Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable well-documented report which meets basic scientific principles.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1972
Report date:
1972
Reference Type:
publication
Title:
OECD SIDS Dimethylformamide
Author:
OECD
Year:
2004
Bibliographic source:
also cited in OECD SIDS Dimethylformamide, Final April 2004

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
- Principle of test: BASF internal method (in principle comparable to OECD Guideline 401).
- Short description of test conditions: 5 animals/sex were treated by single gavage application with an aqueous solution of DMF.
- Parameters analysed / observed: The animals were observed for mortality and for clinical symptoms of toxicity for 7 days. Surviving animals were sacrificed for the purpose of necropsy; as well as the animals that died during the observations period.
GLP compliance:
no
Test type:
other: comparable with OECD 401
Limit test:
no

Test material

Constituent 1
Reference substance name:
Dimethylformamide
IUPAC Name:
Dimethylformamide
Details on test material:
- Name of test material (as cited in study report): Dimethylformamid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Zentralinstitut für Versuchstierzucht Hannover
- Weight at study initiation: male: 153 g (mean), female: 135 g (mean)
- Diet: Wayne-Lab-Blox, Allied Mills, Chicago, ad libitum
- Water: water ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
no details
Doses:
6400, 4000, 3200, 2500, 2000, 1600 mL/kg bw (6016, 3760, 3008, 2350, 1880, 1504 mg/kg bw - conversation in mg/kg is based on the density: d = 0.94 g/cm3).
No. of animals per sex per dose:
6016 mg/kg: 3 females and 2 males
3760, 3008, 2350, 1880, 1504 mg/kg: 5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 010 mg/kg bw
95% CL:
2 480 - 3 650
Remarks on result:
other: conversion in mg/kg is based on the density: d= 0.94 g/cm³.
Mortality:
6016 mg/kg: 1 female died within 48 h and all animals died within 7 days.
3760 mg/kg: 1 female died within 48 h and 1 male and 4 female died within 7 days.
3008 mg/kg: 3 males and 3 females died within 7 days.
1880 mg/kg: 1 male and 1 female died within 7 days.
1504 mg/kg: 1 male died within 7 days.
Clinical signs:
6016 mg/kg: 24 h post application staggering, piloerection, paresis of fore limbs was noted.
3760, 3008, 2350 mg/kg: piloerection, slight apathy.
1880 mg/kg: 4 days post application slight staggering, piloerection.
1504 mg/kg: piloerection, slight apathy.
Body weight:
no data.
Gross pathology:
6016 mg/kg: 2x decomposition, 1x hydrothorax and lung filled with liquid. Pale liver, kidney and spleen with autolytic alterations.
3760 mg/kg: 1x lung filled with blood. Pale liver with distinct pattern on lobule.
3008 mg/kg: distinct pattern on liver lobule.
1880 mg/kg: 1x hydrothorax, 2x pattern on liver lobule, kidney and spleen decomposed.
Other findings:
- Histopathology: 1x desquamative pneumonia

Any other information on results incl. tables

Mortality:

 Dose (mg/kg)  Gender  Conc.(%)  dead within 1 h  dead within 24 h  dead within 48 h  dead within 7 days
6016  male 50 0/2 0/2 0/2 2/2
6016  female 50 0/3 0/3 1/3 3/3
3760  male 25 0/5 0/5 0/5 1/5
3760  female 25 0/5 0/5 1/5 4/5
3008  male 25 0/5 0/5 0/5 3/5
3008  female 25 0/5 0/5 0/5 3/5
2350  male 25 0/5 0/5 0/5 0/5
2350  female 25 0/5 0/5 0/5 0/5
1880  male 25 0/5 0/5 0/5 1/5
1880  female 25 0/5 0/5 0/5 1/5
1504  male 25 0/5 0/5 0/5 1/5
1504  female 25 0/5 0/5 0/5 0/5

May be harmful if swallowed.

Applicant's summary and conclusion

Interpretation of results:
other:
Remarks:
EU GHS criteria not met
Conclusions:
Main symptoms observed were apathy and staggering after oral intake.
The LD50 for both sexes was determined to be 3010 mg/kg bw/day.
Executive summary:

Study design

This non GLP-study was performed similar to the OECD Test Guideline 401: Acute Oral Toxicity, following a BASF internal method.

In the study DMF was administered once by gavage as aqueous solution in concentrations of 25 % (doses from 1504 mg/kg to 3760 mg/kg bw day) and 50 % (at dose of 6016 mg/kg bw/day), respectively, to 10 Sprague-Dawely rats per group at the dose levels of 1504, 1880, 2350, 3008, and 3760 mg/kg/ bw/day and to 5 rats per group at 6016 mg/kg bw/day. Mortality and signs of toxicity were recorded 1, 24 and 48 hours and 7 days after the substance administration. Animals that died and the surviving animals were sacrificed and necropsied after the 7 -day post observation period.

Results

48 hours after substance application one animal each at both highest dose levels (6016 and 3760 mg/kg bw/day) died. After 7 days all animals died at 6016 mg/kg bw/day, 5 of 10 rats died at 3760 mg/kg bw/day and 6 of 10 rats at 3008 mg/kg bw/day. There were no dead animals at 2350 mg/kg bw/day and 2 of 10 and 1of 10 rats were dead after 7 days at 1880 and at 1504 mg/kg bw/day, respectively. At necropsy all animals that died and those sacrificed at the end of the study, discoloured livers were seen. In relation to the dose administered the main symptoms observed were apathy and staggering.

Conclusion

Main symptoms observed were apathy and staggering after oral intake. The LD50 for both sexes was determined to be 3010 mg/kg bw/day.