4,4'-methylenebis(cyclohexylamine)

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Exposure: 04 April 2002 - 03 June 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

other: "Testing Methods for New Chemical Substances" (Notifications of Kanpogyo No. 5; Yakuhatsu No. 615, 49; Kikyoku No. 392 (1974, revised in 1998)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 305 C (Bioaccumulation: Test for the Degree of Bioconcentration in Fish)

Version / remarks:

-replaced-

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD 305-I; (2012): Aqueous Exposure Bioconcentration Fish Test

GLP compliance:

yes

Radiolabelling:

no

Vehicle:

yes

Details on preparation of test solutions, spiked fish food or sediment:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method:
1) Preparation of Feed Stock Solution (1st Concentration Level):
Test substance 8 g + 2-methoxyethanol (25 ppm v/v); dissolution to constant volume 1000 mL (test substance concentration: 8000 mg/L)

2) 2nd Concentration Level:
100 mL of 1st concentration level feed stock solution + 2-methoxyethanol (25 ppm v/v); dissolution to constant volume 1000 mL
Test substance concentration: 800 mg/L

3) Control:
1000 mL dilution water + 2-methoxyethanol (25 ppm v/v)

(Preparation frequency: approx. every 32 days)

- Chemical name of vehicle (organic solvent, emulsifier or dispersant): 2-methoxyethanol
- Concentration of vehicle in test medium (stock solution and final test solution(s) at different concentrations and in control(s)): 25 ppm (v/v)

Test organisms (species):

Cyprinus carpio

Details on test organisms:

TEST ORGANISM
- Common name: Common carp
- Source: Sankyo Suisan Co., Ltd.; 1-1, Ichigayatamachi, Shinjuku-ku, Tokyo
- Date supplied: 12. November 2001
- Batch/Lot#: 01-K-1112
- Length at study initiation (lenght definition, mean, range and SD): 8 ± 4 cm
- Weight at study initiation (mean and range, SD): approx. 5 g
- Age at study initiation: approx. 1 year
- Lipid content of fish: at study initiation: 6.6% (n= 3, 6.1 to 7.1%)
at end of the study: 6.5% (n = 3, 4.6 to 8.5%)

ACCLIMATION
- Acclimation conditions (same as test): flow through at 25 ± 2 °C
- Type and amount of food: Baby Gold, manufactured by Kyorin Co., Ltd.; at rate of 2% of the total body weight
- Feeding frequency: daily
- Health: observing of body shape, swimming and ingestion

Route of exposure:

aqueous

Test type:

flow-through

Water / sediment media type:

natural water: freshwater

Total exposure / uptake duration:

60 d

Test temperature:

24 ± 2 °C

pH:

6.0 to 8.5

Dissolved oxygen:

≥60% of saturation (5 mg/L or more at 24°C)

Details on test conditions:

TEST SYSTEM
- Test vessel:
- Material, size, headspace, fill volume: glass tanks, volum = 50 L
- Renewal rate of test solution (frequency/flow rate): 800 ml/min (water replacements: 16 times a day)
- No. of vessels per concentration: 1
- No. of fish per concentration: 44 (at study initiation)
- No. of vessels per control: 1
- No. of fish per control: 24 (at study initiation)
- Aeration: yes

TEST MEDIUM / WATER PARAMETERS
- Holding medium different from test medium: no
- Intervals of water quality measurement: once a week

TEST CONCENTRATIONS
- The setting of test concentrations is based on the results of an acute toxicity test (96h LC50: 32mg/L; for details see IUCLID ch. 6.1.1)

OTHER
- Light conditions: 16 : 8 (L : D); Hf fluorescent lamps (wavelength: 400 to 700 nm)

Nominal and measured concentrations:

nominal: 0 mg/l (control), 0.2 mg/l (high concentration level) and 0.02 mg/l (low concentration level)
Measured: (no data for control), 0.195 - 0.020 mg/L (high concentration level) and 0.0192 - 0.0220 mg/L (low concentration level)

Reference substance (positive control):

no

Lipid content:

>= 6.1 - <= 7.1 %

Time point:

start of exposure

Remarks on result:

other: average value: 6.6%

Lipid content:

>= 4.6 - <= 8.5 %

Time point:

end of exposure

Remarks on result:

other: average value: 6.5%

Conc. / dose:

0.2 mg/L

Temp.:

24 °C

Type:

BCF

Value:

< 6 L/kg

Basis:

whole body w.w.

