Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The substance was tested in several in vitro Ames (NTP 2004, Hüls AG 1988, Florin 1980, NCI 1994) and a Mouse Lymphoma assay (NCI 1992) and was found to be not genotoxic in bacterial systems in vitro (Ames test). In the Mouse Lymphoma test, results were negative and equivocal, without and with metabolic activation, respectively (NCI 1994).

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991-06-03 to 1992-05-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study
Principles of method if other than guideline:
Mouse lymphoma assay, suspension plate, no further details
GLP compliance:
yes
Type of assay:
mammalian cell gene mutation assay
Target gene:
tymidin kinase gene
Species / strain / cell type:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Metabolic activation system:
 Aroclor 1254-induced rat liver S9 mix
Test concentrations with justification for top dose:
-S9: 30-50 and 35-47.5 µg/ml;
+S9: 1-15 and 10-20 µg/ml
Vehicle / solvent:
 DMSO
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
 3-methylcholanthrene with S9-mix   Migrated to IUCLID6: without S9-mix
Details on test system and experimental conditions:
Mouse lymphoma assay
Metabolic activation system: Aroclor 1254-induced rat liver S9 mix
ADMINISTRATION: 
- Dosing:   
-S9: 30, 35, 40, 45, 50 µg/ml  
 +S9:  1, 2.5, 5, 10, 15 µg/ml  
follow-up -S9: 35, 40, 42.5, 45, 47.5 µg/ml   
follow-up +S9: 10, 12.5, 15, 17.5, 20 µg/ml  
solvent: DMSO
- Number of replicates: 2
- Positive and negative control groups and treatment:    
positive: ethylmethanesulfonate (-S9); 3-methylcholanthrene (+S9)   
negative: solvent and untreated
- Pre-incubation time: two-day expression period
Evaluation criteria:
CRITERIA FOR EVALUATING RESULTS: dose-dependent increase in mutant  frequency
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
ambiguous
Cytotoxicity / choice of top concentrations:
other: see Results
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
GENOTOXIC EFFECTS:  Initial study: 
- positive with and without metabolic activation
- validity questionable due to findings in controls
Follow-up study:
- negative without metabolic activation
- equivocal with metabolic activation (the only cultures exhibiting a  significant increase in mutant frequency had less than 10% total growth)
Controls:    Positive controls were as expected in both studies.   
Negative controls showed unacceptably high mutant frequencies in the  initial study and were as expected in the follow-up study.
CYTOTOXIC CONCENTRATION:
- Toxicity screening study:   Complete toxicity >= 100 µg/ml, almost complete at 50 µg/ml (-S9);   complete toxicity >= 50 µg/ml (+S9)
- Initial study:   "too toxic to clone" at 52 µg/ml (-S9) and 20 µg/ml (+S9)
- Follow-up study:    "too toxic to clone" at 50 µg/ml (-S9) and 22.5 µg/ml (+S9)
Remarks on result:
other: other: L5178Y TK+/-
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results (migrated information):
negative

In a mouse lymphoma test tetrahydronaphthalene showed no relevant genotoxic effects.
Executive summary:

In a mouse lymphoma test, a negative result was obtained in the absence of a metabolic activation system (dose range 35-47.5 μg/ml), while with the addition of S-9 mix the test was equivocal (dose range 10-20 μg/ml): The only cultures exhibiting a significant increase in mutant frequency had less than 10 % total growth.

