Sodium N-(hydroxymethyl)glycinate

Endpoint summary

Description of key information

In all tested animals with unwashed eyes, a positive response of corneal opacity ≥ 1 and iritis ≥ 1, and both conjunctival redness and conjunctival oedema (chemosis) ≥ 2. The same was found in two out of three animals with eyes washed out after exposure. In all cases, the effects were observed to be reversible within ≤ 14 days.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation / corrosion, other

Remarks:

Animal study from the period before entry into force of the in-vitro skin irritation requirement.

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study was subject to the EPA Guidelines for Good Laboratory Practice Standards 40 CFR Parts 160 & 792. The test method was performed according to the internationally accepted EPA guideline 81-5. Test substance data lacked purity.

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: Ace Animals, Boyertown, PA - Quarantine period of at least one week.- Sex: males- Weight at study initiation: 2.0 -2.2 kg.- identification: cage notation and a uniquely numbered metal eartag.- Housing: individually in wire-meshed cages with bedding. - Diet: Fresh Purina Rabbit Chow (Diet #5321).- Water: ad libitum.- Identification: ear tags and color coded cage cards- Animal room: reserved exclusively for rabbits on acute tests, temperature controlled with a 12 hour light/dark cycle, and kept clean and vermin free.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

5 % or 0.5 %

Controls:

not required

Amount / concentration applied:

100% -Test substance as such

Duration of treatment / exposure:

4h

Observation period:

72 h in total

Number of animals:

6

Details on study design:

TEST SITE- Clipping: The day prior to application of the test article, the dorsal area of the trunk of each animal was clipped free of hair. The prepared site was approximately 1 O x 15 cm and remained intact. - Application: TEST SUBSTANCE:- 0.5 g of the test article was placed under a 2.5 x 2.5 cm, moistened 4 ply, surgical gauze patch. Gentle pressure was applied to the gauze to aid in the distribution of the test substance over the prepared site. The patch was secured with non-irritating tape. The torso was wrapped with plastic in a semi-occlusive manner and secured with non-irritating tape which completely covered the plastic.SCORING:- The test sites were scored for dennal irritation at 30 to 60 minutes after removal of wrappings. Reactions were scored again at 24, 48 and 72 hours following patch removal. - Erythema and edema were scored according to the numerical Draize technique below. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction. EVALUATION:Erythema & Eschar:- 0= No erythema - 1= Very slight erythema (barely perceptible) - 2= Well defined erythema - 3= Moderate to severe erythema - 4= Severe erythema (beet redness) to slight eschar formation (injuries in depth) Edema: - 0= No edema - 1= Very slight edema (barely perceptible) - 2= Slight edema (edges of area well-defined by definite raising) - 3= Moderate edema (raised approximately 1.0 mm) - 4= Severe edema (raised more than 1.0 mm, extending beyond the area of exposure)- In evaluating the average irritation, scores for individual intact and abraded exposure sites were recorded separately for each of the two scoring time intervals. A total for erythema and eschar formation was added to a total for edema then divided by 4 to yield the individual animal score. - The mean of the three scores was calculated and this score represents the mean primary irritation score. Analysis of Data:- Dermal irritation is the production of reversible inflammatory changes in the skin following exposure to the test article. - Dermal corrosion is the production of irreversible tissue damage to the skin fallowing exposure to the test article.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 30-60 minutes

Score:

0.5

Remarks on result:

other: Individual scores: 0;0;0;1;1;1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24h

Score:

0.33

Remarks on result:

other: Individual scores: 0,0,0,1,0,1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 48 + 72 h

Score:

0

Reversibility:

fully reversible

Remarks on result:

other: Individual scores: 0; 0; 0; 0; 0; 0.

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 30 - 60 minutes

Score:

0.17

Remarks on result:

other: Individual scores: 0;0;0;0;0;1.

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 + 48 + 72 h

Score:

0

Reversibility:

fully reversible

Remarks on result:

other: Individual scores: 0;0;0;0;0;0.

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Suttocide®A was determined to be slightly irritating to the skin of rabbits, when administered as such.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

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: GLP study performed according to an internationally accepted guideline. Exact purity of the test substance not specified.

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS- Source: Ace Animals, Boyertown, PA on 1/07/97 - Weight at study initiation: 2.0 - 2.3 kilograms (young adults)- System of Identification: Cage number and ear tag.- Housing: individually in cages sized in accordance with bedding.- Diet: Fresh Purina Rabbit Chow (Diet #5321), ad libitum.- Water: fresh tap water, ad libitum. ENVIRONMENTAL CONDITIONS- Light cycle - 12 hours light, 12 hours dark.