Calculation basis:

steady state

Remarks on result:

other: Conc.in environment / dose:0.2 mg/l

Conc. / dose:

0.02 mg/L

Temp.:

24 °C

Type:

BCF

Value:

< 60 L/kg

Basis:

whole body w.w.

Calculation basis:

steady state

Remarks on result:

other: Conc.in environment / dose:0.02 mg/l

Measured concentration rates (BCFss) during uptake phase

Uptake period		Day 7	Day 14	Day 27	Day 42	Day 60
High concentration level	Average concentration in water (mg/L)	0.195	0.200	0.197	0.200	0.202
	Concentration rate (BCFss): Sample 1                               Sample 2	< 6 < 6	< 6 < 6	< 6 < 6	6 < 6	< 6 < 6
Low concentration level	Average concentration in water (mg/L)	0.0192	0.0203	0.0209	0.0214	0.0220
	Concentration rate (BCFss): Sample 1                                Sample 2	< 60 < 60	< 57 < 57	< 55 < 55	< 54  54	< 53 < 53

BCFss = BCF in steady state

Reference 2

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

GLP guideline study (OECD 305c) of the structural analogue DM-PACM (CAS 6864-37-5). PACM and DM-PACM are considered read-across analogues based on structural similarity and similar physico-chemical and toxicological properties. The common structural features of the two substances are: a common functional primary amine group; the amines are bound to a cyclic aliphatic organic substituent; there are no elements other than carbon, hydrogen and nitrogen; identical structures except for a methyl group on each cyclohexane, ortho to the amine on DM-PACM similar molecular weights, both under 500 daltons, qualifying as “low molecular weight” compounds. For a detailed read across justification see also the attached justification document.

Reason / purpose for cross-reference:

read-across source

Lipid content:

>= 6.1 - <= 7.1 %

Time point:

start of exposure

Remarks on result:

other: average value: 6.6%

Lipid content:

>= 4.6 - <= 8.5 %

Time point:

end of exposure

Remarks on result:

other: average value: 6.5%

Conc. / dose:

0.2 mg/L

Temp.:

24 °C

Type:

BCF

Value:

< 6 L/kg

Basis:

whole body w.w.

Calculation basis:

steady state

Remarks on result:

other: Conc.in environment / dose:0.2 mg/l

Conc. / dose:

0.02 mg/L

Temp.:

24 °C

Type:

BCF

Value:

< 60 L/kg

Basis:

whole body w.w.

Calculation basis:

steady state

Remarks on result:

other: Conc.in environment / dose:0.02 mg/l

Measured concentration rates (BCFss) during uptake phase

Uptake period		Day 7	Day 14	Day 27	Day 42	Day 60
High concentration level	Average concentration in water (mg/L)	0.195	0.200	0.197	0.200	0.202
	Concentration rate (BCFss): Sample 1                               Sample 2	< 6 < 6	< 6 < 6	< 6 < 6	6 < 6	< 6 < 6
Low concentration level	Average concentration in water (mg/L)	0.0192	0.0203	0.0209	0.0214	0.0220
	Concentration rate (BCFss): Sample 1                                Sample 2	< 60 < 60	< 57 < 57	< 55 < 55	< 54  54	< 53 < 53

BCFss = BCF in steady state

Reference 3

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Remarks:

Parameter domain: The chemical fulfils the general properties requirements Structural fragment domain: The chemical is out of the interpolation structural space (Fragments not present in the training chemicals – 13.33%) Mechanistic domain: The chemical is in the mechanistic domain of the model.

Justification for type of information:

1. SOFTWARE
CATALOGIC 5.14.1

2. MODEL (incl. version number)
BCF base-line model v.04.11

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See section 'Test Material'.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF.

