Registration Dossier

Administrative data

Description of key information

Oral: The acute oral LD50 was determined to be approx. 552 mg/kg bw in rats. 
Inhalation: The acute inhalation LC50 was > 400 mg/m³ (5 hours) or > 650 mg/m³ (3 hours) in rats,
Dermal: The acute dermal LD50 was determined to be 1340 mg/kg bw (females) and approx. 1350 mg/kg bw (males) in rats.

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: No OECD guideline or GLP defined, acceptable restrictions (incomplete documentation).
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
other: 10 males, single oral application by gavage of undiluted test substance, observation time: 14 d
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann
- Weight at study initiation: 160 - 180 g
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
0.8; 1.0; 1.2; 1.3; 1.5 mL/kg bw
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: no
Statistics:
LD50 calculation according to Fink and Hund.
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 1.15 mL/kg bw
Based on:
test mat.
95% CL:
1.05 - 1.25
Remarks on result:
other: corresponding to 1127 mg/kg bw
Mortality:
1.5 mL/kg bw: 10/10;
1.3 mL/kg bw: 6/10;
1.2 mL/kg bw: 6/10;
1.0 mL/kg bw: 3/10;
0.8 mL/kg bw: 0/10
Clinical signs:
Diarrhea, sedation, respiratory disorders and tonical cramps.
Body weight:
A reduction in the bodyweight development was observed.

The LD50 of 1.15 mL/kg bw corresponds to approx. 1127 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
552 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No OECD Guideline and GLP defined, acceptable restrictions (incomplete documentation).
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
other: single application (exposure time 3 or 5h), observation time: 7 d. Rats were exposed to a stream of vapour-saturated air. The vapour-air mixture was generated by passing 200 L/h of dried air at room temperature through 5 cm of the test substance contained in a gas-washing bottle.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: mean 209.9 g (male); mean 172.9 g (male)
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Analytical verification of test atmosphere concentrations:
no
Concentrations:
0.4 mg/L (exposure time: 5 h); 0.65 mg/L (exposure time: 3 h)
No. of animals per sex per dose:
3m/3 f (exposure time: 5 h)
6m/6f (exposure time: 3 h)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 0.4 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
5 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 0.65 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
3 h
Mortality:
Male:
0/6 (exposure time: 3 h)           
1/3 (exposure time: 5 h)

Female:
0/6 (exposure time: 3 h)           
0/3 (exposure time: 5 h)
Clinical signs:
Severe Irritation of the mucous membrane, dyspnea (exposure time: 3 and 5 h).
Body weight:
No impairment of bodyweight development (exposure time: 3 and 5 h).
Gross pathology:
Exposure time: 5 h
1 male died: heart: blunted, both heart ventricles poorly contracted, filled with blood; liver: congestion.
All other animals without gross pathology findings.

Exposure time: 3 h
All animals without gross pathology findings.

At BASF’s Department of Toxicology, acute toxicity testing was performed according to published methods, which were adapted and standardized for the specific needs of the company, well before Test Guidelines for these methods were established by the OECD beginning 1982. These methods were comparable to the Union Carbide (now a DOW company) range finding toxicity data which have been published in the early toxicological literature (1944-1949). The results of these studies were reported until the early 1980s in summary reports called „Ergebnis der gewerbetoxikologischen Vorprüfung“ or „Toxikologische Grundprüfung“, which do not present details of the methods used, but focus on a summary presentation of the results.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed

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:
other: No OECD guideline or GLP defined, acceptable restrictions (incomplete documentation).
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
other: single dermal application of undiluted test substance for 24 hours, fixed with a dressing, observation time: 14 d
GLP compliance:
not specified
Test type:
other: Acute dermal toxicity study in rats
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann
- Weight at study initiation: 160 - 180 g
Type of coverage:
other: dressing (no further details)
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
1.00, 1.25, 1.30, 1.50, 2.50, 5.00 g/kg bw
No. of animals per sex per dose:
1.0 g/kg bw = 10 animals/sex/dose
1.25 g/kg bw =10 animals/sex/dose
1.30 g/kg bw =10 animals/sex/dose (only male animals!)
1.50 g/kg bw =10 animals/sex/dose
2.50 g/kg bw =10 animals/sex/dose
5.00 g/kg bw = 5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: no
Statistics:
LD50 calculation according to Fink and Hund.
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 1.35 other: g/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
1.34 other: g/kg bw
Based on:
test mat.
Mortality:
5.00 g/kg bw: 5/5 males and 5/5 females;
2.50 g/kg bw: 10/10 males and 10/10 females;
1.50 g/kg bw: 10/10 males and 9/10 females;
1.30 g/kg bw: 3/10 males;
1.25 g/kg bw: 0/10 males and 2/10 females;
1.00 g/kg bw: 0/10 males and 0/10 females
Clinical signs:
All animals showed clinical signs after the treatment with the test substance.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 340 mg/kg bw

