Propane-1,2-diyl dibenzoate

Endpoint summary

Description of key information

Key data is available for propylene glycol dibenzoate (PGDB). This data is supported by relevant information available from a structural analogue Dipropylene glycol dibenzoate (DPGDB). The justification for read across is provided as an attachment included in Section 13 of the IUCLID dossier.

Acute oral LD₅₀ (Rat): 4571 mg/Kg (males) and 2661 mg/Kg (females)

Acute inhalation LC₅₀ (Rat): >5.32 mg/L (4-hour)

Acute dermal LD₅₀ (Rat): >2000 mg/Kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

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.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

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

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 or test system 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

Key result

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:

other: Refer to full list of clinical signs in "Remarks on results" section, below.

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, waddling/unsteady gait, lethargy 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: Not classified

Remarks:

According to Directive 67/548/EEC Criteria used for interpretation of results: EU

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:

Key data is available for propylene glycol dibenzoate (PGDB). This data is supported by relevant information available from a structural analogue Dipropylene glycol dibenzoate (DPGDB). The justification for read across is presented as an attachment included in Section 13 of the IUCLID dossier.

 

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).

Reference 2

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: The test procedure is acceptable by current standards but there is no QA statement in the report. Study performed before GLP was in place.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Remarks:

pre-GLP study

Test type:

standard acute method

Species:

rat

Strain:

other: Spartan

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

corn oil

Doses:

1585, 2512, 3980, 6308 and 10000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: continuously for first hour, after 24 hours and once daily thereafter for a total of 14 days.
- Frequency of observations and weighing: bodyweights recorded at the start and end of the study.
- Necropsy of survivors performed: yes/no
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other:

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

4 571 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

2 661 mg/kg bw

Based on:

test mat.

Mortality:

At 1585 mg/kg, 1 female died
At 2512mg/kg, 2 females died
At 3980 mg/kg, 1 male and 4 females died
At 6308 and 10000, all females (5/5) and males died (5/5)

Clinical signs:

other: Not reported

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of propylene glycol dibenzoate to male and female rats was 4571 and 2661 mg/Kg bodyweight, respectively. Propylene glycol dibenzoate is unclassified, according to EU Regulation 1272/2008.

Executive summary:

The acute oral median lethal dose (LD₅₀) of propylene glycol dibenzoate to male and female rats was 4571 and 2661 mg/Kg bodyweight, respectively. Propylene glycol dibenzoate is unclassified, according to EU Regulation 1272/2008.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 661 mg/kg bw

Quality of whole database:

The test procedure is acceptable by current standards although there is no QA statement in the report and the study was performed before GLP was in place.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 days minimum

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: New study performed to GLP and internationally accepted guidelines.

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Species:

rat

Strain:

other: Crl:CD (SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Reputable supplier
- Age at study initiation: 68 to 96 days
- Weight at study initiation: 378 - 419g (males), 259 to 292g (females)
- Housing: 3 per single sex cage
- Diet (e.g. ad libitum): Mouse No. 1 Maintenance Diet.
- Water (e.g. ad libitum): Potable water via sipper tubes
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23
- Humidity (%): 40 - 70
- Air changes (per hr): 40
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 01/05/2014 To: 27/05/2014

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Aerosol generator (stainless steel concentric jet atomiser) and a snout only exposure chamber.
- Exposure chamber volume: 30.0 litres
- Method of holding animals in test chamber: Restraints
- Source and rate of air: Compressed air at 20 litres/minute
- Method of conditioning air: Filter
- System of generating particulates/aerosols:
- Method of particle size determination: Marple Model 296 Personal Cascade Impactor
- Treatment of exhaust air: Filter
- Temperature and humidity in air chamber: Temperature 22.8 ºC ± 0.25 (SD), Humidity 43.5% ± 1.60 (SD).

TEST ATMOSPHERE
- Brief description of analytical method used: 4 hour acute inhalation toxicity LC50 testing.
- Samples taken from breathing zone: Yes

TEST ATMOSPHERE
- Particle size distribution: 77.5% ≤ 3.50µm, 100% ≤ 9.80µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):The mean MMAD value was within the ideal range of 1 to 4 microns indicating that the propylene glycol dibenzoate atmosphere was highly respirable to the rats.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.32 mg/L Propylene glycol dibenzoate (Mean) ± 0.099mg/L (SD), close to the target concentration of 5 mg/L.

No. of animals per sex per dose:

3 animals per sex per dose.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days minimum

- Frequency of observations and weighing: The animals were observed intermittently for signs of reaction to the test substance during
exposure (as well as1 and 2 hours after exposure) and at least twice daily throughout the observation period, on the day of termination observations were recorded in the morning only.. The weight of each animal was recorded once during the acclimatisation period and on Days 1 (prior to dosing) 2, 4, 8 and 15.