5. APPLICABILITY DOMAIN
See attached QPRF.

6. ADEQUACY OF THE RESULT
- The model is scientifically valid (see attached QMRF).
- The model estimates the bioconcentration factor (BCF) as required information point under Regulation (EC) No 1907/2006 [REACH], Annex IX, 9.3.2 Bioaccumulation in aquatic species, preferably fish (see also attached QPRF).
- See attached QPRF for reliability assessment.

Principles of method if other than guideline:

Calculation using OASIS Catalogic v.5.14.1.5, BCF base-line model v.04.11 - November, 2019

GLP compliance:

no

Details on estimation of bioconcentration:

BASIS FOR CALCULATION OF BCF
- Estimation software: OASIS Catalogic v.5.14.1.5, BCF base-line model v.04.11 - November, 2019]

INPUT DATA USED BY THE MODEL:
- logD @ pH7 = -1.5 (SPARC calculator)
- 3980 mg/L (BASF SE 13E02271, 2014)

Type:

other: log BCF (max)

Value:

0.965

Remarks on result:

other: Without considering the mitigating factors

Type:

other: BCF max

Value:

9.22

Remarks on result:

other: Without considering the mitigating factors

Type:

other: log BCF

Value:

0.57

Remarks on result:

other: Considering the mitigating factors size and water solubility (other factors without effect)

Type:

BCF

Value:

3.72

Remarks on result:

other: Considering the mitigating factors size and water solubility (other factors without effect)

DOMAIN APPLICABILITY

With regard to the parametric and mechanistic domain, the test substance is within the applicability domain of the model. However, the substance is out of the structural domain as 13.33% of the atom centered fragments (ACF) are unknown.

 

MOLECULE SIZE

Maximum diameter: 10.563 - 14.608 Å

Average maximum diameter: 12.611 Å

 

EFFECTS OF MITIGATING FACTORS

Concomitant predictions :
logBCFmax = 0.965 log(L/kg) wet
relative mitigating effect of Acids= 0.000
relative mitigating effect of Metabolism= 0.000
relative mitigating effect of Phenols= 0.000
relative mitigating effect of Size3= 3.466E-003
relative mitigating effect of Watersolubility= 0.991

RESULTS AND DISCUSSION

The BCF base-line model estimates the log BCF for the test item at 0.57+- 0.06 (BCF = 3.72) indicating low potential for bioaccumulation.

The maximum log BCF value was calculated to be 0.965 (BCF = 9.23). Mitigating factors like metabolism, molecule size and the water solubility were considered by the model. Molecular size and water solubility had a decreasing effect on the bioaccumulation potential.

 

According to the OECD 305 technical guidance document, the degree of transformation of the parent is decisive for the effect of metabolism (i.e.. the reproduction of subsequent steps is less critical for the prediction of the BCF).

Besides metabolism also molecular size and, to a minor degree, water solubility reduce the log BCF as estimated by the model. Water solubility and molecular size are discussed within the literature whether certain threshold values are suitable as cut-off criteria for indication of limited bioaccumulation. Regarding molecular size, the PBT working group on hazardous substances discussed a maximum diameter of > 17.4 Å (Comber et al., 2006). The maximum diameter of the test item is determined to be 10.563 - 14.608 Å. The average maximum diameter is 12.611 Å.

 

CONCLUSIONS

- The molecular size and the low water solubility reduce the bioaccumulation potential.

- The substance is therefore not expected to exhibit a significant bioaccumulation potential.

- The substance does not belong to 100% to the applicability domain of the model.

Reference 4

Endpoint:

bioaccumulation: aquatic / sediment

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: is a validated QSAR model; included in OECD (Q)SAR Toolbox.

Justification for type of information:

QSAR prediction

Qualifier:

no guideline followed

Principles of method if other than guideline:

Parameter estimation by QSAR, using BCFBAF v3.00, a QSAR model within Estimation Programs Interface Suite™ for Microsoft® Windows, v4.0, from the United States Environmental Protection Agency (EPA), a validated QSAR program which is part of the OECD (Q)SAR Toolbox.

GLP compliance:

no

Remarks:

not applicable

Radiolabelling:

no

Type:

BCF

Value:

10.15 L/kg

Basis:

whole body w.w.

