Dodecanedioic acid

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No mutagenic activity was noted with or without metabolic activation in two in vitro studies using microbial test systems and in a study using mammalian cells.

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:

key study

Study period:

1999-10-05 to 1999-10-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

Directive 92/69/EEC, B.14

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Target gene:

mutated gene loci responsible for histidine auxotrophy

Species / strain / cell type:

other: Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100, TA 102

Metabolic activation:

with and without

Metabolic activation system:

Phenobarbital / beta-naphthoflavone co-induced rat liver S9 fraction

Test concentrations with justification for top dose:

313; 625; 1250; 2500; 5000 µg/plate (+/- metabolic  activation)

Vehicle / solvent:

dimethyl sulfoxide (DMSO)

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

dimethyl sulfoxide (DMSO)

True negative controls:

yes

Positive controls:

yes

Positive control substance:

other: without S9 sodium azide (TA 1535, TA 100); 9-aminoacridine (TA 1537); cumene hydroperoxide (TA 102); 2-nitrofluorene (TA 98) with S9: 2-aminoanthracene

Details on test system and experimental conditions:

Ames test
SYSTEM OF TESTING
- Metabolic activation system:    Phenobarbital / beta-naphthoflavone co-induced rat liver S9 fraction,  batch 99/7, 
prepared from male Sprague-Dawley rats
ADMINISTRATION: 
- Dosing:    Preliminary toxicity test (1 replicate): 50; 158; 500; 1580; 5000  µg/plate (+/- metabolic activation)   
Plate incorporation test: 313; 625; 1250; 2500; 5000 µg/plate (+/-  metabolic activation)   repeated for TA 102 (+/- metabolic activation) due to 
gross bacterial  contamination of all plates prepared with this strain   
Pre-incubation test: 313; 625; 1250; 2500; 5000 µg/plate (+/- metabolic  activation)
- Number of replicates: 3
- Application: Solvent dimethyl sulfoxide (CAS No. 67-68-5)
- Positive and negative control groups and treatment:    
positive, TA 1535: 1 µg sodium azide/plate (- S9) / 1 µg  2-aminoanthracene/plate (+ S9)   
positive, TA 1537: 50 µg 9-aminoacridine/plate (- S9) / 1 µg  2-aminoanthracene/plate (+ S9)   
positive, TA 102: 100 µg cumene hydroperoxide/plate (- S9) / 10 or 20  µg 2-aminoanthracene/plate (+ S9)   
positive, TA 98: 2 µg 2-nitrofluorene/plate (- S9) / 1 or 2 µg  2-aminoanthracene/plate (+ S9)   
positive, TA 100: 1 µg sodium azide/plate (- S9) / 1 or 2 µg  2-aminoanthracene/plate (+ S9)   
negative: untreated / solvent control (100 µl/plate) (pre-incubation:  50 µl/plate)   
sterility control including positive control   
activity of metabolic system: 2-aminoanthracene and benzo(a)pyrene / TA  100
- Pre-incubation: 30 minutes at 37 °C   incubation approximately 72 hours at 37 °C

Evaluation criteria:

CRITERIA FOR EVALUATING RESULTS:    ratio of revertant rates treated/control >= 2 with generally positive  dose-response relationship in any strain, reproducible

Species / strain:

S. typhimurium, other: strains TA 1535, TA 1537, TA 98, TA 100, TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: No toxicity at <= 5000 µg/plate (= highest dose level)

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

GENOTOXIC EFFECTS: 
- With metabolic activation: None
- Without metabolic activation: None   
The positive controls were functional.
PRECIPITATION CONCENTRATION: The solubility of the test substance in DMSO  was initially determined to be 100 mg/ml.

Remarks on result:

other: other: Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100, TA 102

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results (migrated information):
negative

No genotoxic effects in a battery of microbial tester strains in the presence or absence of metabolic activation.

Executive summary:

The test substance dodecanedioic acid was examined for mutagenic activity by assaying for reverse mutation to histidine prototrophy in the prokaryotic organism Salmonella typhimurium.tester strains TA1535, TA1537, TA98, TA100 and TA102. Experiments were performed both in the absence and presence of metabolic activation, using liver S9 fraction from rats pre-treated with phenobarbitone and betanaphthoflavone. Test substance solutions were prepared using dimethylsulphoxide.

