Butylamine

Endpoint summary

Description of key information

The substance is acutely toxic after oral, dermal or inhalation exposure. The following LD/LC50 values were determined in experimental studies:

oral, rat: 372 mg/kg bw

dermal, guinea pig: 429 mg/kg bw

inhalation, rat: 4200 mg/m³

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions, only short communication, sufficiently documented

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

vehicle: corn oil instead of aqueous solution; survivors not examined at the end of the 14-d observation period

Principles of method if other than guideline:

Comparative study including tert. butylamine, sec-butylamine,  isobutylamine and n-butylamine.

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, MA
- Age at study initiation: not stated
- Weight at study initiation: males: 195 +/- 20.5 g; females: : 156 +/- 16.8 g
- Fasting period before study: yes, overnight
- Housing: two animals per cage
- Diet: Rodent Laboratory Chow from Ralston Puirna Co. , St. Louis, MO; ad libitum
- Water: tap water ad libitum
- Acclimation period: 2 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-26
- Humidity (%): 22-49
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: treatement To: end of 14-day observation period

Route of administration:

oral: gavage

Vehicle:

other: corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: variable dose
- Amount of vehicle (if gavage):
- Justification for choice of vehicle: no data


MAXIMUM DOSE VOLUME APPLIED: 4 mL/kg bw

Doses:

100, 200, 300, 400, 500, 600 mg/kg bw (in 4 ml corn oil)

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not reported, probably daily
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight (bw not documented), necropsy of animals that died

Statistics:

Statistical data evaluation: LD50-values were calculated using the probit  method of Finney (1971). Data for male and female animals were compared statistically for each compound by the chi-square contingency table analysis (Snedecor and Cochran, 1967).

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

371.8 mg/kg bw

95% CL:

307.8 - 458.4

Remarks on result:

other: in corn oil

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

365.7 mg/kg bw

95% CL:

283.6 - 475.8

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

382.4 mg/kg bw

95% CL:

278.1 - 490.5

Mortality:

Number of deaths: not reported
Time to death: generally 1 - 3 h post-administration

Clinical signs:

other: Sedation, ataxia, salivation, nasal discharge, gasping, and at higher  doses, also convulsions 

Gross pathology:

Deceased animals mainly exhibited pulmonary edema. 
Surving animals appeared normal after 14 d and were not further examined.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the experimental conditions an oral LD50 of 371.8 mg/kg bw was determined in male/female rats.

Executive summary:

The acute oral LD₅₀value of n-butylamine was determined in male and female Sprague-Dawley CD rats in a dose range of 100 -600 mg/kg bw. Signs of toxicity observed after single oral doses of the monobutylamines included sedation, ataxia, nasal discharge, gasping, and salivation followed by convulsions and death at the higher dose levels. Gross pathological examination of animals that died after the monobutylamine treatment revealed pulmonary edema. The LD50 values were calculated by the probit method of D. J. Finney. The LD50 for n-butylamine after an observation period of 14 days was 365.4 mg/kg bw in male rats and 382.7 mg/kg bw for female rats (mean 371.8 mg/kg bw).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

372 mg/kg bw

Quality of whole database:

sufficient for evaluation

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

BASF-Test.

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: WIGA, Sulzfeld and MUS RATTUS, Brunnthal, Germany
- Weight at study initiation: 185 ± 15 g.
- Diet: Herilan MRH ( EGGERSMANN KG, Rinteln/Weser, Germany), ad libitum
- Water: tap water ad libitum

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: continuous infusion pump leading to a vaporisation unit, heatad to 70 °C, vapour mixed with fresh air to achieve the tst atmosphere
- Exposure chamber volume: 200 L
- Method of holding animals in test chamber: in cages within the inhalation chamber


TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography (HP 5840 A)
- Samples taken from breathing zone: no

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

nominal: 1.48, 7.38, 8.9, 11.1 mg/L
analytical: 0.98, 3.11, 4.94, 7.29 mg/L

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: several times on the day of exposure and daily thereafter
- Frequency of weighing: days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

4.2 mg/L air (analytical)

95% CL:

3.6 - 4.7

Exp. duration:

4 h

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

4.7 mg/L air (analytical)

95% CL:

3.7 - 5.7

Exp. duration:

4 h

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

3.7 mg/L air (analytical)

Exp. duration:

4 h

Mortality:

See details in remarks on results.