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988-08-05 to 1988-08-18
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions: TA 102 or E.coli WP2 were not tested, not required by guidelines prior to 1997
Qualifier:
according to guideline
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Deviations:
no
Principles of method if other than guideline:
Ames BN et al. (1975). Mutat. Res. 31 (6) 347-364
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay
Target gene:
mutated gene loci responsible for histidine auxotrophy
Species / strain / cell type:
other: Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537, TA 1538
Metabolic activation:
with and without
Metabolic activation system:
aroclor induced rat liver S9 mix
Test concentrations with justification for top dose:
10; 50; 100; 250; 500; 1000; 5000 ug/plate
Vehicle / solvent:
DMSO
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
yes
Positive controls:
yes
Positive control substance:
other: 2.5 µg nitrofluorene/plate: TA 98, TA 1538 (pos.)    2.5 µg sodium azide/plate: TA 100, TA 1535 (pos.)    50 µg aminoacridine/plate: TA 1537 (pos.)    10 µg aminoanthracene/plate: TA 100 (enzymatic activity)
Details on test system and experimental conditions:
Ames test
SYSTEM OF TESTING
- Metabolic activation system:    aroclor induced rat liver S9 mix; enzymatic activity tested with  aminoanthracene
ADMINISTRATION: 
- Number of replicates: 3
- Application: solvent dimethyl sulfoxide
- Positive and negative control groups and treatment:    
2.5 µg nitrofluorene/plate: TA 98, TA 1538 (pos.)   
2.5 µg sodium azide/plate: TA 100, TA 1535 (pos.)   
50 µg aminoacridine/plate: TA 1537 (pos.)   
10 µg aminoanthracene/plate: TA 100 (enzymatic activity)   
negative control: no
- Pre-incubation: twice
Evaluation criteria:
CRITERIA FOR EVALUATING RESULTS:    
mutagenic effects (i.e  ratio of revertant rates treated/control >= 2)  at <= 5000 µg/plate with generally positive dose-response relationship in  
any strain
Key result
Species / strain:
S. typhimurium, other: TA 98, TA 100, TA 1535, TA 1537, TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: >= 50 ug/plate (-S9); >= 500 ug/plate (+S9)
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
PRECIPITATION CONCENTRATION:   
-S9: >= 250 ug/plate  
+S9: >= 250 ug/plate
Positive controls were functional.
Remarks on result:
other: other: Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537, TA 1538
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results (migrated information):
negative

Tetrahydronaphthalene was not genotoxic in both the presence or absence of metabolic activation in a microbial mutagenicity assay.
Executive summary:

In a reverse gene mutation assay in bacteria, strains TA98, TA100, TA1535, TA1537 and TA1538 of Salmonella typhimurium were exposed to tetrahydronaphthalene using acetone as a vehicle at concentrations of 10 - 5000 µg/plate, with and without S-9 activation in a preincubation assay according to EEC guidance Dir. 84/449/EEC, B.14.

The test article was tested at six dose levels along with appropriate vehicle and positive controls on the tester strains mentioned above in the presence and absence of S9-mix. All dose levels, vehicle and positive controls were plated in triplicate.

Cytotoxicity was noted at 50 -500 µg/plate.

No positive mutagenic responses were observed with any of the strains used, in the presence as well as in the absence of microsomal enzymes. These results were confirmed in an independent assay.

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment. Restriction:
Principles of method if other than guideline:
Haworth et al. (1983). Environ. Mutagen. 5 (Suppl. 1), 3-142 (with minor modifications).
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Target gene:
mutated gene loci responsible for histidine auxotrophy
Species / strain / cell type:
other: Salmonella typhimurium TA 100, TA 1535, TA 97, TA 98
Metabolic activation:
with and without
Metabolic activation system:
 S9 from Aroclor 1254-induced Sprague-Dawley rats and Syrian hamsters
Test concentrations with justification for top dose:
0; 0.3; 1; 3; 10; 33; 100; 333 µg/plate
Vehicle / solvent:
DMSO
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Details on test system and experimental conditions:
Ames test
SYSTEM OF TESTING
- Metabolic activation system:  S9 from Aroclor 1254-induced Sprague-Dawley rats and Syrian hamsters
ADMINISTRATION: 
- Dosing: at least 5 doses, limited by toxicity or solubility or 10  mg/plate
- Number of replicates: 3
- Positive and negative control groups and treatment:    
solvent (DMSO) control and positive controls; no details
- Pre-incubation time: 20 minutes
Evaluation criteria:
CRITERIA FOR EVALUATING RESULTS:    
positive: reproducible, dose related increase in histidine-independent  (revertant) colonies in any strain   
equivocal: not dose related or not reproducible
Key result
Species / strain:
other: Salmonella typhimurium TA 100, TA 1535, TA 97, TA 98 (1st test) and S. typhimurium strains TA98 and TA100 and with Escherichia coli strain WP2 uvrA/pKM101 (2nd test)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'. Remarks: Salmonella typhimurium
Conclusions:
Interpretation of results (migrated information):
negative

1,2,3,4-tetrahydronaphthalene was not mutagenic in Salmonella typhimurium strains (Ames test).
Executive summary:

1,2,3,4-tetrahydronaphthalene (0.3 to 333 μg/plate) was not mutagenic in Salmonella typhimurium strains TA97, TA98, TA100, or TA1535 when testing was conducted with or without induced rat or hamster liver metabolic activation enzymes. A second bacterial mutagenicity assay conducted with the same lot of tetralin (2 to 500 μg/plate) used in the 2‑year study showed no mutagenicity in S. typhimurium strains TA98 or TA100 or in Escherichia coli strain WP2 uvrA, with or without rat liver activation enzymes.