No toxicity was observed with any tester strain in the toxicity test with a maximum dose-level of 5000µg/plate.

Using the plate incorporation method, and in a subsequent independent assay the preincubation method the test substance was assayed at a maximum dose-level of 5000 µg/plate and at 2500, 1250, 625 and 313 µg/plate.

The test substance did not induce two-fold increases in the number of revertantcolonies in the plate incorporation or pre-incubation assay, at any dose-level, in any tester strain, in the absence or presence of S9 metabolism.

Reference 2

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:

1999-01-26 to 1999-05-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Principles of method if other than guideline:

Method: other: OECD Guideline 476 (1997) and Directive 87/302/EEC, part B, p. 61

GLP compliance:

yes

Type of assay:

mammalian cell gene mutation assay

Target gene:

HGPRT

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Metabolic activation system:

S9 mix based on S9 fraction from  phenobarbital / betanaphthoflavone induced male Sprague-Dawley rat liver

Test concentrations with justification for top dose:

125 - 2000 mg/l

Vehicle / solvent:

dimethyl sulfoxide (DMSO)

Untreated negative controls:

yes

Remarks:

=solvent control (DMSO)

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Remarks:

without metabolic activation

Positive control substance:

ethylmethanesulphonate

Remarks:

positive with metabolic activation: dimethylbenz(a)anthracene (DMBA)

Details on test system and experimental conditions:

HGPRT assay
SYSTEM OF TESTING
- Species/cell type: Chinese hamster V79 cells from Dr. J. Thacker (MRC  Radiobiology Unit, Harwell, UK)
- Metabolic activation system: S9 mix based on S9 fraction from  phenobarbital / betanaphthoflavone induced male Sprague-Dawley rat livers  
(batch 98/11), efficacy checked in Ames test with 2-aminoanthracene and  benzo(a)pyrene in S. typhimurium TA 100
ADMINISTRATION: 
- Dosing:    
(1) Preliminary toxicity test (1 replicate, no positive control):   7.81; 15.6; 31.3; 62.5; 125; 250; 500; 1000; 2000 mg/l (+/- S9)   
(2) First main test: 125; 250; 500; 1000; 2000 mg/l (+/- S9)   
(3) Second main test: 400; 800; 1200; 1600; 2000 mg/l (+/- S9)
- Number of replicates: 2 (positive controls: 1)
- Application:   2,000,000 cells/75 cm2 flask, left overnight, thereafter exposure for 3  hours at 37 °C   Solvent dimethyl sulfoxide (DMSO)
- Positive and negative control groups and treatment:    
positive (- S9): 10 mM ethyl methanesulfonate (EMS) in ethanol   
positive (+ S9): 10 mg 7,12-dimethylbenz(a)anthracene (DMBA)/l in DMSO   
negative (+/- S9): solvent (1 %)

Evaluation criteria:

CRITERIA FOR EVALUATING RESULTS:   
(1) Five (or more) fold increase in mutation frequency over solvent  control at two consecutive concentration levels or at the highest  practicable 
concentration without unacceptable toxicity AND   
(2) Statistically significant (ANOVA) dose-response relation

Statistics:

Results were subjected to an Analysis of Variance in which the effect of replicate culture, expression time and dose-level in explaining the observed
variation was examined

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: approx. 2000 mg/l (+/- S9)

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

GENOTOXIC EFFECTS: 
- With metabolic activation: none
- Without metabolic activation: none   
Normal mutation rates in all negative controls   
Marked responses in all positive controls
PRECIPITATION CONCENTRATION:   
Solubility was observed at 500 g/l in DMSO   
Precipitation upon addition (1:100) to minimal medium of >= 200 g/l DMSO   
Precipitation in cytotoxicity test and main tests at 1000-2000 mg/l   
Addition of the test substance solution had no obvious effect on  osmolality or pH of the treatment medium.

Remarks on result:

other: other: Chinese Hamster V79 cells

Remarks:

Migrated from field 'Test system'.

