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 presented as an attachment included in Section 13 of the IUCLID dossier.

Studies for skin irritation and corrosivity, and for eye irritation have been conducted and have demonstrated that the test material, propylene glycol benzoate, and the read across analogue dipropylene glycol dibenzoate do not present any adverse effects.

Skin Irritation - Not a skin irritant

Ocular Irritation - Not an ocular irritant

Respiratory Irritation - No data available

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Remarks:

in vivo study performed

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 July 1997 - 20 July 1997

Reliability:

1 (reliable without restriction)

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 798.4470 (Acute Dermal Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture Forestry and Fisheries Requirements for Safety Evaluation of Agricultural Chemicals and Testing Guidelines for Toxicology Studies, Acute Dermal Irritation Study 59 NohSan No. 4200 Agricultural Production Bureau Jan 28 1985

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Interfauna (UK) Ltd., Huntingdon, Cambridgeshire, England
- Age at study initiation: 10 to 12 weeks.
- Weight at study initiation: 2.4 to 2.8 kg
- Housing: Individually housed in metal cages with perforated floors
- Diet: access to SDS Stanrab (P) SQC Rabbit diet (ad libitum)
- Water (e.g. ad libitum): access to mains drinking water (ad libitum)
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15.5 to 21.5°C
- Humidity (%): 57 to 74%
- Air changes (per hr): 19
- Photoperiod: 12 hrs dark / 12 hrs light

- Air changes (per hr): approximately 19 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial light per 24 hour period


IN-LIFE DATES: From: 17 July 1997 To: 20 July 1997

Type of coverage:

semiocclusive

Preparation of test site:

other: Hair removed with electric clippers

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5mL

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

6 males

Details on study design:

TEST SITE
- Area of exposure: 25 x 25 mm
- Type of wrap if used: Semi-occlusive gauze pad.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Treatment site washed with physiological saline.
- Time after start of exposure: 4 hours


SCORING SYSTEM: Consistent with the scoring system described in OECD test guideline 404.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: All time points (1, 24, 48 and 72 hours after exposure)

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

mean

Time point:

other: All time points (1, 24, 48 and 72 hours after exposure)

Score:

0

Max. score:

0

Reversibility:

other: Not applicable

Irritant / corrosive response data:

No dermal reaction to treatment was observed in any animal throughout the study

Other effects:

There were no signs of toxicity or ill health in any rabbit during the observation period.

Interpretation of results:

other: Not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

A single semi-occlusive application of DPGDB to intact rabbit skin for four hours elicited no dermal reaction..

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 skin irritation potential of DPGDB to the rabbit. The study was conducted in accordance with OECD, EC, US EPA and Japanese test guidelines, and in compliance with GLP.

 

Approximately 0.5 mL of the test substance was applied under a semi-occlusive gauze pad to 6 rabbits;  after a period of 4 hours the application site was washed with physiological saline. The animals were then observed for a period of 72 hours.

 

No dermal reactions were observed following this single semi-occlusive application of DPGDB to intact rabbit skin for four hours. There were no signs of toxicity or ill health in any of the rabbits during the observation period.

 

Therefore DPGDB is not irritating to the skin and is not considered to be a primary skin irritant.

Reference 2

Endpoint:

skin irritation: in vivo

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 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

not specified

Remarks:

Pre-GLP study

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

other: The skin at all application sites was clipped and for half the rabbits the skin was abraded.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 ml of substance

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

6 (3 females and 3 males)

Details on study design:

TEST SITE
- Area of exposure: Back of rabbit. Skin on back of 3/6 animals was abraded prior to application of the test material.
- % coverage:
- Type of wrap if used: Gauze bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with tepid tap water
- Time after start of exposure: 4 h

SCORING SYSTEM: Scored for Erythema and Eschar formation and for Edema formation. Scoring system similar to subsequent OED 404 scoring system.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

not fully reversible within: 72h

Remarks on result:

other: intact skin test group - one animal was fully reversible within 72 h and one animal was not

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

not reversible

Remarks:

at 72h

Remarks on result:

other: abraded skin test group 3 out of 3 animals showed erythema at 72h

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 4h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 24h

Remarks on result:

other: abraded skin test group only 1 out of 3 animals showed edema at 4h

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: Individual, mean animal scores at the 24/48/72 hour timepoint not available

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: Individual, mean animal scores at the 24/48/72 hour timepoint not available

Irritant / corrosive response data:

Very slight erythema was present for up to 72 hours and very slight oedema was present in 2 rabbits with abraded skin at 4 hours after dosing

Interpretation of results:

other: Not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Propylene glycol dibenzoate would not be considered a primary skin irritant and does not present a corrosive hazard to the skin.