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

Genetic toxicity in vivo

Description of key information

Two in vivo murine micronucleus tests following oral exposure (Hüls AG 1993; 2000 mg/kg bw single dose) or inhalation exposure (NTP 1997; up to 660 mg/m³ 6h/5d per week for three month) according to OECD TG 474) gave not indication for a genotoxic potential.

Link to relevant study records

Referenceopen allclose all

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
Study period:
1993-04-26 to 1993-05-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Type of assay:
micronucleus assay
Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ORGANISMS: 
- Age: young adults
- Source: Winkelmann, Borchen (Germany)
- Weight at study initiation:    
test group, male: 32.2 +/- 6.4 g   
test group, female: 27.2 +/- 5.4 g
- No. of animals per dose: 5 males, 5 females per test duration
Route of administration:
oral: gavage
Vehicle:
corn-oil
Details on exposure:
ADMINISTRATION: 
- Vehicle: corn oil
- Duration of test: 24 hours; 48 hours
- Sampling times and number of samples: 24 hours; 48 hours
- Control groups and treatment:   
positive control cyclophosphamide (vehicle physiol. NaCl),   dose 100 mg/kg bw, 24 hours   
negative control corn oil (= vehicle)
Duration of treatment / exposure:
one single application (10 ml/kg bw)
Frequency of treatment:
one time
Post exposure period:
24 and 48 hours
Remarks:
Doses / Concentrations:
2000 mg/kg
Basis:
actual ingested
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
5 animals per sex
cyclophosphamide (vehicle physiol. NaCl),   dose 100 mg/kg bw, 24 hours   
Details of tissue and slide preparation:
EXAMINATIONS: 
- Clinical observations: yes
- Organs examined at necropsy: femur bone marrow
- Criteria for selection of M.T.D.: maximum dose <= 2000 mg/kg bw  without  mortalities within 48 hours
Evaluation criteria:
- Criteria for evaluating results: statistically significant and  biologically relevant increase in frequency of micronucleated  polychromatic 
erythrocytes of at least one test group as compared to the  negative control group of the same sampling time
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
MORTALITY: No mortality in dose finding test within 48 hours at 2000  mg/kg bw. Two females from the satellite group died within 30 hours  post  treatment. CLINICAL SIGNS: piloerection, apathy, dark coloured urine; normality  within 48 hours
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
MORTALITY: No mortality in dose finding test within 48 hours at 2000  mg/kg bw. Two females from the satellite group died within 30 hours 
post  treatment.
CLINICAL SIGNS: piloerection, apathy, dark coloured urine; normality  within 48 hours

A significant decrease in the PCE/NCE (NCE = normochromatic erythrocytes)  relation in the treated animals proved that the test substance or its  
metabolites had reached the bone marrow.

