Allyl alcohol

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

- Ames test: negative (Principe P et al, 1981)
- two Ames tests (with two different concentrations: 0-166 µg/plate and 0-333 µg/plate): negative (NTP, 1995)

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: peer-reviewed data

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

not applicable

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Target gene:

-

Species / strain / cell type:

S. typhimurium, other: TA 1535, TA 97, TA 98 and TA 100

Metabolic activation:

with and without

Test concentrations with justification for top dose:

Concentration: 0-333 µg/plate

Species / strain:

S. typhimurium, other: TA 1535, TA 97, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Positive controls validity:

valid

Conclusions:

Under the conditions employed in the assay described in this report, the data suggest that the test article allyl alcohol shows no genetic toxicity.

Interpretation of results: negative.

Reference 2

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: peer-reviewed data

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

not applicable

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Target gene:

no data

Species / strain / cell type:

S. typhimurium, other: TA 1535, TA 97, TA 98 and TA 100

Metabolic activation:

with and without

Test concentrations with justification for top dose:

Concentration: 0-166 µg/plate

Species / strain:

S. typhimurium, other: TA 1535, TA 97, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Conclusions:

Under the conditions employed in the assay described in this report, the data suggest that the test article allyl alcohol shows no genetic toxicity.

Interpretation of results: negative.

Reference 3

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: peer-reviewed journal

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

not applicable

Principles of method if other than guideline:

The ability of 2-propen-1-ol (0.05 µl) to induce reversion in Salmonella typhimurium tester strains TA1535, TA1537, TA1538, TA98, TA100 was investigated using a spot test in the absence or presence of S9 (SD rat, Arochlor 1254 induction). The authors state that the system used was suitable for testing volatile substances. Ethyl methansulfonate (5 µl/plate; TA1535), 9-aminoacridine (10 µg/plate; TA1537), 4-nitro-o-phenyldiamine (10 µg/plate; TA1538 and TA98), ethyl methansulfonate (1 µl/plate; TA100) were used as positive control substances in the absence of S9. 2-Aminoanthracene (1 µg/plate) was used as positive control substance for all tester strains in the presence of S9.
PLATE INCORPORATION ASSAY
Mutagenic activity was also investigated in TA1535, TA100 and TA98 using a plate incorporation assay and 0.025, 0.05, 0.1 µl 2-propen-1-ol/plate in the absence or presence of S9. Comment: Concentrations in excess of 0.05 µl (= 50 nl; spot test) or 0.10 µl (= 100 nl; plate incorporation assay) were cytotoxic.

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Target gene:

no data

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Test concentrations with justification for top dose:

Concentration: 0.025, 0.05, 0.10 µl/plate

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

>0.10 µl/plate

The number of his+ revertants per plate was highly comparable in control and test cultures for all 5 tester strains both in the absence or presence of S9. A satisfactory response was obtained with the positive control substances.

PLATE INCORPORATION ASSAY

There was no increase in revertants in any of the 3 tester strains in the absence or presence of S9.

Conclusions:

Under the conditions of the test, 2-propen-1-ol (highest non-toxic concentration) was not mutagenic in a spot test (5 stains of Salmonella typhimurium including TA100 and TA1535) or a plate incorporation assay (3 tester strains).

Interpretation of results: negative.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

two Micronucleus tests (mouse: oral route; rat: intraperitoneal route): negative (NTP, 1995)

Link to relevant study records

Reference

Reference 1

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: peer-reviewed data

Qualifier:

according to guideline

Guideline:

other: Standard NTP Protocol for in-vivo toxicology study

Deviations:

no

Principles of method if other than guideline:

