Dodecane-12-lactam

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In all in vitro genotoxicity studies (Ames test according to OECD TG 471 (Hüls AG, 1991 and LPT, 2016), HPRT test according to OECD TG 476 (Hüls AG, 1991); testing above limit of solubility neither required nor performed) and a chromosomal aberration test in human lymphocytes in compliance with OECD TG 473 (Hazleton, 1991), dodecane-12-lactam showed negative results. Therefore it is expected that the chemical is not genotoxic in vivo.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-11-02 - 1991-02-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Version / remarks:

(1983)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)

GLP compliance:

yes

Type of assay:

in vitro mammalian chromosome aberration test

Target gene:

not applicable

Species / strain / cell type:

lymphocytes: Human

Details on mammalian cell type (if applicable):

Human lymphocyte cultures from a single male donor, duplicate cultures

Metabolic activation:

with and without

Metabolic activation system:

male Sprague-Dawley rat liver post-mitochondrial fraction (S-9) from Aroclor 1254 induced animals

Test concentrations with justification for top dose:

30.06; 37.58; 46.98; 58.72; 73.40; 91.75; 114.7; 143.4; 179.2; 224.0; 280.0; 350.0 mg/l

Vehicle / solvent:

Solvent: dimethyl sulfoxide (DMSO)

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

solvent

True negative controls:

yes

Positive controls:

yes

Positive control substance:

cyclophosphamide

methylmethanesulfonate

Details on test system and experimental conditions:

- No. of metaphases analyzed: 100 from each culture if possible, i.e. 200 metaphases / dose group
- Number of replicates: 2
- Application:
with S-9: 3 hours treatment + 17 or 41 h recovery period
without S-9: 20 or 44 h treatment
Chromosome aberrations were analysed in cells sampled 20 hours after the start of treatment at 3 consecutive dose levels. The highest concentrations chosen for analysis at this time, 280 and 350 ug/ml, induced approximately 61% and 46% mitotic inhibition in the absence and presence of S-9, respectively.

Evaluation criteria:

The proportions of cells with structural aberrations excluding gaps for each treatment condition were compared with the proportion in negative controls using Fisher's exact test, p <= 0.05; binominal dispersion test demonstrated acceptable homogenity between replicate cultures; proportion of cells with strucural aberrations without gaps in negative controls fell within the normal range; at least 160 cells out of an intended 200 were analysable at each treatment level; positive control chemicals both induced clear increases in number of cells with structural aberrations; test chemical is considered to be positive if: statistically significant increases in the proportion of structurally aberrant cells without gap ocurred at one or more concentrations and the proportion of aberrant cells at such data points exceeded the normal range; increases in numbers of cells with gaps or increases in numbers of cells with structural aberrrations not exceeding the normal range or occuring only at very high or toxic concentrations were likely to be concluded as "equivocal" or "probably of no biological importance". Cells with exchange aberrations or cells with greater than one aberration were to be considered of greater biological significance

Statistics:

Fisher's exact test, p <= 0.05

Key result

Species / strain:

lymphocytes: Human

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

- With metabolic activation: 46 % mitotic inhibition at 350 mg/l - Without metabolic activation: 61 % mitotic inhibition at 280 mg/l

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Treatment of cultures with lauryl lactam in both the absence and presence of S-9 resulted in frequencies of aberrant cells which were similar to and not significantly different from those observed in concurrent negative controls. Proportions of aberrant cells in all treated cultures fell within historical negative control ranges.

Remarks on result:

other: other: Human Lymphocytes

Remarks:

Migrated from field 'Test system'.

no further remarks

Conclusions:

It is concluded that lauryl lactam was unable to induce chromosome aberrations in human lymphocytes when tested to its solubility limit in either the absence or presence of S-9.

Executive summary:

The test item lauryl lactam was tested in an in vitro cytogenetics assay using duplicate human lymphocyte cultures from a single male donor. The highest dose level used, 350 µg/ml was close to the solubility limit of lauryl lactam in culture medium. Treatments were performed both in the absence and presence of metabolic activation by a rat liver post-mitocondrial fraction (S-9). Appropriate negative (solvent) controls and positive controls (methylmethanesulphonate; cyclophosphamide) were included in the test system. Treatment of cultures with lauryl lactam in both the absence and presence of S-9 resulted in frequencies of aberrant cells which were similar to and not significantly different from those observed in concurrent negative controls. Proportions of aberrant cells in all treated cultures fell within historical negative control ranges. It is concluded that lauryl lactam was unable to induce chromosome aberrations in human lymphocytes when tested to its solubility limit in either the absence or presence of S-9.