EFFECT ON MITOTIC INDEX OR PCE/NCE RATIO: 
---------------------------------------------------------
- positive control, 24 h: PCE statistically significant
  males   362 micronuclei / 10,011 PCE (3.62 +- 1.49 %)
           43 micronuclei / 47,756 NCE (0.11 +- 0.05 %)
           PCE/NCE = 0.24 +- 0.08
  females 350 micronuclei / 10,005 PCE (3.50 +- 0.33 %)
           24 micronuclei / 45,909 NCE (0.06 +- 0.04 %)
           PCE/NCE = 0.27 +- 0.16
- negative control, 24 h:
  males    18 micronuclei / 10,030 PCE (0.18 +- 0.07 %)
           24 micronuclei / 17,855 NCE (0.13 +- 0.05 %)
           PCE/NCE = 0.59 +- 0.13
  females  13 micronuclei / 10,023 PCE (0.13 +- 0.07 %)
           11 micronuclei / 17,407 NCE (0.07 +- 0.07 %)
           PCE/NCE = 0.66 +- 0.23
- test substance, 24 h: PCE not statistically significant
  males    16 micronuclei / 10,013 PCE (0.16 +- 0.15 %)
           89 micronuclei / 66,679 NCE (0.13 +- 0.05 %)
           PCE/NCE = 0.17 +- 0.06
  females   7 micronuclei / 10,009 PCE (0.07 +- 0.07 %)
           30 micronuclei / 42,428 NCE (0.07 +- 0.03 %)
           PCE/NCE = 0.26 +- 0.08
- negative control, 48 h:
  males    20 micronuclei / 10,019 PCE (0.20 +- 0.12 %)
           24 micronuclei / 28,511 NCE (0.09 +- 0.05 %)
           PCE/NCE = 0.39 +- 0.12
  females  16 micronuclei / 10,023 PCE (0.16 +- 0.07 %)
           10 micronuclei / 15,394 NCE (0.07 +- 0.05 %)
           PCE/NCE = 0.67 +- 0.12
- test substance, 48 h: PCE not statistically significant
  males    13 micronuclei / 10,006 PCE (0.13 +- 0.04 %)
           66 micronuclei / 89,554 NCE (0.08 +- 0.05 %
           PCE/NCE = 0.19 +- 0.14
  females   7 micronuclei / 10,009 PCE (0.07 +- 0.06 %)
           19 micronuclei / 45,881 NCE (0.05 +- 0.01 %)
           PCE/NCE = 0.23 +- 0.07

---------------------------------------------------------

Conclusions:
Interpretation of results (migrated information): negative
In a murine micronucleus test tetrahydronaphthalene exhibited no genotoxic activity in vivo.
Executive summary:

In a micronucleus assay in NMRI mice according to OECD TG 474 (1983) five mice per sex and test duration received one single application with 2,000 mg 1,2,3,4- tetrahydronaphthalene/kg bw in corn oil (10 ml/kg bw) by gavage. The selected dose was the maximum dose without mortalities within 48 hours. Sampling times were 24 and 48 hours after test substance administration. 1,2,3,4-Tetrahydronaphthalene treatment did not result in an increase in the frequency of micronucleated polychromatic erythrocytes (PCE), but it significantly reduced the PCE/NCE ratio in male and female animals at both sampling times. This clearly indicates that the

target organ (the bone marrow) had been reached in this 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:
supporting study
Study period:
1996-08-19 to 1996-11-22
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study without detailed documentation
Principles of method if other than guideline:
NTP Test Protocol, part of a subchronic inhalation toxicity study acc. to McGregor et al.
GLP compliance:
yes
Type of assay:
micronucleus assay
Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ORGANISMS -
- Source: Taconic, Germantown (New York, USA)
- Age: approximately 6 weeks at first exposure
- Number of animals: 10 per dose and sex
Route of administration:
inhalation
Vehicle:
air
Details on exposure:
ADMINISTRATION: 
- Type of exposure: whole-body inhalation
- Vehicle: air
- Control groups and treatment: concurrent no treatment
Duration of treatment / exposure:
13 weeks, 6 h/day, 5 days/week; additionally: last sunday before terminal sacrifice
Frequency of treatment:
6 h/day, 5 days/week; additionally: last sunday before terminal sacrifice
Remarks:
Doses / Concentrations:
0; 7.5; 15; 20; 60; 120 ppm = 0; 41.2; 82.4; 165; 330; 660 mg/m3
Basis:

No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Positive control(s):
not included in study
Details of tissue and slide preparation:
EXAMINATIONS: 
- Micronuclei in erythrocytes: Two blood smears were taken from all core  study animals at necropsy. One of these slides was subject to 
micronuclei  determination.
- 2000 peripheral blood erythrocytes (NCE) counted
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
No mortalities but reduced body weight at higer dose levels
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
not specified

