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Description of key information

Studies of skin and eye irritation in the rabbit are available for sodium formate

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): natriumformiat
- Substance type: salt
- Physical state: white powder
- Analytical purity: 97%
Species:
rabbit
Strain:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Weight at study initiation: 2.9 kg

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 20-40
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg
Duration of treatment / exposure:
Single treatment
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm²


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 4 hours


SCORING SYSTEM: according to table contained in OECD TG 404
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
There were no skin reactions noted except from a slight (grade 1) edema seen in one of 3 animals at 24 hours after application of the test substance. This reaction was fully reversible within one day.
Interpretation of results:
GHS criteria not met
Conclusions:
Sodium formate was not a skin irritant.
Executive summary:

 In an OECD guideline 404 study, sodium formate was tested for its skin irritating properties under GLP conditions in three rabbits. Skin reactions were scored at 24, 48, and 72 hours after treatment according to the table contained in the guideline. There were no skin reactions noted except from a slight (Grade 1) Oedema in one of 3 animals at 24 hours after application. This reaction was fully reversible within one day.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
OECD TG 404 requires skin reactions immediately after patch removal and after 24, 48, and 72 hours thereafter. Study report contains only 72 hour readings. The report is either incomplete, or there are methodological defienciencies, e.g. 24 hour skin contact.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
either no readings at 24 and 48 hours, or the study report is incomplete
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material (as cited in study report): C-1261, sodium formate
Species:
rabbit
Strain:
not specified
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
physiological saline
Controls:
not required
Amount / concentration applied:
Concentration: 100 %
Duration of treatment / exposure:
24 hour(s)
Number of animals:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hours
Score:
0
Max. score:
4

There was no skin reaction (score = 0) at any treated site in any of the four animals tested.

Interpretation of results:
study cannot be used for classification
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Remarks:
Secondary source (ECB IUCLID 2000). The full report was not available for review.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Specific details on test material used for the study:
Sodium Formate.
Species:
rabbit
Strain:
not specified
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
not specified
Irritation parameter:
erythema score
Time point:
other: Not specified
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Time point:
other: Not specified
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation

Score: 0/8, no edemas or erythemas occurred.

Interpretation of results:
study cannot be used for classification
Conclusions:
No evidence of skin irritation was seen under the conditions of this study.
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

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
The nature and purity of the test material is unclear
Qualifier:
according to guideline
Guideline:
EPA OTS 798.4500 (Acute Eye Irritation)
GLP compliance:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): C-1261, sodium formate.
- Physical state: solid
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Summit View Farm,Hazleton, Pennsylvania, USA
- Age at study initiation: at least 8 weeks at study initiation.
- Housing: individually, in stainless steel cages
- Diet: standard rabbit diet ad libitum
- Water: tap water ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-21
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
Single dose
Observation period (in vivo):
Group I: 7 days (data not shown, because no readings made at 24 and 48 hours)
Group II: 17 days
Number of animals or in vitro replicates:
Group I: 4 animals
Group II: 6 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: according to EPA test guideline [similar to the table contained in OECD guideline No. 405 (1987)].

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
1.89
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
All six animals showed moderate to severe conjunctival irritation (redness, chemosis, and reversible changes) that was fully reversible. The mean redness score was 1.89 across all animals and readings at 24, 48, and 72 hours.
There were no effects on cornea or iris.

 

Eye reactions after instillation of 0.1 mL of sodium formate powder:

 

-      cornea: not affected

-      Iris: not affected

-      conjunctivae: all six animals exhibited moderate to severe conjunctival irritation, necrosis was seen in 4 of 6 animals. Necrosis was not further specified, but irritation and “necrosis” were reversible and absent in 5 animals on day 7 and in all animals on day 17.

Detail results are tabulated below.

 

 

Effect

Time

(hours)

Animal No.

1

2

3

4

5

6

Cornea

opacity

24

0

0

0

0

+

+

 

 

48

0

0

0

0

0

0

 

 

72

0

0

0

0

0

0

 

area

24

0

0

0

0

1

1

 

 

48

0

0

0

0

0

0

 

 

72

0

0

0

0

0

0

 

Ulceration

24

0F

0F

0F

0F

0F

0F

 

 

48

0F

0F

0F

0F

0F

0F

 

 

72

0

0

0

0

0

0

Iris

 

24

0

0

0

0

+

0

 

 

48

0

0

0

0

0

0

 

 

72

0

0

0

0

0

0

Conjunctivae

redness

24

2

2

2

2

2

2

 

 

48

2

2

2

2

2

2

 

 

72

1

2

2

2

2

1

Means

(24-72 h)

1.67

2.0

2.0

2.0

2.0

1.67

 

chemosis

24

0

1

1

1

1

1

 

 

48

0

1

1

0

1

0

 

 

72

0

0

0

0

0

0

 

 

 

Ulceration / necrosis

24

0

0

N

N

N

0

 

 

48

0

0

N

N

N

N

 

 

72

0

0

N

N

N

N

 

 

Day 7 or 17

0

0

0

0

0

0

 

N = necrosis
F = confirmed with 
fluorescein
+ = slight reaction

 

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Instillation of sodium formate powder caused reversible moderate to severe conjunctival reactions without affecting cornea or iris.
Four of the six animals have mean values for conjunctival redness of at least 2 (24/48/72 hours following installation of the test material) which was fully reversible within 7 days.
Executive summary:

