Resin acids and Rosin acids, barium salts

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The substance was found to be non-mutagenic in the Salmonella typhimurium/Escherichia coli reverse mutation assay in the absence and the presence of metabolic activation according to OECD Guideline 471.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Okt. 2019 - Jan. 2020

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:

21. Jul 1997

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch number of test material: EXP NR.3757-01
- Expiration date of the lot/batch: 31 Dec 2029

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: refrigerator
- Stability under storage conditions: The stability of the test substance under storage conditions is guaranteed until 31 Dec 2029 as indicated by the sponsor.
- Solubility and stability of the test substance in the solvent/dispersant/vehicle/test medium: The stability of the test substance in the vehicle DMSO was not determined analytically, because the test substance was administered immediately after preparation and is usually stable.
- Reactivity of the test substance with the solvent/vehicle /test medium (if applicable): Due to the insolubility of the test substance in water, DMSO was used as vehicle, which had been demonstrated to be suitable in bacterial reverse mutation tests and for which historical control data are available.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test substance dissolved in dimethyl sulfoxide and used immediately after preparation
- Final preparation of a solid: The test substance was weighed and topped up with the chosen vehicle to achieve the required concentration of the stock solution. The test substance was suspended in dimethyl sulfoxide (DMSO). To achieve homogeneity of the test substance in the vehicle, the test substance preparation was treated with ultrasonic waves and was shaken thoroughly. The further concentrations were diluted according to the planned doses. To keep the test substance homogeneously in the vehicle, the test substance preparation was carefully pipetted before removal. All test substance formulations were prepared immediately before use.

FORM AS APPLIED IN THE TEST (if different from that of starting material) : no difference

Target gene:

his, trp

Species / strain / cell type:

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

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

Type and composition of metabolic activation system:
- source of S9 : liver of 5 adult male Wistar rats induced by a combination of phenobarbital and ß-naphthoflavone
- method of preparation of S9 mix: 24 hours after the last administration, the rats were sacrificed, and the livers were prepared. The livers were weighed, washed and homogenized in KCl solution. After centrifugation of the homogenate, portions of the supernatant (S9 fraction) were stored at -70°C to -80°C. The S9 mix was prepared freshly prior to each experiment. For this purpose, a sufficient amount of S9 fraction was thawed at room temperature and 1 part of S9 fraction is mixed with 9 parts of S9 supplement (cofactors). This mixture of both components (S9 mix) was kept on ice until used.
- concentration or volume of S9 mix and S9 in the final culture medium: 0.5 mL S9 mix
- quality controls of S9 (e.g., enzymatic activity, sterility, metabolic capability): To demonstrate the efficacy of the S9 mix in this assay, the S9 batch was characterized with benzo(a)pyrene.

Test concentrations with justification for top dose:

0; 33; 100; 333; 1000; 2500 and 5000 μg/plate
In agreement with the recommendations of current guidelines 5 mg/plate or 5 μL/plate.

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

- Justification for choice of solvent/vehicle: Due to the insolubility of the test substance in water, DMSO was used as vehicle, which had been demonstrated to be suitable in bacterial reverse mutation tests and for which historical control data are available.

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

9-aminoacridine

other: 2-aminoanthracene (2.5 μg/plate, 60 μg/plate; dissolved in DMSO; with S9-mix); N-methyl-N'-nitro-N-nitrosoguanidine (5 μg/plate; dissolved in DMSO; without S9-mix); 4-nitro-o-phenylenediamine (10 μg/plate; dissolved in DMSO; without S9-mix)

Details on test system and experimental conditions:

NUMBER OF REPLICATIONS:
- Number of cultures per concentration : triplicate
- Number of independent experiments : 2

METHOD OF TREATMENT/ EXPOSURE:
- Cell density at seeding (if applicable): Fresh cultures of bacteria were grown up to late exponential or early stationary phase of growth (approximately 10^9 cells per mL). These cultures grown overnight were kept in iced water from the beginning of the experiment until the end in order to prevent further growth.
- Test substance added: Standard plate test, Preincubation Test

TREATMENT AND HARVEST SCHEDULE:
- Preincubation period, if applicable: about 20 minutes
- Exposure duration/duration of treatment: 48 – 72 hours

METHODS FOR MEASUREMENT OF CYTOTOXICITY
- Method, e.g.: background growth inhibition

Evaluation criteria:

Generally, the experiment was considered valid if the following criteria were met:
• The number of revertant colonies in the negative controls was within the range of the historical negative control data for each tester strain.
• The sterility controls revealed no indication of bacterial contamination.
• The positive control substances both with and without S9 mix induced a distinct increase in the number of revertant colonies compatible with the range of the historical positive control data or above.
• Fresh bacterial culture containing approximately 10^9 cells per mL were used.

