Registration Dossier

Administrative data

Description of key information

Acute toxicity oral:

DEGDB:

- Key study, reliability 1, OECD 401, rat, oral gavage - LD50 = 4190 mg/kg bw

- Supporting study, reliability 2, rats, oral gavage - LD50 = 2562 mg/kg bw

- Supporting study, reliabiltiy 2, mice, oral gavage - LD50 = 3382 mg/kg bw

- Supporting study, reliabiltiy 2, rat, oral gavage - LD50 = 3455 mg/kg bw

DPGDB:

- Key study, reliability 1, OECD 401, rat, oral gavage - LD50 = 3914 mg/kg bw

- Supporting study, reliability 2, rats, oral gavage - LD50 = 4673 mg/kg bw

- Supporting study, reliabiltiy 2, mice, oral gavage - LD50 = 4462 mg/kg bw

Acute toxicity inhalation:

DEGDB:

- Key study, reliability 2, rat, inhalation aerosol - LC50 (4h) > 200 mg/L air

DPGDB:

- Key study, reliability 2, rat, inhalation aerosol - LC50 (4h) > 200 mg/L air


Acute toxicity dermal:

DEGDB:

- Key study, reliability 1, OECD 402, rat, occlusive dermal exposure - LD50 > 2000 mg/kg bw

- Supporting study, reliability 4, rabbits, occlusive dermal exposure - LD50 > 2000 mg/kg bw

DPGDB:

- Key study, reliability 1, OECD 402, rat, occlusive dermal exposure - LD50 > 2000 mg/kg bw

- Supporting study, reliability 2, rabbits, occlusive dermal exposure - LD50 > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 February 1997 - 25 March 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD, EC, EPA, and Japanese test guidelines, and in compliance with GLP.
Qualifier:
according to
Guideline:
EPA OTS 798.1175 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japan Ministry of International Trade and Industry (MITI), Directive, concerning the conduct of acute toxicity studies
Deviations:
no
Qualifier:
according to
Guideline:
other: EPA Pesticide Assessment Guidelines, Subdivision F. Hazard Evaluation: Human and Domestic Animals 81-1 Acute oral toxicity study (Revised Edition November 1984). Subdivision F provides detailed information relating to data requirements of 40 CFR Part 158.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England
- Age at study initiation: approximately 7 to 10 weeks
- Weight at study initiation: 201 to 231 g
- Fasting period before study: Animals were fasted overnight before dosing and for approximately 4 hours after dosing.
- Housing: Housed in groups of up to five rats of the same sex in metal cages with wire mesh floors.
- Diet (e.g. ad libitum): Standard laboratory rodent diet provided ad libitum
- Water (e.g. ad libitum): Drinking water was provided ad libitum.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 - 23°C
- Humidity (%): 38 - 57 % RH
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12 hours light per 24 hour period

IN-LIFE DATES: From: 25 February 1997 To: 25 March 1997
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Not applicable - administered as supplied by sponsor.

MAXIMUM DOSE VOLUME APPLIED: 4.270 mL/kg (5000 mg/kg group)


Doses:
3200 mg/kg (Preliminary test, one animal per sex)
2000, 3200 and 5000 mg/kg (main test groups - 5 animals per sex per group).
No. of animals per sex per dose:
5 (Main test groups)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations (clinical signs) taken frequently on day of dosing then twice daily for remainder of observation period. Bodyweights recorded on days 1 (day of dosing), 8, and 15, or on death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic pathology.
Statistics:
The acute median lethal oral dose (LD50) to male and female rats was calculated using the method of Finney [FINNEY, D.J. (1971) Probit Analysis, 3rd ed., Cambridge University Press, Cambridge]
Sex:
male
Dose descriptor:
LD50
Effect level:
4 843 mg/kg bw
95% CL:
4 198 - 5 588
Sex:
female
Dose descriptor:
LD50
Effect level:
3 535 mg/kg bw
95% CL:
2 892 - 4 322
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 190 mg/kg bw
95% CL:
3 504 - 5 072
Mortality:
One female at 3200 mg/kg and three males and all females at 5000 mg/kg died during the study. All deaths occurred within five days of dosing.
Clinical signs:
Refer to full list of clinical signs in "Remarks on results" section, below.
Body weight:
A slightly low bodyweight gain was recorded on Day 15 for one female at 2000 mg/kg and for one further female at 3200 mg/kg. All other surviving rats were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No abnormalities were observed among animals surviving treatment and killed at study termination on Day 15.
The gross pathological examination of the animals which died were:
3200 mg/kg (one female): Congestion (characterised by prominent blood vessels) in the brain and gaseous distension in the stomach and along the alimentary tract.
5000 mg/kg (three males and all (five) females): Congestion (characterised by dark appearance / prominent blood vessels / inflammation) in brain, heart, lungs, liver, spleen and kidneys. Congestion or pallor with fluid contents, gaseous distension and black patches were also seen in the stomach and along the alimentary tract.

