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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
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
Study period:
26 November 1991 to 11 February 1332
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP. Read-across to the registered substance is considered scientifically justified.

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)
Deviations:
yes
Remarks:
only 1000 PCE per animal were scored for micronuclei
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Manston Road, Kent

- Age at study initiation: 5-7 weeks

- Weight at study initiation: 27-30 g (males) 18-23 g (females)

- Assigned to test groups randomly: yes

- Fasting period before study: no information

- Housing: individually in polypropylene/stainless steel cages

- Diet: ad libitum

- Water: ad libitum

- Acclimation period: at least 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19

- Humidity (%): 38

- Air changes (per hr): no information

- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: corn oil

- Justification for choice of solvent/vehicle: none given; standard vehicle

- Concentration of test material in vehicle: sufficient to give required dose in appropriate volume of vehicle
- Amount of vehicle (if gavage or dermal): 10 mg/ml/day
Duration of treatment / exposure:
Animals were dosed on three consecutive days.
Frequency of treatment:
daily
Post exposure period:
96 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
500, 1000, 2000 mg/kg bw/day
Basis:
nominal conc.
No. of animals per sex per dose:
5 (positive control, low and mid dose) or 10 (vehicle control, high dose)
Control animals:
yes, concurrent vehicle
Positive control(s):
- Positive control substance: cyclophosphamide

- Justification for choice of positive control(s): none given - standard positive control

- Route of administration: no information

- Doses / concentrations: 40 mg/ kg bw

Examinations

Tissues and cell types examined:
Bone marrow
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: no deaths occurred in preliminary toxicity assay

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): Animals dosed at 0, 24 and 48 hours; samples taken at 72 and 96 hours

DETAILS OF SLIDE PREPARATION: Air dried slides were fixed in methanol then stained with 1% May-Grunwald for 5 minutes then counterstained in 15% Giesma for 15 minutes

METHOD OF ANALYSIS: 1000 PCE scored for micronuclei; PCE/NCE ratio was determined for 300 cells, using x 1000 oil immersion objective


Evaluation criteria:
An increase in micronucleus frequency of greater than 0.28%.
Statistics:
No statistical evaluation described.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid

Any other information on results incl. tables

Table 1 Results of in vivo micronucleus study

 

Treatment

mg/kg.bw /day

 

Time of dosing (h)

 

Time of sampling (h)

 

 

Sex

 

No. of surviving dosed mice

Erythrocytes

Polychromatic cells (PCE)

 

Mean PCE/NCE

 

 

PCE Analysed

No. of MN-PCE

% MN-PCE

Negative control

0+24+48

72

M/F

10

10000

14

0.14

0.93

96

M/F

10

10000

10

0.10

1.02

Positive control

0+24+48

72

M/F

10

10000

150*

1.50

0.46

500

0+24+48

72

M/F

10

10000

9

0.09

1.00

1000

0+24+48

72

M/F

10

10000

9

0.09

0.94

2000

0+24+48

72

M/F

10

10000

8

0.08

0.86

96

M/F

10

10000

24

0.24

0.90

PCE = Polychromatic erythrocytes                                                           

MN-PCE = Micronucleated PCE

MN-PCE = Micronucleated NCE

* = Positive response in PCE

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Fatty alcohol blend has been tested according to OECD 474 and under GLP. Male and female mice were dosed with 500, 1000 and 2000 mg/kg bw. No increase in the number of micronucleated PCE was observed (1000 PCE scored per animal). It is concluded that the test substance is negative for the induction of micronuclei under the conditions of the test. No toxicity to bone marrow or general toxicity was observed.