The test substance was considered positive in this assay if the following criteria were met:
• A dose-related and reproducible increase in the number of revertant colonies, i.e. at least doubling (bacteria strains with high spontaneous mutation rate, like TA 98, TA 100 and E.coli WP2 uvrA) or tripling (bacteria strains with low spontaneous mutation rate, like TA 1535 and TA 1537) of the spontaneous mutation rate in at least one tester strain either without S9 mix or after adding a metabolizing system.
A test substance was generally considered non-mutagenic in this test if:
• The number of revertants for all tester strains were within the range of the historical negative control data under all experimental conditions in at least two experiments carried out independently of each other.

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 98

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Data on pH: no data
- Data on osmolality: no data
- Water solubility: insoluble
- Precipitation and time of the determination: Test substance precipitation was observed at and above 2500 μg/plate with and without S9 mix.

RANGE-FINDING/SCREENING STUDIES (if applicable):
1st Experiment
Strains: TA 1535, TA 100, TA 1537, TA 98 and E. coli WP2 uvrA
Doses: 0; 33; 100; 333; 1000; 2500 and 5000 μg/plate
Type of test: Standard plate test with and without S9 mix
Number of plates: 3 test plates per dose or per control

STUDY RESULTS
- Concurrent vehicle negative and positive control data : see Tab. 1, 2 and 3

Ames test:
- Signs of toxicity : see Tab. 1, 2 and 3
- Individual plate counts : see Tab. 1, 2 and 3
- Mean number of revertant colonies per plate and standard deviation : see Tab. 1, 2 and 3

HISTORICAL CONTROL DATA (with ranges, means and standard deviation, and 95% control limits for the distribution as well as the number of data)
see Tab. 4 and 5

Tab. 1: Assay conditions: Standard plate test ( Experiment: 1st_SPT)

Key to plate postfix codes

P Precipitation

T Technical fault

Without metabolic activation
Strain	Test group	Dose (μg/plate)	Mean revertants per plate	Standard deviation	Factor	Individual revertant colony counts
TA 1535	DMSO	-	19.7	5.5	-	14, 20, 25
	Test item	33	9.0	5.3	0.5	15, 5, 7
		100	7.3	1.2	0.4	8, 6, 8
		333	10.0	1.0	0.5	9, 10, 11
		1000	12.0	1.0	0.6	13, 12, 11
		2500	6.3	2.1	0.3	4 P, 7 P, 8 P
		5000	6.7	1.5	0.3	8 P, 7 P, 5 P
	MNNG	5.0	3988.7	655.2	202.8	4489, 4230, 3247
TA 100	DMSO	-	96.0	1.0	-	96, 95, 97
	Test item	33	90.0	1.0	0.9	91, 89, 90
		100	100.3	14.2	1.0	107, 110, 84
		333	104.3	2.1	1.1	102, 106, 105
		1000	99.0	10.6	1.0	107, 87, 103
		2500	118.0	5.6	1.2	119 P, 123 P, 112 P
		5000	102.0	33.9	1.1	78 P, - T P, 126 P
	MNNG	5.0	1984.7	139.5	20.7	1825, 2046, 2083
TA 1537	DMSO	-	12.0	6.1	-	8, 9, 19
	Test item	33	9.7	3.1	0.8	13, 7, 9
		100	8.7	1.5	0.7	9, 10, 7
		333	10.3	2.5	0.9	8, 10, 13
		1000	9.7	2.1	0.8	9, 12, 8
		2500	4.3	1.2	0.4	5 P, 5 P, 3 P
		5000	4.7	3.1	0.4	8 P, 4 P, 2 P
	AAC	100	760.7	197.6	63.4	844, 903, 535
TA 98	DMSO	-	22.0	2.6	-	20, 25, 21
	Test item	33	18.3	3.1	0.8	19, 15, 21
		100	14.3	2.5	0.7	17, 12, 14
		333	22.3	4.5	1.0	22, 18, 27
		1000	18.7	2.9	0.8	17, 22, 17
		2500	18.3	4.0	0.8	16 P, 23 P, 16 P
		5000	17.7	3.2	0.8	14 P, 20 P, 19 P
	NOPD	10	804.7	43.3	36.6	819, 839, 756
E. coli	DMSO	-	29.0	1.7	-	31, 28, 28
	Test item	33	34.3	8.6	1.2	42, 25, 36
		100	31.7	12.0	1.1	20, 44, 31
		333	23.7	9.1	0.8	32, 25, 14
		1000	19.7	2.3	0.7	21, 21, 17
		2500	21.3	3.5	0.7	25 P, 21 P, 18 P
		5000	20.0	5.3	0.7	24 P, 22 P, 14 P
	4-NQO	5	1368.7	190.8	47.2	1589, 1255, 1262