Time of plateau:

4 wk

Calculation basis:

steady state

Remarks on result:

other: Time to plateau is dependent upon time to steady state

Remarks:

Conc.in environment / dose:Not applicable for QSAR estimation

--------------------------------- BCFBAF v3.00 --------------------------------

Summary Results:

 Log BCF (regression-based estimate): 1.01 (BCF = 10.1 L/kg wet-wt)

 Biotransformation Half-Life (days) : 1.61 (normalized to 10 g fish)

 Log BAF (Arnot-Gobas upper trophic): 1.08 (BAF = 12 L/kg wet-wt)

 

=============================

BCF (Bioconcentration Factor):

=============================

Log Kow (estimated) : 3.26

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: 2.03 (user entered)

 

Equation Used to Make BCF estimate:

  Log BCF = 0.6598 log Kow - 0.333 + Correction

 

     Correction(s):                   Value

      No Applicable Correction Factors

 

  Estimated Log BCF = 1.006 (BCF = 10.15 L/kg wet-wt)

 

Validity criteria fulfilled:

yes

Remarks:

validated QSAR model, part of OECD (Q)SAR Toolbox

Conclusions:

The estimated BCF for 4,4'-methylenebis(cyclohexylamine) is 10.15 L/kg wet weight. Log BCF is 1.01.

Additional information

According to Regulation (EC) No.1907/2006, Annex IX, Section 9.3.2, Column 2, studies to determine bioaccumulation in aquatic species need not be conducted if the substance has a low potential for bioaccumulation (for instance a log Kow < 3) and/or a low potential to cross biological membranes.  PACM (4,4'-methylenebis(cyclohexylamine)) has a log Kow of 2.03 as determined by the shake flask method. Since 4,4'-methylene-dicyclohexanamine is an ionizable substance the bioaccumulation potential was addressed by a read across to the structural analogue substance 4,4'-methylenebis(2-methylcyclohexanamine) (CAS 6864-37-5, DMDC) and supported by QSAR.

For 4,4'-methylenebis(2-methylcyclohexanamine)a valid study was performed by NITE Japan (2002) according to OECD 305C (replaced); OECD 305-I (2012), with Cyprinus carpio as test species and using a flow-through procedure. This study was selected as key study. After 60 days, a max. BCF of < 60 was measured, indicating that the substance will not significantly bioaccumulate in organisms.

The outcome of the read across is supported by calculated data that also indicate that bioaccumulation is not to be expected:

- BCFBAF v3.01 (EPI Suite v4.10): BCF = 10.15

- Catalogic v.5.14.1.5, BCF base-line model v.04.11 BCF = 21.7 (effective mitigating factors like molecular size and water solubility)

 

 

 

 

Bioaccumulation potential of modelled metabolites of 4,4'-methylene-dicyclohexanamine (CAS 1761-71-3):

ECHA Guidance on information requirements and chemical safety assessment (v3.0, June 2017), Chapter R.11.4.1 specifies that “Constituents, impurities and additives should normally be considered relevant for the PBT/vPvB assessment when they are present in concentration of ≥ 0.1% (w/w)” […] “Similar arguments apply to relevant transformation/degradation products”.

In order to identify the relevant degradation products of 4,4'-methylene-dicyclohexanamine (CAS 1761-71-3) as a standard information requirement according to Column 1, Section 9.2.3. of Annex IX to REACH and for purposes of an assessment of potential PBT/vPvB properties, the metabolites were modelled using CATALOGIC 301C v11.16 (OASIS CATALOGIC v5.14.1.5).

Overall, the CATALOGIC 301C v11.16 calculated 77 metabolites (Table 1) identifying 15 metabolites as relevant degradation products in terms of PBT/vPvB assessment, with an estimated quantity of ≥0.1% (equivalent to quantity setting in OASIS CATALOGIC: ≥ 0.001 [mol/mol parent]).

None of the relevant modelled degradation products of the substance were estimated to exhibit log Kow values of ≥ 4.5 (see Table 1), thus they do not fulfil the screening criteria for bioaccumulation (B/vB) as laid down in Section 3.1 of REACH Annex XIII.

