Registration Dossier

Administrative data

Description of key information

No specific testing was performed on the reaction mass. However, the two main components of the reaction mass were found to be not irritating or corrosive to eyes or skin. Therefore the reaction mass is also not expected to be irritating or corrosive to eyes and skin.

Skin irritation:

DEGDB:

- Key study, reliabiltiy 1, OECD 404, rabbit - not irritating

- Supporting study, reliability 2, rabbits - not irritating

DPGDB:

- Key study, reliability 1, OECD 404, rabbits - not irritating

- Supporting study, reliability 2, rabbits - not irritating

Eye irritation:

DEGDB:

- Key study, reliabiltiy 1, OECD 405, rabbit - not irritating

- Supporting study, reliability 2, OECD 405, rabbits - irritating

DPGDB:

- Key study, reliability 1, OECD 405, rabbits - not irritating

- Supporting study, reliability 2, OECD 405, rabbits - not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 July 1997 - 20 July 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 798.4470 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
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 and environmental conditions:
TEST ANIMALS
- Source: Harlan Interfauna (UK) Ltd., Huntingdon, Cambrigeshire, England
- Age at study initiation: 11 to 13 weeks
- Weight at study initiation: 2.5 to 3.1 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 - 74%
- 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): Approximately 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
Six males
(Note that the "animal management " section of the report states that 3 animals were used, however the results section lists data from 6 animals).
Details on study design:
TEST SITE
- Area of exposure: 25 mm 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
Max. 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
Max. score:
0
Reversibility:
other: Not applicable
Remarks on result:
no indication of irritation
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:
Remarks:
EU-GHS criteria not met
Conclusions:
A single semi-occlusive application of DEGDB to intact rabbit skin for four hours elicited no dermal irritation.
Executive summary:

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

No dermal reactions were observed following a single semi-occlusive application of DEGDB to intact rabbit skin for four hours. DEGDB is not irritant to the skin.

DEGDB is not considered to be a primary skin irritant

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 July 1997 - 20 July 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 798.4470 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
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 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:
animal: All animals
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal: All animals
Time point:
24/48/72 h
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:
Remarks:
EU-GHS criteria not met
Conclusions:
A single semi-occlusive application of DPGDB to intact rabbit skin for four hours elicited no dermal reaction.
Executive summary:

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 July 1997 - 26 July 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted in accordance with EPA, OECD, EC, and Japanese test guidelines, and in compliance with GLP.
Qualifier:
according to
Guideline:
EPA OTS 798.4500 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
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:
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 12 weeks
- Weight at study initiation: 2.4 to 2.9 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: At least 18 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15.5 - 21.5°C
- Humidity (%): 50 - 74%
- Air changes (per hr): 19 per hour
- Photoperiod (hrs dark / hrs light): 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:
animal: All animals
Time point:
24 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 2 days
Irritation parameter:
cornea opacity score
Basis:
animal: All animals
Remarks:
all animal
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: All animals
Remarks:
average score
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
All animals
Basis:
animal:
Time point:
48 h
Score:
1
Max. score:
1
Reversibility:
not specified
Remarks on result:
probability of mild irritation
Irritation parameter:
conjunctivae score
Basis:
animal:
Time point:
72 h
Score:
0 - 0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal: all animals
Remarks:
all animals
Time point:
24/48/72 h
Score:
0 - 0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
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.
Other effects:
There were no signs of ill health in any rabbit during the observation period.
Interpretation of results:
other:
Remarks:
EU-GHS criteria not met
Conclusions:
Instillation of DEGDB into the eye of the rabbit did not elicit a positive response according to the established test criteria.
Executive summary:

An assessment of the potential of the test material DEGDB to cause eye irritation in rabbits was undertaken. The study was conducted according to EPA, OECD, EC, and Japanese test guidelines, and in compliance with GLP.

The neat test material (0.1 mL) was instilled into one eye of six healthy adult rabbits, and the effects observed for three days (72h).

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.

Instillation of DEGDB into the rabbit eye did not elicit a positive response according to the established test criteria.

DEGDB is not irritant to the eye.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 July 1997 - 26 July 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to EPA, OECD, EC and japanese test guidelines and in compliance with GLP.
Qualifier:
according to
Guideline:
EPA OTS 798.4500 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
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:
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:
animal: all animals
Time point:
24/48/72 h
Score:
0.11
Max. score:
0.33
Reversibility:
fully reversible within: 2 days
Irritation parameter:
chemosis score
Basis:
animal: all animals
Time point:
24/48/72 h
Score:
0.11
Max. score:
0.33
Irritation parameter:
cornea opacity score
Basis:
animal: all animals
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal: all animals
Time point:
24/48/72 h
Score:
0
Max. score:
0
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:
Remarks:
Eu-GHS criteria not met
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:

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 irritant to the eye.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

This substance is a reaction mass 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. 

The results of the skin and eye irritancy studies indicate that the components of the reaction mass are not classified for irritancy; therefore the reaction mass itself is also not classified for irritancy.

All key studies were performed according to international test guidelines and in compliance with GLP. Earlier supporting studies were not in compliance with GLP.

 

Skin irritation

In the key studies there was a single semi-occlusive application of the substance for four hours to the intact skin of six male rabbits. In the supporting studies, there was a single application to three male and three female rabbits with both intact skin and abraded skin. The test substance was left in contact with the skin for either 4 or 24 hours (DPDGB and DEGDB, respectively).

Neither of the components of the reaction mass are considered to be skin irritants.

DEGDB

In the key study, no dermal reactions were observed.

A second study supports this result. Barely perceptible erythema was observed in all abraded animals and two animals with skin intact at the end of the exposure period; barely perceptible erythema was observed in one rabbit with abraded skin 72 hours after the end of the exposure period.

 

DPGDB

In the key study, no dermal reactions were observed.

A second study supports this result. 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.

 

Eye irritation

In the main studies there was a single application of the test substance into one eye of six rabbits. Neat test material (0.1 mL) was instilled into the eye and effects observed for 72 hours. The eyes were not washed. In the supporting studies the same volume was applied. For DPGDB, the eyes were washed after either 5 minutes (five rabbits) or 24 hours (three rabbits) and the effects were observed for 7 days. For DEGDB the eyes were not washed.

Neither of the components of the reaction mass are considered to be eye irritants.

 

DEGDB

In the key study, 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.

In the supporting study,slight or very slight conjunctival redness was seen in all rabbits tested at 24 hours after exposure; this reversed over the 7-day observation period and after 7 days, only very slight redness was seen in one animal. No corneal damage was seen in any of the animals tested.

DPGDB

In the key study, transient, very slight conjunctival irritation was observed which had resolved in all instances by one or two days after instillation. No corneal damage or iridial inflammation was observed.

In the supporting studyfor animals with 24 hour exposures, slight conjunctival redness was seen in one out of three rabbits at 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.

Justification for classification or non-classification

On the basis of the findings in the reported skin and eye irritation 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 irritation to skin and eyes, respectively.