6-nonyl-1,3,5-triazine-2,4-diamine

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Based on the results of the full set of in-vitro genotoxicity tests required by REACH regulation including read-across information form structural related source substances, Caprinoguanamine does not need to be classified for germ cell mutagenicity according to CLP, EU GHS (Regulation (EC) No 1272/2008).

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

For detailed justification for read across, please refer to section 13.2

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Species / strain:

lymphocytes: human

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Key result

Species / strain:

lymphocytes: human

Metabolic activation:

without

Genotoxicity:

ambiguous

Remarks:

significant increase in the frequency of cells with structural chromosome aberrations when dosed above solubility level. This may be an artifact due to the precipitation of Benzoguanamine.

Key result

Species / strain:

other: CHL/IU

Metabolic activation:

with and without

Genotoxicity:

positive

Key result

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: Information from Benzoguanamine

Conclusions:

Based on read across Caprinoguanamine was considered not to have a potential for chromosom abberation

Reference 2

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

For detailed justification for read across, please refer to section 13.2

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

ambiguous

Remarks:

see additional information

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

no signs of toxicity were observed up to concentrations 2500 µg/mL in the presence of metabolic activation (S9 mix). In the absence of S9 mix, there is a small dose-related reduction in plating efficiency with Benzoguanamine.

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Benzoguanamine:
There were no statistically significant increases in the mutation frequency at any dose level tested without metabolic acitvation (S9).
In the presence of S9, the mutation frequency was significantly higher at the 625 µg/ml dose level. A precipitate of Benzoguanamine was observed at and above 625 µg/ml and therefore NO significant increase in mutation frequency was observed within the soluble dose range of Benzoguanamine.

Remarks on result:

other: Information from Acetoguanamine

Conclusions:

Based on read across Caprinoguanamine was considered to have no gene mutation characteristics

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:

2016-02-19 to 2016-03-29

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:

(adopted 21st July, 1997)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(dated May 30, 2008)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine locus

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Metabolic activation system:

S9 liver microsomal fraction (phenobarbital and ß-naphthoflavone induced)

Test concentrations with justification for top dose:

Experiment I:
3.16, 10.0, 31.6, 100, 316, and 1000 µg/plate; in addition 0.316, 1.00 µg/plate only TA 100 without metabolic activation
Experiment II:
0.316, 1.0, 3.16, 10.0, 31.6, 100, 316, and 1000 µg/plate
Precipitation was observed in all tester strains used in experiment I and II (with and without metabolic activation) at concentrations of 1000 µg/plate and higher.

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: pretest

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

sodium azide

methylmethanesulfonate

other: 4-nitro-o-phenylene-diamine, 2- aminoanthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: experiment I in agar (plate incorporation)
experiment II preincubation

DURATION
- Preincubation period: 60 min at 37 °C
- Exposure duration: at least 48 h at 37 °C

SELECTION AGENT (mutation assays): Histidin

NUMBER OF REPLICATIONS: 3 plates per concentration and strain


DETERMINATION OF CYTOTOXICITY
- Method: background lawn, reduction in the number of revertants down to a mutation factor of approx. < 0.5 in relation to the solvent control.

OTHER: Colonies were counted using a ProtoCOL counter (Meintrup DWS Laborgeräte GmbH). If precipitation of the test item precluded automatic counting the revertant colonies were counted by hand.
Tester strains TA 1535 and TA 1537 were counted manually.

Evaluation criteria:

Validity:
A test is considered acceptable if for each strain:
- the bacteria demonstrate their typical responses to ampicillin
- the negative control plates with and without S9 mix are within laboratory historical ranges
- corresponding background growth on negative control, solvent control and test plates is observed
- the positive controls show a distinct enhancement of revertant rates over the control plate
- at least five different concentrations of each tester strain are analysable.

Evaluation of Mutagenicity:
A test item is considered as mutagenic if:
- a clear dose-related increase in the number of revertants occurs and/or
- a biologically relevant positive response for at least one of the dose groups occurs
in at least one tester strain with or without metabolic activation.

