Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
June to July 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well documented study according to OECD test guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Version / remarks:
adopted May 1983
Deviations:
no
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): NATRIUM-CUMOLSULFONAT (40%-ig in Wasser)- Substance type: 40% aqueous solution of pure active substance- Physical state: clear liquid- Lot/batch No.: 3630/81312- Expiration date of the lot/batch: March 1992- Storage condition of test material: ambient temperature

Test animals

Species:
mouse
Strain:
other: BOR:NMRI (SPF)
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: water- Justification for choice of solvent/vehicle: no data- Concentration of test material in vehicle: 40 %- Amount of vehicle: 16.8 ml/kg bw
Frequency of treatment:
single oral application
Post exposure period:
24, 48 and 72 hours
Doses / concentrations
Remarks:
Doses / Concentrations:4467 mg/kg bwBasis:actual ingested
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle

Examinations

Tissues and cell types examined:
bone marrow; polychromatic erythrocytes (PCE), normochromatic erythrocytes (NCE)

Results and discussion

Test results
Key result
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid

Any other information on results incl. tables

The statistically significant increase in frequency of micronuclei is considered to be of no biological relevance for the following reasons:

- The frequency of micronuclei at this sampling time point (0.18%) is not above the frequency of micronuclei of controls generally observed in this test laboratory (0.07 - 0.22%). The statistical significance in this case is caused by the low frequency of micronuclei in the control group (0.02%) which deviates downwards from the so far observed frequencies for controls. After addition of male and female animals of sampling time point 72 h into one group there is no more a statistically significant difference.

- A delayed effect based on slow excretion is improbable for sodium cumenesulphonate as sulphonic acids in general are readily absorbed and do not show any tendency for accumulation. But this kind of detention is regarded as prerequisite to explain based on the kinetic of erythrocyte maturation an impact on micronuclei frequency at sampling time point of 72 hours.

The results of the positive control affirm the sensitivity of the mouse strain to mutagenic substances.The frequency of micronuclei in polychromatic erythrocytes was considerably increased compared to the control group.

Table 1: Results of in vivo micronucleus test for male animals (mean ± standard deviation)

      Neg. control   test substance 4467 mg/kg bw      Pos. control
  sampling time    24 h  48 h  72 h  24 h  48 h  72 h 24 h 
micronuclei in 1000 PCE  0.8  ± 0.8 1.8  ± 0.8   0.4 ± 0.5 0.6 ± 0.5    0.8  ± 0,8   0.2  ± 0.4 48.0* ± 19.6
 % PCE with micronuclei 0.08  0.18  0.04 0.06  0.08 0.02  4.8
PCE / NCE  1.0 ± 0.2 1.4 ± 0.3  1.6 ± 0.3  1.0 ± 0.3 1.1 ± 0.4   1.9 ± 0.9 0.8  ± 0.1

*p < 0.05

Table 2: Results of in vivo micronucleus test for female animal (mean ± standard deviation)

      Neg. control   test substance 4467 mg/kg bw      Pos. control
  sampling time    24 h  48 h  72 h  24 h  48 h  72 h 24 h 
micronuclei in 1000 PCE 1.4  ± 1.7 1.8  ± 1.1   0.2 ± 0.4 2.2 ± 1.1    1.2  ± 0,8   1.8*  ± 1.5 36.8* ± 9.8
 % PCE with micronuclei 0.14  0.18  0.02 0.22  0.12 0.18 3.6
PCE / NCE  1.2 ± 0.2 1.4 ± 0.2  2.4 ± 0.6  1.0 ± 0.2 1.3 ± 0.3   1.3 ± 0.5 1.0  ± 0.1

*p< 0.05

Table 3: Results of in vivo micronucleus test for male + female animals (mean ± standard deviation)

      Neg. control   test substance 4467 mg/kg bw      Pos. control
  sampling time    24 h  48 h  72 h  24 h  48 h  72 h 24 h 
micronuclei in 1000 PCE  1.1  ± 1.3 1.8  ± 0.9  0.3 ± 0.5 1.4 ± 1.2    1.0  ± 0.8   1.0  ± 1.3 42.4* ± 15.7
 % PCE with micronuclei 0.11  0.18  0.03 0.14  0.10 0.10  4.24
PCE / NCE  1.1 ± 0.2 1.4 ± 0.3  2.0 ± 0.6  1.0 ± 0.2 1.2 ± 0.4   1.6 ± 0.8 0.9  ± 0.1

* p < 0.05

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negativeAll male mice treated with the test substance showed no statistically significant increase in micronucleus frequency at any sampling time compared to control animals. For the female mice treated with the test substance at sampling times 24 and 48 hours after treatment also no statistically significant increase in micronucleus frequency was observed. Only at sampling time point 72 hours a statistically significant increase of polychromatic erythrocytes with micronuclei compared to control animals was observed. This effect was regarded as biologically not relevant as this increase ís based on the exceptional low micronucleus frequency of vehicle control group.Sodium cumenesulphonate under these test conditions is regarded as not mutagenic in the micronucleus test.