With metabolic activation
Strain	Test group	Dose (μg/plate)	Mean revertants per plate	Standard deviation	Factor	Individual revertant colony counts
TA 1535	DMSO	-	11.7	2.3	-	13, 13, 9
	Test item	33	6.5	3.5	0.6	9, - C, 4
		100	8.7	3.2	0.7	11, 10, 5
		333	10.3	3.5	0.9	14, 7, 10
		1000	11.0	4.6	0.9	16, 10, 7
		2500	9.3	6.1	0.8	4 P, 8 P, 16 P
		5000	8.0	1.7	0.7	9 P, 9 P, 6 P
	2-AA	2.5	264.7	23.1	22.7	238, 278, 278
TA 100	DMSO	-	104.7	23.6	-	107, 80, 127
	Test item	33	93.7	5.9	0.9	87, 96, 98
		100	108.0	2.6	1.0	110, 105, 109
		333	104.3	10.2	1.0	97, 100, 116
		1000	97.3	9.6	0.9	87, 106, 99
		2500	100.3	8.0	1.0	92 P, 108 P, 101 P
		5000	100.7	9.9	1.0	96 P, 112 P, 94 P
	2-AA	2.5	2801.3	134.5	26.8	2913, 2839, 2652
TA 1537	DMSO	-	13.7	2.1	-	16, 12, 13
	Test item	33	8.3	2.9	0.6	10, 10, 5
		100	7.3	2.5	0.5	10, 7, 5
		333	6.0	4.0	0.4	6, 2, 10
		1000	9.3	3.2	0.7	8, 7, 13
		2500	7.3	1.2	0.5	6 P, 8 P, 8 P
		5000	6.3	3.1	0.5	9 P, 3 P, 7 P
	2-AA	2.5	168.7	9.7	12.3	171, 177, 158
TA 98	DMSO	-	25.7	3.1	-	25, 29, 23
	Test item	33	21.0	3.0	0.8	18, 21, 24
		100	24.7	2.5	1.0	27, 25, 22
		333	20.0	4.4	0.8	17, 25, 18
		1000	20.3	2.5	0.8	18, 23, 20
		2500	12.3	1.5	0.5	12 P, 14 P, 11 P
		5000	13.3	1.5	0.5	15 P, 13 P, 12 P
	2-AA	2.5	1997.0	344.7	77.8	1599, 2196, 2196
E. coli	DMSO	-	24.7	6.7	-	17, 28, 29
	Test item	33	28.3	2.5	1.1	28, 26, 31
		100	25.7	11.1	1.0	27, 14, 36
		333	22.7	1.5	0.9	21, 23, 24
		1000	33.3	5.5	1.4	33, 28, 39
		2500	24.0	5.6	1.0	30 P, 23 P, 19 P
		5000	19.0	4.4	0.8	21 P, 22 P, 14 P
	2-AA	60	191.3	12.4	7.8	199, 198, 177

 

Tab. 2: Assay conditions: Standard plate test ( Experiment: 2nd-SPT)

Key to plate postfix codes

P Precipitation

Without metabolic activation
Strain	Test group	Dose (μg/plate)	Mean revertants per plate	Standard deviation	Factor	Individual revertant colony counts
TA 1535	DMSO	-	9.7	1.2	-	9, 9, 11
	Test item	33	9.0	2.6	0.9	6, 10, 11
		100	8.0	1.7	0.8	6, 9, 9
		333	7.0	1.0	0.7	8, 6, 7
		1000	7.3	1.2	0.8	8, 8, 6
		2500	7.3	2.3	0.8	10 P, 6 P, 6 P
		5000	9.3	0.6	1.0	10 P, 9 P, 9 P
	MNNG	5.0	5816.3	326.2	601.7	5746, 5531, 6172

 

 

Tab. 3: Assay conditions: Preincubation test ( Experiment: 3rd-PIT)

