  80 
                     

means of groups of 10 rats

Results of clinical chemistry examinations

 concentrationmg/l SGOT mU/ml  SGPTmU/ml  APmU/ml  Ureamg/100ml Creatinine mg/100 ml Glucose mg/100 ml  Bilirubin    mg/100 ml     
 Males                    
 0  30.7 18.1  22.6  55.0  0.88  86.5  0.18       
 0.3  33.6 21.1  239  56.1  0.95  86.6  0.10       
 0.9  28.5 17.0  212  58.1  0.85  85.0  0.10       
 3.2  28.1 18.5  218  51.5  0.90  89.6  0.14       
                     
 Females                    
 0  33.8 15.8  156  51.9  0.92  87.1  0.15       
 0.3  33.6 15.5  146  52.1  0.93  88.2  0.12       
 0.9  33.0 15.9  149  48.2 0.94  85.2  0.16       
 3.2  33.7 15.6  153   48.9 0.90  89.2  0.17       
                     
                     

means of groups of 10 rats

Absolute and relative organ weights

 Sex andconcentration (mg/l) Organ                            weights   Terminal body weight
   Thyroid Thymus  Heart  Lung  Liver   Spleen Kidneys  Adrenals  Gonads     
 Absolut organ weight (mg)                      
 Males                      
 0  10.1 140   718  1027  7565  393  1733  30.0  2886    252
 0.3  10.2  151  723  1051  8097  388  1810  29.6  2821    261
 0.9  10.7  145  705  1046  7128  386  1659  27.8  2986    213
 3.2  10.7  155  721  1026  7630  382  1794  30.1  2869    244
                       
 Females                      
 0  9.0  133  518  847  4974  292  1407  37.7  42.9    167
 0.3  9.1  150  535  881 4907   305  1418  35.8  44.5    168
 0.9  9.3  151  542  831  5105  290  1407  36.3  42.9    169
 3.2  9.4  142  515  851  4886  291  1386  36.4  41.0    701
                       
 Relative organ weight (mg/100 g bw)                      
 Males                      
 0  4.0  55  285  409  3003  157  689  11.9  1167    
 0.3  3.9  58  278  403  3095  149  693  11.3  1061    
 0.9  4.3  58  284  423  2970 155   666  11.2  1205    
 3.2  4.3  63  296  422  3121  157  717  12.3  1181    
                       
 Females                      
 0  5.4  80  310  488  2970 175   857  22.6  25.7    
 0.3  5.4  89  319  527  2925  182  841  21.3  26.5    
 0.9  5.5  89  321  493  3027  172  835  21.5  25.4    
 3.2  5.5  88  320  530  2981  180  832  22.7  25.8    

Applicant's summary and conclusion