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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:
Sedation, ataxia, salivation, nasal discharge, gasping, and at higher  doses, also convulsions 
Body weight:
no data
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

Referenceopen allclose all

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.

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
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.