GENOTOXIC EFFECTS: 
- With metabolic activation: none
- Without metabolic activation: none
  Normal mutation rates in all negative controls
  Marked responses in all positive controls
  -------------------------------------------
  Main test 1: Mutation frequencies (+ S9)
  -------------------------------------------
  Dose-level    Survival     Day 6      Day 9
  -------------------------------------------
     0 mg/l       100 %       6.98       8.00
   125 mg/l       115 %      18.40       9.64
   250 mg/l       111 %       9.82      12.56
   500 mg/l       119 %       8.61       3.10
  1000 mg/l       107 %      24.07      13.25
  2000 mg/l        90 %       4.95       5.57
  DMBA             33 %     836.07     719.24
  -------------------------------------------
  Main test 1: Mutation frequencies (- S9)
  -------------------------------------------
  Dose-level    Survival     Day 6      Day 9
  -------------------------------------------
     0 mg/l       100 %      14.98       8.37
   125 mg/l       107 %      19.80      17.27
   250 mg/l       119 %      11.47       9.52
   500 mg/l       108 %       3.23       5.50
  1000 mg/l        97 %       7.85      17.25
  2000 mg/l        57 %       8.86      18.44
  EMS              59 %    1409.21    1375.24
  -------------------------------------------
  Main test 2: Mutation frequencies (+ S9)
  -------------------------------------------
  Dose-level    Survival     Day 6      Day 9
  -------------------------------------------
     0 mg/l       100 %      10.63       4.20
   400 mg/l        96 %       2.74      17.30
   800 mg/l        85 %      19.67      19.37
  1200 mg/l        77 %      12.97      10.19
  1600 mg/l        60 %      16.07       1.23
  2000 mg/l        69 %      18.01      15.11
  DMBA             21 %    1100.28    1028.13
  -------------------------------------------
  Main test 2: Mutation frequencies (- S9)
  -------------------------------------------
  Dose-level    Survival     Day 6      Day 9
  -------------------------------------------
     0 mg/l       100 %      23.25      20.14
   400 mg/l       109 %       6.14       3.94
   800 mg/l       101 %       9.72       4.70
  1200 mg/l        97 %       6.90      15.13
  1600 mg/l        80 %       5.30      25.60
  2000 mg/l        48 %       8.43      14.52
  EMS              53 %    1122.58    2630.77
  -------------------------------------------
PRECIPITATION CONCENTRATION:
  Solubility was observed at 500 g/l in DMSO
  Precipitation upon addition (1:100) to minimal medium of >= 200 g/l DMSO
  Precipitation in cytotoxicity test and main tests at 1000-2000 mg/l
  Addition of the test substance solution had no obvious effect on  

osmolality or pH of the treatment medium.

Conclusions:

Interpretation of results (migrated information):
negative

No genotoxic effects in Chinese hamster V79 cells in the presence or absence of metabolic activation was observed for the test substance dodecanedioic acid under the conditions of this study.

Executive summary:

The test substance dodecanedioic acid was examined for mutagenic activity by assaying for the induction of 6-thioguanine resistant mutants in Chinese hamster V79 cells after in vitro treatment. Experiments were performed both in the absence and presence of metabolic activation, using liver S9 fraction from rats pre-treated with phenobarbitone and betanaphthoflavone. Test substance solutions were prepared using dimethylsulphoxide.

A preliminary cytotoxicity showed slight toxicity at 2000 µg/mL, the highest dose tested.

Two independent assays for mutation to 6-thioguanine resistance were performed.

In the first experiment, the test substance was^.assayed at the maximum dose level of 2000 µg/mL and 1000, 500, 250 and 125 µg/mL. The second experiment was performed using dose-levels of 2000, 1600, 1200, 800 and 400 µg/mL.

No five-fold increases in mutant numbers or mutant frequency were observed following treatment with the test substance at any dose-level, in the absence or presence of S9 metabolism. In both mutation assays moderate toxicity was observed at the highest dose-level in the absence of S9 metabolism. Slight toxicity was observed in the second experiment at higher dose-levels, in the presence of S9.

Negative and positive control treatments were included in each mutation experiment in the absence and presence of S9 metabolism. Marked increases were obtained with the positive control treatments indicating the correct functioning of the assay system.

It is concluded that dodecanedioic acid does not induce gene mutation in Chinese hamster V79 cells after in vitro treatment in the absence or presence of S9 metabolic activation, under the reported experimental conditions.