- Necropsy of survivors performed: Yes

- Other examinations performed: Clinical signs, body weight and macropathology.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.32 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There were no unscheduled deaths.

Clinical signs:

other: During exposure - 1/3 females noted to have wet fur. Immediately after exposure - Chin rubbing evident for all animals (both male and female), all females were noted as having red staining of the head and wet fur. Clinical signs of wet fur and red stainin

Body weight:

Slight body weight losses were observed in 2/3 males and 3/3 females on the day following exposure. Growth was evident at the next weighing occasion (Day 4) for all animals.

Gross pathology:

The macroscopic examination performed after a single exposure followed by a 14 day observation period revealed no findings in any test animal.

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the LC50 (4 hour) of propylene glycol dibenzoate is in excess of 5.32 mg/L for male and female rats.
Propylene glycol dibenzoate is unclassified, according to EU Regulation 1272/2008.

Executive summary:

Under the conditions of this study, the LC₅₀ (4 hour) of propylene glycol dibenzoate is in excess of 5.32 mg/L for male and female rats.

Propylene glycol dibenzoate is unclassified, according to EU Regulation 1272/2008.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

5 320 mg/m³ air

Quality of whole database:

New study performed to GLP and internationally accepted guidelines.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

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.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1100 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

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 or test system 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

Key result

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:

other: There were no signs of systemic reaction to treatment observed in any animal throughout the study.

Gross pathology:

No abnormalities were recorded at the macroscopic examination on Day 15.

Interpretation of results:

other: Not classified

Remarks:

According to Directive 67/548/EEC Criteria used for interpretation of results: EU

Conclusions:

The acute lethal dermal dose to rats of DPGDB was demonstrated to be greater than 2000 mg/Kg bodyweight.

Executive summary:

Key data is available for propylene glycol dibenzoate (PGDB). This data is supported by relevant information available from a structural analogue Dipropylene glycol dibenzoate (DPGDB). The justification for read across is presented as an attachment included in Section 13 of the IUCLID dossier.

 

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.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The test procedure is acceptable by current standards but there is no QA statement in the report. Study performed before GLP was in place.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Pre-Guideline, pre-GLP study. Limit test at one dose level only, testing performed to support classification for transport

GLP compliance:

no

Remarks:

Pre-GLP study

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Weight at study initiation: 2423 to 3000g
- Fasting period before study: No
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage:
- Type of wrap if used: wrapped with a gauze bandage and occluded with Saran wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washing with tepid tap water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Concentration (if solution): undiluted
- Constant volume or concentration used: yes

Duration of exposure:

24h

Doses:

2000 mg/kg bw.

No. of animals per sex per dose:

2 per sex, skin of 1 male and 1 female rabbits were abraded with a scalpel blade

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (or other?) 14 days
- Frequency of observations and weighing: weighed at the start of the study and at unspecified intervals during the study
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight,

Statistics:

None

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: none

Gross pathology:

n/a

Other findings:

- Organ weights:
- Histopathology:
- Potential target organs:
- Other observations:

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Based upon the results obtained, the dermal LD50 of propylene glycol dibenzoate is in excess of 2000 mg/Kg bw for male and female rats. Propylene Glycol Dibenzoate would not be considered a toxic substance by the dermal route of administration.

Propylene glycol dibenzoate is unclassified, according to EU Regulation 1272/2008.

Executive summary:

Based upon the results obtained,  the dermal LD₅₀ of propylene glycol dibenzoate is in excess of 2000 mg/Kg bw for male and female rats. Propylene Glycol Dibenzoate would not be considered a toxic substance by the dermal route of administration.

Propylene glycol dibenzoate is unclassified, according to EU Regulation 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The test procedure is acceptable by current standards but there is no QA statment in the report. Study performed before GLP was in place.

Additional information

Key data is available for propylene glycol dibenzoate (PGDB). This data is supported by relevant information available from a structural analogue Dipropylene glycol dibenzoate (DPGDB). The justification for read across is provided as an attachment included in Section 13 of the IUCLID dossier.

Acute Oral Toxicity

In a key pre-GLP acute oral toxicity study (IRDC, 1975a; Klimisch score = 2) that followed a procedure similar to current guidelines, groups of 10 (5 males and 5 females) rats were dosed via oral gavage with suspensions of PGDB in corn oil at 1585, 2512, 3980, 6308 and 10000 mg/Kg. Clinical signs were not reported and mortality was observed in both sexes. The acute oral LD₅₀ of propylene glycol dibenzoate in male and female rats was determined to be 4571 and 2661 mg/Kg bodyweight, respectively.