In a study of eye irritating properties, 0.1 mL sodium formate was instilled into one eye of six rabbits. The study is equivalent to a guideline study (an OECD 405) and was conducted under GLP conditions. Eye reactions were evaluated according to the provisions of the OECD guideline No. 405. The observation period of up to 17 days allowed effects to subside. Following treatment, all six animals showed moderate to severe conjunctival irritation (redness, chemosis, and reversible changes) that was fully reversible. Chemosis was absent after 3 and redness after 7 days. The mean redness score was 1.89 across all animals and readings at 24, 48, and 72 hours, although four animals showed a mean score of grading at 24, 48 and 72 hours of at least 2.0. Changes of the nictitating membrane and conjunctivae subsided within 7 days in five and were absent in all animals on day 17 after treatment. There were no effects on cornea or iris noted at any time after dosing (Biodynamics, 1990).

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 30th - November 3rd 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes
Specific details on test material used for the study:
SAFEWAY SE; >97% Sodium formate; >98% purity. White crystalline powder
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: EA Prinzhorn, Germany
- Age at study initiation: Not reported
- Weight at study initiation: Not reported
- Housing: Individual
- Diet: Not reported
- Water: Not reported
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 30th October 1995 To: 3rd November 1995
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
Not applicable; single exposure
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
Three rabbits
Details on study design:
0.1 g of the unchanged test material was instilled into one (left) eye of three male NZW rabbits. The untreated (right) eye of each animal acted as a control. Ocular reactions were scored at up to 72 hours using the Draize scale.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
erythema
Basis:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of mild irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.11
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
probability of mild irritation
Other effects:
Slight ocular secretion was also noted in all animals at the 1-hour observation.

Summary of ocular findings

Finding

1h

24h

48h

72h

Mean (24-72h)

Cornea

Opacity

0,0,0

0,0,0

0,0,0

0,0,0

0.00

Iris

0,0,0

0,0,0

0,0,0

0,0,0

0.00

Conjunctivae

Erythema

2,2,3

1,0,1

1,0,0

0,0,0

0.33

Chemosis

1,1,2

0,0,1

0,0,0

0,0,0

0.11

Interpretation of results:
GHS criteria not met
Conclusions:
The results of this study indicate that sodium formate causes moderate transient eye irritation and is not classified for eye irritation according to the CLP criteria.
Executive summary:

The eye irritation potential of sodium formate was investigated in a GLP- and guideline (OECD 405)-compliant rabbit study. 0.1 g of the unchanged test material was instilled into one (left) eye of three male New Zealand White rabbits.  The untreated (right) eye of each animal acted as a control.  Ocular reactions were scored at up to 72 hours using the Draize scale.There were no corneal or iridic effects in any rabbit. There were no corneal or iridic effects in any rabbit. Initial conjunctival erythema (Grade 2 or 3) was seen in all animals but had resolved or decreased in severity to Grade 1 by 24 hours. Findings had resolved in all animals by 72 hours. Initial conjunctival chemosis (Grade 1 or 2) was seen in all animals but had resolved or decreased in severity to Grade 1 by 24 hours. Findings had resolved in all animals by 48 hours. Slight ocular secretion was also noted in all animals at the 1-hour observation. The results of this study indicate that sodium formate causes moderate transient eye irritation and is not classified for eye irritation according to the CLP criteria.

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:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Remarks:
Secondary source (ECB IUCLID 2000). The full report was not available for review.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Specific details on test material used for the study:
Sodium Formate.
Species:
rabbit
Strain:
not specified
Interpretation of results:
not irritating
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In an OECD guideline 404 study, sodium formate was tested for its skin irritating properties under GLP conditions in three rabbits. Skin reactions were scored at 24, 48, and 72 hours after treatment according to the table contained in the guideline. There were no skin reactions noted except for slight (Grade 1) oedema in one of 3 animals at 24 hours after application of the test substance. This reaction was fully reversible within one day. Thus, sodium formate lacks skin irritating properties (Försvarets Forskningsanstalt, 1988).

 

Eye irritation

In one study on the eye irritating properties, 0.1 mL sodium formate was instilled into one eye of six rabbits. The study is equivalent to a guideline study (OECD 405) and was conducted under GLP conditions. Eye reactions were evaluated according to the provisions of the guideline. The observation period of up to 17 days allowed effects to subside. Following treatment, all six animals showed moderate to severe conjunctival irritation (redness, chemosis, and reversible changes) that was fully reversible. Chemosis was absent after 3 and redness after 7 days. The mean redness score was 1.89 across all animals and readings at 24, 48, and 72 hours. Changes of the nictitating membrane and conjunctivae subsided within 7 days in five and were absent in all animals on day 17 after treatment. There were no effects on cornea or iris noted at any time after dosing (Biodynamics, 1990).  Although this study is guideline-compliant, the nature and purity of the test material is unclear and not reported. The study is not therefore considered to be adequately reliable for the purposes of hazard identification and classification. In an additional eye irritation study performed to GLP and OECD 405 and with characterised test material (Medcon, 1995), moderate transient eye irritation was seen but reactions are not sufficient to trigger classification according to the CLP criteria. Based on the results of reliable studies, sodium formate is not classified as a skin or eye irritant.

Justification for classification or non-classification

Based on the results of reliable studies, sodium formate is not classified as a skin or eye irritant according to the CLP criteria.