Executive summary:

A primary skin irritation and corrosive hazard test was conducted in 6 albino rabbits. The backs of the animals were shaved, the skin from 3/6 rabbits was abraded with a scalpel blade prior to applicaton of the test material. After application the application site was covered with a gauze bandage for 4 hours after which the skin was washed with tepid tap water and assessed for any reaction to the test material. The test material was found not to be a primary skin irritant that does not present a corrosive hazard to the skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Remarks:

in vivo study performed

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 July 1997 - 26 July 1997

Reliability:

1 (reliable without restriction)

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 798.4500 (Acute Eye Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

Note - study report refers to the guideline as number 404 "Acute Eye Irritation / corrosion", adopted 24 February 1987.

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF, Requirements for Safety Evaluation of Agricultural Chemicals and Testing Guidelines for Toxicology Studies, Primary Eye Irritation Study, 59 NohSan No 4200, Agricultural Production Bureau, January 28, 1985.

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Interfauna UK Ltd., Huntingdon, Cambridgeshire, England
- Age at study initiation: 10 to 13 weeks.
- Weight at study initiation: 2.3 to 3.0 kg
- Housing: Housed individually in metal cages with perforated floors
- Diet : SDS Stanrab (P) SQC Rabbit Diet, provided ad libitum
- Water: mains drinking water provided ad libitum
- Acclimation period: 18 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15.5 to 21.5°C
- Humidity (%): 50 to 74%
- Air changes (per hr): 19 hours
- Photoperiod: 12 hours artificial light per 24 hour period


IN-LIFE DATES: From: 21 July 1997 To: 26 July 1997

Vehicle:

unchanged (no vehicle)

Controls:

other: The eye contralateral to the treated eye remained untreated in each animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

Not applicable - a single instillation of test substance was made with no subsequent washing.

Observation period (in vivo):

3 days (observations made 1, 24, 48, and 72 hours after instillation).

Number of animals or in vitro replicates:

Six

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): None

SCORING SYSTEM: The scoring system used is consistent with that described in OECD test Guideline 405.

TOOL USED TO ASSESS SCORE: handheld light

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Time point:

24/48/72 h

Score:

0.11

Max. score:

0.33

Reversibility:

fully reversible within: 2 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.11

Max. score:

0.33

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Instillation of DPGDB into the rabbit eye did not elicit a positive response according to the established test criteria.
A single instillation of DPGDB into the eye of the rabbit elicited transient very slight conjunctival irritation.

Other effects:

There were no signs of ill health in any rabbit during the observation period.

Interpretation of results:

other: Not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Instillation of DPGDB into the eye of the rabbit did not elicit a positive response according to the established test criteria.
A single instillation of DPGDB into the eye of the rabbit elicited transient very slight conjunctival irritation.

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 eye irritation potential of DPGDB to the rabbit. The study was conducted in accordance with OECD, EC, US EPA and Japanese test guidelines, and in compliance with GLP.

Approximately 0.1 mL of the test substance was instilled into one eye of 6 rabbits, and the effects observed for 72 hours. The eyes were not rinsed after instillation of the test material.

Transient hyperaemia of blood vessels only was observed in all animals. These reactions had resolved in all instances by one or two days after instillation. No corneal damage or iridial inflammation was observed.

There were no signs of toxicity or ill health in any of the rabbits during the observation period.

Instillation of DPGDB into the rabbit eye did not elicit a positive response according to the established test criteria. DPGDB is not an irritant to the eye.

Reference 2

Endpoint:

eye irritation: in vivo

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 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

not specified

Remarks:

pre-GLP study

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

other: Left eye served as a control

Amount / concentration applied:

0.1 ml instilled into conjunctival sac of the right eye

Duration of treatment / exposure:

The exposure period was 5 minutes for 5 rabbits and 24 hours for 3 rabbits. After this period the eyes were washed with 300 ml water

Observation period (in vivo):

7 days after dosing

Number of animals or in vitro replicates:

4 females and 4 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water
- Time after start of exposure: 5minutes or 24 hours

SCORING SYSTEM: the eyes were examined and any lesions present scored using a scoring system similar to current OECD guidelines at 1,24,48 and 72 hours and 7 days after dosing.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 1h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 72h

Remarks on result:

other: 5 min wash

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 1h

Score:

2

Reversibility:

not fully reversible within: within 7days 1 animal recovered within72h and 1 animal did not

Remarks on result:

other: 24h wash

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: Individual, mean animal scores at the 24/48/72 hour timepoint not available

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: Individual, mean animal scores at the 24/48/72 hour timepoint not available

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: Individual, mean animal scores at the 24/48/72 hour timepoint not available

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: Individual, mean animal scores at the 24/48/72 hour timepoint not available

Irritant / corrosive response data:

In the Group 1 animals (5 minute exposure) slight redness of the conjunctivae was seen in one animal up to 72 hours after instillation; no redness was seen at 7 days.
In the Group 2 animals (24 hours exposure) Slight redness of the conjunctival tissue was seen in 2 rabbits at 72 hours and in 1 rabbit at 7 days 7 days following dosing but there was no corneal damage.