A biologically relevant increase is described as follows:
- if in tester strains TA98, TA100 and TA 102 the number of reversions is at least twice as high
- if in tester strains TA 1535 and TA 1537 the number of reversions is at least three times higher
than the reversion rate of the solvent control.

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation:
Precipitation was observed in all tester strains used in experiment land II (with and without
rnetabollc activation) at concentrations of 1000 μg/plate and higher.


RANGE-FINDING/SCREENING STUDIES:
The test item was tested in the pre-experiment with the following concentrations:
3.16,10.0,31.6,100,316,1000,2500 and 5000 μg/plate

HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data: valid
- Negative (solvent/vehicle) historical control data: valid

CYTOTOXICITY:
In experiment I toxie effeets of the test item were observed in tester strain TA 98 at eoneentrations of
100 μg/plate and higher (without metabelle aetivation) and at eoneentrations of 316 μg/plate and
higher (with metabelle aetivation). In tester strains TA 100, TA 1535 and TA 1537 toxie effeets ofthe
test item were noted at eoneentrations of 316 μg/plate and higher (with and without metabolie
aetivation). (see table 12.1.2)
In experiment II toxie effeets of the test item were noted in tester strain TA 98 at eoneentrations of
316 μg/plate and higher (without metabolie aetivation) and at a eoneentration of 1000 μg/plate (with
rnetabollc aetivation). In tester strains TA 100 and TA 1537 toxie effeets of the test item were noted
at eoneentrations of 100 μg/plate and higher (without metabelle aetivation) and at eoneentrations of
316 μg/plate and higher (with metabelle aetivation). In tester strain TA 1535 toxie effeets of the test
item were observed at eoneentrations of 100 μg/plate and higher (without metabolie aetivation) and
at a eoneentration of 1000 μg/plate (with metabolic aetivation). In tester strain TA 102 toxie effeets of
the test item were noted at a eoneentration of 1000 μg/plate (without metabelle aetivation). (see
table 12.1.3)

Cytotoxicity:

In experiment I toxic effects of the test item were observed in tester strain TA 98 at concentrations of 100 μg/plate and higher (without metabolic activation) and at concentrations of 316 μg/plate and higher (with metabolic activation). In tester strains TA 100, TA 1535 and TA 1537 toxic effects of the test item were noted at concentrations of 316 μg/plate and higher (with and without metabolic activation).

In experiment II toxic effects of the test item were noted in tester strain TA 98 at concentrations of 316 μg/plate and higher (without metabolic activation) and at a concentration of 1000 μg/plate (with metabolic activation). In tester strains TA 100 and TA 1537 toxic effects of the test item were noted at concentrations of 100 μg/plate and higher (without metabolic activation) and at concentrations of 316 μg/plate and higher (with metabolic activation). In tester strain TA 1535 toxic effects of the test item were observed at concentrations of 100 μg/plate and higher (without metabolic activation) and at a concentration of 1000 μg/plate (with metabolic activation). In tester strain TA 102 toxic effects of the test item were noted at a concentration of 1000 μg/plate (without metabolic activation).

Conclusions:

Caprinoguanamine is considered to be non-mutagenic in this bacterial reverse mutation assay.

Executive summary:

In a reverse gene mutation assay in bacteria according to OECD guideline 471, strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 of S. typhimurium were exposed to Caprinoguanamine, at concentrations of 3.16, 10.0, 31.6, 100, 316, and 1000 µg/plate; in addition 0.316, 1.00 µg/plate only TA 100 without metabolic activation in experiment I and at concentrations of 0.316, 1.0, 3.16, 10.0, 31.6, 100, 316, and 1000 µg/plate in experiment II.

The first experiment was conducted as plate incorporation assay, the second as pre-incubation test, both in the absence and presence of a mammalian metabolic activation.

Precipitation of the test item was observed at 1000 µg/plate and higher in all experiments.

 

Toxic effects of the test item were noted in most tester strains used in experiment I and II at concentrations of 100 µg/plate and higher (without metabolic activation) and at concentrations of 316 µg/plate and higher (with metabolic activation), depending on the particular tester strain.

 

No biological relevant increases in revertant colony numbers of any of the five tester strains were observed following treatment with Caprinoguanamine at any concentration level, neither in the presence nor absence of metabolic activation in experiment I and II.