Key to plate postfix codes

P Precipitation

B Reduced background growth

Without metabolic activation
Strain	Test group	Dose (μg/plate)	Mean revertants per plate	Standard deviation	Factor	Individual revertant colony counts
TA 1535	DMSO	-	6.0	1.0	-	6, 5, 7
	Test item	33	5.7	2.5	0.9	3, 8, 6
		100	6.3	2.1	1.1	7, 4, 8
		333	6.7	1.5	1.1	7, 5, 8
		1000	5.3	2.3	0.9	8, 4, 4
		2500	6.7	5.5	1.1	13 P, 3 P, 4 P
		5000	5.3	1.2	0.9	6 P, 6 P, 4 P
	MNNG	5.0	4658.3	735.6	776.4	5502, 4322, 4151
TA 100	DMSO	-	90.7	2.5	-	93, 91, 88
	Test item	33	95.7	15.2	1.1	93, 112, 82
		100	93.3	7.5	1.0	89, 102, 89
		333	77.0	6.0	0.8	77, 71, 83
		1000	77.0	12.5	0.8	73, 91, 67
		2500	95.0	11.0	1.0	106 P, 84 P, 95 P
		5000	93.7	9.8	1.0	88 P, 88 P, 105 P
	MNNG	5.0	2707.0	67.4	29.9	2720, 2634, 2767
TA 1537	DMSO	-	5.7	3.8	-	4, 10, 3
	Test item	33	6.0	1.0	1.1	6, 7, 5
		100	3.3	2.5	0.6	3, 6, 1
		333	4.0	1.7	0.7	3, 6, 3
		1000	3.7	2.9	0.6	2, 2, 7
		2500	4.0	1.0	0.7	4 P B, 3 P B, 5 P B
		5000	0.0	0.0	0.0	0 P B, 0 P B, 0 P B
	AAC	100	640.0	204.4	112.9	876, 527, 517
TA 98	DMSO	-	17.3	1.2	-	18, 18, 16
	Test item	33	14.0	3.0	0.8	11, 17, 14
		100	15.0	3.5	0.9	11, 17, 17
		333	12.7	4.7	0.7	11, 9, 18
		1000	14.0	2.0	0.8	16, 14, 12
		2500	14.3	3.2	0.8	12 P, 13 P, 18 P
		5000	18.3	3.5	1.1	15 P, 22 P, 18 P
	NOPD	10	874.0	38.6	50.4	837, 914, 871
E. coli	DMSO	-	20.3	3.1	-	21, 23, 17
	Test item	33	19.0	1.0	0.9	20, 18, 19
		100	18.3	7.1	0.9	26, 12, 17
		333	21.0	2.0	1.0	19, 23, 21
		1000	15.0	1.0	0.7	15, 14, 16
		2500	23.7	5.5	1.2	29 P, 24 P, 18 P
		5000	20.7	5.0	1.0	26 P, 20 P, 16 P
	4-NQO	5	692.7	25.4	34.1	721, 672, 685

With metabolic activation
Strain	Test group	Dose (μg/plate)	Mean revertants per plate	Standard deviation	Factor	Individual revertant colony counts
TA 1535	DMSO	-	7.3	2.9	-	9, 4, 9
	Test item	33	7.0	3.0	1.0	10, 7, 4
		100	9.7	2.1	1.3	9, 8, 12
		333	8.7	5.0	1.2	8, 4, 14
		1000	7.7	1.2	1.0	7, 7, 9
		2500	6.7	1.2	0.9	8 P, 6 P, 6 P
		5000	7.7	3.8	1.0	12 P, 6 P, 5 P
	2-AA	2.5	257.3	10.5	35.1	247, 268, 257
TA 100	DMSO	-	87.3	9.3	-	90, 77, 95
	Test item	33	97.3	10.1	1.1	92, 109, 91
		100	90.3	6.0	1.0	91, 96, 84
		333	94.0	3.6	1.1	97, 90, 95
		1000	96.3	12.7	1.1	90, 111, 88
		2500	96.0	4.4	1.1	94 P, 101 P, 93 P
		5000	125.7	8.5	1.4	132 P, 129 P, 116 P
	2-AA	2.5	2436.0	80.7	27.9	2412, 2526, 2370
TA 1537	DMSO	-	5.3	1.5	-	5, 7, 4
	Test item	33	4.3	3.1	0.8	5, 7, 1
		100	5.3	2.9	1.0	7, 7, 2
		333	4.0	1.0	0.8	4, 5, 3
		1000	4.3	1.2	0.8	3, 5, 5
		2500	3.3	1.2	0.6	4 P, 2 P, 4 P
		5000	3.0	1.7	0.6	5 P, 2 P, 2 P
	2-AA	2.5	170.7	17.8	32.0	190, 167, 155
TA 98	DMSO	-	22.0	5.0	-	22, 17, 27
	Test item	33	23.0	5.3	1.0	19, 21, 29
		100	18.0	4.6	0.8	17, 14, 23
		333	16.3	6.0	0.7	10, 22, 17
		1000	15.0	4.4	0.7	13, 20, 12
		2500	19.0	2.0	0.9	21 P, 17 P, 19 P
		5000	18.3	3.5	0.8	22 P, 15 P, 18 P
	2-AA	2.5	2271.3	74.0	103.2	2270, 2198, 2346
E. coli	DMSO	-	19.0	1.7	-	20, 20, 17
	Test item	33	24.0	1.0	1.3	25, 24, 23
		100	24.0	2.0	1.3	22, 26, 24
		333	18.7	2.9	1.0	17, 17, 22
		1000	20.3	10.5	1.1	10, 31, 20
		2500	20.3	6.1	1.1	15 P, 19 P, 27 P
		5000	18.3	4.9	1.0	24 P, 16 P, 15 P
	2-AA	60	73.3	7.4	3.9	79, 76, 65

