Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15.09.1982 - 02.11.1982 (animal testing) - 17.08.1983 (Issuance of Study report)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards and is described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Principles of method if other than guideline:
Method: BASF-Test
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
gas
Details on test material:
- Name of test material (as cited in study report): "Monomethylamine" and "Aminomethan"
- Molecular Formula: CH3 - NH2
- physical state: gaseous, colourless
- Stability: at least 2 years under normal conditions
- Storage conditions: normal conditions (ambient temperature; normal athmospheric pressure)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: SPF-Wistar/Chbb :THOM
- Source: Dr. K. Thomae GmbH, Biberach
- Age at study initiation: 8 weeks
- Weight at study initiation: male: 248 +/- 35 g; female: 175 +/- 15 g
- Housing: 5 animals per cage (without litter)
- Diet (e.g. ad libitum): Haltungsdiaet fuer Ratten, Maeuse und Hamster SSNIFF R 10 mm Pellet (Ssniff-Versuchetierdiäten GmbH, 4770 Soest)
- Water (e.g. ad libitum): tap water ad libitum

ANIMAL IDENTIFICATION
- Animals were uniquely marked via claw amputation

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


Administration / exposure

Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
whole body inhalation system (the animals were kept in groups of 5 in wire cages, which were placed into a 200 Litre Glas-Steel-Inhalation chamber)
Aminomethane was taken from a gas bottle. The dosage was accomplished using a Whitley needle valve (SS-22 R52 TFE). By supplying blower air, a substance gas-air mixture was generated.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
4.5, 2.9, 2.1, 0.72 mg/L
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 -15 days
- Frequency of weighing: beginning of the study, 7 days and 14 days after exposurt to the test (The body weight of the animals was measured pre-trial, after 7 days and at the end of the follow-up period. Moreover, it was graphically represented. The clinical findings were recorded from Monday to Friday. The lethality was checked daily.)
- Necropsy of survivors performed: yes (Following the 14 and 15-day follow-up period, the surviving animals were killed by CO2 and subjected to a pathological-anatomical examination (like all other animals deceased before)).
- Other examinations performed: clinical signs, body weight, histopathology and survival were recorded
Statistics:
The statistical evaluation of the concentration effect relationship was based on a probit analysis of D. J. Finney (Finney, D. J.: Probitanalysis 1971, page 1 - 150.
Published by the Syndics of the Cambridge University Press, Bentley House, 200 Euston Road, London N. W. 1) . The calculation was carried out in the BASF data center.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
>= 2.1 - <= 2.9 mg/L air
Exp. duration:
4 h
Mortality:
Dose 0.72 mg/L: 2/20 animals died within ten first days
Dose 2.1 mg/L: 5/20 animals died; three females died within the first day and one male each did in the first and second week, respectively
Dose 2.9 mg/L: 17/20 animals died within the first two days afte exposure
Dose 4.5 mg/L: 20/20 animals died
Clinical signs:
other:
Body weight:
Compared to the controls, the body weight of the male animals was especially affected after 7 days.
In the females, body weight after 7 days was also affected.
Gross pathology:
Animals found dead: often slight to moderate emphysema (lung); trachea file with mucous, effects of acute corrosion (nose)
Sacrificed animals: nothing abnormal detected

Any other information on results incl. tables

Mortality       

 Dose (mg/L)  No. of animals  died within 4h  1 day  2 days  7 days  14 days
 4.5  10 male  2/10  9/10  10/10 -  -
   10 female  2/10  9/10  10/10  -  -
 2.9  10 male  1/10  5/10  8/10  8/10  8/10
   10 female  1/10  3/10  9/10  9/10  9/10
 2.1  10 male  0/10  0/10  0/10  1/10  2/10
   10 female  0/10  3/10  3/10  3/10  3/10
 0.72  10 male  0/10  0/10  0/10  0/10  0/10
   10 female  0/10  2/10  2/10  2/10  2/10

Symptoms and findings

During exposure:

Fierce to extraordinarily strong eye and nose secretion, Snout wipe, eyelid closure, pulling to snapping breathing, suffocation cramps and abdominal position.

After exposure:

Pulling to snapping breathing with sounds at the inspiration, partly milky clouded corneae, etching wounds to noses and eyes and circulatory relief posture. The surviving ones were not yet free of symptoms.

