N,N'-bis(1,4-dimethylpentyl)-p-phenylenediamine

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

limited documented study report (e.g. no individual data available for clinical observations, organ weights, histopathological data; treatacycline treatment during the study was not recorded), with methodological deficiencies (e.g. particle size distribution not determinate).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Materials and methods

Principles of method if other than guideline:

other: limited subacute inhaation study with methodological deficiencies

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N'-bis(1,4-dimethylpentyl)-p-phenylenediamine

EC Number:

221-375-9

EC Name:

N,N'-bis(1,4-dimethylpentyl)-p-phenylenediamine

Cas Number:

3081-14-9

Molecular formula:

C20H36N2

IUPAC Name:

N1,N4-bis(5-methylhexan-2-yl)benzene-1,4-diamine

Details on test material:

Santoflex 77

Test animals

Species:

rat

Strain:

other: Charles River

Sex:

female

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

clean air

Remarks on MMAD:

MMAD / GSD: not determinated

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

6 hours per day, 5 days per week, for 4 weeks (20 exposures

Frequency of treatment:

daily (5days/week)

Doses / concentrations

Remarks:

Doses / Concentrations:
target: 50, 250, 500 mg/m3 (analytical: 54, 236, 477 mg/m3, gravimetric: 59, 248, 487)
Basis:

No. of animals per sex per dose:

5 per sex and dose

Control animals:

yes, concurrent no treatment

Results and discussion

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Mortality

One male and one female from the T-I group died during blood collection. One T-II. female was sacrificed in extrenus on weekend after exposure.

Untreated Control M 0/5, F 0/5

T-I: M 1/5, F 1/5

T-II: M 1/5, F 2/5

T-III: M 4/5, F 4/5*

*includes animal sacrificed in extremis

Clinical observation:

T-I animals: lacrimation

T-II animals: hypoactivity, lacrimation, redness around eyes and noses, loos of hair around eyes, nose, feet and on the back of the head, labored breathing and emaciation

T-III:

animals: hypoactivity, lacrimation, redness around eyes and noses, loos of hair around eyes, nose, feet and on the back of the head, labored breathing and emaciation, red discharges around the eyes and nose

Body weight:

Statisticaily significantly lower body weight gains were exhibited by the T-Il males (P <0. 0l) and the T-IIl males (P <0.05) when compared to those of the untreated control. males. T-III females exhibited statisticaily significantly (P <0 05) lower, body weight gains than those of the untreated control females. All other analyses showed no statistical differences between any of the other test groups- and the untreated control group.

Organ weights:

T-II and T-IlI males exhibited statistically significant (p<0. 05) higher liver to body weight ratios than those of the untreated control males. T-II females exhibited statistically significantly (p<0.05) lower absolute gonad weights than those of the untreated control females. All other analyses showed no statistical differences between any of the test groups and the untreated control group.

Hematology:

Mean values for total leukocyte and erythrocyte counts, hemoglobin concentration, hematocrit and erythrocyte indices (

MCV, MCH and MCHC) determined in samples obtained from treated rats were similar to the values determined in samples obtained from control (untreated) rats after four weeks of treatment. However, MCH was significantly (p<O.Ol) lower in

all test males than in control males. A dose related apparent increase in mean values for segmented neutrophils (with a concurrent apparent decrease in lymphocytes) was observed in differential leukocyte counts of treated rats when compared to control (untreated) rats after 4 weeks of treatment. However, the apparent differences were not statistically significantly.

Clinical chemistry:

Statistical analysis of clinical data indicated that: glucose was elevated significantly in T-I males and reduced significantly in T-II and T-III females; BUN was elevated significantly in T-III males and unchanged in females; SGPT was elevated significantly in T-II and T-III females and unchanged in males; SAP was unchanged in males and females.

Mean values for the content of blood, ketones, glucose and protein in urine, and for microscopic constituents of urinary sediments determined in samples obtained from treated rats were similar to the values obtained for control (untreated) rats alter 4-weeks of testing. Urine pH was elevated significantly in T-I males. and unchanged in females. In the absence of histopathologic changes attributable to the test material the meaning of the clinical pathology changes is uncertain.

Pathology:

No gross or histopathologic alterations attributable to the effects of the test material were observed in any of the treated rats examined.