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:

1991-02-26 - 1991-05-02

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No testing beyond the limit of solubility under the test conditions, i.e. at concentrations resulting in visible precipitation (not required by 1984 version of guideline)

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(1984)

Deviations:

no

GLP compliance:

yes

Type of assay:

mammalian cell gene mutation assay

Target gene:

hypoxanthine-guanine phosphoribosyl-transferase (HPRT) locus

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Details on mammalian cell type (if applicable):

CHO-K1 cells (Salvage Laboratories, Meckenheim, Germany)

Metabolic activation:

with and without

Metabolic activation system:

from Aroclor 1254 induced Wistar rat liver (Cytotest Cell Research, Rossdorf, Germany)

Test concentrations with justification for top dose:

0; 8; 20; 40; 60; 80 mg/l

Vehicle / solvent:

ethanol, dimethyl sulfoxide (1%)

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

for details see below

True negative controls:

yes

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

Remarks:

positive control with metabolic activation: 3-Methylcholanthrene Migrated to IUCLID6: (without metabolic activation)

Details on test system and experimental conditions:

- Number of replicates: with and without metabolic activation each of them in 2 independent tests
- Application: 2E+05 cells/25 cm2 flask; exposure time 4 h
- Negative control groups and treatment:
negative, no metab. activ.: HO medium with 0.4 % ethanol; HO medium only
negative, with metab. activ.: HO medium with 0.4 % ethanol; HO medium only; DMSO (1%)

Evaluation criteria:

Statistically significant, dose related increase in mutant frequency at concentrations of the test substance resulting in > 10 % cell survival.
Mean frequency > maximum spontaneous frequency.

Statistics:

t-test

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Remarks:

not observed below solubility limit (80 mg/l)

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Statistically significant increases in mutant frequencies of the test item laurolactam treated cells relative to the solvent controls were observed at the following dose levels: - without metabolic activation: 8, 60 mg/l (test no. 2); 80 mg/l (test no. 1). However neither of these increased frequencies prooved to be reproducible in the correspondent second HPRT test. Furthermore, only the mean mutant frequency at 60 mg/l (test no. 2) was slightly above the maximum spontaneous mutant frequency, while the other frequencies lay well in the range of this biological background level. - with metabolic activation: 8 mg/l; 80 mg/l (test no. 2). Neither of these two results was reproducible in HPRT test no. 1. In addition, both frequencies lay well inside the range of the spontaneous mutant frequency of this test system. The observed increases are therefore considered to be biologically insignificant. In general a dose related increase in mutant frequency (with and without metabolic activation) was not observed in the tests.

Remarks on result:

other: other: Chinese hamster ovary (CHO) K1 cells

Remarks:

Migrated from field 'Test system'.

no further remarks

Conclusions:

Interpretation of results (migrated information):
negative

The results of both tests with and without metabolic activation indicate, that LAUROLACTAM, under the experimental conditions described, does not demonstrate mutagenic potential in this in vitro test system.

Executive summary:

The test item Laurolactam was tested for its ability to induce forward mutation at the hypoxanthine-guanine phosphoribosyl-transferase (HPRT) locus in Chinese hamster ovary (CHO) cells in vitro both in the presence and the absence of exogenous metabolic activation(by Arochlor 1254 -induced rat liver S9). The substance was tested in concentrations of 8 mg/l to the solubility limit of 80 mg/l with and without S9 mix. In this concentration range, Laurolactam did not induce any detectable cytotoxicity. Compared to the solvent control, ethanol, treatment with laurolactam in both assays (with and without metabolic activation) did not result in any reproducible statistically or biologically significant increase of the mutation frequency of the HPRT locus.

It is concluded that Laurolactam, in the presence as well as in the absence of S9 mix, demonstrates no mutagenic potential in this in vitro mammalian cell assay.

