Reaction mass of 7-azatridecane-1,13-diamine and hexamethylenediamine

Specific investigations: other studies

Administrative data

Endpoint:

biochemical or cellular interactions

Type of information:

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

Adequacy of study:

supporting study

Study period:

No data

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Documentation insufficient for assessment (sparse details about material and methods).

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1988

Materials and methods

Principles of method if other than guideline:

Inhibition of alpha1-antitrypsin by Hexamethylene diamine (HMD or 1,6-hexane diamine; HDA) and influence of the phenotype

GLP compliance:

no

Type of method:

in vitro

Endpoint addressed:

respiratory sensitisation

Test material

Test material information

Constituent 1

Reference substance name:

Hexamethylenediamine

EC Number:

204-679-6

EC Name:

Hexamethylenediamine

Cas Number:

124-09-4

Molecular formula:

C6H16N2

IUPAC Name:

hexane-1,6-diamine

Details on test material:

- Name of test material (as cited in study report): 1,6-hexane diamine; HDA

Test animals

Species:

human

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

Twenty-six persons (18 healthy blood donors, 5 members of laboratory staff and 3 patients from pulmonary wards)

Administration / exposure

Route of administration:

other: not applicable, as experiments were performed in vitro

Vehicle:

not specified

Details on exposure:

The serum specimens (0.5 mL) were incubated overnight with 0, 1, 2, 2.5, 3, 4 or 5 mM HDA (final concentration) at room temperature.

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

Overnight

Frequency of treatment:

Once

Post exposure period:

No data

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 1, 2, 2.5, 3, 4 or 5 mM
Basis:
no data

No. of animals per sex per dose:

26

Control animals:

yes, concurrent no treatment

Details on study design:

No data

Examinations

Examinations:

In vitro alpha1-antitrypsin activity (see table 1)
Alpha1-antitrypsin phenotype

Positive control:

No

Results and discussion

Details on results:

No data

Any other information on results incl. tables

Table 1: decreased activity of human serum alpha1 -antitrypsin in vitro by 5 mM HDA

Phenotype	N	Control	Treated
Homozygous M	13	1.03 ± 0.15	0.70 ± 0.20
Heterozygous M	7	0.98 ± 0.15	0.48 ± 0.19 **
Heterozygous MS or MZ	4	0.67 ± 0.21	0.36 ± 0.07 **
Homozygous SS or ZZ	2	0.34 ± 0.28	0.16 ± 0.21 **

Each figure represents the mean activity (mg trypsin inhibited x min^-1x mL^-1)

** Differs from the treated homozygous M at P < 0.01

Applicant's summary and conclusion

Conclusions:

The data suggest that heterozygous antitrypsin carriers may be more susceptible to the effects of inhaled amines, included Hexamethylene diamine, despite their "normal" phenotypic constitution.

Executive summary:

Blood donors and patients from pulmonary wards gave serum specimens for the assay of their alpha1-antitrypsin activity and phenotype. The same specimens were then incubated at the room temperature overnight with increasing concentrations of 1,6-hexane diamine. The 5 mM amine concentration caused a significant decrease in heterozygous antitrypsins (M1 M2, M1 M3, M2 M3 and M1 S) activity while it was less in the homozygous (M1M1 and M2M2) antitrypsin phenotypes. The SS and ZZ phenotypes showed a very low initial activity which was, however, further reduced. Analysis for the antitrypsin protein showed a simultaneous loss of its activity. The data suggest that heterozygous antitrypsin carriers may be more susceptible to the effects of inhaled amines, included HMD, despite their "normal" phenotypic constitution.