Trimethylenediamine

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1954

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

pre-GLP, no guideline available at time of study performance Trimethylenediamine is structurally very similar to the test substance ethylenediamine (difference: chain length / one CH2-group). Thus, the test result is justified for read across with respect to trimethylenediamine.

Data source

Reference

Reference Type:

publication

Title:

Response of rats to repeated inhalation of ethylenediamine vapours

Author:

Pozzani, U.C , Carpenter C.P

Year:

1954

Bibliographic source:

Industrial hygiene and occupational medicine,9,1954,223-225

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Deviations:

not specified

Principles of method if other than guideline:

Four exposure groups of 30 rats (15 female/15 male) were exposed to EDA vapour. Each exposure group had a control group.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethylenediamine

EC Number:

203-468-6

EC Name:

Ethylenediamine

Cas Number:

107-15-3

Molecular formula:

C2H8N2

IUPAC Name:

ethane-1,2-diamine

Test animals

Species:

rat

Strain:

Sherman

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Remarks on MMAD:

MMAD / GSD: Not determined.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Chamber air was passed through an acidified glassbead adsorption tube. The captured Ethylenediamine was quantified by titration.

Duration of treatment / exposure:

6 weeks

Frequency of treatment:

7 h/day, 5 days/week

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
484 ppm
Basis:
analytical conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
225 ppm
Basis:
analytical conc.

Doses / concentrations 3

Remarks:

Doses / Concentrations:
182 ppm
Basis:
analytical conc.

Doses / concentrations 4

Remarks:

Doses / Concentrations:
59 ppm
Basis:
analytical conc.

No. of animals per sex per dose:

15 male and 15 female

Control animals:

yes

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Effect levels

1

Dose descriptor:

NOAEC

Effect level:

59 ppm (analytical)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: clinical signs; body weight; organ weights

2

Dose descriptor:

NOAEC

Effect level:

144 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: clinical signs; body weight; organ weights (as above)

Remarks on result:

other: calculated from 59 ppm

3

Dose descriptor:

NOAEL

Effect level:

48 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Recalculated using rat weight 0.425 kg (mean male/female) and inhalation volume 0.33 m3/7h (values from guidance document)

4

Dose descriptor:

LOAEC

Effect level:

132 ppm (analytical)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

mortality

5

Dose descriptor:

LOAEC

Effect level:

323 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

mortality

Remarks on result:

other: calculated from 132 ppm

6

Dose descriptor:

LOAEL

Effect level:

107 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Recalculated using rat weight 0.425 kg (mean male/female) and inhalation volume 0.33 m3/7h (values from guidance document)

7

Dose descriptor:

NOAEC

Effect level:

177.6 mg/L air (analytical)

Based on:

test mat.

Remarks:

/calculated from EDA to trimethylenediamine

Sex:

male/female

Basis for effect level:

other: /calculated from EDA to trimethylenediamine

Remarks on result:

other: /calculated from EDA to trimethylenediamine

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

132 ppm: The death of 4/30 animals was attributed to lung infection (not substance-related); slight depilation; body weight gain and relative weights of liver and kidney were not affected; no substance-related macroscopic or histologic changes.

225 ppm: The death of 16/30 was substance-related and another 10 death were considered not to be substance-related; the 4 rats which survived showed significantly lower weight gain and higher relative weights of liver and kidney; cloudy swelling of the liver and of the loop and convoluted tubules of the kidney; lung congestion was observed in exposed as well as in control rats in similar proportions.
484 ppm: All rats died within 20 days of initial exposure; depilation was first observed on the 6th day of exposure; cloudy swelling of the liver (in 23/28 animals), cloudy swelling and degeneration of convoluted tubules (in 7/28 animals); congestion of the lung (in 17/28 animals) and of the adrenal cortex (in 5/28 animals).
59 ppm: No effect on weight gain or organ weights. No depilation. No significant damage to examined tissues; lung, liver and kidney.

In conclusion.

NOAEC in a subacute inhalation study was 144 mg/m³ air (EDA, analytical), corresponding to a NOAEC of 177.6 mg/m³ air trimethylenediamine (read across).