Piloerection was observed in all rats within eight minutes of dosing. This sign persisted and was accompanied in rats later during the study by:

- hunched posture, waddling unsteady gait, lethargy and ungroomed appearance, in all rats at all dosages

- respiratory distress (characterised by increased / decreased / gasping or noisy respiration in all rats at 2000 mg/kg all males and four females at 3200 mg/kg and three males and all females at 5000 mg/kg

- pallid etremities in all females at 2000 mg/kg and all rats at 3200 and 5000 mg/kg

- increased salivation in one male at 2000 mg/kg four females at 3200 mg/kg and all males and four females at 5000 mg/kg

- walking on toes in all rats at 2000 and 5000 mg/kg and all males and four females at 3200 mg/kg

- increased lacrimation in one female at 2000 and 3200 mg/kg and all males and two females at 5000 mg/kg

- body tremors in one male and one female at 2000 mg/kg four females at 3200 mg/kg and all males and two females at 5000 mg/kg

- cold body surfaces in all males at 2000 mg/kg and in all rats at 3200 and 5000 mg/kg

- sensitivity to handling in one male and all females at 2000 mg/kg all rats at 3200 mg/kg and four males and two females at 5000 mg/kg

- partially closed eyelids in two females at 3200 mg/kg and in all rats at 5000 mg/kg

- faecal disturbances (characterised by soft to liquid or lack of faeces) in all females at 2000 mg/kg and in two males at 5000 mg/kg

- clonic convulsions in four males at 5000 mg/kg

- hyperactivity in one male at 5000 mg/kg

- prostration in one female at 3200 mg/kg and four males and two females at 5000 mg/kg

- stained muzzle and lor urogenital area in two females at 2000 mg/kg in all rats at 3200 mg/kg and in four males and two females at 5000 mg/kg

- thin appearance in one female at 3200 mg/kg and one male at 5000 mg/kg

- straub tail in two males at 5000 mg/kg

Recovery of surviving rats was complete with the exception of piloerection and unsteadiness in males at 5000 mg/kg by either Day 10 (3200 mg/kg) Day 11 (2000 mg/kg) or Day 13 males 5000 mg/kg

Interpretation of results:
other:
Remarks:
EU-GHS criteria not met
Conclusions:
The acute median lethal oral dose (LD50) and 95% confidence limits to male and female rats of DEGDB were calculated to be:
Males only: 4843 (4198 to 5588) mg/kg bodyweight
Females only: 3535 (2892 to 4322) mg/kg bodyweight
Combined sexes: 4190 (3504 to 5072) mg/kg bodyweight.
Executive summary:

A study was performed to assess the acute oral toxicity of the test material DEGDB when administered to rats. The study was conducted according to OECD, EC, US EPA, and Japanese (MITI) test guidelines, and in compliance with GLP.

In the definitive test, ten rats (five male and five female) in each treatment group were dosed at 5000, 3200, or 2000 mg/kg bodyweight, by oral gavage. Observations were taken for 14 days following dosing, and macroscopic pathology was performed on all animals.

