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Administrative data

Description of key information

Oral (similar to OECD 401), rat: LD50 = 1656 mg/kg bw (female), 1767 mg/kg bw (male)

Dermal (similar to OECD 402), rabbit: LD50 > 2000 mg/kg bw

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
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.
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
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
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.
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.

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                                 

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: Acute oral toxicity 4, H302
DSD: Xn, R22
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 656 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2), and is thus sufficient to meet the standard information requirements set out in Annex VIII-IX, 8.6, of Regulation (EC) 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

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
Study period:
03 - 24 Feb 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions. As a worst-case scenario, the skin was abraded and the dressing was occlusive.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
skin was abraded and the dressing was occlusive
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.7 ± 0.2 kg
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: the animals' abdomen was shaved and the skin was abraded with a blunt hypodermic needle without causing bleeding, with the abrasions approximately 2-3 cm apart
- Type of wrap if used: the test substance was applied to the shaved skin area, which was covered with gauze and a sheet of impervious rubberized cloth. The trunk was enclosed in a flexible stainless steel protective screen held in place by tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the test area was cleaned
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: no, volume adjusted according to weight of the rabbit
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
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 daily, the body weight was recorded before dosing and on day 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: the treated skin area was examined regularly to assess the local irritating effects

In a range-finding study, one rabbit was exposed to 1000 mg/kg bw and one rabbit to 2000 mg/kg bw. As no mortality was observed, only 2000 mg/kg bw was used in the main study.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality during the study period.
Clinical signs:
No clinical signs were observed during the study period.
Body weight:
There were no effects on body weight.
Gross pathology:
The internal organs in all the rabbits were normal, except for the small intestines in some of the animals that showed adhesions. This is not considered to be a treatment-related effect as no dose-related effect was observed.
Other findings:
- Other observations: at the end of the 24 hours exposure period, the treated skin areas in all the rabbits were black in color. By day 7, the same skin areas were hard with eschar formation. At necropsy, the treated areas were necrotic at the abraded sites.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2), and is thus sufficient to meet the standard information requirements set out in Annex VIII-IX, 8.6, of Regulation (EC) 1907/2006.

Additional information

Acute toxicity: oral

An acute oral toxicity study was performed in a manner comparable to OECD 401 (version adopted in 1981), although few details were given in the report (Parekh, 1982). 10 male and female rats per dose level were administered 950, 1500, 1900, 2400 and 3000 mg/kg bw 2-dimethylamino-2-methyl-1-propanol (DMAMP), by gavage. The mortality was 1, 1, 7, 10 and 10 for the males and 0, 4, 7, 9 and 10 for the females, respectively, listed by increasing dose. Lethargy, ataxia and other signs of severe discomfort was observed in females in the 1500 mg/kg bw group, and in males and females administered 1900, 2400 and 3000 mg/kg bw from 4 hours after dosing. The effects lasted up to 24 hours in the 1500 mg/kg bw group and until day 4-5 or death in the remaining dose groups. In the rats that died, severe stomach- and intestinal hemorrhage was noted, indicating a local irritating effect of the test substance due to the alkaline pH value (12.5). The calculated LD50 for females was 1656 mg/kg bw, and for males the LD50 was 1767 mg/kg bw.

 

Acute toxicity: dermal

In an acute dermal toxicity study performed similarly to OECD 402 (version adopted in 1981) with some major deviations, rabbits were exposed to DMAMP (Parekh, 1982). The animals' abdomens were shaved free of hair, and the test area was abraded. 2000 mg/kg bw of the test substance was spread over the prepared abdominal skin area, which was then covered with an occlusive dressing. After 24 hours, the skin area was cleaned and the animals were observed for 14 days following administration. No mortality was observed. There were no signs of toxicity, no effects on body weight and no unusual gross pathological findings were noted. Within 24 hours of application, the exposed skin areas were black in colour. By day 7 the same skin areas were hard with eschar and at necropsy the abraded sites were necrotic, due to the alkaline properties of DMAMP (pH 12.5). The LD50 is considered to be > 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint

There is only one study available.

Justification for selection of acute toxicity – inhalation endpoint

No study required since the exposure of humans via the inhalation route will only occur with solutions containing ≤ 1% of the test substance. The potential for acute toxicity via the inhalation route will be negligible.

Justification for selection of acute toxicity – dermal endpoint

There is only one study available.

Justification for classification or non-classification

The available data on the acute oral toxicity of the test substance meet the criteria for classification as acute oral toxicity 4 (H302) according to Regulation (EC) 1272/2008 and as Xn, R22 according to Directive 67/548/EEC.

The available data on the acute dermal toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.