Reference 3

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:

1991-02-26 - 1991-04-15

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)

Version / remarks:

(1981)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Version / remarks:

Cited as Directive 84/449/EEC, B.14

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Target gene:

mutated gene loci responsible for histidine auxotrophy

Species / strain / cell type:

S. typhimurium, other: TA 98, TA 100, TA 1535, TA 1537, TA 1538

Additional strain / cell type characteristics:

other: histidine auxotroph

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced S9 fraction (Wistar rat liver), activity checked on TA 100 with aminoanthracene

Test concentrations with justification for top dose:

8, 40, 200, 1,000, 5000 µg/plate (main test), and 125, 250, 500, 1,000, 2,000 µg/plate (pre-incubation test)

Vehicle / solvent:

dimethyl sulfoxide

Untreated negative controls:

yes

Remarks:

untreated

Negative solvent / vehicle controls:

yes

Remarks:

dimethyl sulfoxide

True negative controls:

no

Remarks:

untreated

Positive controls:

yes

Remarks:

for details see below

Positive control substance:

other: without metabolic activation: Nitrofluorene (TA 98; TA 1538), Sodium azide (TA 100; TA 1535), Aminoacridine (TA 1537); with metabolic activation: Aminoanthracene (TA 100)

Details on test system and experimental conditions:

Type: Ames test
- Dosing:
pre-incubation test: 40 g/l in dimethyl sulfoxide
125; 250; 500; 1000; 2000 µg/plate
main test: 50 g/l in dimethyl sulfoxide
8; 40; 200; 1000; 5000 µg/plate
- Number of replicates: 3
- Positive controls:
TA 98, TA 1538: nitrofluorene (2.5 µg/plate)
TA 100, TA 1535: sodium azide (2.5 µg/plate)
TA 1537: aminoacridine (50 µg/plate)
Enzymatic activity: TA 100 / aminoanthracene (10 µg/plate)
- Negative control: solvent (dimethyl sulfoxide); untreated
- Pre-incubation time: 30 minutes (30 °C)

Evaluation criteria:

According to Ames (1975): Mutagenic effects (i.e ratio of revertant rates treated/control > 2) at <= 5000 µg/plate with generally positive dose-response relationship in any strain

Statistics:

The stated means, standard deviations and factors were calculated through a computer program written by Messrs BIOSYS. The usual statistical methods were used for the calculations.

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:

cytotoxicity

Remarks:

1000, 2000, and 5000 µg/plate (details acc. to strains see under "Additional information on results")

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

GENOTOXIC EFFECTS:
- With metabolic activation: None (even at cytotoxic concentrations)
- Without metabolic activation: None (even at cytotoxic concentrations)
PRECIPITATION CONCENTRATION: > 1000 µg/plate
CYTOTOXIC CONCENTRATION (including effects on background lawn):
TA 98: 5000 µg/plate (+ S9); 2000 µg/plate (- S9)
TA 100: 5000 µg/plate (- S9)
TA 1535: 5000 µg/plate (+ S9), 2000 µg/plate (- S9)
TA 1537: 1000 µg/plate (+/- S9)
TA 1538: None

Remarks on result:

other: strain/cell type: S. typhimurium: TA 98, TA 100, TA 1535, TA 1537, TA 1538

Remarks:

Migrated from field 'Test system'.

no further remarks

Conclusions:

Under the conditions of the study the test item lauryl lactam proved to be non-mutagenic, both in the presence and in the absence of Arochlor-induced liver microsomes, for all test strains used in this study.

Executive summary:

The substance lauryl lactam was tested in the Ames Salmonella mutagenicity test for any mutagenic activity. The test organisms were five histidine-auxotrophic Salmonella typhimurium strains (TA 1535; TA 1537; TA 1538; TA 98 and TA 100). Under the conditions of the study the test item lauryl lactam proved to be non-mutagenic, both in the presence and in the absence of Arochlor-induced liver microsomes, for all test strains used in this study.

Reference 4

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:

2016-02-03 to 2016-02-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1997

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Target gene:

mutated gene loci resposible for histidine auxotropy

Species / strain / cell type:

E. coli WP2 uvr A pKM 101

Details on mammalian cell type (if applicable):

- obtained from Trinova Biochem according to Dr. Bruce N. AMES,

Additional strain / cell type characteristics:

other: histidine auxotroph

Metabolic activation:

with and without

Metabolic activation system:

Arochlor 1254 induced rat liver S9; male rats, obtained from Trinova Biochem

Test concentrations with justification for top dose:

Plate incorporation test: 10.0, 31.6, 100, 316, 1000 and 3160 µg per plate;
Preincubation test: 10.0, 31.6, 100, 316, 1000 and 3160 µg per plate;

Vehicle / solvent:

The test item was completely dissolved in ethanol . The vehicle ethanol was employed as the negative control. Fresh preparations of the test item were used for the treatment in all experimental parts.