The acute median lethal oral doses (LD50) to male and female rats of DEGDB were calculated to be: 4843 mg/kg bodyweight (males), 3535 mg/kg bodyweight (females), and 4190 mg/kg bodyweight (both sexes).

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 February 1997 - 25 March 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD, EC EPA and Japanese test guidelines and in compliance with GLP.
Qualifier:
according to
Guideline:
EPA OTS 798.1175 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japan Ministry of International Trade and Industry MITI Directive concerning the conduct of acute toxicity studies
Deviations:
not specified
Qualifier:
according to
Guideline:
other: EPA Pesticide Assessment Guidelines, Subdivision F. Hazard Evaluation: Human and Domestic Animals 81-1 Acute oral toxicity study (Revised Edition November 1984). Subdivision F provides detailed information relating to data requirements of 40 CFR Part 158.
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England
- Age at study initiation: approximately 7 to 8 weeks
- Weight at study initiation: 200 to 249 g
- Fasting period before study: Animals were fasted overnight before dosing and for approximately 4 hours after dosing.
- Housing: Housed in groups of up to five rats of the same sex in metal cages with wire mesh floors
- Diet: A standard laboratory rodent diet provided ad libitum
- Water: Drinking water was provided ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 to 23°C
- Humidity (%): 38-57% RH
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12 hours light per 24 hour period

IN-LIFE DATES: From: 25 February 1997 To: 25 March 1997
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Not applicable - administered as supplied by sponsor.

MAXIMUM DOSE VOLUME APPLIED: 5.714 mL/kg (6400 mg/kg group)
Doses:
3200 mg/kg (Preliminary test, one animal per sex)
2000, 3200, 5000 and 6400 mg/kg (main test groups - 5 animals per sex per group, except 3200 mg/kg: 5 females only, 6400 mg/kg: 5 males only).
No. of animals per sex per dose:
5, except for the dose rates of 2000 mg/kg and 5000 mg/kg for which 10 rats were used, 5 female and 5 male.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations (clinical signs) taken frequently on day of dosing then twice daily for remainder of observation period. Bodyweights recorded on days 1 (day of dosing), 8, and 15, or on death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic pathology.
Statistics:
The acute median lethal oral dose (LD50) to male and female rats was calculated using the method of Finney [FINNEY, D.J. (1971) Probit Analysis, 3rd ed., Cambridge University Press, Cambridge]
Sex:
male
Dose descriptor:
LD50
Effect level:
5 072 mg/kg bw
95% CL:
4 455 - 5 774
Sex:
female
Dose descriptor:
LD50
Effect level:
3 295 mg/kg bw
95% CL:
2 857 - 3 801
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 914 mg/kg bw
95% CL:
2 957 - 4 844
Mortality:
Two females at 3200 mg/kg, two males and all females at 5000 mg/kg and all males at 6400 mg/kg died during the study. All deaths occurred within three days of dosing.
Clinical signs:
Refer to full list of clinical signs in "Remarks on results" section, below.
Body weight:
All surviving rats were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
Macroscopic examination of males at 5000 mg/kg that survived treatment and killed at study termination revealed congestion (characterised by dark tissue and prominent blood vessels) in the brain. No abnormalities were observed among all other animals surviving treatment and killed at study termination.

Piloerection was observed in all rats within fifteen minutes of dosing. This sign persisted and was accompanied in rats later during the study by:

- hunched posture (in all rats);

- waddling/unsteady gait (in all rats);

- lethargy (in all rats) and

- pallor of the extremities (in all rats);

- partially closed eyelids (in three males at 2000 mg/kg four females at 3200 mg/kg, in all rats at 5000 mg/kg and in all males at 6400 mg/kg);

- increased salivation (in all males at 2000 mg/kg, one female at 3200 mg/kg, all rats at 5000 mg/kg and three males at 6400 mg/kg);

- walking on toes (in all rats at 2000 and 5000 mg/kg and four females at 3200 mg/kg);

- ungroomed appearance (in all males at 2000 and 6400 mg/kg, four females at 3200 mg/kg and in all rats at 5000 mg/kg);