Reference 3

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1989-02-14 to 1989-03-01

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions: Incomplete documentation, TA 102 or E.coli WP2 were not tested

Principles of method if other than guideline:

Ames BN et al. (1975). Mutat. Res. 31, 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 1535, TA 1537, TA 1538, TA 98, TA 100

Metabolic activation:

with and without

Metabolic activation system:

Luminal induced rat liver S9 mix

Test concentrations with justification for top dose:

10 to 5000 µg/plate

Vehicle / solvent:

dimethyl sulfoxide (DMSO)

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

dimethyl sulfoxid

True negative controls:

no

Positive controls:

yes

Details on test system and experimental conditions:

Ames test
SYSTEM OF TESTING
- Metabolic activation system:   Luminal induced rat liver S9 mix, male Bor: W/SW (SPF/TNO) rats, enzyme  activity tested with endoxan
ADMINISTRATION: 
- Number of replicates: 2
- Application: solvent dimethyl sulfoxide (CAS No. 67-68-5)
- 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.)   
negative: untreated plus solvent
- Pre-incubation: with and without

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

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:

other: >= 500 µg/plate

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

other: other: Salmonella typhimurium TA 1535, TA 1537, TA 1538, TA 98, TA 100

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results (migrated information):
negative

No genotoxic effects in a battery of microbial tester strains in the presence or absence of metabolic activation were observed for the test substance dodecanedioic acid under the conditions of the study.

Executive summary:

The test substance dodecanedioic acid was examined for genotoxicity in an Ames test. No genotoxic effects in a battery of microbial tester strains in the presence or absence of metabolic activation were observed under the conditions of the study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

No clastogenic activity was noted in vivo in a murine bone marrow micronucleus test.

Link to relevant study records

Reference

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:

1992-02-24 to 1992-05-12

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)

Qualifier:

according to guideline

Guideline:

EPA OTS 798.5395 (In Vivo Mammalian Cytogenics Tests: Erythrocyte Micronucleus Assay)

GLP compliance:

yes

Type of assay:

micronucleus assay

Species:

mouse

Strain:

CD-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ORGANISMS: 
- Source: Charles River Canada Inc., Montreal (Quebec, Canada)
- Age: 56 days (49+6+1)
- Weight at study initiation:   males 27.6 - 34.0 g, mean 30.6 g   females 22.6 - 28.2 g, mean 25.2 g
- No. of animals per dose: 5 males + 5 females per sampling time

Route of administration:

oral: gavage

Vehicle:

0.5 % methyl cellulose in deionized water

Details on exposure:

ADMINISTRATION: 
- Vehicle: 0.5 % methyl cellulose in deionized water
- Control groups and treatment:    
negative: vehicle   
positive: 20 mg cyclophosphamide (CPA)/kg bw/day (in sterile water for  irrigation)
- Total volume applied: 15 ml/kg bw/administration on 2 days each in all  groups
- Duration of test: 72 hours
- Sampling times and number of samples: 24 hours (all dose levels) and 48  hours (all except positive control) after last treatment

Duration of treatment / exposure:

2 equal exposures separated by approx. 24 hours

Post exposure period:

Clinical observations: First 3-5 hours after administration; once daily  thereafter

Remarks:

Doses / Concentrations:
5000; 2000; 1000 mg/kg bw/day
Basis:

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

20 mg cyclophosphamide (CPA)/kg bw/day (in sterile water for  irrigation)

Details of tissue and slide preparation:

EXAMINATIONS: 
- Clinical observations: First 3-5 hours after administration; once daily  thereafter
- Organs examined at necropsy: femur bone marrow   1000 PCE (polychromatic erythrocytes) per animal were analysed for  micronuclei
- Criteria for selection of M.T.D.: Initial study with 2 applications  each of 1250; 2500; 5000 mg/kg bw separated by 1 day; 
2 males + 2 females  / dose level; 2 days post dose observation.   
The top dose for the cytogenetic test was selected as the maximal  non-lethal dose.

Evaluation criteria:

- Criteria for evaluating results: Statistically significant (p<=0.05)  and biologically relevant increase in frequency of micronucleated  polychromatic 
erythrocytes of at least one test group as compared to the  negative control group

Statistics:

Following transformation using the arcsine method data were analysed by one-way ANOVA. In case of significance individual dose groups were compared to the negatiove control using Dunnett's test.