Untreated negative controls:

no

Remarks:

solvent test will be used as negative reference item

Negative solvent / vehicle controls:

yes

Remarks:

Ethanol

True negative controls:

no

Positive controls:

yes

Remarks:

for details see below

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

with metabolic activation: 2-aminoanthracene in DMSO

Details on test system and experimental conditions:

Bacterial Reverse Mutation Test
SYSTEM OF TESTING
- Pre-Experiment: plate incorporation cytotoxicity test (+/- metabolic activation) in the Escherichia coli strain WP2 uvrA [pKM101].
- The test item was examined in two preliminary cytotoxicity tests (plate incorporation test without and with metabolic activation).
- Ten concentrations ranging from 0.316 to 5000 µg/plate were tested.
- Pronounced cytotoxicity (scarce background lawn and reduction of the number of revertants by more than 50%) was noted starting at
concentrations of 3160 and 5000 µg/plate. Hence, 3160 µg test item/plate were chosen as top concentration for the main study in the plate
incorporation test and in the preincubation test.
- Main test: 1st - Standard plate incorporation method, 2nd - Preincubation method
- Metabolic activation assay: Arochlor 1254 induced rat liver S9 fraction.
ADMINISTRATION
- Dosing:
* Plate incorporation test: 10.0, 31.6, 100, 316, 1000 and 3160 µg per plate.
* Preincubation test: 10.0, 31.6, 100, 316, 1000 and 3160 µg per plate.
- Data : 2 independent experiments with and without metabolic activation
- Number of replicates: 3 per concentration and experiment
- Positive and negative control groups and treatment:
- without metabolic activation:
* 4-nitroquinoline-N-oxide in DMSO (5 µg/plate) for E.coli WP2 uvrA [pKM101].
- with metabolic acivation
* 2-aminoanthracene in DMSO (2 µg/plate) for E.coli WP2 uvrA [pKM101]
- negative control: the vehicle Ethanol was used as negative reference item.
- Incubation time: 48 h to 72 h at 37 °C in the dark
- Pre-incubation time: 20 min at 37 °C;

NUMBER OF REPLICATIONS: 3 per concentration and experiment

NUMBER OF CELLS EVALUATED: approximately 10E8 viable cells in the late exponential or early stationary phase

DETERMINATION OF CYTOTOXICITY
- Method: In the plate incorporation test and in the preincubation test, each carried out without and with metabolic activation, pronounced
cytotoxicity (scarce background lawn and reduction of the number of revertants by more than 50%) was noted at the top concentration of
3160 µg test item/plate, in the Escherichia coli strain WP2 uvrA [pKM101].

Evaluation criteria:

A test item is considered to show a positive response if
- the number of revertants is significantly increased (p the solvent control to at least 2-fold of the solvent control for the Escherichia coli test strain WP2 uvrA [pKM101] in both independent experiments.
- in addition, a significant (p
Biological relevance of the results should be considered first.
- Positive results have to be reproducible and the tryptophan independence of the revertants has to be confirmed by streaking random samples on
tryptophan-free agar plates.
- A test item for which the results do not meet the above mentioned criteria is considered as non-mutagenic in the AMES test.
- The range of spontaneous reversion frequencies of Escherichia coli WP2 uvrA [pKM101] of 25 to 65 revertant colonies per plate is based on
KIRKLAND (1990). The numbers may be slightly different on plates with S9 and may vary slightly from experiment to experiment.
- Cytotoxicity is defined as a reduction in the number of colonies by more than 50% compared with the vehicle control and/or a scarce background
lawn.
- Historical background data of revertant colony numbers of the negative and positive controls without and with metabolic activation for the
experiments of the years 2013 to 2015 (most recent background data, not audited by the QAU-department) are given in Appendix 1.

Statistics:

According to the OECD Guideline 471, a statistical analysis of the data is not mandatory

Key result

Species / strain:

E. coli WP2 uvr A pKM 101

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

cytotoxicity (scarce background lawn and reduction of the number of revertants by more than 50%) was noted at the top concentration of 3160 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

GENTOXIC EFFECTS:
- With metabolic activation: negativ
- Without metabolic activation: negativ

CYTOTOXICITY EFFECTS:
In the plate incorporation test and in the preincubation test, each carried out without and with metabolic activation, pronounced cytotoxicity (scarce background lawn and reduction of the number of revertants by more than 50%) was noted at the top concentration of 3160 µg test item/plate, in the
Escherichia coli strain WP2 uvrA [pKM101].

see attchached document

Conclusions:

In conclusion, under the present test conditions, the test item tested up to the cytotoxic concentration of 3160 µg/plate, caused no mutagenic
effect in the Escherichia coli strain WP2 uvrA [pKM101], neither in the plate incorporation test nor in the preincubation test, each carried out without
and with metabolic activation.

