Hexylamine

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and Guideline study Please refer to section 13 (read across statement).

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

2002

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

yes

Remarks:

according to OECD Guideline 414 (Prenatal Developmental Toxicity Study) [see 7.8.2]

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Butylamine

EC Number:

203-699-2

EC Name:

Butylamine

Cas Number:

109-73-9

IUPAC Name:

butan-1-amine

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: K. Thomae GmbH/Boehringer Ingelheim, Biberach/Germany
- Age at study initiation: approx. 70 d
- Weight at study initiation: 198 - 246 g
- Housing: single
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 d before mating


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:glass-steel inhalation exposure chamber, 1.4 m3, space for 6x6 cages
- Method of holding animals in test chamber: 1 animal/cage
- Source and rate of air: charcoal-filtered air
- System of generating particulates/aerosols: In a thermostated vaporiser (25 - 35 °C), the vapor-air mixture was generated by spraying the TS
with compressed air into a counter current of conditioned air, followed by further mixing with air to achieve required
exposure concentrations.
- Temperature, humidity, pressure in air chamber: 21.2 - 22.5 °C; 50.5 - 62.0 %
- Air change rate: Air changes: 20/hour


TEST ATMOSPHERE
- Brief description of analytical method used: GC/FID after absorption in DMF
- Samples taken from breathing zone: yes

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

- Method: GC with FID detection
- Sampling time: 2 times during each exposure (for controls 2 times during the study)

Duration of treatment / exposure:

14 d (6 - 19 day of gestation)

Frequency of treatment:

6 h/d

Doses / concentrations

Remarks:

Doses / Concentrations:
51.4 +-2.2; 151.8 +-9.2; and 460 +-17.5 mg/m3 (= 17, 50.1, and 151.8 mL/m3)
Basis:
analytical conc.

No. of animals per sex per dose:

20 - 24 pregnant female rats

Control animals:

yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: 3x during exposure, other days 1x

BODY WEIGHT: Yes
- Time schedule for examinations: on day 1, 3, 6, 8, 10, 13, 15, 17, 19 and 20

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: ovary, uterus, placenta
- macroscopy of dams
- histopathological examination of 4 sections of the nasal cavity

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not examined

Details on results:

- Mortality: none
- Body weight: no treatment related effects
- Clinical signs: no treatment related effects
- Gross pathology incidence and severity: no treatment related effects [incidental congestion, oedema and/or marginal emphysema of the lungs (due to method of sacrifice)
- Histopathology incidence and severity: anterior nasal section showing squamous metaplasia, inflammatory cells and hyperplasia of transitional cells at all concentrations (dose dependent effect). At 450 mg/m3, necrosis of the nasal mucosa (5 animals) and the underlying nasal bone (1 animal).

Effect levels

1

Dose descriptor:

NOAEC

Effect level:

> 17 ppm

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Histopathology: nasal irritation

2

Dose descriptor:

NOAEC

Effect level:

> 51 mg/m³ air (analytical)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Histopathology: nasal irritation

3

Dose descriptor:

LOAEC

Effect level:

51 mg/m³ air (analytical)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Histopathology: nasal irritation

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table 1: Nasal irritation in dams following inhalation exposure to n-butylamine during gestation (14 d)

	Percentage of dams showing lesions exposed to the following concentrations in ppm [mg/m^3], nominal
Histopathological findings	0	17 [50]	50 [150]	150 [450]
Squamous cell metaplasia	No data	10	50	100
Purulent to mixed inflammatory cell infiltration	No data	30	90	100
Focal necrosis of nasal mucosa	No data	0	0	50
Necrosis of nasal bone	No data	0	0	10