Additional information

Acute oral toxicity

In the key acute oral toxicity study (BASF AG, 1971), groups of 10 male and female rats per dose level were exposed by single oral gavage to the test item diluted in water in concentrations of 250, 320, 400, 500, 640, 800, 1000 or 1250 mm³/kg bw (6 % solution in water v/v). Animals were observed for 7 days. Clinical signs like squating, apathy, exophthalmus, secretion oral cavity, hemorrhargic incrustations in the eye, the nose and the snout ( 400 - 1250 mm³/kg bw) and dyspnea, posture, convulsions, secretion oral cavity ( 250 - 320 mm³/kg bw) were observed. The clinical signs were reversible 6 days post application. The oral LD50 was determined to be 563 mm³/kg bw (95% CL: 483 - 655) in male and female rats, corresponding to approximately 552 mg/kg bw.

In the key acute oral toxicity study (Bayer AG, 1977), groups of 10 male Wistar rats per dose level were exposed by single oral gavage to the test item (unchanged) in concentrations of 0.8, 1.0, 1.2, 1.3 and 1.5 mL/kg bw. Animals were observed for 14 days. Clinical signs like diarrhea, sedation, respiratory disorders and tonical cramps as well as a body weight reduction were observed. The oral LD50 was determined to be approx. 1.15 mL/kg bw (corresponding to approx. 1127 mg/kg bw) in male rats.

Acute inhalation toxicity

In an acute inhalation toxicity study (BASF AG, 1971), a group of three rats per sex was exposed by inhalation route (whole body) to the test item for 5 hours at a single concentration of 0.4 mg/L. A second group of 6 rats per sex was exposed to the test item (whole body) for 3 hours at a single concentration of 0.65 mg/L. Animals then were observed for 7 days. One male animal in the 5 hours exposure time dose group died during the course of the study. Macroscopic examination of this animal revealed heart blunted, both heart ventricles poorly contracted and filled with blood, and congestion of the liver. The animals showed severe Irritation of the mucous membrane and dyspnea (exposure time: 3 and 5 h). On this basis, the LC50 was > 400 mg/m³ and > 650 mg/m³ after 5 hour and 3 hour exposure, respectively.

Acute dermal toxicity

In an acute dermal toxicity study (BAYER AG, 1977) the potential of the test item to exert systemic toxicity was examined in groups of 10 Wistar rats, respectively 5 animals in the high dose group, that were occlusively exposed for 24 hours and then observed for 14 days. Animals were treated at 1.00, 1.25, 1.30, 1.50, 2.50 or 5.00 g/kg bw (5 mL/kg bw). All animals showed clinical signs after the treatment with the test substance. The identified LD50 value was approx. 1.35 g/kg bw in male and 1.34 g/kg bw in female rats.

Other route

In an acute toxicity study (BASF AG, 1971) the test item was administered to 10 mice per sex via intraperitoneal injection at a dose of 50, 64, 80, 100, 125, 160 or 200 mm³/kg bw. Observation period was until day 13 following treatment. Gross pathology revealed intestinal atony and congestion in the liver. In animals necropsied at the end of the study, abdominal adherences were observed. In all dose groups dyspnea and spastic gait was observed. The clinical signs were reversible 12 days post application. The LD50 was determined to be 115 mm³/kg bw in male and female mice, 107 mm³/kg in male and 123 mm³/kg in female mice.

Justification for selection of acute toxicity – oral endpoint
From the two available key studies, the study with the lowest LD50 value was selected.

Justification for selection of acute toxicity – inhalation endpoint
The key study was selected.

Justification for selection of acute toxicity – dermal endpoint
The key study was selected.

Justification for classification or non-classification

Benzylamine is currently classified with Xn; R21/22 and Acute Tox 4; H312, H302 according to Directive 67/548/EEC and Regulation (EC) No 1272/2008, respectively. This classification is supported by the key acute toxicity studies.