3,5-dimethyl-1,2-dioxolane-3,5-diol

Endpoint summary

Description of key information

SKIN: 
The acute dermal irritation potential of Trigonox 44B (CAS 37187 -22 -7) was assessed in New Zealand White rabbits (4 hour exposure, semi-occluded) under OECD 404 test guideline (key study by Rees, 1993). No dermal response was observed at anytime except slight erythema in 2 rabbits during the first 24 hours after treatment. Under the criteria of the EEC, the test substance was classified as non irritant to the skin. 
EYE: 
The acute eye irritation potential of Trigonox 44B (CAS 37-187-22-7) was assessed (key study by Rees, 1990) in 3 New Zealand White rabbits under the OECD 405 test guideline. Due to the severe response observed in one animal at 1 and 24 hours, this animal was humanely sacrificed. The test material was considered to be irritating to the eye with the potential to cause serious ocular damage. However, the ocular scores for the animals used on this study did not reach the EEC limit values for a positive result. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

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 generally satisfies the GLP regulations and specific test guidelines. Minor deficiiencies: the concentration, purity and stability of the test substance could not be verified from the Certificate of Analysis for the batch of test material.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

The test substance characterization/stability data were not presented in accordance with the (GLP) standard. The report stated that this deviation was not expected to impact the study results. This was considered as a minor deficiency only.

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

The test substance characterization/stability data were not presented in accordance with the (GLP) standard. The report stated that this deviation was not expected to impact the study results. This was considered as a minor deficiency only.

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Supplied by Rosemead Rabbits, Rosemead, Waltham Abbey, Essex, England.
- Age at study initiation: 3 - 3.5 months at dose initiation.
- Weight at study initiation: 2.6 - 2.99 kg
- Housing: Individually housed in suspended stainless cages
- Diet (e.g. ad libitum): standard pelleted rabbit diet, ad libitum.
- Water (e.g. ad libitum): free access to tap water
- Acclimation period: Acclimatized rabbits were used; 8 -1 4 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 22 degrees Celcius
- Humidity (%): 45 - 56%
- Air changes (per hr): 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: To: 5 October, 1992 to 22 October, 1992.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: For each animal, the right test site served as the respective control site.

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

Four hours

Observation period:

72 hours

Number of animals:

Three

Details on study design:

Test Site:
- Area of exposure: 3x2 cm
- Type of wrap if used: Semi-occlusive (treated area covered with an unmedicated gauze patch held in place by strips of Blenderm), covered by cottonwool and elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: Exposure (4 hours) was followed by gentle washing of the sites with warm water

SCORING SYSTEM: According to the Criteria of Draize (1959), cited in the Study Report.

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 24 h

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

other: Mean values of erythema score and edema score were calculated for each animal from 1, 24, 48 and 72 hour post-treatment observations.

Basis:

animal: Three males

Time point:

other: 1, 24, 48 and 72 hours

Score:

ca. 0.3

Reversibility:

fully reversible within: 48 hours (Erythema score)

Remarks on result:

other: Mean Erythema scores and Mean Edema scores were calculated from 24, 48, and 72 hours data for each animal. The only dermal reaction to Trigonox 44B was erythema in two animals (1 hour) and one animal (24 hour), which were reversible.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No dermal response was observed at anytime except slight erythema in two rabbits during the first 24 hours after treatment. Under the criteria of the EEC, Trigonox 44B was classified as non irritant to the skin.

Executive summary:

The acute dermal irritation potential of Trigonox 44B (CAS 37187 -22 -7) was assessed in three New Zealand White rabbits (4 hour exposure, semi-occluded) under OECD 404 test guideline. No dermal response was observed at anytime except slight erythema in two rabbits during the first 24 hours after treatment. Under the criteria of the EEC, the test substance was classified as non irritant to the skin.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

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

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The test generally satisfies the GLP regulations and specific test guideline (OECD 405). Minor deficiiencies: the concentration/purity of the test substance could not be verified from the Certificate of Analysis

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

(The test substance characterization and stability data, while available, were not developed in accordance with the (GLP) standard. The report stated that this deviation was not expected to impact the study results.)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source:Supplied by Rosemead Rabbits, Rosemead, Waltham Abbey, Essex, England.
- Age at study initiation: 3.5 - 4.5 months.
- Weight at study initiation: 3.04 - 3.44 kg
- Housing: Individually housed in suspended stainless cages
- Diet (e.g. ad libitum): standard pelleted rabbit diet, ad libitum.
- Water (e.g. ad libitum): free access to tap water
- Acclimation period: Acclimatized rabbits were used; 8 -1 4 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 19 degrees Celcius
- Humidity (%): 49 - 56%
- Air changes (per hr): 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 5 October, 1992 to 18 November, 1992.

Vehicle:

other: None

Controls:

no

Amount / concentration applied:

0.1 ml of the test substance, as provided by the Sponsor.

Duration of treatment / exposure:

Test material was instilled once into the right eye.

Observation period (in vivo):

1, 24, 48, and 72 hours and 7 days after treatment.

Number of animals or in vitro replicates:

Three rabbits

Details on study design:

A standard study design was used. Rabbits were observed at 1,24, 48, 72 hours and 7 days after treatment and ocular lesions were scored. For each animal, the left eye (untreated eye) was used for comparison for assessing the ocular lesions.

REMOVAL OF TEST SUBSTANCE
- Washing: Exposure was not followed by washing

SCORING SYSTEM: According to the Guidelines on Eye Irritation Tests (Draize Eye Test), UK Home Office, (1986).