- respiratory distress (characterised by increased or decreased respiration) (in all males at 2000 mg/kg, four females at 3200 mg/kg and in all rats at 5000 mg/kg);

- soft to liquid faeces (in one female at 2000 mg/kg);

- clonic convulsions (in three males at 5000 mg/kg);

- increased lacrimation and body tremors (in three females at 3200 mg/kg and all rats at 5000 mg/kg);

- cold body surfaces (in three males and all females at 2000 mg/kg, four females at 3200 mg/kg and all rats at 5000 mg/kg);

- prostration (in one female at 3200 mg/kg and two males and two females at 5000 mg/kg);

- red brown stain around the muzzle (in four females at 3200 mg/kg and two males and one female at 5000 mg/kg);

- red brown stain around the urogenital area (in three females at 3200 mg/kg and one male at 5000 mg/kg);

- sensitivity to handling (in four females at 3200 mg/kg and two males at 5000 mg/kg);

- aggressive behaviour to cagemates (in three females at 3200 mg/kg);

- brown staining on dorsal area (in three females at 3200 mg/kg);

Recovery of surviving rats was complete with the exception of piloerection, by either Day 4 (females 2000 mg/kg), Day 5 males (2000 mg/kg), Day 8 (males 5000 mg/kg) or Day 15 (females 3200 mg/kg).

Interpretation of results:
other:
Remarks:
EU-GHS criteria not met
Conclusions:
The acute median lethal oral dose (LD50) and 95% confidence limits to male and female rats of DPGDB were calculated to be:
Males only: 5072 (4455 to 5774) mg/kg bodyweight
Females only: 3295 (2857 to 3801) mg/kg bodyweight
Combined sexes: 3914 (2957 to 4844) mg/kg bodyweight.
Executive summary:

A study was performed to assess the acute oral toxicity of the test material DPGDB when administered to rats. The study was conducted according to OECD, EC, EPA, OECD and Japanese (MITI) test guidelines, and in compliance with GLP.

In the definitive test, ten rats (five male and five female) were dosed at 2000 and 5000 mg/kg bodyweight. Five females were dosed at 3200 mg/kg bodyweight and five males were dosed at 6400 mg/kg bodyweight. Doses were administered by oral gavage. Observations were taken for 14 days following dosing, and macroscopic pathology was performed on all animals.

Two females at 3200 mg/kg, two males and all females at 5000 mg/kg and all males at 6400 mg/kg died during the study. All deaths occurred within three days of dosing. Macroscopic examination revealed a generalised congestion in the majority of organs and tissues. Macroscopic examination of males at 5000 mg/kg that survived treatment and killed at study termination revealed congestion characterised by dark tissue and prominent blood vessels in the brain. No abnormalities were observed among all other animals surviving treatment and were killed at study termination.

 

The acute median lethal oral doses (LD50) to male and female rats of DPGDB were calculated to be: 5072 mg/kg bodyweight (males), 3295 mg/kg bodyweight (females), and 3914 mg/kg bodyweight (both sexes).

Endpoint conclusion
Dose descriptor:
LD50
Value:
3 914 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

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.
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
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
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)
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
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
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.

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.
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
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
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: 212 to 235 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)
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:
Approximately 200 mg/L. of DPGDB
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
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 DPGDB 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 period.
Gross pathology:
None.
Interpretation of results:
GHS criteria not met
Remarks:
EU-GHS criteria not met
Conclusions:
No deaths were seen in rats exposed to a 200 mg/L atmosphere of DPGDB in air for four hours. On this basis, DPGDB would not be considered a toxic material by the inhalation route of administration.
Executive summary:

A study was performed to assess the acute inhalation toxicity of the test material DPGDB when administered to rats. The study, conducted in 1975, was not performed according to any specific testing guideline, and not in compliance with GLP. The acute inhaled toxicity assessment was performed in groups of five female and five male rats, exposed to a whole-body aerosol atmosphere containing approximately 200 mg/L of DPGDB for four hours, then observed for 14 days post exposure.  