Original tables in the study report:

Table 1

Time until letal outcome

groups (conzentration)
1  (4,5 mg/L) 2 (2,9 mg/L) 3 (2,1 mg/L) 4 (0,72 mg/L)
No. Of animals deceased No. Of animals exposed
m f m f m f m f
4 h 2/10 2/10 1/10 1/10 0/10 0/10 0/10 0/10
1 d 9/10 9/10 5/10 3/10   3/10   2/10
2 d 10/10 10/10 8/10 9/10        
7 d         1/10      
14 d         2/10      
No. at the end of experiment 20/20 17/20 5/20 2/20
m = male f = female
h = hour/s, d = day/s
 - = Letality unchanged

Table 2 - Bodyweight (gr.)
Mean Bodyweight pre-trial after 7 days after 14 /15 days
m w m w m w
Group 1 - Bodyweight - in grams
(No. Of Animals)
247
(10)
175
(10)
       
Group 2 - Bodyweight in grams
(No. Of Animals)
239
(10)
175
(10)
191
(2)
177
(1)1
240*
(2)
213*
(1)
Group 3 - Bodyweight in grams
(No. Of Animals)
257
(10)
179
(10)
243
(9)
178
(7)
292
(8)
200
(7)
Group 4 - Bodyweight in grams
(No. Of Animals)
250
(10)
170
(10)
248
(10)
175
(8)
294
(10)
202
(8)

Control group (exposed to air) - Bodyweight in grams 

(No. Of Animals)

231 176 274 197 311 214

Procedural and analytical measurement results

Calibration: The calibration curve had a linearity range of 0.5 to 4 mg.

Concentration provisions: Each sample (11 - 15 ; 21 - 25, 30 - 34, 40 - 44) was analysed (sample numbers 1 - 10, 16 - 20, 26- 29, 35 39 characterize technical preliminary tests)

The following individual values of the concentration groups were retrieved

Table 3 - Analytical concentration - Group 1
Sample-ID analytical conzentration (mg/L)
30 3,60
31 3,92
32 4,24
33 4,56
Mean 4,08
(Fritten bottle) 34 + 0,41
Mean of Sum 4,5
S.E. of the mean  + 0,41 mg/L

Table 4 - Analytical concentration - Group 2
Sample-ID analytical conzentration (mg/L)
40 2,36
41 2 ,80
42 2,65
43 2,67
Mean 2,62
(Fritten bottle) 44 + 0,31
Mean of Sum 2,9
S.E. of the mean  + 0,19 mg/L

Table 5 - Analytical concentration - Group 3
Sample-ID analytical conzentration (mg/L)
21 1 ,48
22 1 ,86
23 2,16
24 1 ,93
Mean 1 ,86
(Fritten bottle) 44 + 0,23
Mean of Sum 2,1
S.E. of the mean  + 0,28 mg/L

Table 6 - Analytical concentration - Group 4
Sample-ID analytical conzentration (mg/L)
11 0,61 5
1 2 0,565
13 0,645
1 4 0,800
Mean 0,656
(Fritten bottle) 44 + 0,066
Mean of Sum 0,72
S.E. of the mean  + 0,10 mg/L

Pathology

Section findings:

Dead (male and female) animals:

- General congestion hyperemia

- Lung: Often mild to moderate emphysema.

- Trachea: Multiple subtotal with tough rubbery mucus filled tracheas.

- Stomach opening: Smeared several times with bloody secretion.

- Kidneys: 2 female animals in the Rindenmark border finest white-grey radiar streak.

- Nose mirror: Occasionally corroded with bonding until detachment skin and hair. Occasionally cyanosis of tongue and gums.

Killed (male and female) animals:

- Organs without observations

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Methylamine is highly irritating if inhaled.

Statistical evaluation:
LC50 values (4 hours exposure): LC50 (males + female) : 2,1 mg/L < LC50 < 2,9 mg/L // LC50 (males): 2.5 mg/L ( 2,1 - 2,9) *// LC50 (females): ca. 2,3 mg/ L
The statistical security for the specified trust limits is 95 %.
A change in concentration by the slope factor 1.21 results in a change of the effect by 1 probit in the Calculation for male animals.

Conversion of the above mentionned 4-hour LC50 values according to the Haber rule C x t = k:
LC50 values (1 hour exposure): LC50 (males + female) :8,3 < LC50 < 11,7 mg/L // LC50 (males): 9,9 mg/L // LC50 (females): ca. 9.2 mg/ L
Executive summary:

An inhalation acute toxicity test was performed by a dynamic inhalation method by BASF AG (1983). Each 10 male and female rats (strain: Wistar) were exposed to whole body gas inhalation within a time period of 4 hours. After the 4 h MMA exposure, the animals were observed for 14 days. The concentrations of the test substance were 4.5, 2.9, 2.1, 0.72 mg/L. Deaths occurred in a dose-dependent manner. During exposure the animals showed eyelid closure, eye & nose discharge, dragging & gasping respiration, convulsions and after exposure dragging & gasping respiration, blurred cornea, effects of acute corrosion occurred. The clinical effects were irreversible in some animals. The mortality found was as follows: 0.72 mg/L: two of twenty animals died within 10 days, at 2.1 mg/L five of twenty animals died; at 2.9 mg/L already 17 of twenty animals died within 2 days. At the highest concentration tested (4.5 mg/L) all animals died. The LC50 value was determined to be between 2.1 and 2.9 mg/L air for both sexes. Slight to moderate emphysema of lungs; trachea file with mucous, effects of acute corrosion of nose have been recorded in necropsied animals..