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Toxicological information

Repeated dose toxicity: inhalation

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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:
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

Reference
Name:
Unnamed
Type:
Constituent

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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
484 ppm
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
225 ppm
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
182 ppm
Basis:
analytical conc.
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

open allclose all
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
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
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)
Dose descriptor:
LOAEC
Effect level:
132 ppm (analytical)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
mortality
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
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)
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).

Applicant's summary and conclusion