Clinical signs seen during the 4 hour exposure period included decreased motor activity, eye squint, erythema, clear nasal discharge, salivation, lacrimation, tachypnea and slight dyspnea.  In addition, at the termination of the exposure period both ocular and nasal porphyrin discharge, flaccidity and ataxia were observed. At 24 hours and for the remainder of the 14 day observation period, several rats exhibited flaccidity. Other signs recorded during the study period were; hypersensitivity to touch in two rats at 24 through 72 hours and in one rat at 4 days. Ataxia was present in one or two rats at 24 through 72 hours and 6, 12, 13 and 14 days. Drying of the corneal surface in one rat at 6, and 7 days; corneal opacity in one to three rats from 7 through 14 days, and chemosis in one or two rats from 9 through 12 days. Lacrimation in a few rats at 7, 8 and 9 days and clear nasal discharge in a few rats at 9, 10, 11 and 14 days.

None of the rats exposed to the test material died during the course of the observation period.

On this basis, DPGDB would not be considered a toxic material by the inhalation route of administration.

Endpoint conclusion
Dose descriptor:
LC50
Value:
20 000 mg/m³

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 July 1997 - 30 July 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to EPA, EEC, OECD, and Japanese test guidelines, and in compliance with GLP.
Qualifier:
according to
Guideline:
EPA OTS 798.1100 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japan Ministry of International Trade and Industry (MITI), Directive, concerning the conduct of acute toxicity studies.
Deviations:
no
GLP compliance:
yes
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England.
- Age at study initiation: seven to eight weeks
- Weight at study initiation: 230 to 261g
- Housing: Housed individually in metal cages with wire mesh floors.
- Diet (e.g. ad libitum): Standard laboratory rodent diet (Special Diet Services RM1(E) SQC expanded pellet), available ad libitum
- Water (e.g. ad libitum): Drinking water was made available ad libitum.
- Acclimation period: A minimum of six days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24.5°C
- Humidity (%): 45 - 63%
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12 hours per 24 hour period.

IN-LIFE DATES: From: 16 July 1997 To: 30 July 1997
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 50 mm x 50 mm
- % coverage: Approximately 10% of the total body surface area
- Type of wrap if used: porous gauze held in place with a non irritating dressing, further covered by a waterproof dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Skin washed with warm water (30°C to 40°C), then blotted dry with absorbent paper.
- Time after start of exposure:24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bodyweight
- Constant volume or concentration used: no (variable amount depending on bodyweight of test animal)
Duration of exposure:
24 hours
Doses:
Single limit dose of 2000 mg/kg bodyweight
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: Observations for mortality and clinical signs were performed at least twice daily. Body weights were recorded on days 1 (Prior to dosing), 8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic pathology
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no deaths following a single dermal application of dose of DEGDB to a group of ten rats (five males and five females) at a dosage of 2000 mg/kg bodyweight.
Clinical signs:
There were no signs of systemic reaction to treatment observed throughout the study.
Body weight:
A slightly low bodyweight gain was recorded for one female on Day 15. All other rats were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No abnormalities were recorded at the macroscopic examination on Day 15.
Interpretation of results:
other:
Remarks:
EU-GHS criteria not met
Conclusions:
The acute lethal dermal dose to rats of DEGDB was demonstrated to be greater than 2000 mg/kg bodyweight.
Executive summary:

An acute dermal toxicity study in rats was performed to determine the toxicity by dermal exposure of the test material DEGDB. The study was conducted according to international test guidelines, and in compliance with GLP.

Ten rats (five males and five females) were exposed to a 2000 mg/kg dose of DEGDB by the dermal route for 24 hours, then observed for 14 days following test material removal.