Executive summary:

The purpose of this study was to evaluate Lauryl lactam for mutagenic activity (gene mutation) in the Escherichia coli strain WP2 uvrAwithout and with the addition of a mammalian metabolic activation system as originally described by AMES et al. (1973, 1975) and revised by MARON and AMES (1983).

The test item was examined in the Escherichia coli strain WP2 uvrA [pKM101] in two independent experiments, each carried out without and with metabolic activation (a microsomal preparation derived from Aroclor 1254-induced rat liver). The first experiment was carried out as a plate incorporation test and the second as a preincubation test.

Test item was completely dissolved in ethanol. The vehicle ethanol was employed as the negative control.

Preliminary test

Test item was examined in two preliminary cytotoxicity tests (plate incorporation test without and with metabolic activation) in the Escherichia coli strain WP2 uvrA [pKM101]. Ten concentrations ranging from 0.316 to 5000 µg/plate were tested. Pronounced cytotoxicity (scarce background lawn and reduction of the number of revertants by more than 50%)was noted starting at concentrations of 3160 and 5000 µg/plate.Hence, 3160 µg test item/plate were chosen as top concentration for the main study in the plate incorporation test and in the preincubation test.

Main study

Six concentrations ranging from 10.0 to 3160 µg test item/plate were employed in the plate incorporation test and in the preincubation test, each carried out without and with metabolic activation.

Cytotoxicity

In the plate incorporation test and in the preincubation test, each carried out without and with metabolic activation, pronounced cytotoxicity (scarce background lawn and reduction of the number of revertantsby more than 50%) was noted at the top concentration of 3160 µg test item/plate, in the Escherichia coli strain WP2 uvrA [pKM101].

Mutagenicity

No increase in revertant colony numbers as compared with control counts was observed for test item, tested up to the cytotoxic concentration of 3160 µg/plate,in the Escherichia coli test strains in two independent experiments without and with metabolic activation, respectively (plate incorporation and preincubation test).

 

The positive control items showed a significant increase in the number of revertant colonies of the respective test strain and confirmed the validity of the test conditions and the sensitivity of the test system.

In conclusion, under the present test conditions, the test item tested up to the cytotoxic concentration of 3160 µg/plate, caused no mutagenic effect in the Escherichia coli strain WP2 uvrA [pKM101], neither in the plate incorporation test nor in the preincubation test, each carried out without and with metabolic activation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

No studies with respect to this endpoint have been performed.

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In vitroStudies

 

In an Ames test performed according to OECD TG 471(1981) with Salmonella typhimuriumTA 1535, TA 1537, TA 1538, TA 98 and TA 100, test substance concentrations of up to 5,000 µg/plate were employed in the presence and absence of Aroclor 1254-induced rat liver S9 mix. An increase in mutant frequency was not observed (Hüls AG, 1991).

In a HPRT test with Chinese Hamster ovary (CHO) cells, dodecane-12-lactam concentrations of 8-80 mg/l (+/- S9 mix from Aroclor 1254 induced rat livers) did not increase the mutant frequency of treated cells. In accordance with OECD TG 476 (1984), the chemical was tested up to the limit of solubility under culture conditions, i.e. under culture conditions 80 mg/l was the highest concentration showing no precipitation. (The 1997 version of OECD TG 476 requires testing up to concentrations leading to visible precipitation.) Cytotoxicity was not observed at any of the concentrations tested (Hüls AG 2, 1991).

In a cytogenetic assay with human lymphocytes (according to OECD TG 473), concentrations of 30 - 350 mg/l (+/-S9 mix from Aroclor 1254-induced rat livers) were employed. A significant increase in chromosomal aberrations was not observed even at cytotoxic concentrations (Hazleton, 1991).

 

In vivoStudies

No studies with respect to this endpoint have been performed.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

According to the criteria of EC Directive 67/548/EEC and EC Regulation 1272/2008 and based on the results of the studies Dodecane-12-lactam is not classified.