Vehicle:

unchanged (no vehicle)

Remarks:

50%-solution

Controls:

not required

Amount / concentration applied:

0.1 ml equivalent (90 mg)/treated eye

Duration of treatment / exposure:

The test substance was placed in one eye of each animal by gently pulling the lower lid away from the eyeball (conjunctival cul-de-sac) to form a cup. The upper and lower lids were then gently held together for one second to prevent loss of material. The contralateral eye remained untreated and served as a control. The eyes of six rabbits remained unwashed. The eyes of the other three were washed with 20 ml of distilled water 30 seconds postdose.

Observation period (in vivo):

at 1, 24, 48 and 72 hours and on Days 7 and 14 after treatment

Number of animals or in vitro replicates:

9

Details on study design:

Scoring and grading of irritation was according to the method of Draize J.H. (1965), Appraisal of the Safety of chemicals in Food, Drugs and Cosmetics - Dermal Toxicity, page 49-52. Association of Food and Drug Officials of the U.S., Topeka, Kansas.

Irritation parameter:

overall irritation score

Remarks:

No wash out

Basis:

animal #1

Time point:

other: 1 to 14 days

Score:

>= 0 - <= 41

Max. score:

110

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Max individual irritation score: 3 (Conjunctivae)

Irritation parameter:

overall irritation score

Remarks:

No wash out

Basis:

animal #2

Time point:

other: 1 to 14 days

Score:

>= 0 - <= 39

Max. score:

110

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Max individual irritation score: 3 (Conjunctivae)

Irritation parameter:

overall irritation score

Remarks:

No wash out

Basis:

animal #3

Time point:

other: 1 to 14 days

Score:

>= 0 - <= 49

Max. score:

110

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Max individual irritation score: 3 (Cornea and conjunctivae)

Irritation parameter:

overall irritation score

Remarks:

No wash out

Basis:

animal #4

Time point:

other: 1 to 14 days

Score:

>= 0 - <= 24

Max. score:

110

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Max individual irritation score: 3 (Conjunctivae)

Irritation parameter:

overall irritation score

Remarks:

No wash out

Basis:

animal #5

Time point:

other: 1 to 14 days

Score:

>= 0 - <= 39

Max. score:

110

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Max individual irritation score: 3 (Conjunctivae)

Irritation parameter:

overall irritation score

Remarks:

No wash out

Basis:

animal #6

Time point:

other: 1 to 14 days

Score:

>= 0 - <= 27

Max. score:

110

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Max individual irritation score: 2 (Cornea and conjunctivae)

Irritation parameter:

overall irritation score

Remarks:

Washed out

Basis:

animal #1

Time point:

other: 1 to 14 days

Score:

>= 0 - <= 6

Max. score:

110

Reversibility:

fully reversible within: 2 days

Remarks on result:

other: Max individual irritation score: 2 ((Conjunctivae: discharge)

Irritation parameter:

overall irritation score

Remarks:

Washed out

Basis:

animal #2

Time point:

other: 1 to 14 days

Score:

>= 0 - <= 27

Max. score:

110

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Max individual irritation score: 3 (Conjunctivae: redness)

Irritation parameter:

overall irritation score

Remarks:

Washed out

Basis:

animal #3

Time point:

other: 1 to 14 days

Score:

>= 0 - <= 29

Max. score:

110

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Max individual irritation score: 3 (Conjunctivae: chemosis)

Interpretation of results:

slightly irritating

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

When administered as a 50% aqueous solution: the degree of ocular irritation was minimal to slight and involved only the conjunctivae. The irritation was also reversible by day 10 after instillation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Most studies reported show only a slight irritation of the skin of test animals exposed to the substance.

Eye irritation:

When administered as a 50% aqueous solution in the key study, the degree of ocular irritation was slight to moderate and involved the cornea, iris and conjunctivae. In all tested animals with unwashed eyes, a positive response of corneal opacity ≥ 1 and iritis ≥ 1, and both conjunctival redness and conjunctival oedema (chemosis) ≥ 2. The same was found in two out of three animals with eyes washed out after exposure. In all cases, the effects were observed to be reversible within ≤ 14 days. Other supporting studies confirmed the slight to moderate eye irritancy of the substance, which was reversible within the observation periods.

Justification for selection of skin irritation / corrosion endpoint:
GLP study according to an internationally accepted guideline with substance applied as such moistened with destilled water.

Justification for selection of eye irritation endpoint:
GLP study according to an internationally accepted guideline.

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: moderately irritating

Justification for classification or non-classification

The results of the studies on skin and eye irritation confirm a low to mild potency of irritation due to exposure to the substance. The data of the key study supports classification of sodium n-(hydroxymethyl) glycinate as irritating to eyes category 2. The key studies on skin irritation show that the potency of sodium n-(hydroxymethyl) glycinate to induce irritation is not conclusive to support classification.