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Toxicological information

Genetic toxicity: in vivo

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Administrative data

in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Type of genotoxicity: other: lethal mutation (mainly chromosome damage)
Type of information:
experimental study
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published data, peer-reviewed and appears representative for the endpoint under evaluation. The method used followed a guideline similar to OECD 478.

Data source

Reference Type:
Malformed foetuses and karyotype abnormalities in the offspring of cyclophosphamide and allyl alcohol-treated male rats.
Jenkinson, P.C., Anderson, D.
Bibliographic source:
Mutation Research, 229: 173-184

Materials and methods

Test guideline
equivalent or similar to guideline
OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)
GLP compliance:
not specified
Type of assay:
rodent dominant lethal assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Allyl alcohol
EC Number:
EC Name:
Allyl alcohol
Cas Number:
Molecular formula:
Details on test material:
Allyl alcohol was obtained from Aldrich Chemical Company, Gillingham, Dorset.

Test animals

Details on test animals or test system and environmental conditions:
- Source: Olac (Bicester, Oxon, UK).
- Age at study initiation: 9-11 week old
- Housing: caged (1 male rat with 2 female rats)
- Diet (e.g. ad libitum): Rat No.3 expanded diet (Special diet services, Witham, Essex) ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: 10 days minimum

Administration / exposure

Route of administration:
other: oral gavage is deduced from published paper (not specifically stated)
Saline (0.85%)
Details on exposure:
Allyl alcohol was diluted in saline each day immediately before use, and was administered at a dose volume of 10 ml/kg.

Duration of treatment / exposure:
15 weeks
Frequency of treatment:
7 days a week up to week 12 and then 5 days per week
Doses / concentrations
Doses / Concentrations:
25 mg/kg
nominal conc.
No. of animals per sex per dose:
Groups of 6 males (total number not known). Each male rat was caged with 2 virgin female rats in dosing weeks 2-12.
Control animals:
yes, concurrent vehicle
Positive control(s):
Cyclophosphamide (obtained from Sigma Chemicals) was given at a dose of 3.5 mg/kg for the first 4 weeks and 5.1 mg/kg subsequently, for 33 weeks. A total of 18 male rats were dosed with cyclophosphamide. Each rat from the control group was caged with 2 virgin female rats on weeks 1-11, 21 and 30.


Tissues and cell types examined:
- Day 20 of pregnancy: females from mating week 1-11 and 21 were killed and the uteri are examined for the total number of corpora lutea, total implants, live foetuses, dead foetuses, late deaths and early deaths.
- Foetuses were weighed and examinations were carried out to observe for any gross abnormalities. Samples of liver were also taken for chromosome preparation. Where karyotype abnormalities were seen, these were analysed. Skeletal staining and evaluation was also performed.
- After mating periods, each male underwent a gross post-mortem and haematology assessment. Control rats were post-mortemed 33 weeks after the initiation of dosing, whereas, AA-treated rats were post-mortemed after 15 weeks of dosing.
Details of tissue and slide preparation:
Liver samples were taken from each abnormal pup and slides prepared for karyotype analysis. Skeletal staining was employed to investigate abnormal pups

Results and discussion

Test results
no effects
Vehicle controls validity:
Negative controls validity:
Positive controls validity:
other: cyclophosphamide treatement produced implant deaths and foetal malformations
Additional information on results:
Paternal effects:
- Mean bodyweights of the allyl alcohol-treated groups were lower than that of the control groups (549 +/- 49 and 635 +/- 74 g respectively), however this difference can be explained by the different postmortem dates of the control and allyl alcohol groups.
- Allyl alcohol induced significant increases in the relative weights of the liver 3.41 +/- 0.47 vs 2.71 +/- 0.47) and spleen (0.22 +/- 0.03 vs 0.18 +/- 0.02) and non-significant increases in the relative weights of the kidneys and testes.
- Allyl alcohol did not appear to have a significant effect on red blood cell count, mean cell volume, percentage cell volume or the haemoglobin levels when compared to the control group.
- In allyl alcohol treated groups, the white cell count did not significantly differ from the controls (5.6 +/- 2.2 and 6.3 +/- 5.6 x 10^9/l respectively). However the white blood cell differential count showed that there was a significant increase in lymphocytes in parallel with significant depression in eosinophil and neutrophil counts.
- Allyl alcohol had no significant effect on the relative weights of the testes and cauda. In addition the total sperm count or sperm per microlitre of epididymal fluid were not significantly affected when compared to the control group.

Reproduction parameters:
- a total of 1669 live implants from 125 pregnancies in the control groups (13.4 live implants/litter) compared to 1371 implants from 108 litters in the allyl alcohol treated group (12.7 live implants/litter) showed no significant inter-group difference
- no significant differences in the preimplantation loss rate were seen between the allyl alcohol-treated and the control groups (11.7 +/- 6.2% and 12.8 +/- 5.4% respectively).
- The dominant lethality (post implantation loss) rates within the allyl alcohol group was similar to that of the control group.

Foetal abnormalities:
- Incidences of runted and abnormal foetuses were comparable in the control and allyl alcohol treated groups (see table 1).
- The abnormalities seen in the litters were: anasarca, exencephaly, craniofacial and skeletal abnormality. The combined incidence of gross abnormalities was not significantly different between the control and allyl alcohol treated groups.

Karyotypic analysis (see table 2):
- karyotypic abnormalities were observed in 3 of 12 scoreable slides prepared from abnormal foetuses from the allyl alcohol treated group
- no abnormal karyotype was seen in 5 control slides prepared from abnormal foetuses
no significance is attributed to these findings.

Any other information on results incl. tables

Table 1. Summary of litter data (treated males).

  Control Allyl alcohol
Total number of pregnant females 125 108
Total number of live implants  1669 1371
Live implants/litter 13.4 12.7
Total number of runts (%)  13 (0.78) 13 (0.95)
Runts/litter 0.1 0.12
Total number of gross abnormalities (%)  0.0 (0.0) 3 (0.22)
Gross abnormalities/litter 0.0 0.03
Total number of abnormal foetuses  13 (0.78) 16 (1.17)
Abnormal foetuses/litter 0.1 0.15

Table 2. Karyotype analyses

  Control Treated
No. of abnormal foetuses evaluated 8 14
Slides with scorable metaphases 5 12
Slides with no karyotypic abnormality 5 9
Slides with karyotypic abnormality 0 3

Applicant's summary and conclusion

Interpretation of results (migrated information): negative
In this experiment, allyl alcohol is negative for dominant lethality.
Executive summary:

In this dominant lethal test, male rats were exposed to allyl alcohol at concentrations of 25 mg/kg for 33 weeks. Totals of 1669 live implants from 125 pregnancies in the control groups (13.4 implants/litter) compared to 1371 implants from 108 litters in the allyl alcohol treated group (12.7 implants/litter) proved not significantly different. No significant differences in the preimplantation loss rate were seen between the allyl alcohol-treated and the control groups (11.7 +/- 6.2% and 12.8 +/- 5.4% respectively). Post implantation loss (dominant lethality) rate within the allyl alcohol group was also similar to that of the control group.

Allyl alcohol proved negative for dominant lethality.