Interpretation of results:

other: Not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Propylene glycol dibenzoate is not an eye irritant

Executive summary:

An eye irritation study was conducted in two groups of rabbits, Group 1 (5 animals) to which were exposed to the test material for 5 minutes prior to washing, and Group 2 (3 animals) which were exposed to the test material for 72 hours prior to washing. The only symptoms seen were a slight reddening of the conjunctival tissues of 3 rabbits; in one rabbit the redness was still visible up to 72 after instillation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

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 presented as an attachment included in Section 13 of the IUCLID dossier.

Skin Irritation

In a key pre-GLP primary skin irritation and corrosive hazard test (IRDC, 1975a; Klimisch score = 2) that followed a study design similar to current

OECD guidelines, the backs of 6 albino rabbits were shaved and skin from 3/6 rabbits was abraded with a scalpel blade prior to applicaton of the test material (PGDB). After application, the application site was covered with a gauze bandage for 4 hours post which the skin was washed with tepid tap water and assessed for any reaction to the test material. The test material was found not to be a primary skin irritant that does not present a corrosive hazard to the skin.

In a key OECD Guideline 404 read across primary skin irritation study (Huntingdon Life Sciences, 1998h; Klimisch score = 1), the skin irritation potential of DPGDB was assessed in rabbits. No dermal reactions were observed following a single semi-occlusive application of DPGDB to intact rabbit skin for four hours. DPGDB was considered to be not irritating to the skin.

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

In a supporting read across study (IRDC, 1975b; Klimisch score = 2), the primary skin irritation potential of DPGDB was evaluated using 3 male and 3 female rabbits (with intact skin and with abraded skin). Very slight erythema was observed in all abraded animals and two animals with skin intact at the end of the observation period. No edema was observed in any animal at any timepoint. DPGDB was not considered to be a primary skin irritant.

 

Eye Irritation

In a key pre-GLP primary eye irritation study (IRDC, 1975a; Klimisch score = 2) that followed a study design similar to current OECD guidelines, the eye irritation potential of PGDB was evaluated using two groups of rabbits. Group 1 (5 animals) were exposed to the test material (PGDB) for 5 minutes prior to washing, and Group 2 (3 animals) were exposed to the test material for 72 hours prior to washing. A slight effect of conjunctival redness was observed in 2 animals that had been exposed to the test material for 24 hours; that redness reduced and was only apparent in one animal after 7 days. No other effects on the eyes of the test rabbits were observed.

In a key OECD Guideline 405 read across primary eye irritation study (Huntingdon Life Sciences, 1998i; Klimisch score = 1), 0.1 mL of DPGDB was instilled

into one eye of six healthy adult rabbits, and the effects observed for three days (72h). A single instillation of DPGDB into the eye of the rabbit elicited transient, very slight conjunctival irritation. These reactions had resolved in all instances by one or two days after instillation. No corneal damage or iridial inflammation was observed. DPGDB was therefore not considered to be irritating to the eye.

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

In a supporting read across study (IRDC, 1975b; Klimisch score = 2), the primary eye irritation potentianl of DPGDB was evaluated in rabbits. This study did not formally follow any official test guidelines, but was similar to OECD Guideline 405, although in all animals the eyes were washed, either after 5 minutes or 24 hours. For animals with 24 hours exposure, slight conjunctival redness was seen in one out of three rabbits one hour and 48 hours after exposure, in two out of three 72 hours after exposure, reverting to one out of three animals after 7 days. For animals with 5 minutes exposure, the results were broadly in line with those for the longer exposure time. No redness was observed at the end of the 7 day observation period. No corneal damage was seen in any of the animals tested. Based on the results obtained, DPGDB was not considered to be an eye irritant.

Justification for classification or non-classification

Based on available data, propylene glycol dibenzoate (PGDB) is not considered to be a primary skin irritant; does not present a corrosive hazard to the skin; and is not an ocular irritant. PGDB is therefore, not classified for skin and ocular irritation under the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.