Males
---------------------------------------------------------
Dose (ppm)   Percent NCE     Micronucleated/1000      P
---------------------------------------------------------
   0.0      98.86 +/- 0.10      0.9 +/- 0.1
   7.5      98.20 +/- 0.15      0.7 +/- 0.1        0.8081
  15.0      97.81 +/- 0.13      0.8 +/- 0.2        0.6940
  30.0      97.67 +/- 0.11      0.8 +/- 0.2        0.7537
  60.0      97.81 +/- 0.11      1.1 +/- 0.1        0.3759
 120.0      97.41 +/- 0.11      0.5 +/- 0.1        0.9527
---------------------------------------------------------
Females
---------------------------------------------------------
Dose (ppm)   Percent NCE     Micronucleated/1000      P
---------------------------------------------------------
   0.0      98.25 +/- 0.10      1.1 +/- 0.2
   7.5      98.06 +/- 0.15      1.6 +/- 0.2        0.0653
  15.0      98.11 +/- 0.31      1.3 +/- 0.3        0.2776
  30.0      98.06 +/- 0.12      1.0 +/- 0.2        0.5621
  60.0      97.49 +/- 0.23      1.2 +/- 0.2        0.3814
 120.0      97.30 +/- 0.26      0.9 +/- 0.2        0.6846

Conclusions:
Interpretation of results (migrated information): negative
In this in vivo micronucleus assay the test substance was not genotoxic in vivo.
Executive summary:

1,2,3,4-Tetrahydronaphthalene did not induce micronuclei in peripheral erythrocytes taken from B6C3F1 mice (10 per dose and sex) which were exposed for 13 weeks on 6 h/day, 5 days/week to concentrations of 7.5; 15; 30; 60; 120 ppm = 41.2; 82.4; 165; 330; 660 mg/m3

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

Additional information

Cited from SIAR to SIAM 19 (Berlin, 19-22 October 2004)

In vitro Studies

In an Ames test performed according to the original publication by B. Ames (1975) with Salmonella typhimurium TA 1535, TA 1537, TA 1538, TA 98, and TA 100, test substance concentrations of 10; 50; 100; 250; 500; 1000; 5000 μg/plate were employed in the presence and absence of Aroclor induced rat liver S9 mix. Cytotoxicity was observed at > 50 μg/plate (-S9) and > 500 μg/plate (+S9), respectively. At non-toxic test substance concentrations, a significant increase in mutant frequency was not observed (Hüls AG, 1988). A negative result in the Ames test (+/- Aroclor 1254 induced rat liver S9 mix) was also obtained by Florin et al. (1980) using the same strains except TA 1538 and doses of 0.03; 0.3; 3; 30 μmol/plate (ca. 4; 40; 400; 4,000 μg/plate). These authors observed cytotoxicity at >= 3 μmol/plate (ca. 400 μg/plate). The chemical was also tested negative in an Ames test performed within the frame of the U.S. National Toxicology Program (NTP, 2004)

In a mouse lymphoma test, a negative result was obtained in the absence of a metabolic activation system (dose range 35-47.5 μg/ml), while with the addition of S-9 mix the test was equivocal (dose range 10-20 μg/ml): The only cultures exhibiting a significant increase in mutant frequency had less than 10 % total growth (National Cancer Institute / Microbiological Associates, 1992).

In vivo Studies

In a micronucleus assay in NMRI mice according to OECD TG 474 (1983) performed by Hüls AG (1993), five mice per sex and test duration received one single application with 2,000 mg 1,2,3,4-tetrahydronaphthalene/kg bw in corn oil (10 ml/kg bw) by gavage. The selected dose was the maximum dose without mortalities within 48 hours. Sampling times were 24 and 48 hours after test substance administration. 1,2,3,4-Tetrahydronaphthalene treatment did not result in an increase in the frequency of micronucleated polychromatic erythrocytes (PCE), but it significantly reduced the PCE/NCE ratio in male and female animals at both sampling times. This clearly indicates that the target organ (the bone marrow) had been reached in this test.

1,2,3,4-Tetrahydronaphthalene did not induce micronuclei in peripheral erythrocytes taken from B6C3F1 mice (10 per dose and sex) which were exposed for 13 weeks on 6 h/day, 5 days/week to concentrations of 7.5; 15; 30; 60; 120 ppm = 41.2; 82.4; 165; 330; 660 mg/m3 (NTP, 1997 a; NTP, 2004).


Justification for classification or non-classification

The test substance was not genotoxic in bacterial systems in vitro (Ames test). In a Mouse Lymphoma test, results were negative and equivocal, without and with metabolic activation, respectively. In vivo, no mutagenic activity was detectable in two micronucleus assays on mice according to OECD TG 474 using the oral and inhalation routes of administration.

Based on the results of the in vitro and in vivo gentoxicity studies, it can be concluded that the test substance is not genotoxic and therefore must not be classified according to the criteria of CLP Regulation 1272/2008.