 

Tab. 4: Historical Negative Controls

Strain                        S9 Mix	Vehicle	No. of     Plates	No. of    Values	Min	Max	Mean	SD
TA 1535                    Without	(All)	222	84	8	19	13	2.3
With	(All)	222	84	7	19	12	2.3
TA 100                       Without	(All)	231	84	18	133	110	14.3
With	(All)	231	86	82	145	110	12.0
TA 1537                     Without	(All)	228	84	5	15	10	2.1
With	(All)	225	84	6	16	10	1.9
TA 98                         Without	(All)	228	85	14	30	20	3.4
With	(All)	234	85	16	37	26	4.4
E. coli                         Without	(All)	216	83	13	40	27	4.7
With	(All)	216	83	17	39	27	3.7

Tab. 5: Historical Positive Controls

Strain	S9 Mix	Positive	No. of	No. of	Min	Max	Mean	SD
		control	Plates	Values

TA 1535                     Without	MNNG	180	66	1517	6912	4122	1569.6
With	2-AA	180	66	97	421	207	76.5
TA 100                       Without	MNNG	183	66	573	6005	3058	1305.3
With	2-AA	186	68	816	3693	1826	687.5
TA 1537                    Without	AAC	183	66	187	1400	829	198.7
With	2-AA	180	66	66	270	151	50.7
TA 98                        Without	NOPD	186	67	531	1148	857	109.2
With	2-AA	192	67	392	2791	1457	641.4
E. coli                        Without	4-NQO	174	66	348	1638	1090	408.3
With	2-AA	171	66	81	278	215	39.2

 

Conclusions:

Under the experimental conditions of this study, the test substance is not mutagenic in the Salmonella typhimurium/Escherichia coli reverse mutation assay in the absence and the presence of metabolic activation.

Executive summary:

The test substance was tested for its mutagenic potential based on the ability to induce point mutations in selected loci of several bacterial strains, i.e. Salmonella typhimurium and Escherichia coli, in a reverse

mutation assay.

STRAINS: TA 1535, TA 100, TA 1537, TA 98 and E. coli WP2 uvrA

DOSE RANGE: 33 μg - 5000 μg/plate (SPT); 33 μg - 5000 μg/plate (PIT)

TEST CONDITIONS: Standard plate test (SPT) and preincubation test (PIT) both with and without metabolic activation (liver S9 mix from induced rats).

SOLUBILITY: Precipitation of the test substance was observed at and above 2500 μg/plate with and without S9 mix.

TOXICITY: A bacteriotoxic effect was observed depending on the strain and test conditions at and above 1000 μg/plate.

MUTAGENICITY: A relevant increase in the number of his+ or trp+ revertants (factor ≥ 2: TA 100, TA 98 and E.coli WP2 uvrA or factor ≥ 3: TA 1535 and TA 1537) was not observed in the standard plate test or in the preincubation test without S9 mix or after the addition of a metabolizing system.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Mode of Action Analysis / Human Relevance Framework

No data available.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. No indication of genotoxicity was observed in the Ames test (OECD 471, GLP). As a result, the substance is not considered to be classified for mutagenicity under Regulation (EC) No. 1272/2008,as amended for the fourteenth time in Regulation (EC) No. 2020/217.