Additional scoring systems were used for the assessment of pain response and ocular lesions in Cornea (not a component of regulatory guidelines).

TOOL USED TO ASSESS SCORE: An ophthalmoscope was used to inspect the eyes. Corneal lesions were confirmed by fluorescein treatment.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

(Animal Number and Sex: 28TD 468M)

Time point:

24/48/72 h

Score:

0.3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Pain Evaluation Response: 3

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

(Animal Number and Sex: 28TD 468M)

Time point:

24/48/72 h

Score:

0.7

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Remarks:

(Redness)

Basis:

animal #1

Remarks:

(Animal Number and Sex: 28TD 468M)

Time point:

24/48/72 h

Score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Remarks:

(Chemosis of Conjunctiva)

Basis:

animal #1

Remarks:

(Animal Number and Sex: 28TD 468M)

Time point:

24/48/72 h

Score:

0.7

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

(Animal Number and Sex: 28TD 479M)

Time point:

24/48/72 h

Score:

0

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

(Animal Number and Sex: 28TD 479M)

Time point:

24/48/72 h

Score:

0.3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Remarks:

(Redness)

Basis:

animal #2

Remarks:

(Animal Number and Sex: 28TD 479M)

Time point:

24/48/72 h

Score:

1.7

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Remarks:

(Chemosis of Conjunctiva)

Basis:

animal #2

Remarks:

Animal Number and Sex: 28TD 479M)

Time point:

24/48/72 h

Score:

0

Irritation parameter:

overall irritation score

Remarks:

(Cornea, Iris and Conjunctiva (redness and chemosis) were evaluated similar to other animals)

Basis:

animal #3

Remarks:

(Animal Number and Sex: 28TD 480M)

Time point:

other: 1 and 24 hours post-treatment

Reversibility:

not reversible

Remarks on result:

other: A diffuse crimson-red conjuctival appearance, severe discharge, moderate chemosis, stippling of the cornea/iritis was evident an hour of treatment. Additional lesions and hemorrhage were also seen at 24 hrs. The rabbit was humanely killed immediately.

Irritant / corrosive response data:

Data provided above.

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Due to the severe response observed in one animal, the test material was considered to be irritating to the eye with the potential to cause serious ocular damage, although the ocular scores for the animals used on this study did not reach the EEC limit value for a positive result.

Executive summary:

The acute eye irritation potential of Trigonox 44B was assessed in three New Zealand White rabbits under the OECD 405 test guideline. Due to the severe response observed in one animal at 1 and 24 hours, this animal was humaley sacrificed. The test material was considered to be irritating to the eye with the potential to cause serious ocular damage, although the ocular scores for the animals used on this study did not reach the EEC limit values for a positive result.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin:The acute dermal irritation potential of Trigonox 44B (CAS 37187 -22 -7) was assessed in New Zealand White rabbits (4 hour exposure, semi-occluded) under OECD 404 test guideline (key study by Rees, 1993). No dermal response was observed at anytime except slight erythema in 2 rabbits during the first 24 hours after treatment. Under the criteria of the EEC, the test substance was classified as non irritant to the skin.

The test substance, compound SN4 -l38 -38 (CAS number not provided), was evaluated (supportive study by Wazeter, 1965) for primary skin irritation in the albino rabbit using what appears to be a standard technique in 1965. The results indicate that the test substance does not produce dermal irritation. The lack of explicit identity of the test item and the minimally described experimental procedure are the deficiencies of the report.

Overall, the skin irritation study results indicate that the test item is not irritating to the skin.

Eye: The acute eye irritation potential of Trigonox 44B (CAS 37-187-22-7) was assessed (key study by Rees, 1990) in 3 New Zealand White rabbits under the OECD 405 test guideline. Due to the severe response observed in one animal at 1 and 24 hours, this animal was humanely sacrificed. The test material was considered to be irritating to the eye with the potential to cause serious ocular damage. However, the ocular scores for the animals used on this study did not reach the EEC limit values for a positive result.

The compound tested in the study by Wazeter, 1965 (supportive study), was SN4 -138 -38 (hand written as D- 224, LUPERSOL-224), and is presumed to be CAS 37187 -22 -7. Instillation of the test agent into the unwashed eye of albino rabbits was evaluated (0.1 ml / rabbit) for evidence of irritation and damage. Observations were made for up to 7 days. Washing the eyes after the instillation of the test item was also evaluated. Scoring was done according to Lehman et al., 1959. The test was done with the critical elements of eye irritation testing approaches that were in practice in 1965, but no standard test guideline was cited. It was concluded that SN4-l38-38 is a severe eye irritant to the unwashed eye of the rabbit, but damage can be largely prevented by washing the eye immediately after instillation of the material. Delayed washing enhances the degree of irritation. Although the test was done with the critical elements of eye irritation testing approaches in practice in 1965, it has certain deficiencies, and thus resulted in a lower reliability rating.

Overall, the eye irritation study results, based on the Weight of Evidence, indicate that the test item can be irritating to the eye.

Justification for selection of skin irritation / corrosion endpoint:
A well conducted and well described, relatively recent key GLP study, according to OECD guidelines.

Justification for selection of eye irritation endpoint:
An apparently well conducted key GLP study, according to OECD guidelines.

Effects on eye irritation: irritating

Justification for classification or non-classification

Overall, the skin irritation results indicate that the test item is not irritating to the skin. The data are conclusive, but not sufficient for classification. Overall, the eye irritation results, based on the Weight of Evidence, indicate that the test item can be irritating to the eye and meets the criteria for Category 2. The data are conclusive, and the substance is classified as an irritating to the eye.