Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03 Nov - 02 Dec 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions. The documentation of materials and methods, and results is limited.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
limited documentation
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-Dimethylamino-2-methyl-1-propanol, 73% DMAMP, Polymeen A (P-2614)
- Substance type: clear, pale yellow liquid
- Analytical purity: 72.03%
- Lot/batch No.: 730H18DF36
- pH: 12.5

Test animals

Species:
rat
Strain:
other: Cox-SD albino
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 187 ± 8.8 g
- Fasting period before study: yes

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: test substance is soluble in the vehicle (water)
Doses:
950, 1500, 1900, 2400 and 3000 mg/kg bw
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 and weighing: the animals were observed for mortality and signs of toxicity several times during the first day after dosing and daily thereafter. All animals were weighed before dosing, on day 7 and on day 14.
- Necropsy of survivors performed: yes. Animals that died during the study period were necropsied immediately and the surviving animals were necropsied after sacrifice on day 14.

In a range-finding study, the maximum dose possible to administer was 3000 mg/kg bw. Therefore this was selected as the highest dose in the main study.
Statistics:
The oral LD50 values, the 95% confidence limits (shown in parenthesis), and the slope (+SE) were calculated according to Finney (Probit Analysis, Cambridge University Press, 1971) adapted to BASIC computer program.

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
1 656 mg/kg bw
Based on:
test mat.
95% CL:
1 395 - 1 878
Sex:
male
Dose descriptor:
LD50
Effect level:
1 767 mg/kg bw
Based on:
test mat.
95% CL:
1 600 - 1 946
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 712 mg/kg bw
Based on:
test mat.
Mortality:
950 mg/kg bw: 1/10 males and 0/10 females died
1500 mg/kg bw: 1/10 males and 4/10 females died
1900 mg/kg bw: 7/10 males and 7/10 females died
2400 mg/kg bw: 10/10 males and 9/10 females died
3000 mg/kg bw: 10/10 males and 10/10 females died

Most of the animals died within 24 hours of dosing, while one female administered 2400 mg/kg bw and 2 males administered 1900 mg/kg bw died on day 5, 5 and 6, respectively. The mortality was caused by the local irritating effect of the test substance, as the main findings were hemorrhaging in the stomach and intestines.
Clinical signs:
1500 mg/kg bw: lethargy, eye squint, hunched posture, and ataxia by the fourth hour after dosing in females, fully reversible within 24 h.
1900 mg/kg bw: lethargy, eye squint, hunched posture, and ataxia by the fourth hour after dosing in females and males, fully reversible within 5 days (males) or 6 days (females) in surviving animals.
2400 mg/kg bw: lethargy, eye squint, hunched posture, and ataxia by the fourth hour after dosing in females and males, fully reversible by day 6 in surviving females.
3000 mg/kg bw: lethargy, eye squint, hunched posture, and ataxia by the fourth hour after dosing in females and males, 2/10 males and 10/10 females had bloody nares (nostrils) after 2 hours.

Two males in the 950 mg/kg bw group developed an inner ear infection on day 7. As the effect is not dose-related and only observed in these animals, it is not considered to be a treatment-related effect.
Body weight:
There were no treatment-related effects.
Gross pathology:
In the animals that died during the study period, the stomach and intestine were severely haemorrhaged. These effects are probably due to local irritation by the very alkaline test substance.

The presence of dark organs is not dose-related and may be a result of the method of sacrifice (the method was not reported).

1900 mg/kg bw: 5/10 males and 6/10 females had a dark spleen, while 1/10 females also had dark adrenals
2400 mg/kg bw: 3/10 females had a dark spleen
3000 mg/kg bw: 4/10 females had a dark spleen, kidneys and adrenals

One female administered 950 mg/kg bw had severe lung infection. This is not considered to be a treatment-related effect, as only one animal had this condition and no dose-related trend was observed. All other organs were grossly normal.

Any other information on results incl. tables

Table 1. Results, acute oral toxicity study

 

Dose
[mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Males

950

1/0/10

-

Day 5

10

1500

1/0/10

-

Day 1

10

1900

7/10/10

3 h – day 5

Day 1 (5 rats),

Day 5 (1 rat),

Day 6 (1 rat)

70

2400

10/10/10

1 h - death

Day 1

100

3000

10/10/10

1 h - death

Day 1

100

LD50 = 1767 mg/kg bw (male)

 

Females

950

0/0/10

---

---

0

1500

4/10/10

3 h – day 1

Day 1

40

1900

7/10/10

3 h – day 6

Day 1

70

2400

9/10/10

2 h - death

Day 1 (8 rats) and 5 (1 rat)

90

3000

10/10/10

1 h - death

Day 1

100

LD50 = 1656 mg/kg bw (female)

                                                                                   

* first number = number of dead animals                                   

 second number = number of animals with clinical signs           

 third number = number of animals used                                 

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: Acute oral toxicity 4, H302
DSD: Xn, R22