sec-butylamine

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Isopropylamine

EC Number:

200-860-9

EC Name:

Isopropylamine

Cas Number:

75-31-0

Molecular formula:

C3H9N

IUPAC Name:

propan-2-amine

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

air

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

6 h/d, 5d/wk

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

20 mg/m³ air (analytical)

Remarks:

Doses / Concentrations:
20, 101, and 499 mg/m3
Basis:
analytical conc.

Doses / concentrations 2

Dose / conc.:

101 mg/m³ air (analytical)

Doses / concentrations 3

Dose / conc.:

499 mg/m³ air (analytical)

No. of animals per sex per dose:

15

Control animals:

yes, concurrent no treatment

Results and discussion

Results of examinations

Clinical signs:

effects observed, non-treatment-related

Description (incidence and severity):

A low level female and a high level male died approxtiately
12 weeks into the study. The reason for the death of the low <-
level female could not be determined, but it was not thought to’
be treatment-related. The death of the high level animal was due
to mechanical trauma and was not treatment-related. There were
no clinical observations which were clearly related to test
material exposure (Table 1).

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

The mean body weight of high exposure level males was reduced throughout
much of the study. The mean body weight of high exposure level males was reduced (approximately 6-9%) throughout most of the study (Table 4).
Slight (approximately 4-6%) body weight reductions were also noted in high level females during weeks 6-13. The mean body
weights of low and mid exposure level antials were unchanged.

Ophthalmological findings:

no effects observed

Description (incidence and severity):

Ophthahic examinations revealed no
treatment-related eye lesions.

Haematological findings:

effects observed, non-treatment-related

Description (incidence and severity):

The WBC count was significantly decreased in high exposure level
males (Table 10). Erythrocyte parameters (RBC, HCT, HGB) were
increased in all male exposure groups. The reticulocyte count
was decreased in high level males. The MCHC values were
decreased in all three female’exposure groups. However, the
changes were minimal (<3.5%), not dose-related, and thus not
considered to be treatment-related.

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

Serum glucose was decreased. Sodium was decreased in mid and high level
females, but the changes were minimal (<1.4%) and not consideredto be biologically significant. Increased serum potassium values in mid and high level males were not dose-related and thus not considered to be treatment-related.

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

The increased absolute and relative adrenal weights in high level
females were probably treatment-related and may have been a
non-specific response to stress. The reduced spleen weights in
high level males were due, at least in part, to the decreased
body weights in these animals

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

The absolute and relative adrenal weights were significantly increased (approximately 18 and 22%, respectively) in high level females (Tables 17 and 18). Absolute spleen weights were significantly decreased (approximately 15%) in high level males.
There was no gross pathology change which was considered to be treatment-related (Table 12). The only microscopic change which occurred at a statistically significant incidence was inflammation of the nasal mucosa in high level females
(Table 15).
There were slight increases in centrilobular hepatocellular hypertrophy and individual hepatocellular necrosis in livers of high dose males relative to controls. The severity levels for both lesions were minimal in all but one instance in which ~~
hepatocellular necrosis occurred at moderate severity. These < changes were not considered to have been related to treatment since there were no comparable increases in females and since “’. these changes at minimal levels of severity are often observed in untreated rats of this strain,and age.
Likewise, mononuclear cell infiltrate occurred in kidneys of high dose females at a slightly higher incidence than for controls.
This is an extremely common lesion in untreated animals of this strain and age and therefore, the” small numbers obsemed were
considered to be spontaneous and unrelated to chemical exposure.

Effect levels

1

Key result

Dose descriptor:

NOAEC

Effect level:

500 mg/m³ air (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: systemic effects (excluding local effects)

2

Key result

Dose descriptor:

NOAEC

Effect level:

100 mg/m³ air

Sex:

male/female

Basis for effect level:

other: local effects: histopathology (nose)

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The NOAEC was 100 mg/m3for local effects and 500 mg/m³ for systemic effects.

Executive summary:

In a study conducted in a manner equivalent or similar to OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day), groups of 15 male and female Sprague-Dawley rats were exposed by vapor inhalation for 6 h/d, 5d/w for 13 weeks to 20, 101, and 499 mg/m³isopropylamine(Heydens and Thake, 1988). The highest concentration, 500 mg/m³(LOAEC), produced nasal inflammation (females), a slight decrease in body weight of < 7 % (males), and a slight decrease in serum-glucose level (females). The systemic effects were considered to be of no pathological relevance.

The NOAEC was 100 mg/m³for local effects and 500 mg/m³ for systemic effects.

Because of the highly irritating activity of isopropylamine, oral and dermal application was not indicated.

The following information is taken into account for any hazard / risk assessment:

Isopropylamine produced no systemic but local effects (nasal inflammation in rats exposed to 500 mg/m3 for 13 weeks), while 100 mg/m3 showed no adverse effects at all.