1,1,3,3-tetramethylguanidine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

other: cross reference to skin irritation study

Adequacy of study:

weight of evidence

Study period:

11 May 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 May 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

(occlusive dressing; no information on skin reactions after 3 min of exposure)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Morton Commercial Rabbits, Parsonage Farm, Stansted, Essex, UK
- Age at study initiation: at least 11 weeks
- Weight at study initiation: 3.46 kg
- Housing: single in a grid floor cage
- Diet: Standard Rabbit Diet (Special Diets Services Ltd., Stepfield, Witham, Essex, UK), ad libitum
- Water: mains water, ad libitum
- Acclimation period: at least 3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 13 - 20
- Humidity (%): 40 - 47
- Photoperiod (hrs dark / hrs light): 10 / 14

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

1 h (the study was terminated after 1 h for humane reasons)

Observation period:

The study was terminated after 1 h of treatment for humane reasons.

Number of animals:

1 female animal (owing to the very high pH of the diluted test article)

Details on study design:

TEST SITE
- Area of exposure: back (6 cm2)
- Type of wrap if used: gauze patch; the patch was occluded and secured using a strip of impermeable adhesive tape (Sleek, Smith & Nephew, Welwyn Garden City, Herts, UK)

REMOVAL OF TEST SUBSTANCE
- Washing: The skin wiped gently with a disposable paper towel moistened with water.
- Time after start of exposure: 1 h

SCORING SYSTEM: Immediately on removal of the patches severe tissue damage was observed. No scoring of the skin irritation could be made. The animal was killed and the study terminated for humane reasons.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

> 4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: corrosive

Remarks:

The study was terminated after 1 h and the severe tissue damage precluded any scoring of erythema or edema. The animal was killed for humane reasons and the study terminated. Hence, reversibility of the local effects could not be determined.

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

> 4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: corrosive

Remarks:

The study was terminated after 1 h and the severe tissue damage precluded any scoring of erythema or edema. The animal was killed for humane reasons and the study terminated. Hence, reversibility of the local effects could not be determined.

Irritant / corrosive response data:

Vocalisation was noted 2 minutes after application of the test article. The patch was removed after one hour and the severe tissue damage precluded any scoring of erythema or edema. The animal was killed for humane reasons and the study terminated.

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: Skin corr. 1B, H314

Executive summary:

The study was performed 1982, following the DOT (Transport Classification) Guidelines. The study was terminated after 1 h and the animal was killed for humane reasons. Therefore, the substance is classified as skin corrosive 1B, H314 according to Regulation (EC) 1272/2008.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD 404

Version / remarks:

As the test substanceis a strong base (pH > 11.5) and meets the classification criteria both for Skin corr. 1B, H314 and Flam. Liquid 3 according to Regulation EC 1272/2008, no eye irritation study is needed to fulfill the data requirements defined in REACH Annex VII.

Deviations:

not applicable

Remarks:

OECD 405 was not performed due to classification as corrosive.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

1,1,3,3-tetramethylguanidine

EC Number:

201-302-7

EC Name:

1,1,3,3-tetramethylguanidine

Cas Number:

80-70-6

Molecular formula:

C5H13N3

IUPAC Name:

N,N,N',N'-tetramethylguanidine

Details on test material:

- Name of test material (as cited in section 1): 1,1,3,3-Tetramethylguanidine

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Morton Commercial Rabbits, Parsonage Farm, Stansted, Essex, UK
- Age at study initiation: at least 11 weeks
- Weight at study initiation: 3.46 kg
- Housing: single in a grid floor cage
- Diet: Standard Rabbit Diet (Special Diets Services Ltd., Stepfield, Witham, Essex, UK), ad libitum
- Water: mains water, ad libitum
- Acclimation period: at least 3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 13 - 20
- Humidity (%): 40 - 47
- Photoperiod (hrs dark / hrs light): 10 / 14

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 mL test material in the skin irritation study

Duration of treatment / exposure:

1 h (the study was terminated after 1 h for humane reasons).

Observation period (in vivo):

1 h (the study was terminated after 1 h for humane reasons)

Number of animals or in vitro replicates:

1 female animal (owing to the very high pH of the diluted test article)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: < 1 h

Score:

>= 3

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other: corrosive

Remarks:

As the test substance is a strong base (pH > 11.5) and meets the classification criteria for skin corr. 1B, the eye irritation was not performed, hence the score based on the GHS/CLP criteria.

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: < 1h

Score:

> 1.5

Max. score:

1.5

Reversibility:

not reversible

Remarks on result:

other: corrosive

Remarks:

As the test substance is a strong base (pH > 11.5) and meets the classification criteria for skin corr. 1B, the eye irritation was not performed, hence the score based on the GHS/CLP criteria.

Irritant / corrosive response data:

Vocalisation was noted 2 minutes after application of the test article in the skin irritation test. The patch was removed after one hour and the severe tissue damage precluded any scoring of erythema or edema. The animal was killed for humane reasons and the study terminated.
As the test substance is a strong base (pH > 11.5) and meets the classification criteria both for Skin corr. 1B, H314 and Flam. Liquid 3 according to Regulation EC 1272/2008, no eye irritation study is needed to fulfill the data requirements defined in REACH Annex VII.
Therefore, the score based on the GHS/CLP criteria.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

According to Column 2 of REACH Annex VII an in vivo eye irritation study (required in Section 8.2 of REACH Annex VII) does not need to be conducted if 1) the available information indicates that the criteria are met for classification as corrosive to the skin or irritating to eyes, or 2)
the substance is flammable in air at room temperature. As the test substanceis a strong base (pH > 11.5) and meets the classification criteria both for Skin corr. 1B, H314 and Flam. Liquid 3 according to Regulation EC 1272/2008, no eye irritation study is needed to fulfill the data requirements defined in REACH Annex VII.

Executive summary:

According to Column 2 of REACH Annex VII an in vivo eye irritation study (required in Section 8.2 of REACH Annex VII) does not need to be conducted if 1) the available information indicates that the criteria are met for classification as corrosive to the skin or irritating to eyes, or 2) the substance is flammable in air at room temperature. As the test substanceis a strong base (pH > 11.5) and meets the classification criteria both for Skin corr. 1B, H314 and Flam. Liquid 3 according to Regulation EC 1272/2008, no eye irritation study is needed to fulfill the data requirements defined in REACH Annex VII. The score based on the GHS/CLP criteria. Therefore, the substance will be classified as serious eye damage category 1, H318 according to GHS criteria.