Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2005-08-08 to 2005-12-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Read-across
The basis for the read-across concept for this project is the equilibrium between sulfites, hydrogensulfites, and metabisulfites in aqueous solutions depending on pH value which is clearly described in published literature and summarised in the following equations:[1],[2]
SO2 + H2O <->`H2SO3´ H2SO3<->H+ + HSO3- <-> 2H+ +SO32- 2HSO3- <->H2O +S2O52 –
As the nature of the cation should make no significant difference in this case concerning toxicity and solubility (all compounds are very soluble in water), only the chemical and biological properties of the anion are considered relevant. Based on the described equilibrium correlations, we propose unrestricted read-across between the groups of sulfites, hydrogensulfites and metabisulfites. Additionally, it is known that sodium dithionite disproportionates in water to form sodium hydrogen sulfite and sodium thiosulfate (equation II) so that this substance can also be added to the read-across concept.[2],[1]
It is expected for this case that the substance is not stable enough under physiological conditions to fulfil the requirements of study guidelines and so the products of decomposition have to be considered.
2 S2O42-+ H2O→2HSO3-+ S2O32 -

All sulfite, hydrogensulfite and metabisulfite substances are highly soluble in water, establishing upon dissolution an equilibrium that depends on solution pH as follows: ,

1. SO2 + H2O <-> H2SO3
2. H2SO3 <-> H+ + HSO3- <-> 2H+ + SO32-
3. 2 HSO3- <-> H2O + S2O52-

Under oxidising conditions, e.g., in surface waters, sulfite is oxidized to sulfate catalytically by (air) oxygen or by microbial action. A half-life of 77 hour was measured in deionized water, already suggesting substantial abiotic degradation. However, the presence of metal cations in the environment, such as copper, iron and manganese, accelerates the oxidation rate. In soils, HSO3- and SO32- ions are unstable and quickly oxidise. Further, because of the instability of SO32-, metal sulfites are generally too soluble to persist in soils. Thus, the most stable and predominant sulfur form in freshwater and in all but highly reduced environments is sulfate (SO42-). In highly reduced soils and sediments, sulfites may be reduced to sulfides (Lindsay, 1979; OECD SIDS, 2012).

Only the properties of the sulfite anion are considered relevant determinants of environmental toxicity since respective cations, i.e. ammonium, calcium, magnesium, sodium and potassium, are not assumed to contribute substantially to differences therein. Sulfite, although naturally present in the environment and also a metabolite and intermediate of sulfur-containing amino acids in organisms, may have an impact on the environment at elevated levels. Sulfites do not bioaccumulate.

In sum, unrestricted read-across between the sulfites, hydrogensulfites and metabisulfites is justified.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2002-04-24
Deviations:
yes
Remarks:
, according to the guideline distilled water or saline should be used for rinsing the eye after treatment with the test item, but in the study tap water was used for rinsing the eye.
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Name of test material (as cited in study report): Hydrosulfit PF
- Physical state: Solid

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Strain: New Zealand White A1077 INRA (SPF)
- Source: Centre Lago S.A., 01540 Vonnas, France
- Age at study initiation: 3 - 4 months
- Weight at study initiation: 2.92 kg - 3.05 kg (Individual weights of the three animals: 2.92 kg (male), 3.00 kg (female), and 3.05 kg (male))
- Housing: The animals were housed individually. The animals were housed in fully air-conditioned rooms. Stainless steel wire mesh cages with grating, floor area: 3000 cm^2.
- Diet: Kliba-Labordiaet ((Kaninchen & Meerschweinchenhaltung "GLP") Provimi Kliba SA, Kaiseraugst, Basal, Switzerland), about 130 g/animal per day
- Water (ad libitum): Tap water
- Acclimation period: At least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24 °C
- Relative humidity: 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Each animal received a single application of 0.1 ml bulk volume (about 53 mg of the comminted test substance) of undiluted test substance into the conjunctival sac of the right eye. The untreated eye served as negative control.
Duration of treatment / exposure:
about 1 hour
Observation period (in vivo):
7 days; Readings of eye irritation were made approx. 1, 24, 48, and 72 h after application and on day 7.
Number of animals or in vitro replicates:
2 males / 1 female
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eye of the animal(s) was rinsed with 3 to 6 mL of hand warm tap water for 1 to 2 minutes using a syringe with a blunt probe.
- Time after start of exposure: About 1 hour after application of the solid test substance.

SCORING SYSTEM: Draize scoring system
In addition, evaluations were made of discharge from the eye and the area of cornea affected by the lesions.
Area of cornea involved (ar):
1 = >0≤1/4
2 = > 1/4< 1/2
3 = > 1/2 < 3/4
4 = >3/4

Discharge (di):
0 = No discharge
1 = Any amount different from normal (does not inlcude small amounts observed in inner canthus of normal animals)
2 = Discharge with moistening of the lids and hairs just adjacent to lids
3 = Discharge with moistening of the lids and hairs, and considerable area around the eye

TOOL USED TO ASSESS SCORE: Daylight tubes "Lumilux" (L 58W/860 PLUS ECO 25X1, Osram, Germany)

ADDITIONAL OBSERVSATION:
It was checked for dead or moribund animals twice each workday (beginning and end) and once on saturdays, sundays and on public holidays.
the body weight was determined just before application of the test substance and after the last reading.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
2.67
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
Moderate or severe conjunctival redness (grade 2 or 3) were noted in the animals from 1 hour up to 72 hours after application. Slight or moderate conjunctival chemosis (grade 1 or 2) were noted in all animals 1 hour after application. Slight conjunctival chemosis, observed in two animals after 24 and 48 hours, persisted in one animal up to 72 hours. Slight or moderate discharge (grade 1 or 2) was noted in all animals 1 hour after application, only.
Additionally, injected scleral vessels in a circumscribed area or circular were noted in all animals up to 24 hours after application.
The ocular reactions were reversible in all animals within 7 days after application.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Hydrosulfit PF is considered to be irritant to the eye.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is classified as Category 2.