N,N-dimethyl-alkyl-1-amines, reaction products with alkali hydroxide and chloroacetic acid

Acute Toxicity: oral

Administrative data

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. Limited documentation.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1969

Report date:

1969

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

limited documentation

Principles of method if other than guideline:

Study performed before actual guideline was established.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Test animals

Species:

rat

Strain:

other: CFY

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: range 59 - 86 g
- Fasting period before study: overnight

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: unchanged and water, respectively

Details on oral exposure:

- Amount of vehicle (if gavage): 0, 1.6, 2.5, 3.2, 4.0, 5.0, 8.0 ml/kg bw of test substance (aqueous solution)
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw (in the report stated as minimum volume-dosage, which very likely must be a typing error)

Doses:

0, 1.6, 2.5, 3.2, 4.0, 5.0, 8.0 ml/kg bw (approximately equivalent to mg/kg bw)

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 and weighing: observations several times on the day of application; weighing at dosing and weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, time to death, clinical signs, body weight

Statistics:

From the mortality data the LD50 value and its 95 % confidence limits were calculated by the method of Litchfield and Wilcoxon (1949).

Results and discussion

Preliminary study:

Range finder with 1 animal per sex and dose at dosages of 0, 5.0 and 10 ml/kg bw indicated a median lethal dose (LD50) in the region of 5 ml/kg bw. Subsequently dosing was extended to groups of 5/sex/dose in order to locate the LD50 more precisely.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 202.5 mg/kg bw

Based on:

test mat.

95% CL:

2 775.5 - 3 629.5

Remarks on result:

other: calculated from 3 mL/kg bw based on the density of 1.0675 g/cm³

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 mL/kg bw

Based on:

test mat.

95% CL:

2.6 - 3.4

Mortality:

Males:
8.0 ml/kg: 5/5 (after 5 - < 22 h)
5.0 ml/kg: 5/5 (after 5 - < 22 h)
4.0 ml/kg: 5/5 (after < 21 h)
3.2 ml/kg: 2/5 (after < 22 h)
2.5 ml/kg: 0/5
1.6 ml/kg: 0/5
control: 0/5

Females:
8.0 ml/kg: 5/5 (after < 22 h)
5.0 ml/kg: 5/5 (after < 22 h)
4.0 ml/kg: 4/5 (after < 21 h)
3.2 ml/kg: 4/5 (after < 22 - 24 h)
2.5 ml/kg: 2/5 (after < 23 - 27 h)
1.6 ml/kg: 0/5
control: 0/5

Clinical signs:

other: Lethargy and diuresis were observed at dosages of 3.2 ml/kg bw or more. Death was preceded by ataxia and coma and usually occurred within 5 to 27 hours following dosing. Recovery of the survivors was apparently complete five days after dosing, as judged

Gross pathology:

The deceased animals showed inflammation of the intestines which were devoid of solid content. The autopsies of the survivors revealed no treatment-related findings.

Any other information on results incl. tables

Conclusion:

The findings in the deceased animals demonstrate mortality due to local irritant effects in form of gastro-intestinal inflammation rather than systemic toxicity. According to the criteria of the DSD and the CLP regulation the substance does not have to be classified for acute oral toxicity.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

CLP: not classified
DSD: not classified