The reference mutagen induced a distinct increase of revertant colonies indicating the validity of the experiments.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Negative data from a micronucleus assay in mouse bone marrow of mice are available from the read-across substance Benzoguanamine.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes (incl. QA statement)

Type of assay:

micronucleus assay

Species:

mouse

Strain:

NMRI

Sex:

male/female

Route of administration:

oral: gavage

Remarks:

Doses / Concentrations:
male mice; 75, 150, 300 mg/kg b.w. |female mice; 50, 100, 200 mg/kg b.w.
Basis:

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

This substance was not mutagenic in bacteria [OECD TG 471]. It induced chromosomal aberration in CHL/IU cells with and without an exogenous metabolic activation system even under the soluble concentrations. It also gave a positive response in the human lymphocytes tested [OECD TG 473] and the mouse lymphoma TK assay [OECD TG 476] but only under the insoluble dose levels. The cytogenetic effect observed in in vitro assays however, could not be reproduced in the micronucleus tests in vivo [OECD TG 474].

STATISTICAL RESULTS:
-The highest dose (300 mg/kg for males and 200 mg/kg b.w. for females) was estimated by five pre-experiments to the suitable since higher concentrations were lethal. After treatment with the test item the number of NCEs was not substantially increased as compared to the mean value of NCEs of the vehicle control thus indicating that this substance at the indicated concentrations had no cytotoxic effectiveness in the bone marrow.
There was no biologically and statistically relevant enhancement in the frequency of the detected micronuclei after administration of the test item at any dose level or sampling time as compared to vehicle controle. 40 mg/kg b.w. cyclophosphamide administered orally was used as positive control which showed a substantial increase of induced micronucleus frequency.

-micronucleus test results
(A)Male animals

Test group  Dose      Sampling     Sampling       NCEs per
---        mg/kg b.w.  time (hr)   micronuclei(%)  2000 PCEs
vehicle        0         24          0.02          1566
BG            75         24          0.08          1562
BG           150         24          0.09          1814
BG           300         24          0.02          1582
CP            40         24          1.11          2033

Vehicle        0         48          0.01          1694
BG            75         48          0.02          1639
BG           150         48          0.08          1795
BG           300         48          0.07          1755

Vehicle        0         72          0.03          1610
BG            75         72          0.04          1417
BG           150         72          0.03          1549
BG           300         72          0.02          1645

(B)Female animals

Test group   Dose      Sampling    Sampling       NCEs per
---        mg/kg b.w.  time (hr)   micronuclei(%) 2000 PCEs
vehicle       0          24         0.03          1652
BG           50          24         0.03          1563
BG          100          24         0.09          1463
BG          200          24         0.04          1889
CP           40          24         0.98          1755

Vehicle       0          48         0.01          2113
BG           50          48         0.04          1727
BG          100          48         0.01          1628
BG          200          48         0.02          1945

Vehicle       0          72         0.02          1577
BG           50          72         0.02          1408
BG          100          72         0.04          1638
BG          200          72         0.01          1492

BG = benzoguanamine (2,4-diamino-6-phenyl-1,3,5-triazine)
CP = cyclo phosphamide

Conclusions:

Interpretation of results: negative
not genotoxic in vivo

Executive summary:

In a CD-1 mouse bone marrow micronucleus assay, 5 male and female were treated oral gavage with this substance at doses of 0, 75, 150, 300 mg/kg bw in male mice and 0, 50, 100, 200 mg/kg/bw.  Bone marrow cells were harvested at 24, 48, 72 hr post-treatment.  The vehicle was corn oil. 

 

There were no signs of toxicity during the study.The positive control induced the appropriate response. There was not a significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow after any treatment time.

 

This study satisfiesthe requirement for Test Guideline OECD 474 for in vivo cytogenetic mutagenicity data.