 

 

Table 1: QSAR prediction for CAS 1761-71-3 using CATALOGIC 301C v11.16 (OASIS CATALOGIC v5.14.1.5; metabolites with a quantity > 0.001 mol/mol parent after 28 d are highlighted by grey background and bold type; metabolite no: according to (Q)SAR model Catalogic v11.16)

 

#	Metabolite (no)	Smiles	Quantity (mol/mol parent)	LogKow	BOD prediction (% after 28 d)
1	11	NC1CCC(CC(O)(CC(O)=O)C(O)=O)CC1	0,2413	-3	53
2	23	C=C	0,1722	1	10
3	14	NC1CCC(O)(CC(O)=O)CC1	0,1639	-3	55
4	parent	NC1CCC(CC2CCC(N)CC2)CC1	0,1358	2	42
5	15	NC1CCC(=O)CC1	0,1302	-0,419	38
6	3	NC1CCC(CC2CCC(=O)OCC2)CC1	0,09323	2	61
7	17	O=C1CCC(=O)CCO1	0,02389	0,434	53
8	19	OC(=O)CCC(O)=O	0,01969	-0,754	90
9	42	NC1CCC(CCC(O)=O)CC1	0,002273	-1	67
10	56	NC1CCC(CC(CCC(N)CO)C(O)=O)CC1	0,001727	-3	60
11	68	NC1CCC(CC=O)CC1	0,001571	1	60
12	54	NC1CCC(CC(=O)CC(O)=O)COC1=O	0,001571	-5	73
13	58	NC(CCCCC1CCC(=O)CC1)CO	0,001571	0,99	74
14	59	NC1CCC(CCCCC(=O)CO)CC1	0,001571	2	76
15	16	O=C1CCC(=O)CC1	0,001552	-0,924	56
16	79	NC(CCC(O)CC(=O)CC(O)=O)CC(O)=O	0,001396	-6	82
17	32	NC1CCC(CC2CCC(N)C(=O)OC2)CC1	0,0008525	0,766	52
18	61	NC1CCC(CC(O)CCC(N)CC(O)=O)CC1	0,0007579	-3	47
19	67	NC1CCC(CC(O)C(O)=O)CC1	0,0007417	-3	51
20	53	NC1CCC(CC(O)(CC(O)=O)C(O)=O)COC1=O	0,0007417	-6	59
21	80	NC1CCC(CC2CCC(N)OC(=O)C2)CC1	0,000672	3	59
22	60	NC1CCC(CC2CCC(N)CC(=O)O2)CC1	0,000672	0,766	51
23	55	NC1CCC(CC2CCC(N)COC2=O)CC1	0,000672	0,766	53
24	78	NC(CCC(O)CC(O)(CC(O)=O)C(O)=O)CC(O)=O	0,0006594	-5	63
25	57	NC(CCCCC1CCC(N)CC1)CO	0,0005148	1	58
26	33	NC1CCC(CC2CCC(=O)C(=O)OC2)CC1	0,0002887	2	78
27	45	NC1CCC(CC2CCC(=O)OCC2)COC1=O	0,0002887	-0,1892	68
28	70	NC(CCC(O)CC1CCC(=O)OCC1)CC(O)=O	0,0002567	-3	67
29	41	NC1CCC(CC(C(O)=O)C(O)=O)CC1	3,95E-05	-3	71
30	49	NC1CCC(CC(CC(O)=O)C=CC(O)=O)COC1=O	0	-4	69
31	62	NC1CCC(CC(O)CCC(=O)CC(O)=O)CC1	0	-3	68
32	34	NC1CCC(CC(CCC(=O)C(O)=O)CO)CC1	0	0,399	78
33	38	NC1CCC(CC(C=CC(O)=O)C(O)=O)CC1	0	-2	77
