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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
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: see 'Remark'
Remarks:
The study was not conducted to a specific test guideline, no claim of GLP complaince was included in the test report, and the level of detail provided in the report was lacking for certain aspects or the study, so the study cannot be considered reliable without restrictions. The methodology described does, however, seem essentialy reliable.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was not conducted according to official test guidelines, no formal claim of GLP compliance is made in the report, and the level of detail contained in the report (specifically regarding the test material itself) is insufficient to confirm the integrity of the study conduct. The methodology described in the report is, however, broadly consistent with modern guidelines, and so the data is considered essentialy reliable.
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Groups of five male and five female rats were dosed orally with the test material suspended in corn oil. The rats were then observed for a total of 14 days for pharmacodynamic signs and mortality. Gross necropsy examinations were conducted on animals which died during the study period.
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
other: Spartan
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 202 to 254 g
- Fasting period before study: Food was withheld overnight before dosing
- Housing: Rats were housed by sex in groups of 5 per cage, elevated above the droppings.
- Diet (e.g. ad libitum): Available ad libitum
- Water (e.g. ad libitum): Available ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Temperature was controlled (although the range was not reported)
- Humidity (%): The humidity was controlled (although the range was not reported)
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50, 79.4, 125, 198.4, 315, 500, and 794 mg/mL.
- Amount of vehicle (if gavage): 10 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg (consistent for all levels)
Doses:
500, 794, 1250, 1984, 3150, 5000, and 7940 mg/kg
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: Frequent observations during the first five hours after dosing, then at 24 hours, and daily thereafter.
- Necropsy of survivors performed: no data
- Other examinations performed: clinical signs, body weight, gross necropsy of animals which died during the study.
Statistics:
Thompson, W. R., Bact. Rev., 11: 115-145, 1947
Sex:
male
Dose descriptor:
LD50
Effect level:
3 969 mg/kg bw
95% CL:
2 881 - 5 467
Sex:
female
Dose descriptor:
LD50
Effect level:
3 008 mg/kg bw
95% CL:
2 398 - 3 772
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 455 mg/kg bw
95% CL:
2 836 - 4 209
Mortality:
All rats dosed at 500, 794, 1250, and 1984 mg/kg dose levels survived until the end of the 14 day observation period.
At 3150 mg/kg, one female rat was found dead at 24 hours, one female and two males were found dead at 48 hours, and one female was found dead at 3 days (a total of 5 deaths). At 5000 mg/kg, three male rats and four female rats were found dead at 24 hours, and at 48 hours a further female rat was found dead (eight deaths found dead total). At 7940 mg/kg, all 10 rats were found dead 24 hours after exposure.
Clinical signs:
Clinical signs included: nasal porphyrin discharge and diarrhea (seen at all dose levels), decreased motor activity (see at 794 mg/kg dose level and above), salivation and flaccidity (seen at 1250 mg/kg dose level and above), urine stained abdomen (1984 mg/kg and above), bradypnea, tremors, ataxia and prostration (3150 mg/kg and above).
Body weight:
All surviving rats exhibited normal body weight gains during the 14 day observation period.
Interpretation of results:
other:
Remarks:
EU-GHS criteria not met
Conclusions:
The acute oral toxicity (LD50) values to rats were determined to be: 3969 mg/kg in males, 3008 mg/kg in females, and 3455 mg/kg in both sexes combined.
Executive summary:

A package of acute toxicity testing (including oral, inhaled, and dermal toxicity assessment) was conducted to assess the acute toxicity characteristics of the test substance DEGDB.

The acute oral toxicity assessment was performed in groups of five female and five male albino rats, dosed with the test material suspended in corn oil, then observed for 14 days post exposure.

The acute oral toxicity (LD50) was found to be 3969 mg/kg in males, 3008 mg/kg in females, and 3455 mg/kg to both sexes combined.