No rats died during the observation period, and no clinical or pathological signs were observed. On the basis of these results, it was concluded that the acute lethal dermal dose to rats of DEGDB was demonstrated to be greater than 2000 mg/kg bodyweight.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 July 1997 - 30 July 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to EPA, EEC, OECD, and Japanese test guidelines, and in compliance with GLP.
Qualifier:
according to
Guideline:
EPA OTS 798.1100 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japan Ministry of International Trade and Industry (MITI), Directive, concerning the conduct of acute toxicity studies.
Deviations:
no
GLP compliance:
yes
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England
- Age at study initiation: seven to eight weeks
- Weight at study initiation: 232 to 257 g
- Housing: Housed individually in metal cages with wire mesh floors
- Diet (e.g. ad libitum): Standard laboratory rodent diet, Special Diet Services RM1(E) SQC expanded pellet, available ad libitum
- Water (e.g. ad libitum): Drinking water was made available ad libitum
- Acclimation period: A minimum of six days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24.5°C
- Humidity (%): 45 - 63%
- Air changes (per hr): 10 to 15
- Photoperiod: 12 hourrs per 24 hour period

IN-LIFE DATES: From: 16 July 1997 To: 30 July 1997
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: approimately 50 x 50 mm.
- % coverage: Approximately 10% of the total body surface area
- Type of wrap if used: Porous gauze held in place with a non-irritating dressing further covered by a waterproof dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The skin was washed with warm water (30 to 40°C), then blotted dry with absorbent paper
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: no (variable amount depending on bodyweight of test animal)
Duration of exposure:
24 hours
Doses:
Single limit dose of 2000 mg/kg bodyweight
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: Observations for mortality and clinical signs were performed at least twice daily. Body weights were recorded on days 1 (Prior to dosing), 8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic pathology
Preliminary study:
None
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no deaths following a single dermal application of dose of DPGDB to a group of ten rats (five males and five females) at a dosage of 2000 mg/kg bodyweight.
Clinical signs:
There were no signs of systemic reaction to treatment observed in any animal throughout the study.
Body weight:
A slightly low bodyweight gain was recorded for one female on Day 8. All other rats were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No abnormalities were recorded at the macroscopic examination on Day 15.
Interpretation of results:
other:
Remarks:
EU-GHS criteria not met
Conclusions:
The acute lethal dermal dose to rats of DPGDB was demonstrated to be greater than 2000 mg/kg bodyweight.
Executive summary:

A study was performed to assess the acute dermal toxicity of the test material DPGDB when administered to rats. The study was conducted according to OECD, EC, US EPA, and Japanese (MITI) test guidelines, and in compliance with GLP. Ten rats (five males and five females) were exposed to a single 2000 mg/kg dose of DPGDB by the dermal route for 24 hours, then observed for 14 days following test material removal. 

No rats died during the observation period and no clinical or pathological signs were observed. No dermal response to treatment was observed in any animal. No abnormalities were observed during macroscopic examination at study termination. The acute lethal dermal dose to rats of DPGDB was demonstrated to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

This substance is a reaction mass consisting of diethylene glycol dibenzoate (DEGDB) and dipropylene glycol dibenzoate (DPGDB). No testing has been performed on the reaction mass itself but data are available for DEGDB and DPGDB. All key studies were performed according to international test guidelines and in compliance with GLP. Earlier, supporting studies were not in compliance with GLP. The results are presented below by the method of dose administration and by component.

The results of the acute oral, dermal and inhalation studies indicate that the components of the reaction mass are not classified for acute toxicity; therefore the reaction mass itself is also not classified for acute toxicity. 

 

Acute oral toxicity

Ten rats, five males and five females, were used at each dose level in the supporting studies, but in the main studies dosing on groups of one sex only was undertaken in some cases. The post-dosing observation period was 14 days in every study. Macroscopicpathology was performed on all animals in the main studies. The key result used in the chemical safety assessment is highlighted.

DEGDB

In the key study, ten rats (five male and five female) were dosed at 5000, 3200 or 2000 mg/kg bodyweight. One female at 3200 mg/kg, three males and all females at 5000 mg/kg died during the study. All deaths occurred within five days of dosing. Macroscopic examination revealed a generalised congestion in the majority of organs and tissues. No abnormalities were observed among all other animals surviving to the end of the study. 

 

The acute median lethal oral doses (LD50) were:

Males: 4843 mg/kg bodyweight;

Females: 3535 mg/kg bodyweight;

Both sexes: 4190 mg/kg bodyweight.