In a key OECD Guideline 401 read across study (Huntingdon Life Sciences, 1998f; Klimisch score = 1), ten rats (five male and five female) were adminstered DPGDB via oral gavage at doses of 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. The acute oral LD₅₀ of dipropylene glycol dibenzoate was determined to be 5072 mg/Kg bodyweight in males), 3295 mg/kg bodyweight in females, and 3914 mg/kg bodyweight (both sexes).

Two supporting read across studies in rats and mice support the above findings.

In a supporting read across acute oral toxicity study (IRDC, 1975b; Klimisch score = 2), groups of five female and five male albino rats, were dosed with 1281, 2034, 3229, 5126, 8137 and 12,918 mg/Kg of DPGDB suspended in corn oil, then observed for 14 days post exposure. The acute oral LD₅₀ was determined to be 5368 mg/Kg bodyweight in males, 4068 mg/Kg bodyweight in females, and 4673 mg/Kg bodyweight in both sexes combined.

In another read across supporting acute oral toxicity study (IRDC, 1975b; Klimisch score = 2), groups of five female and five male albino mice, were dosed with 807, 1281, 2034, 3229, 5126 and 8137 mg/Kg bw of DPGDB suspended in corn oil, then observed for 14 days post exposure. The acute oral LD₅₀ was determined to be 4894 mg/Kg bodyweight in males, 4068 mg/Kg bodyweight in females, and 4462 mg/Kg bodyweight in both sexes combined.

Acute Inhalation Toxicity

In a key Guideline OECD 436 study (Huntingdon Life Sciences, 2014e; Klimisch score = 1), one test group consisting of 3 male and 3 female rats was subjected to a 4-hour snout only exposure of PGDB at a mean achieved aerosol concentration of 5.32 mg/L. There were no unscheduled deaths. Clinical signs were considered not treatment related and no macroscopic abnormalities were observed in any of the animals. After a slight body weight loss on day of exposure, growth was evident at the next weighing occasion (Day 4) for all animals. Therefore, under the conditions of this study, the acute inhalation LC₅₀ (4-hour) of propylene glycol dibenzoate in male and female rats was determined to be >5.32 mg/L.

In a supporting read across acute inhalation toxicity study (IRDC, 1975b; Klimisch score = 2), groups of five female and five male rats, were exposed to a whole-body aerosol atmosphere containing approximately 200 mg/L of DPGDB for a period of four hours, and then observed for 14 days post exposure. Clinical signs observed 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 observed 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. None of the rats exposed to the test material died during the course of the observation period. The acute inhalation LC50 of DPGDB in male and female rats was therefore determined to be >200 mg/L.

Acute Dermal Toxicity

In a key pre-GLP acute dermal toxicity study (IRDC, 1975a; Klimisch score = 2) that followed a procedure similar to current guidelines, the test material (PGDB) was applied to the shaven backs of 4 (2 males and 2 females) New Zealand White rabbits at a dose of 2000 mg/Kg bw under occlusive wrap for a period of 24 hours. No mortality was observed through the study period. Based on the results observed, the acute dermal LD₅₀ of propylene glycol dibenzoate in male and female rats was determined to be >2000 mg/Kg bodyweight.

In a key OECD Guideline 402 read across study (Huntingdon Life Sciences, 1998g; Klimisch score = 1), ten rats (five males and five females) were dermally exposed to DPGDB at a dose of 2000 mg/kg for a period of 24 hours, then observed for 14 days following test material removal. No mortality was observed during the observation period, and no clinical or pathological signs were noted either. Based on the results observed, the acute dermal LD₅₀ of DPGDB in male and female rats was determined to be >2000 mg/Kg bodyweight.

A supporting read across study in rabbits supports the above findings.

In a supporting read across acute dermal toxicity study (IRDC, 1975b; Klimisch score = 2), two male and two female New Zealand White rabbits, were dermally exposed to DPGDB at a dose of 2000 mg/Kg for a period of 24 hours, then observed for 14 days post exposure. No mortality was observed through the study period. Based on the results observed, the acute dermal LD₅₀ of DPGDB in male and female rabbits was determined to be >2000 mg/Kg bodyweight.

Justification for classification or non-classification

Based on an acute oral LD₅₀ of 2661 mg/Kg; an acute inhalation LC₅₀ >5.32 mg/L, and an acute dermal LD₅₀ of >2000 mg/Kg, propylene glycol dibenzoate (PGDB) is not classified for acute lethality by the oral, inhalation, or dermal routes of exposure under the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

 

For non-EU countries, the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) defines a fifth category for acute toxicity for chemicals with oral LD₅₀ values between 2000 and 5000 mg/Kg bw. Based on the results of two key acute oral toxicity studies, propylene glycol dibenzoate (PGDB) meets the criteria for a Category 5 classification under UN GHS for acute oral toxicity.