Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gentoxicity data is provided for both LAS TEA and for two analogues. Bacterial mutation data is available for all three substances but the chromosome aberration and mammalian gene mutation endpoints rely on read across data from the analogues.

LAS TEA:

In an Ames test, strains TA98, TA100, TA1535, TA1537 and TA1538 of S. typhimurium were exposed to LAS TEA at concentrations of 0, 8.4, 43, 217, 1090, and 5430 µg/plate in the presence and absence of mammalian metabolic activation according to the direct plate incorporation method and 0, 68, 136, 272, 543, and 1090 µg/plate in the presence and absence of mammalian metabolic activation according to the preincubation method. There was no evidence of induced mutant colonies over background and hence, LAS TEA was not mutagenic under the conditions of this test.

In an additional Ames test using strain TA102 of S. typhimurium the substance was also not mutagenic.

The other in vitro genotoxicity endpoints for LAS TEA are addressed using data for LAS Na and TEA.

TEA:

TEA was tested in the Ames reverse mutation assay using S. typhimurium strains TA 1535, TA 1537, TA 97, TA 98 and TA 100 at a concentration up to 10000 µg/plate with and without metabolic activation. Treatment with TEA was not associated with reverse mutations in any of the strains tested (Mortelmans, 1986).

Triethanolamine was tested in cultured Chinese hamster ovary (CHO) cells for induction of chromosomal abberations, both in the presence and absence of metabolic activation.The results revealed no induction of chromosomal abberations with or without S9 (Galloway, 1987). The same study also investigated the potential for Sister Chromatid Exchange and found negative results.

In a mammalian cell gene mutation assay (L5178Y TK+/-), mouse lymphoma L5178Y cells cultured in vitro were exposed to triethanolamine in distilled water at concentrations of 0, 50, 100, 250, 500, 1000 and 1500 µg/ml in the presence and absence of mammalian metabolic activation. There was no evidence or a concentration related positive response of induced mutant colonies over background (Dow Chemical Company, 2010).

LAS Na:

LAS Na was not mutagenic in the Ames test.

The potential of the test substance LAS Na to cause chromosomal aberrations in mammalian cells was examined. Chinese hamster ovary cells were exposed to concentrations of 0.32 to 78 ug/ml with S9, and 1.25 to 156 ug/ml without S9. Positive responses were seen at cytotoxic concentrations only in the presence of S9. Concentrations below the level of cytotoxicty with S9 did not show positive results. The test substance is not clastogenic in the absence of metabolic activation, or with metabolic activation below cytotoxic concentrations. Chromosomal abberations seen at cytotoxicity levels can be considered as a secondary effect. The result suggests that LAS is not clastogenic (Murrie & Innes, 1997).

In a mammalian cell gene mutation study, Chinese Hamster Ovary (CHO) cells were exposed to concentrations of 0, 0.6, 1, 1.8, 3, and 6 ug/ml without S9, and 0, 6, 10, 18, 30, and 60 ug/ml with S9. Preliminary tests show the test substance was cytogenic at concentrations of 50 ug/ml or greater with metabolic activation, and 100 ug/ml or above without metabolic activation. There was no biologically significant increase in mutation frequency in the treated groups and hence, LAS is considered not mutagenic to CHO cells both in the presence and absence of S9 (ANON, 1995).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

An in vivo genotoxicity study conducted on the structural analogue showed that there was no significant increases in the number of polychromatic erythrocytes with micronuclei.The substance was negative for genotoxicity in the in vivo mammalian erythrocyte micronucleus test.

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across to K1 study therefore K2 is the maximum Klimisch value.
Justification for type of information:
Read-across approach - see read-across justification in section 13
Reason / purpose:
read-across source
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes (incl. certificate)
Type of assay:
micronucleus assay
Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
Strain NMRI. Animals were approximately 22-26 g (male) and 20-25 g (female) and acclimated for 1 week to the test conditions (20 =/- 3 degrees C, 30-70% relative humidity, 12 hour light/dark cycle). Food was given daily and water was ad libitum. All animals were healthy at the time of test initiation.
Route of administration:
oral: gavage
Vehicle:
NaCl
Duration of treatment / exposure:
72 hours
Frequency of treatment:
single dose
Dose / conc.:
1 122 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
40 males and 40 females per dose
Control animals:
yes
Positive control(s):
Endoxan (cyclophosphamid)
Tissues and cell types examined:
Cells were taken from the thigh.
Details of tissue and slide preparation:
Cells were mixed with cattle serum and suspended, then centrifuged. The sediment was then resuspended. The suspension was seperated in a cellulose chromatography column. This was centrifuged, and mixed with fetal calf serum and EDTA. This was air-dried for 24 hrs and stained with Giemsa.
Evaluation criteria:
number of polychromatid erythrocytes (PCE)
ratio of PCE to normochromatid erythrocytes (NCE)
number of cells with micronucleus
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

No significant increases in the number of polychromatic erythrocytes with micronuclei were observed.

Conclusions:
The substance was negative for genotoxicity in the in vivo mammalian erythrocyte micronucleus test.
Executive summary:

There was no significant increases in the number of polychromatic erythrocytes with micronuclei. The substance was negative for genotoxicity in the in vivo mammalian erythrocyte micronucleus test.

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: GLP laboratory study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes (incl. certificate)
Type of assay:
micronucleus assay
Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
Strain NMRI. Animals were approximately 22-26 g (male) and 20-25 g (female) and acclimated for 1 week to the test conditions (20 =/- 3 degrees C, 30-70% relative humidity, 12 hour light/dark cycle). Food was given daily and water was ad libitum. All animals were healthy at the time of test initiation.
Route of administration:
oral: gavage
Vehicle:
NaCl
Duration of treatment / exposure:
72 hours
Frequency of treatment:
single dose
Dose / conc.:
1 122 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
40 males and 40 females per dose
Control animals:
yes
Positive control(s):
Endoxan (cyclophosphamid)
Tissues and cell types examined:
Cells were taken from the thigh.
Details of tissue and slide preparation:
Cells were mixed with cattle serum and suspended, then centrifuged. The sediment was then resuspended. The suspension was seperated in a cellulose chromatography column. This was centrifuged, and mixed with fetal calf serum and EDTA. This was air-dried for 24 hrs and stained with Giemsa.
Evaluation criteria:
number of polychromatid erythrocytes (PCE)
ratio of PCE to normochromatid erythrocytes (NCE)
number of cells with micronucleus
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

No significant increases in the number of polychromatic erythrocytes with micronuclei were observed.

Conclusions:
The substance was negative for genotoxicity in the in vivo mammalian erythrocyte micronucleus test.
Executive summary:

There was no significant increases in the number of polychromatic erythrocytes with micronuclei.The substance was negative for genotoxicity in the in vivo mammalian erythrocyte micronucleus test.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Justification for classification or non-classification

Based on the results of a selection of in vitro and in vivo genetic toxicity studies for different endpoints, conducted on both the substance and structural analogues, there is no evidence of gentoxicity.