Clinical signs:

other: 3.11, 4.94 and 7.29 mg/l air: watery eye and nose discharge, snout wiping, eyelid closure, dyspnoea, apathy, corneal opacity, squatting posture, trembling gait, ruffled fur. 0.92 mg/l air: watery eye and nose discharge, intermittend and irregular respir

Body weight:

Reduced weight/weight gain. See details in remarks on results.

Gross pathology:

Animals that died:
Heart: acute dilatation, acute congestion;
Lung: slight to moderate distension;
Liver: pivotally lobular pattern.

Sacrificed animals: no abnormalities.

Mortality:

Analytical concentration (mg/l)

male

female

7.29

9/10

10/10

4.94

6/10

9/10

3.11

1/10

2/10

0.92

0/10

0/10

Weight:

Dose (mg/l)	Gender	0 h	7 days	14 days
7.29	male	175	130	156
7.29	female	172	-	-
4.94	male	195	143	173
4.94	female	173	142	209
3.11	male	182	156	181
3.11	female	183	150	158
0.92	male	186	197	239
0.92	female	180	199	211
control	male	186	228	265
control	female	176	189	211

The test substance caused systemic toxicity (including mortality) and local irritation in a dose-dependent manner.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the conditions of the test an LC50 of 4200 mg/m3 was observed in rats.

Executive summary:

Rats (10 male and females per group were exposed to vapour concentrations of 0.92, 3.11, 4.94 or 7.29 mg/L. Mortality was observed at concentrations of >/= 3.11 mg/L. The LC50 was 4.2 mg/L (4200 mg/m3) for males/females and 4.7 mg/L for males and 3.7 mg/L for females. Symptoms of treatment were severe aqueous-reddish discharge from eyes and nose, apathy, dyspnea,hunched posture,staggering gait, milky turbid corneas. Organ changes consisted in cardiac dilatation with acute hyperemic congestion, slight to moderate acute congestion of the lung.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

07 March 1986 to 02 April 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: perspex material
- Exposure chamber volume: ~130 L,
- Method of holding animals in test chamber: single compartments, separated by wire-mesh partitions
- Source and rate of air: base centre of the chamber
- System of generating particulates/aerosols: no aerosols
- Treatment of exhaust air: collection filter
- Temperature: 23.8 +-0.26 °C (test); 24.9 +-0.33 °C (control)


TEST ATMOSPHERE
- Brief description of analytical method used:
Sampling: 5 samples were drawn through an acetone-containing absorption trap (-70 °C). 
Analysis: GC-FID analysis

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

nominal: 5 mg/L (1650 ppm) [target concentration]
analytical: 4.6 mg/L

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: continuously during exposure, at least 2x/d during the observation period
- Frequency of weighing: daily
- Necropsy of survivors performed: yes

Statistics:

not applicable

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.6 mg/L air (analytical)

Exp. duration:

4 h

Mortality:

none

Clinical signs:

other: - Signs of irritation during exposure: abnormal respiration, lacrimation, closure of  eyelids, excessive salivation, abnormal body posture;   - Signs of marked adverse effects post-exposure: abnormal respiration, sneezing, rales, gasping (1 - 5 d p.a. in

Body weight:

Marked weight loss for 2 - 3 d post-exposure, followed by weight gain similar to or higher than controls

Gross pathology:

- Surviving animals: opacity of eyes, red or grey areas found in lungs, in one case congested lung

Abnormal respiration persisted throughout the observation period (14 d). Histopathological changes in the lungs were evident after 14 d. Opacity of the cornea persisted in male rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

4 200 mg/m³ air

Quality of whole database:

sufficient for evaluation

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

other: US regulation, 21 CFR 191.10, application

Principles of method if other than guideline:

Method
A) on the intact skin of abdomen of guinea pigs
B) on the abraded skin of the back of guinea pigs

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

guinea pig

Strain:

Hartley

Sex:

male

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Skin: shaved and depiliated
- Treatment sites:
A) on the intact skin of abdomen of guinea pigs
B) on the abraded skin of the back of guinea pigs
- Area of exposure: 1 square inch of cellulose pad

Duration of exposure:

24 h

Doses:

3 dose groups, no details

No. of animals per sex per dose:

4

Control animals:

not required

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

429 other: mg/kg bw (abdomen, intact skin)

Remarks on result:

other: 0.58 mL/kg bw given in publication

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 100 other: mg/kg bw (back, abraded skin)

Remarks on result:

other: 1.5 mL/kg bw given in publication

Mortality:

Numbers of deaths not reported.
A higher toxicity was observed for butylamine applied to the abdomen. 

Gross pathology:

Quick and severe skin necrosis

Other findings:

A higher toxicity was observed for butylamine applied to the abdomen, which may be explained by the higher sensitivity and responsiveness of the abdominal skin as compared with the dorsal skin.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the conditions of the test a dermal LD50 of 429 mg/kg bw was determined in male guinea pigs.

Executive summary:

The test substances were occlusively applied to the intact abdome skin or abraded back skin of guinea pigs under the conditions laid down in the US regulation, 21 CFR 191.10.

Quick and severe skin necrosis was observed at the application sites.

The LD50 was 0.58 mL/kg bw (429.0 other: mg/kg bw) for exposure to intact abdomen skin and 1.5 mL/kg bw (1100.0 mg/kg bw) for exposure to abraded back skin

The study examined a comparison between guinea pigs and rabbits in their response to various compounds in regard to acute dermal toxicity and primary irritation.

Of the eight compounds tested for acute dermal toxicity, only one (parathion) would have been placed in a higher toxicity classification by the rabbit test than by the intact guinea pig skin test.

The information obtained in the primary irritation tests showed that the intact guinea pig skin test is as sensitive as, or more sensitive than, the rabbit skin test in eliciting dermal reactions.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

429 mg/kg bw

Quality of whole database:

sufficient for evaluation

Additional information

Acute oral LD50 values obtained from studies in rats range from 372 - 720 mg/kg bw. The lowest value was observed in a reliable study and used for risk assessment. After oral ingestion, signs of toxicity were sedation, ataxia, salivation, nasal discharge, gasping, and at higher doses, also convulsions.

The LC50 values for inhalation range from 4.2 to about to >4.6 mg/L vapour atmosphere (analytical values) in two reliable studies. The study by BASF AG (1979) was selected as key study (though it was RL2), because it reported the lower LC50 and is sufficiently reliable for risk assessment compared to the study by Pennwalt (1987, RL1) with a LC50 of 4600 mg/m3. Following inhalation, severe aqueous-reddish discharge from eyes and nose, apathy, dyspnea, hunched posture, staggering gait, milky turbid corneas were observed. Organ changes consisted in cardiac dilatation with acute hyperemic congestion, slight to moderate acute congestion of the lung.

As for dermal application in experimental animals, LD50 values from 429 to >1000 mg/kg bw have been reported. The lowest value was observed in a reliable study with guinea pigs and is used for risk assessment. Necrosis was observed at the application sites.

Justification for classification or non-classification

The harmonised classification according to Regulation (EC) No 1272/2008 with respect to acute toxicity is Category 4 for the dermal, oral and inhalation route (Acute Tox. 4 H302; Acute Tox. 4 H312; Acute Tox. 4 H 332). These are all minimal classifications from the implementation of Regulation (EC) No 1272/2008.

However, based on experimental LD50/LC50 values, n-butylamine has to be classified as acute oral toxic Cat. 4, acute dermal toxic Cat. 3 and acute inhalative toxic Cat. 3 according to the requirements of Regulation (EC) No 1272/2008.