 

Three studies using similar methods on rats and mice support these findings. The combined LD50 for rats was 2562 and 3455 mg/kg bw while the combined LD50 for mice was 3382 mg/kg bw. 

 

DPGDB

In the key study, five female rats were dosed at 2000, 3200 and 5000 mg/kg bodyweight while five male rats were dosed at 2000, 5000 and 6400 mg/kg bodyweight. Two females at 3200 mg/kg, two males and all females at 5000 mg/kg and all males at 6400 mg/kg died during the study. All deaths occurred within three days of dosing. Macroscopic examination revealed a generalised congestion in the majority of organs and tissues. Macroscopic examination of males at 5000 mg/kg that survived treatment and killed at study termination revealed congestion characterised by dark tissue and prominent blood vessels in the brain. No abnormalities were observed among all other animals surviving to the end of the study.

 

The acute median lethal oral doses (LD50) were:

Males: 5072 mg/kg bodyweight;

Females: 3295 mg/kg bodyweight;

Both sexes: 3914 mg/kg bodyweight.

 

Two studies using similar methods on rats and mice support these findings. The combined LD50 for rats was 4673 mg/kg bw and the combined LD50 for mice was 4462 mg/kg bw. 

 

Acute inhalation toxicity

Studies were performed on DEDGB and DPGDB. The studies were not performed in compliance with GLP. Groups offive female and five male rats, were exposed to a whole-body aerosol atmosphere containing approximately 200 mg/L of test material for four hours then observed for 14 days post exposure. The key result used in the chemical safety assessment is highlighted.

DEGDB

None of the rats exposed to the test materials died during the course of the observation period. Clinical signs seen during the 4 hour exposure period included increased followed by decreased motor activity, eye squint, salivation, lacrimation and nasal porphyrin discharge. At 24, 48 and 72 hours decreased motor activity was observed with the addition of salivation at 24 hours. At 4 and 5 days decreased motor activity and ocular porphyrin discharge were observed. At 6 and 7 days only, ocular porphyrin discharge was noted in a few animals. From days 8 through 12 all rats appeared normal. At 13 days two rats showed decreased motor activity while on the 14th day all rats were normal.

 

DPGDB

None of the rats exposed to the test materials died during the course of the observation period. Clinical signs seen during the 4 hour exposure period included decreased motor activity, eye squint,erythema,clear nasal discharge, salivation, lacrimation, tachypnea and slight dyspnea.In addition, at the termination of the exposure period both ocular and nasal porphyrin discharge, flaccidity and ataxia were observed. At 24 hours and for the remainder of the 14 day observation period, several rats exhibited flaccidity.Other signs recorded during the study period were: Hypersensitivity to touch in two rats at 24 through 72 hours and in one rat at 4 days.Ataxia was present in one or two rats at 24 through 72 hours and 6, 12, 13 and 14 days.Drying of the corneal surface in one rat at 6, and 7 days;corneal opacity in one to three rats from 7 through 14 days, and chemosis in one or two rats from 9 through 12 days.Lacrimation was observed in a few rats at 7, 8 and 9 days and clear nasal discharge in a few rats at 9, 10, 11 and 14 days.

The acute lethal inhaled dose to rats of DEGDB and DPGDB was demonstrated to be greater than 200 mg/L (20,000 mg/m3).

Acute dermal toxicity

 

Five male and five female rats were used in the key study. Four New Zealand White rabbits, (two male and two female), were used in the supporting studies. In all cases, the animals were exposed for 24 hours, then observed for 14 days following removal of the test substance. The dose level was 2000 mg/kg in all studies (DEGDB and DPGDB).

No rats died during any of the studies and no clinical or pathological signs were observed in the key study. On the basis of the results obtained the acute lethal dermal dose to rats of DPGDB and DEGDB was demonstrated to be greater than 2000 mg/kg bodyweight.

Justification for classification or non-classification

On the basis of the findings in the reported oral, dermal and inhalation studies, and according to the criteria laid down in EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, the components of the reaction mass do not represent a concern for humans and therefore the reaction mass itself is also not classified for acute toxicity.