Reason / purpose:
reference to same study
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Not reported
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study report does not cite any specific test guidelines followed, no claim of GLP complaince was made, and the study report does not provide sufficient details regarding certain aspects of the study conduct to allow the data to be considered reliable without restrictions. On review of a relevant test guideline (OECD 402), it was concluded that the methodology employed (specifically the use of only two animals per sex, and the abrasion of the skin in some animals) was significantly different from the modern test, and as such, the results of this study could not be considered reliable.
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Qualifier:
no guideline available
Principles of method if other than guideline:
The hair was removed from the back of two male and two female rabbits with an electric clipper. The skin of one male and one female was abraded with a scalpel blade. A single application of the test material was made to the back of each rabbit at a dosage level of 2000 mg/kg. The area of application was wrapped with a gauze bandage and occluded with Saran wrap. After 24 hours, the bandages were removed and the exposure area was washed with tepid water. The rabbits were observed for mortality for a period of 14 days.
GLP compliance:
no
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2539 to 2964 g
- Diet (e.g. ad libitum): Food was available ad libitum
- Water (e.g. ad libitum): Water was available ad libitum

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Not specified but on the back of each rabbit
- Type of wrap if used: Gauze bandages occluded by Saran Wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The exposure site was washed with tepid water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Concentration (if solution): Not applicable - test material used neat
- Constant volume or concentration used: no
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
2 (1 abraded, 1 unabraded)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Bodyweights were recorded prior to dosing, and at the end of the 14 day observation period
- Necropsy of survivors performed: no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: No rabbits died during the 14 day observation period
Mortality:
None of the rabbits died during the observation period.
Body weight:
Three of the four rabbits exhibited weight gains during the study period. One female rabbit exhibited a 147 gram loss in body weight during the 14 day observation period.
Interpretation of results:
study cannot be used for classification
Conclusions:
No rabbits died following the dermal administration of 2000 mg/kg bodweight DEGDB. Based on these results, DEGDB would not be considered a toxic substance by dermal exposure.
Executive summary:

A package of acute toxicity testing (including oral, inhaled, and dermal toxicity assessment) was conducted to assess the acute toxicity characteristics of the test substance DEGDB.

The acute dermal toxicity assessment was performed on two male and two female New Zealand White rabbits, exposed dermally to the test material for a period of 24 hours, then observed for 14 days post exposure. None of the rabbits exposed to the test material died during the course of the observation period. On this basis, DEGDB would not be considered a toxic material by the dermal route of administration.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974
Report Date:
1974

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Five male and five female rats were exposed to an atmosphere containing the test material for 4 hours. During the exposure period the rats were observed for changes in appearance or behaviour, and after the exposure period they were observed for pharmacodynamic or toxic signs. The rats were observed for 14 days following the exposure period, then any surviving animals were sacrificed.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Benzoflex 2-45
- Physical state: Pale yellow liquid

Test animals

Species:
rat
Strain:
other: Spartan
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Not reported
- Weight at study initiation: 208 to 262 g
- Housing: Rats were housed in groups of 5 in metal cages above the droppings.
- Diet (e.g. ad libitum): Purina Laboratory Chow was available ad libitum
- Water (e.g. ad libitum): Water was available ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Temperature was controlled (note that the temperature range was not reported)
- Humidity (%): Humidity was controlled (note that the humidity range was not reported)

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Sealed glass chamber, test material addition controlled by a Dual Syringe Feeder.
- Exposure chamber volume: 59.1 L

TEST ATMOSPHERE
- Brief description of analytical method used: None reported



Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
Calculated to be 200 mg/L of DEGDB.
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: During the 4 hour exposure to the test compound the rats were observed continuously for changes in behavior and or appearance.
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 200 mg/L air
Exp. duration:
4 h
Remarks on result:
other: No deaths seen during exposure or observation periods.
Mortality:
All the rats exposed to DEGDB for the 4-hour exposure duration survived until the end of the observation period.
Clinical signs:
other:
Body weight:
All rats exhibited normal body weight gains during the study.
Gross pathology:
None

Applicant's summary and conclusion

Interpretation of results:
other:
Remarks:
EU-GHS criteria not met
Conclusions:
No deaths were seen in rats exposed to a 200 mg/L atmosphere of DEGDB in air for four hours. On this basis, DEGDB would not be considered a toxic material by the inhalation route of administration.
Executive summary:

A package of acute toxicity testing (including oral, inhaled, and dermal toxicity assessment) was conducted to assess the acute toxicity characteristics of the test substance DEGDB.

The acute inhaled toxicity assessment was performed in groups of five female and five male albino rats, exposed to an atmosphere containing the test material for four hours, then observed for 14 days post exposure.

None of the rats exposed to the test material died during the course of the observation period. On this basis, DEGDB would not be considered a toxic material by the inhalation route of administration.