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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:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well conducted study according to OECD guideline 474.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2003

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
GLP compliance:
not specified
Remarks:
although performed in a GLP-accredited lab.
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
3-chloropropane-1,2-diol
EC Number:
202-492-4
EC Name:
3-chloropropane-1,2-diol
Cas Number:
96-24-2
Molecular formula:
C3H7ClO2
IUPAC Name:
3-chloropropane-1,2-diol
Details on test material:
- Name of test material (as cited in study report): 3-monochloropropan-1,2-diol (3-MCPD is used as abbreviation)
- Analytical purity: 98.5%
- Source: Sigma-Aldrich Chemical Co., Gillingham, UK
- Storage: Stored at room temperature in the dark

Test animals

Species:
rat
Strain:
other: outbred Crl:Han Wist (Glx:BRL) BR
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Ltd., Margate, UK or Harlan (UK) Ltd (Bicester, UK).
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: 190-239g
- Housing: Solid floored polypropylene cages (45x28x20 cm) with wood shavings for bedding
- Diet: special quality control (SQC) rat mouse maintenance diet (RM1 (E) SQC, Special Diet Services Limited, Witham, UK), ad libitum.
- Water: no data
- Acclimation period: 6 days
- Other: Males only were used as no substantial difference in toxicity was apparent between males and females. All procedures carried out as part of this study were subject to the provisions of the UK Animals (Scientific procedures) Act, 1986.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
-Vehicle: Water
Details on exposure:
The test item was diluted in purified water prior to dosing.
Duration of treatment / exposure:
2 days
Frequency of treatment:
daily
Post exposure period:
not applicable
Doses / concentrations
Remarks:
Doses / Concentrations:
15, 30, 60 mg/kg/day
Basis:
nominal conc.
No. of animals per sex per dose:
6 per dose
Control animals:
yes, concurrent vehicle
Positive control(s):
-Postive control: cyclophosphamide (CPA)
- Justification for choice of positive control(s): As described in guideline
- Route of administration: Oral gavage
- Doses / concentrations: Single exposure to 40 mg/kg on the second day of dosing
- Source: Aldrich Chemical Co., Gillingham, UK

Examinations

Tissues and cell types examined:
Bone marrow smears were fixed and ploychromatic erythrocytes scored
Details of tissue and slide preparation:
Bone marrow was sampled 24 hours post treatment. Bone smears were fixed in methanol and stained for 4 min. in 12.5 µg/ml acridine orange made up in 0.1 M phosphate buffer, pH 7.4. Slides were rinsed in phosphate buffer and allowed to dry. Slides were randomised and 2000 polychromatic erythrocytes (PCE) scored for micronuclei per animal. the ratio of PCE to normochromatic erythrocytes (NEC) was determined based on a total of at least 1000 PCE + NCE.
Evaluation criteria:
No data
Statistics:
For each group, inter-individual variation in the numbers of micronucleated PCE was estimated by means of heterogeneity X² test. The numbers of micro nucleated PCE in each treated group were then compared with the numbers in vehicle control groups by using a 2x2 contigency table to determine X² and also compared with the laboratory historical negative control range.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
not specified
Additional information on results:
RESULTS OF RANGE-FINDING STUDY
- Dose range: 10 ml/kg:
- Evidence toxicity: Limited

RESULTS OF DEFINITIVE STUDY
- Mean Micronucleated PCE/1000 cells: 0.25 (control), 0.33 (15 mg/kg/day), 0.42 (30 mg/kg/day), 0.25 (60 mg/kg/day) and 2.83 (positive control)
- Mean Ratio of PCE/NCE: 0.95 (vehicle control), 0.92 (15 mg/kg/day), 0.76 (30 mg/kg/day), 0.54 (60 mg/kg/day) and 0.40 (positive control)
- Statistical evaluation: Group mean ratios of PCE to NCE where lower compared to negative controls, which can be considered as a sign of toxicity and a clear demonstration of exposure of the target cells. Group mean frequencies of micronucleated PCE were similar and not significantly different from the value for the concurrent vehicle control group and fell within the laboratory historical negative control range.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
3-chloro-1,2 propane diol is concluded to be non mutagenic under the present study conditions.

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