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

MORTALITY: 
No deaths occurred during dose finding and main study.
CLINICAL SIGNS: No significant changes in body weight were observed in  any treated group at any sacrifice. Ruffled fur was exhibited by several  
treated and negative control animals. No other clinical signs were  observed. 
EFFECT ON MITOTIC INDEX OR PCE/NCE RATIO:    No significant reduction in PCE/NCE ratio was present in the positive  control group or in any test 
group when compared with the negative  control animals.
GENOTOXIC EFFECTS:    For the positive control a significant and clear increase in the  frequency of micronucleated polychromatic erythrocytes was 
observed.   The mean frequencies of micronucleated polychromatic erythrocytes in  the groups treated with the test item were equivalent to those of 
the  vehicle control group. 

--------------------------------------------------------
Treatment     Sex   Time   % Micron. in PCE    PCE/NCE
--------------------------------------------------------
Vehicle        m    24 h    0.10 +- 0.03    1.24 +- 0.20
Vehicle        f    24 h    0.10 +- 0.03    1.19 +- 0.21
1000 mg TS     m    24 h    0.02 +- 0.02    1.37 +- 0.17
1000 mg TS     f    24 h    0.16 +- 0.07    1.26 +- 0.08
2000 mg TS     m    24 h    0.10 +- 0.03    0.85 +- 0.15
2000 mg TS     f    24 h    0.08 +- 0.04    1.15 +- 0.07
5000 mg TS     m    24 h    0.14 +- 0.07    1.01 +- 0.14
5000 mg TS     f    24 h    0.08 +- 0.06    1.09 +- 0.18
Vehicle        m    48 h    0.20 +- 0.13    1.34 +- 0.27
Vehicle        f    48 h    0.10 +- 0.03    1.21 +- 0.24
1000 mg TS     m    48 h    0.04 +- 0.02    1.18 +- 0.28
1000 mg TS     f    48 h    0.06 +- 0.04    1.24 +- 0.20
2000 mg TS     m    48 h    0.08 +- 0.04    1.14 +- 0.20
2000 mg TS     f    48 h    0.16 +- 0.05    1.61 +- 0.28
5000 mg TS     m    48 h    0.12 +- 0.04    0.87 +- 0.05
5000 mg TS     f    48 h    0.06 +- 0.02    1.57 +- 0.17
20 mg CPA      m    24 h    0.96 +- 0.22 *  0.81 +- 0.10
20 mg CPA      f    24 h    0.76 +- 0.13 *  1.03 +- 0.12
--------------------------------------------------------
TS = test substance; CPA = cyclophosphamide; 
doses in mg/kg bw/day; * p<0.05

Conclusions:

Interpretation of results (migrated information): negative
Under the conditions of this study there was no indication for genotoxicity of the test substance dodecanedioic acid (DDDA) in vivo.

Executive summary:

The ability of Dodecanedioic acid (DDDA) to induce micronuclei in bonemarrow polychromatic erythrocytes (PCEs) was tested in male and female mice according to OECD TG 474.

Doses of 5000, 2000, or 1000 mg/kg bodyveightwere administered twice, approximately 24 hrs apart, by oral intubation. For all groups,bone marrow smears were prepared approximately 24 and 48 hrs after the final dose. Five males and five females per dose group were sacrificedat each sampling time. One thousand polychromatic erythrocytes per animal were evaluated for the presence of micronuclei.

No statistically significant increases in the frequency of micronucleated PCEs were observed in DDDA-treated animals at any sampling time. Nosignificant depression in the ratio of young, polychromatic erythrocytesto mature, normochromatic erythrocytes was observed. Under the conditions of this assay, DDDA did not induce micronuclei; the test material is negative.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

No genotoxic activity was noted in an array of in vitro and in vivo studies. Dodecanedioic acid was not genotoxic in microbial and mammalian in vitro mutagenicity assays, both in the presence and absence of metabolic activation. Also no genotoxic effect was observed in the murine bone marrow micronucleus test in vivo. An additional study on the clastogenic activity in vitro is considered not necessary.

Justification for classification or non-classification

Dodecanedioic acid was not genotoxic in vitro and in vivo, therefore classification is not required.