Registration Dossier

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is reliable with restrictions because it is an acceptable and well-documented study report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
GLP compliance:
yes
Type of assay:
chromosome aberration assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: low viscosity hydrocarbon liquid
Details on test material:
Light catalytically cracked distillate
Sample API 83-07
EC number 265-060-4
EC name Distillates (petroleum), light catalytic cracked

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
intraperitoneal
Duration of treatment / exposure:
Single dose
Doses / concentrations
Remarks:
Doses / Concentrations:
0.2, 0.67 and 2.0 g/kg
Basis:

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes

Any other information on results incl. tables

Immediately after dosing all animals in the 2 g/kg group were lethargic.   

There were some mortalities in the high dose group and where possible  they 

were replaced.  Throughout the study lethargy was observed in the  high dose 

group animals but no toxic signs were seen in any of the other  dose groups.
A summary of the chromosomal results is given in the following table.

Group         Time      Frequency        % cells                Mitotic
                        of                1+        2+        index
                        aberrations        aberrations
                                         Str*        Num**                
Male        
-ve control
               6         0         .024          0        0        4.1
               24        .004         .016         .4        0        2.8
               48        .01         .02           1        0        3.5
+ve control (TEM @1.0 mg/kg)
               24        >1.17         .1           29        18.8     1.3
Test material                                                
0.2            6         .015           .005         1.5       0        2.8
               24        0              .016         0         0        4.3
               48        0              .02          0         0        3.6

0.67           6         0              .04          0         0        5.9
               24        >.02           .03          2         .4       4.1
               48        0              .01          0         0        4.5

2.0            6         0              .028         0         0        3.8
               24        .01            .01          1         0        4.7
               48        0              .02          0         0        3.6

Female
-ve control
               6         .01         .01          1         0        4.2
               24        .012         .024         1.2       0        2.6
               48        0         .036         0         0        4.2
+ve control (TEM @1.0 mg/kg)
               24        >4.199         0            59.9      54.5     .2
Test material

0.2            6         0         .012         0         0        3.1
               24        .004         .04         .4         0        3.3
               48        .004         .012        .4         0        2.9
        
0.67           6         >.016         .044        1.6        .4       4.6
               24        0         .008        0         0        3.6
               48        0         .016        0         0        5.5

2.0            6        0         .032        0         0        4.1
               24        0         .016        0         0        4.9
               48        0         .01         0         0        6.2

For simplicity only standard error values have not been shown in the  above 

table.

The authors make the following interpretation of the results
The test material did not induce a significant increase in the percentage  of 

aberrant cells above the controls for either sex at any of the doses  or kill 

times.  No apparent test article effects on the mitotic index  were noted in 

any of the dose groups.  The positive control (TEM) induced  significant 

increases in the percentage of cells with structural  chromosomal aberrations 

in the male animals (29%).  The positive control  also produced a very high

percentage of cells with structural chromosomal  aberrations in the female 

dose group (59.9%).  However, the data from the  female positive control group 

could not be statistically analyzed since  only 32 metaphase cells could be 

analyzed.  The lack of analyzable  metaphase cells can be attributed to bone 

marrow toxicity induced by the TEM.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
The test material did not induce a significant increase in the percentage of aberrant cells above the controls for either sex at any of the doses or kill times. 
Executive summary:

The authors make the following interpretation of the results
The test material did not induce a significant increase in the percentage
 of aberrant cells above the controls for either sex at any of the doses or kill times. No apparent test article effects on the mitotic index were noted in any of the dose groups. The positive control (TEM) induced significant increases in the percentage of cells with structural chromosomal aberrations in the male animals (29%). The positive control also produced a very high percentage of cells with structural chromosomal aberrations in the female dose group (59.9%). However, the data from the female positive control group could not be statistically analyzed since only 32 metaphase cells could be analyzed. The lack of analyzable metaphase cells can be attributed to bone marrow toxicity induced by the TEM.