Reference 2

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

For detailed justification of read across, please refer to section 13.2

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Conclusions:

Based on read across Caprinoguanamine was considered to have genetic toxicity properties

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

In-vitro studies

Gene mutation in bacteria

Caprinoguanamine

In a reverse gene mutation assay in bacteria according to OECD guideline 471, strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 of S. typhimurium were exposed to Caprinoguanamine, at concentrations of 3.16, 10.0, 31.6, 100, 316, and 1000 µg/plate; in addition 0.316, 1.00 µg/plate only TA 100 without metabolic activation in experiment I and at concentrations of 0.316, 1.0, 3.16, 10.0, 31.6, 100, 316, and 1000 µg/plate in experiment II. The first experiment was conducted as plate incorporation assay, the second as pre-incubation test, both in the absence and presence of a mammalian metabolic activation. Precipitation of the test item was observed at 1000 µg/plate and higher in all experiments.

Toxic effects of the test item were noted in most tester strains used in experiment I and II at concentrations of 100 µg/plate and higher (without metabolic activation) and at concentrations of 316 µg/plate and higher (with metabolic activation), depending on the particular tester strain. 

No biological relevant increases in revertant colony numbers of any of the five tester strains were observed following treatment with Caprinoguanamine at any concentration level, neither in the presence nor absence of metabolic activation in experiment I and II.

 

Acetoguanamine

Data from an Ames test according to OECD guideline 471 (version 1983) in tester strains TA98, TA100, TA1535, TA1537 and TA1538 of S. typhimurium are available for Acetoguanamine. The substance does not induce mutations in the five tested strains, when tested up to 5000 µg/plate in the absence and presence of a rat liver metabolic activation system.

 

Benzoguanamine

In a reverse gene mutation assay in bacteria, Salmonella typhimurium (TA100, TA98,TA1535, TA1537) and E. coli (WP2uvrA)  were exposed to this substance included DMSO at concentrations of 0, 156, 313, 625, 1250, 2500, 5000 µg/plate in the presence and absence of mammalian metabolic activation.  There was no evidence of induced mutant colonies over background, up to limit concentration 5000 µg/plate. 

 

Melamine

In a reverse gene mutation assay in bacteria, strains TA100, TA1535, TA1537 and TA98 of S. typhimurium were exposed to Melamine at concentrations of 0, 3.3, 10, 33, 100, 111, 333, 1000, 1111, 3333, 5550 µg/plate in the presence and absence of mammalian metabolic activation (rat S9 mix and hamster S9 mix) by a pre-incubation method. There was no evidence of induced mutant colonies over background.

 

Mammalian cell gene mutation assay

Acetoguanamine:

In an in vitro Mammalian cell Gene Mutation Test (Thymidine Kinase Locus/TK+/-) in Mouse Lymphoma L5178Y Cells according to OECD 476 Acetoguanamine was assessed for its potential to induce mutations. The selection of the concentrations used in the main experiments was based on data from the pre-experiments. Therefore the test item was investigated at the following concentrations:

Experiment I (4 h short-term exposure assay, with and without metabolic activation): 0.1, 0.2, 0.5, 1.0, 2.5, 5.0, 7.5 and 10.0 mM.

Experiment II (4 h short-term exposure assay, with metabolic activation): 0.15, 0.3, 0.6, 1.5, 3.0, 6.0, 8.0, 10.0 mM.

Experiment II (24 h long-term exposure assay, without metabolic activation): 0.05, 0.1, 0.5, 1.0, 2.5, 4.0, 5.0 and 6.0 mM.

Acetoguanamine is considered to be non-mutagenic in the in vitro mammalian cell gene mutation test (thymidine kinase locus) in mouse lymphoma L5178Y cells.

Benzoguanamine

In a mammalian cell gene mutation assay, Mouse lymphoma cells cultured in vitro were exposed to Benzoguanamine at concentrations of 0, 78.1, 156.25, 312.5, 625, 1250, 2500 µg/mL in the presence and absence of mammalian metabolic activation. No mutagenic effects were observed in the absence of mammalian metabolic activation.

Within the solubility limit no mutagenic effects were observedwith metabolic activation; however above the solubility limitresults were ambiguous.

Melamine:

In a mouse lymphoma assay according to NTP standard protocol, mouse lymphoma L5178Y cells cultured in vitro were exposed to melamine in DMSO at concentrations of 0, 10, 20, 40, 80 and 160 µg/mL in the presence and absence of mammalian metabolic activation.

