Lawsonia inermis, ext.

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Lawsonia Inermis (Henna) is not genotoxic in gene mutation tests in bacteria. All these studies are performed according to GLP. Two of these studies are performed according to the OECD guideline 471 and 476.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

other: SCCS /1511/13

Adequacy of study:

key study

Study period:

11.9.1990-15.10.1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1983

Deviations:

not specified

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

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

Species / strain / cell type:

S. typhimurium TA 1538

Metabolic activation:

with and without

Metabolic activation system:

S9-mix

Test concentrations with justification for top dose:

50, 100, 500, 1000, 2500 and 5000 μg/plate with and without metabolic activation

Vehicle / solvent:

DMSO

Untreated negative controls:

yes

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

not specified

Remarks:

Appropriate negative and po sitive controls were included.

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Conclusions:

No bacteriotoxic effect was observed. Henna Rot did not induce an increase in revertants in the bacterial strains in the tested concentration range between 50 to 5000 μg/plate. The sensitivity and validity of the test system used was demonstrated by the significant induction of revertants by the positive controls. Under the experimental conditions used, Henna Rot was not mutagenic in this gene mutation tests in bacteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Link to relevant study records

Reference

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

other: Mutation Research, 2003

Adequacy of study:

key study

Study period:

na

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Version / remarks:

1997

GLP compliance:

yes

Type of assay:

mammalian bone marrow chromosome aberration test

Species:

mouse

Strain:

CD-1

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

intraperitoneal

Vehicle:

Methylcellulose. Positive control; Vehicle was water

Details on exposure:

300mg/kg

Duration of treatment / exposure:

not specified

Frequency of treatment:

once

Dose / conc.:

300 mg/kg diet

No. of animals per sex per dose:

not specified

Control animals:

yes

Positive control(s):

cyclophosphamide (CPA) 50 mg/kg

Key result

Sex:

not specified

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

not specified

Negative controls validity:

valid

Positive controls validity:

valid

Conclusions:

The results of a further mouse bone marrow MN test with Henna containing HNQ did not indicate an increase in MN frequency at any dose, even though bone marrow toxicity was induced.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Active substance, Lawsone, has a complex toxicity and genetic toxicity profile. It was haematotoxic in an oral subchronic rodent study and positive or borderline-positive in the mouse lymphoma assay and a chromose aberration test in CHO cells, but negative in Salmonella, a CHO-HRPT test and a SHE assay (Kirkland and Marzin, 2003). On the basis of these data, Lawsone, was considered to have getoxic potential in vivo. A non-genotoxic mechanism was supported by the results of an addional micronucleus test, which confirmed haematotoxicity 72h after a single oral dose of Lawsone, and a 24- and 72 h bone marrow chromosome aberration study in mice all of which had negative results. Kirkland and Marzin 2003).

In the literature we found some reported cases which have some indication of positive genotoxic potential and even SCCS reported further consideration on this endpoint is desirable.