The National Toxicology Program, USA (NTP) routinely conducts peripheral blood micronucleus tests on mice that are treated in the 13-week toxicity studies as part of the bioassay program. At the end of the 13-week exposure period (routes of exposure: inhalation, dosed-feed, drinking water, oral gavage, skin painting), a blood sample is obtained from male and female mice in each dose group (usually 10 animals per treatment group per sex) and slides are prepared, fixed and stained as for the bone marrow studies. Sample collection time is typically between 0 (in the case of continuous exposures) and 24 hours (in the case of single daily exposures). 1,000 to 10,000 mature erythrocytes (normochromatic erythrocytes or NCEs) are scored per animal for presence of micronuclei. These mature erythrocytes represent about 95% or more of the circulating erythrocytes. The percent PCE is determined in the blood as a measure of chemical-induced toxicity to the bone marrow. All data are analyzed separately for male and female mice.
The acridine orange staining procedure that is used for micronucleus slides allows the scorer to differentiate between the recently formed, immature erythrocytes (polychromatic or PCE) that are less than 48 hr old, and mature erythrocytes 2-35 days old (normochromatic or NCE) based on their staining characteristics. PCE contain residual RNA and thus they stain differently than the NCE that no longer have residual RNA. MN in PCEs arise from damage that occurred recently (within the past 48 hr) and the NCE population shows the result of damage accumulated over the past month, with the NCE population being in steady state equilibrium in the peripheral blood (newly damaged or undamaged erythrocytes are moving from bone marrow to blood at the same rate as old erythrocytes -- the NCEs-- are being removed from the blood). Thus, for longer-term peripheral blood MN studies, it is usually more appropriate to score MN in the NCE population. The mouse spleen is inefficient in removing damaged erythrocytes from circulation (thus permitting the achievement of steady state), but the rat spleen quickly eliminates micronucleated erythrocytes from circulation. Therefore, only mice can be used in a longer-term peripheral blood MN test that analyzes the NCE population. For acute studies, particularly those in which bone marrow tissue is analyzed, PCEs are scored.

GLP compliance:

not specified

Type of assay:

micronucleus assay

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Route of administration:

oral: gavage

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

five times per week

Post exposure period:

10 to 14 days

No. of animals per sex per dose:

usually 10 animals per treatment group per sex

Tissues and cell types examined:

erythrocytes

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Positive controls validity:

valid

Conclusions:

Under the conditions employed in the assay described in this report, the data suggest that the test article allyl alcohol shows no genetic toxicity.

Interpretation of results: negative.

Reference 2

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: peer-reviewed data

Qualifier:

according to guideline

Guideline:

other: Standard NTP Protocol for in-vivo toxicology study

Deviations:

no

Principles of method if other than guideline:

The National Toxicology Program, USA (NTP) routinely conducts peripheral blood micronucleus tests on mice that are treated in the 13-week toxicity studies as part of the bioassay program. At the end of the 13-week exposure period (routes of exposure: inhalation, dosed-feed, drinking water, oral gavage, skin painting), a blood sample is obtained from male and female mice in each dose group (usually 10 animals per treatment group per sex) and slides are prepared, fixed and stained as for the bone marrow studies. Sample collection time is typically between 0 (in the case of continuous exposures) and 24 hours (in the case of single daily exposures). 1,000 to 10,000 mature erythrocytes (normochromatic erythrocytes or NCEs) are scored per animal for presence of micronuclei. These mature erythrocytes represent about 95% or more of the circulating erythrocytes. The percent PCE is determined in the blood as a measure of chemical-induced toxicity to the bone marrow. All data are analyzed separately for male and female mice.
The acridine orange staining procedure that is used for micronucleus slides allows the scorer to differentiate between the recently formed, immature erythrocytes (polychromatic or PCE) that are less than 48 hr old, and mature erythrocytes 2-35 days old (normochromatic or NCE) based on their staining characteristics. PCE contain residual RNA and thus they stain differently than the NCE that no longer have residual RNA. MN in PCEs arise from damage that occurred recently (within the past 48 hr) and the NCE population shows the result of damage accumulated over the past month, with the NCE population being in steady state equilibrium in the peripheral blood (newly damaged or undamaged erythrocytes are moving from bone marrow to blood at the same rate as old erythrocytes -- the NCEs-- are being removed from the blood). Thus, for longer-term peripheral blood MN studies, it is usually more appropriate to score MN in the NCE population. The mouse spleen is inefficient in removing damaged erythrocytes from circulation (thus permitting the achievement of steady state), but the rat spleen quickly eliminates micronucleated erythrocytes from circulation. Therefore, only mice can be used in a longer-term peripheral blood MN test that analyzes the NCE population. For acute studies, particularly those in which bone marrow tissue is analyzed, PCEs are scored.

GLP compliance:

not specified

Type of assay:

micronucleus assay

Species:

rat

Strain:

Fischer 344

Sex:

male

Route of administration:

intraperitoneal

Duration of treatment / exposure:

72 Hours

Frequency of treatment:

five times per week

Post exposure period:

10 to 14 days

No. of animals per sex per dose:

usually 10 animals per treatment group per sex

Tissues and cell types examined:

erythrocytes

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Positive controls validity:

valid

Conclusions:

Under the conditions employed in the assay described in this report, the data suggest that the test article allyl alcohol shows no genetic toxicity.

Interpretation of results: negative.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Justification for classification or non-classification

According to CLP classification criteria, the substance does not meet the criteria for classification and labelling for this endpoint, as set out in Regulation (EC) No. 1272/2008.