There were no indications of a mutagenic response with and without metabolic activation.

 

Chromosome Aberration:

Benzoguanamine

In a human lymphocyte chromosome aberration assay, Human Lymphocytes cells cultured in vitro were exposed to Benzoguanamine at concentrations of 78, 125, 156.25, 312.5, 625, 1250, 2500 µg/mL in the presence and absence of mammalian metabolic activation. 

Benzoguanamine does not induce chromosomal aberrations over background with and without metabolic activation within the solubility limit. 

Above the solubility limit and the absence of metabolic activation it produced a statistically significant but quite modest increase in the frequency of chromosomal aberrations. This may be an artifact due to the precipitation of Benzoguanamine.

Melamine:

In a Chinese ovary cell chromosome aberration assay according to NTP standard protocol, CHO cells cultured in vitro were exposed to melamine at concentrations of 0, 240, 270 and 300 µg/mL in the presence and absence of mammalian metabolic activation. 

No statistically significant increase in aberration frequency was noted up to the highest tested concentration.

 

In-vivo studies

Benzoguanamine

In a CD-1 mouse bone marrow micronucleus assay, mice were treated by oral gavage with Benzoguanamine at doses of 0, 75, 150, 300 mg/kg bw (male) and 0, 50, 100, 200 mg/kg/bw (female).  Bone marrow cells were harvested at 24, 48, 72 hr post-treatment, at least 2000 PCEs per

Animal were scored. There were no signs of toxicity during the study. There was no biologically and statistically relevant increase in the frequency of detected micronuclei after any treatment time.

An additional result from a mouse bone marrow micronucleus assay was considered inadequate as advised by the Scientific Committee on Food (SCF) of the European Commission (EC).

Justification for read-across

Evaluation of structure-activity relationship is based on data from structural similar substances with the same core structure, an s-triazine ring and different substituents.A detailed justification document for the read-across is attached in the respective target records of IUCID.

 

Conclusion

Negative data from gene mutation studies in bacteria were available for the target substance Caprinoguanamine and all source substance (Acetoguanamine, Benzoguanamine and Melamine).

Information from in-vitro mammalian cell gene mutation assays from Acetoguanamine, Benzoguanamine and Melamine, indicates no mutagenic potential within the solubility limit. Beyond the limit of solubility for Benzoguanamine in increase of mutation frequency was observed, however this might be artificial.

Further data from in-vitrochromosome aberration assays are available for Benzoguanamine and Melamine.No statistically significant increase in aberration frequency was noted in the study with Melamine. Benzoguanamine doesnot induce chromosomal aberrations with and without metabolic activation within the solubility limit. Above the solubility limit and the absence of metabolic activation it produced a statistically significant but quite modest increase in the frequency of chromosomal aberrations. Again this may be an artifact due to the precipitation of Benzoguanamine.

 

In an in-vivo Micronucleus assay with Benzoguanamine there was no biologically and statistically relevant increase in the frequency of detected micronuclei after any treatment time.

Furthermore, the source substance Melamine and Benzoguanamine were High Production Volume (HPV) chemicals and have been investigated within the OECD Screening Programm on HPV chemicals. According to the respective SIDS (Screening Information Data Sets) both substance are considered notmutagenic and not genotoxic.^1,2

 

Based on information from the structurally closely related read-across substances (Acetoguanamine, Benzoguanamine and Melamine) Caprinoguanamine is considered to be non-mutagenic in mammalian cells.

 

References:

1.    OECD SIDS for Melamine, 1998 available at:http://www.inchem.org/documents/sids/sids/108781.pdf  

2.    OECD SIDS for Benzoguanamine, 2001, available at:http://www.inchem.org/documents/sids/sids/91769.pdf

 

 

Justification for classification or non-classification

In conclusion, based on the results of in-vitro genotoxicity tests and additional in-vivo data both including read-across information form structural related source substances; Caprinoguanamine does not need to be classified for germ cell mutagenicity according to CLP, EU GHS (Regulation (EC) No 1272/2008).