34	9	NC1CCC(CC(CC(O)=O)C(=O)CC(O)=O)CC1	0	-3	62
35	66	NC1CCC(CC(O)C(=O)CC(O)=O)CC1	0	-3	60
36	2	NC1CCC(CC2CCC(=O)CC2)CC1	0	3	62
37	4	NC1CCC(CC(CCC(O)=O)CCO)CC1	0	-0,98	65
38	81	NC1CCC(CC(CCC(N)O)CC(O)=O)CC1	0	-3	65
39	82	NC1CCC(CC(CCC=O)CC(O)=O)CC1	0	-1	65
40	69	NC(CCC(O)CC1CCC(=O)CC1)CC(O)=O	0	-3	68
41	44	NC1CCC(CC2CCC(=O)CC2)COC1=O	0	0,2604	69
42	65	NC1CCC(CC(O)C(O)CC(O)=O)CC1	0	-3	60
43	64	NC1CCC(CC(O)C=CC(O)=O)CC1	0	-0,677	62
44	47	NC1CCC(CC(CCC(O)=O)CC=O)COC1=O	0	-4	70
45	48	NC1CCC(CC(CCC(O)=O)CC(O)=O)COC1=O	0	-4	69
46	37	NC1CCC(CC(CCC(O)=O)C(O)=O)CC1	0	-2	77
47	72	NC(CCC(O)CC(CCC(O)=O)CC=O)CC(O)=O	0	-4	73
48	73	NC(CCC(O)CC(CCC(O)=O)CC(O)=O)CC(O)=O	0	-4	72
49	50	NC1CCC(CC(CC(O)=O)C(O)CC(O)=O)COC1=O	0	-5	68
50	39	NC1CCC(CC(C(O)CC(O)=O)C(O)=O)CC1	0	-3	76
51	8	NC1CCC(CC(CC(O)=O)C(O)CC(O)=O)CC1	0	-3	62
52	71	NC(CCC(O)CC(CCC(O)=O)CCO)CC(O)=O	0	-4	73
53	10	NC1CCC(CC(CC(O)=O)C(O)=O)CC1	0	-2	55
54	63	NC1CCC(CC(O)CCC(O)=O)CC1	0	-2	62
55	28	OC(=O)C=O	0	-1	100
56	52	NC1CCC(CC(CC(O)=O)C(O)=O)COC1=O	0	-5	61
57	40	NC1CCC(CC(C(=O)CC(O)=O)C(O)=O)CC1	0	-4	76
58	26	OCC=O	0	-2	100
59	27	OCC(O)=O	0	-1	100
60	18	C=CC(=O)CCC(O)=O	0	0,1537	60
61	24	C1CO1	0	-0,0454	100
62	12	NC1CCC(CC(=O)CC(O)=O)CC1	0	-3	66
63	75	NC(CCC(O)CC(CC(O)=O)C(O)CC(O)=O)CC(O)=O	0	-5	71
64	51	NC1CCC(CC(CC(O)=O)C(=O)CC(O)=O)COC1=O	0	-6	68
65	74	NC(CCC(O)CC(CC(O)=O)C=CC(O)=O)CC(O)=O	0	-4	72
66	29	OC(=O)C(O)=O	0	-2	100
67	6	NC1CCC(CC(CCC(O)=O)CC(O)=O)CC1	0	-1	64
68	31	CC(O)=O	0	0,0868	100
69	35	NC1CCC(CC(CCC(=O)C(O)=O)C=O)CC1	0	0,3744	78
70	46	NC1CCC(CC(CCC(O)=O)CCO)COC1=O	0	-3	70
71	36	NC1CCC(CC(CCC(=O)C(O)=O)C(O)=O)CC1	0	-3	78
72	7	NC1CCC(CC(CC(O)=O)C=CC(O)=O)CC1	0	-2	64
73	76	NC(CCC(O)CC(CC(O)=O)C(=O)CC(O)=O)CC(O)=O	0	-6	71
74	13	NC1CCC(CC(O)=O)CC1	0	-2	58
75	25	OCCO	0	-1	100
76	5	NC1CCC(CC(CCC(O)=O)CC=O)CC1	0	-1	65
77	20	CCC(O)=O	0	0,578	100
78	77	NC(CCC(O)CC(CC(O)=O)C(O)=O)CC(O)=O	0	-5	64